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pubmed_699_14395
Rice production has increased significantly with the efforts of international research centers and national governments in the past five decades. Nonetheless, productivity improvement still needs to accelerate in the coming years to feed the growing population that depends on rice for calories and nutrients. This challenge is compounded by the increasing scarcity of natural resources such as water and farmland. This article reviews 17 ex-post impact assessment studies published from 2016 to 2021 on rice varieties, agronomic practices, institutional arrangements, information and communication technologies, and post-harvest technologies used by rice farmers. From the review of these selected studies, we found that stress-tolerant varieties in Asia and Africa significantly increased rice yield and income. Additionally, institutional innovations, training, and natural resource management practices, such as direct-seeded rice, rodent control, and iron-toxicity removal, have had a considerable positive effect on smallholder rice farmers' economic well-being (income and rice yield). Additional positive impacts are expected from the important uptake of stress-tolerant varieties documented in several Asian, Latin American, and African countries.
10.1016/j.gfs.2022.100628
pubmed_238_512
Ge-core/a-Si-shell nanowires were synthesized in three consecutive steps. Nominally undoped crystalline Ge nanowires were first grown using a vapor-liquid-solid growth mechanism, followed by gold catalyst removal in an etching solution and deposition of a thin layer of amorphous silicon on the nanowire surface using a chemical vapor deposition method. Catalyst removal is necessary to avoid catalyst melting during temperature increase prior to a-Si shell deposition. Field effect transistors based on Ge-core/a-Si-shell nanowires exhibited p-channel depletion-mode characteristics as a result of free hole accumulation in the Ge channel. Scaled on-currents and transconductances up to 3.1 mA μm-1 and 4.3 mS μm-1, respectively, as well as on/off ratios and field-effect hole mobilities up to 102 and 664 cm2 V-1 s-1, respectively, were obtained for these Ge-core/a-Si-shell nanowire FETs. The minimum subthreshold slope was measured to be 300 mV dec-1. The present work also demonstrates for the first time the conductance quantization in one-dimensional Ge-core/a-Si-shell nanowires at low temperatures. The quantization of conductances at discrete values of G 0 = 2e 2/h at low temperatures suggests that our Ge-core/a-Si-shell nanowires are multi-mode ballistic conductors with a mean-free-path up to 500 nm. The results provided here are relevant for the synthesis of high-quality Ge-core/Si-shell nanowires for high-mobility devices with transparent contacts to hole carriers.
10.1039/d0na00023j
pubmed_156_369
Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P < 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.
10.1113/jphysiol.2003.055202
pubmed_497_2738
A series of 58 operations on 36 patients were performed for decompression of the posterior tibial nerve for the treatment of diabetic neuropathy. Preoperative symptoms included lack of sensation, pain, or both. Eleven of the 36 patients had neurotrophic ulcers, which were treated simultaneously. The operation was found to be effective for relief of pain in 24 of the 28 patients with that complaint (86 percent). Restoration of sensation was less consistent with improvement noted in 18 of the 36 patients (50 percent). The follow-up period ranged from 12 to 84 months (mean, 32 months) and five patients had some degree of recurrent symptoms. No patient has developed a new ulcer after nerve decompression. Wound complications were minimal (12 percent), even though ulcers were treated simultaneously. No patient required surgical treatment for the decompression incision, although one did require hospital admission for treatment of a wound infection. In general, the procedure seemed to be a worthwhile treatment, which should be considered ill selected diabetics with symptomatic neuropathy.
10.1097/00006534-200009020-00009
pubmed_963_5170
OBJECTIVES Hypofunctioning benign cystic thyroid nodules are a common occurrence in iodine deficient region. There are reports of resolution of recurrent thyroid cysts with tetracycline instillation. Hence we conducted a study in 20 patients with hypofunctioning benign cystic thyroid nodules to document response to intracystic instillation of tetracycline as a primary modality of treatment. METHODS Twenty patients were thoroughly investigated for the presence of malignancy clinically, radiologically and cytologically. One milliliter of tetracycline was instilled under ultrasonographic guidance. Response to therapy was assessed clinically and ultrasonographically at one, three, six and 12 months. RESULTS Study group comprised of five male and 15 female patients with mean age 30 +/- 8 years. Initial mean volume of nodules was 15 +/- 7 ml (6 to 27 ml), which was decreased to 3 +/- 3 ml at one month, 2 +/- 3 ml at three months, and 1 +/- 2 ml at six months. Maximum number of patients (75%) responded within three months, however two patients required reaspiration and reinstallation of tetracycline. Ultrasonography revealed fibrotic scar as thick wall with internal echodensities in six patients (30%) six month after sclerotherapy. There was high rate of patient satisfaction, as cosmetically tetracycline did not leave any scar, which was unavoidable with surgery. Six patients (30%) reported mild pain after injection, and one patient developed redness at the site of injection. CONCLUSIONS Intracystic tetracycline sclerotherapy is highly effective as primary mode of treatment in hypofunctioning benign cystic thyroid nodule in selected group of patients not at high risk of malignancy.
pubmed_963_5170
pubmed_779_11026
Intracytoplasmic sperm injection (ICSI) is a commonly used in vitro fertilization technique. Selection of sperm for injection is currently done using subjective assessment of morphology, which may not accurately identify the best-quality sperm. Hyaluronic acid receptors on sperm plasma membranes are a marker of maturity, and sperms which are capable of binding immobilized hyaluronic acid in vitro are of higher quality. This can be used as an advanced sperm selection technique to choose sperm for ICSI, termed physiological ICSI (PICSI). Several studies reported improved fertility treatment outcomes when using PICSI compared with conventional ICSI; however, the majority of studies are underpowered. Recently, a large, multicenter, randomized controlled trial, known as the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial, found a significant reduction in miscarriage rates with PICSI, but no significant effect on live birth rate. There are still many avenues through which PICSI may provide an advantage, subject to confirmation by future research, such as improved long-term health of offspring. Other advanced sperm selection techniques include intracytoplasmic morphologically selected sperm injection, magnetic-activated cell sorting, and Zeta potential sperm selection; however, the most recent Cochrane review concluded that there is currently insufficient evidence to ascertain whether these techniques improve clinical outcomes, such as live birth rates.
10.1055/s-0041-1732313
pubmed_64_15578
Studying the human health impacts of pesticides and their endocrine disruptor (ED) effects is a public health concern. The aim of this study is to identify phytopharmaceutical active substances (PAS) that are an ED or are toxic on endocrine glands (TEG), and to propose an ED/TEG effect indicator. Five international official databases were analyzed to identify the occurrence of health outcomes for 458 PAS. Health outcomes targeting seven endocrine systems were selected. For each substance, the level of evidence of the collected information and the number of outcomes were used to affect a level of concern about ED/TEG effects. Among the substances studied, 10% had a global ED/TEG effect classified as 'high concern', 55% as 'medium concern', 9% as 'low concern', and 26% as 'unknown'. Ten of the high ED/TEG concern substances and 170 medium or low concern substances were licensed in 2018 in France. The outcomes were mainly on the reproductive organs, thyroid, and adrenal glands. Eight of the 41 biocontrol products studied were classified: 5 were 'high' or 'medium concern' and 3 had 'unknown effect'. Although the proposed ED/TEG indicator is not an official classification, it can be used as an epidemiological tool for classifying the occupational and environmental risks of substances in retrospective population studies and be useful for occupational health physicians.
10.3390/ijerph18073477
pubmed_251_15028
OBJECTIVE To determine the efficacy and toxicity of paclitaxel in advanced or recurrent adenocarcinoma of the endometrium. METHODS Thirty patients with advanced or recurrent endometrial cancer with measurable disease not previously treated with chemotherapy were treated with paclitaxel, 250 mg/m2, over 24 hr with G-CSF, 5 mcg/kg/day, from Days 2 to 12. The cycle was repeated every 21 days. Patients who had received previous pelvic radiation were treated at an initial paclitaxel dose of 200 mg/m2. Twenty-eight patients were evaluable for response, and 29 patients for toxicity. All patients were Gynecologic Oncology Group performance status 0,1, or 2. RESULTS Complete responses were observed in 4 (14.3%) and partial responses in 6 patients (21.4%) for a response rate of 35.7%. Severe (grade 3 or 4) leukopenia or thrombocytopenia was seen in 18 and 2 patients, respectively. Grade 3 or 4 gastrointestinal toxicity was seen in 5, neurotoxicity in 3, anemia in 2, and cardiac toxicity in 1 patients. Alopecia was reported in 16 patients. CONCLUSIONS This dose and schedule of paclitaxel are active in patients with advanced or recurrent adenocarcinoma of the endometrium and should be considered for inclusion in phase III trials.
10.1006/gyno.1996.0227
pubmed_553_2579
Among 854 coronary angiograms, we found the following abnormalities of the coronary arteries. Three cases had nonatherosclerotic coronary artery aneurysms. One case, a 27-year-old man with a diffuse lesion, expired after two episodes of myocardial infarction. In 2 other cases the lesions were localized and the patients underwent successful coronary bypass surgery. In 2 cases, a small vascular network was found: a 23-year-old man with pheochromocytoma who also had myocardial injury and pulmonary edema, and a case with contusio cordis who had angina pectoris but had normal coronary arteries. In 3 cases the coronary arteries originated abnormally from the aorta. A congenital right coronary artery-right ventricular fistula was detected in a 17-year-old female with multiple cardiac abnormalities. Abnormally wide coronary arteries were also found in 17 cases with apical hypertrophy, a form of hypertrophic nonobstructive cardiomyopathy.
10.1536/ihj.23.725
pubmed_303_6247
After retrospective in intensive care unit of 100 severe cases of pneumococcal infection in three years, the authors analyse the circumstances of onset (occurring in autumn of winter), the general status (without evident high risk population), the symptomatology (84% of meningitis, 30% of pneumonia), the origin of infection (essentialy otitis media in meningitis). The case fatality rate is 39%. Frequency of multiple visceral localisations and of bacteremias is emphasized.
pubmed_303_6247
pubmed_810_20927
Strong evidence has accumulated over the last several years, showing that low sleep quantity and/or quality plays an important role in the elevation of blood pressure. We hypothesized that increasing sleep duration serves as an effective behavioral strategy to reduce blood pressure in prehypertension or type 1 hypertension. Twenty-two participants with prehypertension or stage 1 hypertension, and habitual sleep durations of 7 h or less, participated in a 6-week intervention study. Subjects were randomized to a sleep extension group (48 ± 12 years, N = 13) aiming to increase bedtime by 1 h daily over a 6-week intervention period, or to a sleep maintenance group (47 ± 12 years, N = 9) aiming to maintain habitual bedtimes. Both groups received sleep hygiene instructions. Beat-to-beat blood pressure was monitored over 24 h, and 24-h urine and a fasting blood sample were collected pre- and post-intervention. Subjects in the sleep extension group increased their actigraphy-assessed daily sleep duration by 35 ± 9 min, while subjects in the sleep maintenance condition increased slightly by 4 ± 9 min (P = 0.03 for group effect). Systolic and diastolic beat-to-beat blood pressure averaged across the 24-h recording period significantly decreased from pre- to post-intervention visit in the sleep extension group by 14 ± 3 and 8 ± 3 mmHg, respectively (P < 0.05). Though the reduction of 7 ± 5 and 3 ± 4 mmHg in the sleep maintenance group was not significant, it did not differ from the blood pressure reduction in the sleep extension group (P = 0.15 for interaction effect). These changes were not paralleled by pre- to post-intervention changes in inflammatory or sympatho-adrenal markers, nor by changes in caloric intake. While these preliminary findings have to be interpreted with caution due to the small sample size, they encourage future investigations to test whether behavioral interventions designed to increase sleep duration serve as an effective strategy in the treatment of hypertension.
10.1111/jsr.12011
pubmed_23_11951
Faecal bile acids have long been associated with colon cancer; highly hydrophobic bile acids, which induce apoptosis, have been implicated in the promotion of colon tumours. The moderately hydrophobic chemopreventive agent ursodeoxycholic acid (UDCA) does not induce apoptosis; rather, it causes colon-derived tumour cells to arrest their growth. To investigate the relationship between bile acid hydrophobicity and biological activity we examined 26 bile acids for their capacity to induce apoptosis or alter cell growth. We found that the rapidity with which, and the degree to which, bile acids could induce apoptosis or growth arrest was correlated with their relative hydrophobicities. Of the bile acids tested, only deoxycholic acid (DCA) and chenodeoxycholic acid, the most hydrophobic bile acids tested, could induce apoptosis in less than 12 h in the human colon cancer cell line HCT116. The moderately hydrophobic bile acids hyoDCA, lagoDCA, norDCA, homoUDCA and isoUDCA induced growth arrest at 12 h but longer incubations resulted in apoptosis. Conjugation of glycine or taurine to the bile acids decreased relative hydrophobicity and eliminated biological activity in our assays. In addition, we tested a subset of these bile acids for their ability to translocate across cell membranes. When (14)C-labelled and (3)H-labelled DCA, UDCA and lagoDCA were added to cell cultures, we found only minimal uptake by colon cells, whereas hepatocytes had considerably higher absorption. These experiments suggest that hydrophobicity is an important determinant of the biological activity exhibited by bile acids but that under our conditions these activities are not correlated with cellular uptake.
10.1042/0264-6021:3560481
pubmed_641_1263
Cases of Mallory-Weiss syndrome aged over 75 year were analyzed with regard to their clinical features. In a 5-year period, there were 9 such cases, representing 19% of the total number of Mallory-Weiss syndrome cases. Four patients had a history of retching or vomiting, but in the other 5 patients, Mallory-Weiss tears occurred during endoscopic examination with slight vomiting reflex or even almost vomiting reflex. The latter cases had a spindle-shaped tear which was located on the lesser curvature at the cardia of the stomach. All patients were managed conservatively by observation without endoscopic hemostatic procedure, because the amount of bleeding was small. The 5 patients were thin and three of them had chronic atrophic gastritis. Mucosal weakness is an important etiologic factor in aged patients who develop Mallory-Weiss syndrome.
10.3143/geriatrics.31.374
pubmed_984_3171
BACKGROUND AND AIM End-stage liver failure is associated with severe abnormalities in menstrual and reproductive function. These abnormalities may be reversed by successful orthotopic liver transplantation (OLT). The aim of the study was to investigate menstrual patterns and sex hormone profiles among female liver transplant recipients of reproductive age. METHODS The study group consisted of 24 women of reproductive age with end-stage liver failure who underwent successful OLT. Menstrual patterns and sex hormone profiles were analyzed before as well as 3 and 12 months after OLT. Twenty-seven healthy women of reproductive age served as controls. Biochemical parameters of liver function were assessed before and after OLT. RESULTS Amenorrhea was the most commonly observed abnormality of menstrual cycle in women with end-stage liver failure (71% of patients). The recurrence of regular menstrual cycles was observed in 35% of patients 3 months after OLT. The percentage increased to 70% at 1 year after grafting and was clearly associated with stabilization of liver function. Similar levels of follicle stimulation hormone (FSH), luteinizing hormone (LH), prolactine (PRL), and testosterone (T) as well as lower levels of estradiol (E(2)), dehydroepiandrostendione sulphate (DHEA-S), and progesterone, (P) were observed in patients with liver failure compared with healthy women. We observed normalization of E(2) and DHEA-S levels after OLT. CONCLUSIONS Amenorrhea, the most common menstrual disturbance in women with end-stage liver failure, may be reversed by OLT. One year after OLT menstrual bleedings were noted in 74% of patients of reproductive age. The recurrence of reproductive function indicated the need for effective and safe family planning methods in that group of patients.
10.1016/j.transproceed.2009.03.073
pubmed_835_26241
OBJECTIVES Patients with cystic fibrosis (CF) increasingly require imaging for the diagnosis of abdominal complications. We prospectively evaluated the image quality and signal-to-noise ratio (SNR) of a modern radial volumetric encoding (RAVE) T2/T1 hybrid sequence for abdominal magnetic resonance imaging (MRI). RAVET2/T1 is a three-dimensional radial sequence with fat saturation and blood flow suppression that acquires T2- and T1-weighted contrasts in one scan in an identical slice position during free-breathing. METHODS Sixteen CF patients underwent axial T2 HASTE (1000 ms/93 ms TR/TE), T1 DIXON (6.8 ms/2.4 ms/4.8 ms TR/TE1/TE2), and RAVE T2/T1 hybrid sequence (1200 ms/1.7 ms/3.3 ms/4.9 ms/102 ms TR/TE1/TE2/TE3/TE4) of the upper abdomen at 1.5 Tesla. The SNR values in six different regions were assessed and compared using the Wilcoxon signed-rank test. The image quality criteria were rated on a 5-point Likert scale. RESULTS In all regions, the SNR was significantly higher in the T2 weighted aspect of the RAVE T2/T1 hybrid sequence compared to T2 HASTE (p < 0.05) and significantly lower in the T1 weighted in-phase aspect of the RAVE T2/T1 hybrid sequence compared to the T1 DIXON sequence (p < 0.05). Qualitatively the T2 weighted aspect of the RAVE T2/T1 hybrid sequence was rated significantly higher than the T2 HASTE in 6 of 7 categories (p < 0.05) and the T1 weighted in-phase aspect of the RAVE T2/T1 hybrid sequence was rated significantly higher than the T1 DIXON in 2 of 6 categories (p < 0.05). CONCLUSIONS The abdominal radial RAVE T2/T1 hybrid sequence provided higher image quality and SNR than the T2HASTEsequence. Together with increased robustness against motion artifacts, the RAVE T2/T1 hybrid sequence appears to be a good tool for abdominal imaging in CF patients.
10.1016/j.ejrad.2022.110454
pubmed_6_16353
BACKGROUND Androgen deficiency affects men in the adulthood, causing several harmful effects at the reproductive and behavioural levels. Since aromatase is an enzyme that catalyses the conversion of androgens to estrogens, and it is responsible for an adequate balance of both sex hormones in males and females, the administration of molecules acting as down modulators may contribute to restore an abnormal enzymatic activity. A prospective pilot study was carried out to investigate the effect of D-chiro-inositol, a putative aromatase down-modulator, on serum levels of testosterone, estradiol, estrone, dehydroepiandrosterone and epiandrosterone from a group of adult male volunteers. Glucose, insulin, follicle-stimulating hormone, luteinizing hormone, inhibin B, D-chiro-inositol and myo-inositol serum levels were also measured. RESULTS Male volunteers were selected according to age and body mass index. Subjects with altered glycemia and/or hormonal status, due to advanced age or abnormal weight, were enrolled in the study. Each of the 10 volunteers enrolled took oral D-chiro-inositol (1 g/day) for 1 month. Serum assays of selected markers were performed at baseline (control) and after treatment. D-chiro-inositol administration was associated to reduced serum levels of estrone (- 85.0%) and estradiol (- 14.4%), and increased serum levels of testosterone (+ 23.4%) and dehydroepiandrosterone (+ 13.8%). In addition, epiandrosterone levels were higher (+39%) after treatment. On the other hand, follicle-stimulating hormone, luteinizing hormone and inhibin B did not change. A trend toward a decrease of glycemia, insulinemia and Homeostatic Model Assessment index was observed after D-chiro-inositol treatment, although differences did not reach statistical significance. D-chiro-inositol treatment did not cause any noticeable adverse effect. CONCLUSIONS Increased androgens and decreased estrogens seem to confirm that D-chiro-inositol acts as an aromatase down-modulator, but with a still unknown mechanism of action. This pilot study opens up new perspectives of research and therapeutic applications for D-chiro-inositol at different dosages and length of treatment. Authorization number 005/2020 released by the Local Ethics Committee of Alma Res Fertility Center, Rome. TRIAL REGISTRATION NUMBER NCT04615767 (registry: ClinicalTrials.gov) Date of registration: November 3, 2020.
10.1186/s12610-021-00131-x
pubmed_973_22258
Selective breeding of rats exhibiting differences in novelty-induced locomotion revealed that this trait predicts several differences in emotional behavior. Bred High Responders (bHRs) show exaggerated novelty-induced locomotion, aggression, and psychostimulant self-administration, compared to bred Low Responders (bLRs), which are inhibited and prone to anxiety- and depression-like behavior. Our breeding studies highlight the heritability of the bHR/bLR phenotypes, although environmental factors like maternal care also shape some aspects of these traits. We previously reported that HR vs. LR mothers act differently, but it was unclear whether their behaviors were genetically driven or influenced by their pups. The present study (a) used cross-fostering to evaluate whether the bHR/bLR maternal styles are inherent to mothers and/or are modulated by pups; and (b) assessed oxytocin and oxytocin receptor mRNA expression to examine possible underpinnings of bHR/bLR maternal differences. While bHR dams exhibited less maternal behavior than bLRs during the dark/active phase, they were very attentive to pups during the light phase, spending greater time passive nursing and in contact with pups compared to bLRs. Cross-fostering only subtly changed bHR and bLR dams' behavior, suggesting that their distinct maternal styles are largely inherent to the mothers. We also found elevated oxytocin mRNA levels in the supraoptic nucleus of the hypothalamus in bHR versus bLR dams, which may play some role in driving their behavior differences. Overall these studies shed light on the interplay between the genetics of mothers and infants in driving differences in maternal style.
10.1016/j.yhbeh.2010.02.004
pubmed_195_25709
Traumatic optic neuropathy is an uncommon, yet serious, result of facial trauma. The authors present a novel case of a 59-year-old gentleman who presented with an isolated blunt traumatic left optic nerve hematoma causing vision loss. There were no other injuries or fractures to report. This case highlights the importance of early recognition of this rare injury and reviews the current literature and management of traumatic optic neuropathy.
10.1155/2013/235209
pubmed_463_18000
Extracellular local field potentials (LFPs) and multiunit activity (MUA) reflect the spatially integrated activity of multiple neurons in a given cortical structure. In the cat and primate visual cortices, these signals exhibit selectivity for visual stimulus features, such as orientation, direction of motion or spatial frequency. In the mouse visual cortex, a model which has been increasingly used in visual neuroscience, the visual stimulus selectivity of population signals has not been examined in detail. We recorded LFPs and MUA using multielectrode arrays and two derived measures, the high-pass filtered continuous MUA and the bipolar first spatial derivative of the LFP, in the visual cortex of isoflurane-anesthetized C57Bl/6 mice. We analyzed the onset latency and characterized the receptive fields in addition to the direction, orientation, and spatial and temporal frequency preferences of these signals. Population signals exhibited onset latencies as short as ∼30ms and possessed receptive fields as large as ∼38° with MUA receptive fields smaller than those of LFPs. All four population signals exhibited similar spatial frequency preferences (∼0.1 cycles per degree) and temporal frequency preferences (∼1 cycle per second). However, for all population signals, spatial and frequency tunings were broad and orientation and direction of motion preferences were absent. The characterization of the visual stimulus selectivity of LFPs and MUA in the mouse visual cortex should provide information regarding their usability in characterizing stimulus properties and disclose possible limitations.
pubmed_463_18000
pubmed_1071_14209
The article analyzes the implementation of major 12 diagnostic and 17 treatment technologies applied during medical care of patients with 12 key nosology forms of diseases in departments of the emergency medical care hospital No 2 of Omsk. It is established that key groups of technologies in the implementation of diagnostic process are the laboratory clinical diagnostic analyses and common diagnostic activities at reception into hospital and corresponding departments. The percentage of this kind of activities is about 78.3% of all diagnostic technologies. During the realization of treatment process the priority technologies are common curative and rehabilitation activities, intensive therapy activities and clinical diagnostic monitoring activities. All of them consist 80.1% of all curative technologies.
pubmed_1071_14209
pubmed_515_751
PURPOSE At the University of California San Francisco, daily or weekly three-dimensional images of patients in treatment position are acquired for image-guided radiation therapy. These images can be used for calculating the actual dose delivered to the patient during treatment. In this article, we present the process of performing dose recalculation on megavoltage cone-beam computed tomography images and discuss possible strategies for dose-guided radiation therapy (DGRT). MATERIALS AND METHODS A dedicated workstation has been developed to incorporate the necessary elements of DGRT. Patient image correction (cupping, missing data artifacts), calibration, completion, recontouring, and dose recalculation are all implemented in the workstation. Tools for dose comparison are also included. Examples of image correction and dose analysis using 6 head-and-neck and 2 prostate patient datasets are presented to show possible tracking of interfraction dosimetric endpoint variation over the course of treatment. RESULTS Analysis of the head-and-neck datasets shows that interfraction treatment doses vary compared with the planning dose for the organs at risk, with the mean parotid dose and spinal cord D(1) increasing by as much as 52% and 10%, respectively. Variation of the coverage to the target volumes was small, with an average D(5) dose difference of 1%. The prostate patient datasets revealed accurate dose coverage to the targeted prostate and varying interfraction dose distributions to the organs at risk. CONCLUSIONS An effective workflow for the clinical implementation of DGRT has been established. With these techniques in place, future clinical developments in adaptive radiation therapy through daily or weekly dosimetric measurements of treatment day images are possible.
10.1016/j.ijrobp.2008.12.034
pubmed_1075_19217
This study analyzes the effect of episode-of-care payment and patient choice on waiting time and the comprehensive quality of hospital care. The study assumes that two hospitals are located in two cities with different population sizes and compete with each other. We find that the comprehensive quality of hospital care as well as waiting time of both hospitals improve with an increase in payment per episode of care. However, we also find that the extent of these improvements differs according to the population size of the cities where the hospitals are located. Under the realistic assumptions that hospitals involve significant labor-intensive work, we find the improvements in comprehensive quality and waiting time in a hospital located in a small city to be greater than those in a hospital located in a large city. The result implies that regional disparity in the quality of hospital care decreases with an increase in payment per episode of care.
10.1007/s10198-012-0396-5
pubmed_205_635
Hepatitis C virus (HCV) non-structural protein 5B (NS5B) is an RNA replicase. We expressed full-length NS5B (591 amino acid residues) in Escherichia coli as a fusion protein with maltose binding protein (MBP-NS5B). MBP-NS5B was recovered in the soluble fraction after centrifugation at 40,000 x g and affinity-purified with amylose resin. The purified MBP-NS5B had a high-level of poly (A), oligo (U)-dependent UMP incorporation with a Km of 2 microM for UTP. Surprisingly, the enzymatically active MBP-NS5B was sedimented by ultracentrifugation at 160,000 x g. The pellet contained 16S and 23S ribosomal RNAs, suggesting that ribosomes were associated with MBP-NS5B. Ribosomes and MBP-NS5B were subsequently co-purified on amylose resin. Deletion study revealed that either the N-terminal (amino acid residues 1-107) or the C-terminal (amino acid residues 498-591) region of NS5B were sufficient for this association with ribosomes. We further found that NS5B also bound with human ribosomes. Our results implicate a novel mechanism of coupling between replication and translation of the viral genome in the life cycle of HCV.
10.1111/j.1348-0421.2000.tb02532.x
pubmed_498_23919
Chitosan scaffolds based on blending polymers are a common strategy used in tissue engineering. The objective of this study was evaluation the properties of scaffolds based on a ternary blend of chitosan (Chi), gelatin (Ge), and polyvinyl alcohol (PVA) (Chi/Ge/PVA), which were prepared by cycles of freeze-thawing and freeze-drying. It then was used for three-dimensional BRIN-BD11 beta-cells culturing. Weight ratios of Chi/Ge/PVA (1:1:1, 2:2:1, 2:3:1, and 3:2:1) were proposed and porosity, pore size, degradation, swelling rate, compressive strength, and cell viability analyzed. All ternary blend scaffolds structures are highly porous (with a porosity higher than 80%) and interconnected. The pore size distribution varied from 0.6 to 265 μm. Ternary blends scaffolds had controllable degradation rates compared to binary blend scaffolds, and an improved swelling capacity of the samples with increasing chitosan concentration was found. An increase in Young's modulus and compressive strength was observed with increasing gelatin concentration. The highest compressive strength reached 101.6 Pa. The MTT assay showed that the ternary blends scaffolds P3 and P4 supported cell viability better than the binary blend scaffold. Therefore, these results illustrated that ternary blends scaffolds P3 and P4 could provide a better environment for BRIN-BD11 cell proliferation.
10.3390/polym13142372
pubmed_1031_22320
The isoprenoid pathway including endogenous digoxin was assessed in Creutzfeldt-Jakob Disease (CJD). This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with CJD and in those with right hemispheric chemical dominance. In this group of patients (i) the tryptophan catabolites were increased and the tyrosine catabolites reduced, (ii) the dolichol and glycoconjugate levels were elevated, (iii) lysosomal stability was reduced, (iv) ubiquinone levels were low and free radical levels increased, and (v) the membrane cholesterol:phospholipid ratios were increased and membrane glyco conjugates reduced. On the other hand, in patients with left hemispheric chemical dominance, the reverse patterns were obtained. The role of the isoprenoid pathway in the pathogenesis of CJD and its relation to hemispheric chemical dominance is discussed.
10.1080/00207450390220312
pubmed_348_4448
Sheep choroid plexus epithelium expresses equilibrative nucleoside transporters (ENT) 1 and 2 and concentrative nucleoside transporter 2 at the transcript level. This study aimed to explore the kinetics and functional role of these transporters at the basolateral side of the sheep choroid plexus epithelium perfused in situ. The cellular uptake of [(3)H]adenosine and [(3)H]uridine was insensitive to 1 microm nitrobenzylthioinosine (NBTI), and the uptake of [(3)H]adenosine was reduced significantly when 10 microm NBTI was present in low-Na(+) Ringer solution. This might suggest that ENT2, a transporter sensitive to micromolar NBTI, is functionally active at the basolateral side of the choroid plexus epithelium while ENT1, a transporter sensitive to nanomolar NBTI, is not active. When low-Na(+) Ringer solution was used for the in situ perfusion, the Na(+) concentration in the venous effluent decreased to 14 mm; under these conditions the maximal uptake (U(max)) of [(3)H]adenosine and [(3)H]uridine did not change significantly when compared with the U(max) obtained when Ringer solution that contained 145 mm Na(+) was used. Kinetic analysis revealed apparent Michaelis-Menten constants (K(m,app)) for cellular uptake of [(3)H]adenosine, [(3)H]inosine and [(3)H]thymidine of 1.2 +/- 0.2, 15.7 +/- 2.6 and 3.8 +/- 0.9 microm, respectively. The HPLC and HPLC-fluorometric analysis of the sheep plasma and cerebrospinal fluid revealed nanomolar concentrations of adenosine and thymidine and micromolar levels of inosine and nucleobases. Considering the estimated K(m,app) values, it appears that under normal conditions inosine is the more important nucleoside substrate for uptake by the basolateral membrane of the choroid plexus epithelium than other nucleosides.
10.1113/expphysiol.2007.040980
pubmed_1120_892
The present world-wide interest in haemoglobinopathies and allied disorders has given rise to a very considerable literature over the past two decades. This communication reviews this literature in so far as it refers to the Indian subcontinent. The most common abnormality is thalassaemia, which has been discovered in all regions under consideration: India, Pakistan, Nepal, Bhutan and Ceylon. Haemoglobins S, D and E are also quite common: Hb S has been found mostly in the aboriginal tribes, Hb D in Gujaratis and Punjabis and Hb E in Bengalis, Assamese and Nepalese. A few instances of haemoglobins F, H, J, K, L and M have also been reported. However, there remain many population groups to be investigated.Studies of the distribution of glucose-6-phosphate dehydrogenase deficiency are also reviewed, and the correlation between the various haemoglobin disorders and various environmental factors is discussed, but it is pointed out that the relevant data are still insufficient to allow any definite conclusions to be drawn.
pubmed_1120_892
pubmed_65_16219
BACKGROUND Slowing of motor movements in human aging is a well-known occurrence, but its biologic basis is poorly understood. Reliable quantitation may refine observations of this phenomenon to better aid research on this entity. METHODS A panel equipped with timing sensors under computer control was used to measure upper extremity movement times in two groups of healthy individuals: adults younger than 60 years of age (n = 56; range, 18-58 years) and adults older than 60 years of age (n = 38; range, 61-94 years). RESULTS Fine motor performance was better in the dominant hand (p = 0.0007) regardless of age. Adult and aged groups differed on two basic timing measures, which reflect coarse motor and fine motor performance (p < 0.0001). There were no gender differences on either measure. There was a strong effect of task difficulty with age on coarse motor (p < 0.01) and fine motor (p < 0.0001) measures. The fine motor measure of hand performance in healthy individuals correlated in a nonlinear fashion with age for more difficult tasks (r2 = 0.63) but showed a simple linear relation for less-demanding tasks (r2 = 0.5). CONCLUSION This technique sensitively detects age-related motor performance decline in humans. There may be a critical period in late midlife when fine motor performance decline either begins or abruptly worsens.
10.1212/wnl.53.7.1458
pubmed_113_9820
Ischemic stroke is a leading cause of death and disability. Tissue plasminogen activator is the only U.S. Food and Drug Administration approved thrombolytic therapy for ischemic stroke patients till date. However, its use is limited due to increased risk of bleeding and narrow therapeutic window. Most of the preclinically tested pharmacological agents failed to be translated to the clinic. This drives the need for alternative therapeutic approaches that not only provide enhanced neuroprotection, but also reduce the risk of stroke. Physical exercise is a sort of preconditioning that provides the body with brief ischemic episodes that can protect the body from subsequent severe ischemic attacks like stroke. Physical exercise is known to improve cardiovascular health. However, its role in providing neuroprotection in stroke is not clear. Clinical observational studies showed a correlation between regular physical exercise and reduced risk and severity of ischemic stroke and better outcomes after stroke. However, the underlying mechanisms through which prestroke exercise can reduce the stroke injury and improve the outcomes are not completely understood. The purpose of this review is to: demonstrate the impact of exercise on stroke outcomes and show the potential role of exercise in stroke prevention and recovery; uncover the underlying mechanisms through which exercise reduces the neurovascular injury and improves stroke outcomes aiming to develop novel therapeutic approaches.
10.5853/jos.2020.03006
pubmed_300_21671
Gram-positive Staphylococcus aureus releases classical enterotoxins which aggravates allergic airway diseases. However, little is known about the mechanisms underlying the cell influx exacerbation in asthmatic individuals under exposure to Staphylococcal enterotoxins. We therefore aimed to investigate the effects of airways exposure to Staphylococcal enterotoxin A (SEA) to pulmonary leukocyte recruitment in rats sensitized and challenged with ovalbumin (OVA). Rats were exposed to SEA at 4h prior to OVA challenge or at 4h post-OVA challenge. Bronchoalveolar lavage (BAL) fluid, bone marrow and lung tissue were obtained at 24h after OVA challenge. Pre-exposure to SEA markedly enhanced the eosinophil counts in both BAL fluid and pulmonary tissue in OVA-challenged rats, whereas neutrophil and mononuclear cell counts remained unchanged. In bone marrow, pre-exposure to SEA alone significantly increased the number of eosinophils, and that was further increased in OVA-challenged rats. Exposure to SEA post-OVA challenge did not affect the number of eosinophils, neutrophils and mononuclear cells in BAL fluid. Pre-exposure to the endotoxin lipopolyssacharide (LPS) in OVA-challenged animals rather enhanced the neutrophil number in BAL fluid. In rats pre-exposed to SEA and OVA-challenged, a marked elevation in the levels of TNF-alpha and eotaxin (but not of IL-10) in BAL fluid was observed. The eotaxin levels increased by about of 3-fold in alveolar macrophages treated with SEA in vitro. In conclusion, airways pre-exposure to SEA causes a selective increase in eosinophil number in BAL fluid and bone marrow of OVA-challenged rats by mechanisms involving enhancement of TNF-alpha and eotaxin synthesis.
10.1016/j.intimp.2009.09.017
pubmed_159_24907
The clinical use of first-generation phosphoinositide 3-kinase (PI3K)δ inhibitors in B-cell malignancies is hampered by hepatotoxicity, requiring dose reduction, treatment interruption, and/or discontinuation of therapy. In addition, potential molecular mechanisms by which resistance to this class of drugs occurs have not been investigated. Parsaclisib (INCB050465) is a potent and selective next-generation PI3Kδ inhibitor that differs in structure from first-generation PI3Kδ inhibitors and has shown encouraging anti-B-cell tumor activity and reduced hepatotoxicity in phase 1/2 clinical studies. Here, we present preclinical data demonstrating parsaclisib as a potent inhibitor of PI3Kδ with over 1000-fold selectivity against other class 1 PI3K isozymes. Parsaclisib directly blocks PI3K signaling-mediated cell proliferation in B-cell lines in vitro and in vivo and indirectly controls tumor growth by lessening immunosuppression through regulatory T-cell inhibition in a syngeneic lymphoma model. Diffuse large B-cell lymphoma cell lines overexpressing MYC were insensitive to proliferation blockade via PI3Kδ signaling inhibition by parsaclisib, but their proliferative activities were reduced by suppression of MYC gene transcription. Molecular structure analysis of the first- and next-generation PI3Kδ inhibitors combined with clinical observation suggests that hepatotoxicity seen with the first-generation inhibitors could result from a structure-related off-target effect. Parsaclisib is currently being evaluated in multiple phase 2 clinical trials as a therapy against various hematologic malignancies of B-cell origin (NCT03126019, NCT02998476, NCT03235544, NCT03144674, and NCT02018861). SIGNIFICANCE STATEMENT: The preclinical properties described here provide the mechanism of action and support clinical investigations of parsaclisib as a therapy for B-cell malignancies. MYC overexpression was identified as a resistance mechanism to parsaclisib in DLBCL cells, which may be useful in guiding further translational studies for the selection of patients with DLBCL who might benefit from PI3Kδ inhibitor treatment in future trials. Hepatotoxicity associated with first-generation PI3Kδ inhibitors may be an off-target effect of that class of compounds.
10.1124/jpet.120.265538
pubmed_263_21142
Exo1 belongs to the Rad2 family of structure-specific nucleases and possesses 5'-3' exonuclease activity on double-stranded DNA substrates. Exo1 interacts physically with the DNA mismatch repair (MMR) proteins Msh2 and Mlh1 and is involved in the excision of the mispaired nucleotide. Independent of its role in MMR, Exo1 contributes to long-range resection of DNA double-strand break (DSB) ends to facilitate their repair by homologous recombination (HR), and was recently identified as a component of error-free DNA damage tolerance pathways. Here, we show that Exo1 activity increases the hydroxyurea sensitivity of cells lacking Pol32, a subunit of DNA polymerases δ and ζ. Both, phospho-mimicking and dephospho-mimicking exo1 mutants act as hypermorphs, as evidenced by an increase in HU sensitivity of pol32Δ cells, suggesting that they are trapped in an active form and that phosphorylation of Exo1 at residues S372, S567, S587, S692 is necessary, but insufficient, for the accurate regulation of Exo1 activity at stalled replication forks. In contrast, neither phosphorylation status is important for Exo1's role in MMR or in the suppression of genome instability in cells lacking Sgs1 helicase. This ability of an EXO1 deletion to suppress the HU hypersensitivity of pol32Δ cells is in contrast to the negative genetic interaction between deletions of EXO1 and POL32 in MMS-treated cells as well as the role of EXO1 in DNA-damage treated rad53 and mec1 mutants.
10.1016/j.dnarep.2014.10.004
pubmed_789_16686
The main use of non-ablative fractional photothermolysis today is for the improvement of wrinkles and scars. The purpose of this work was to evaluate the effect of a "classic" non-ablative fractional 1540 nm on facial photodamaged skin and actinic keratoses. Seventeen patients with facial actinic keratoses (AKs) and photodamage underwent two or three laser treatments with fractional 1540-nm erbium glass laser at fluences of 75 mJ, 15 ms pulse duration, and 10-mm spot size in non-contact mode. Two blinded assessors and participants evaluated clinical improvement of treatment areas after 3 months, using a quartile grading scale (no improvement = 0, 1-25% improvement = 1, 26-50% = 2, 51-75% = 3, and 76-100% = 4). Three months after the last treatment, the mean level of improvement was 3.4 ± 0.72 for AK and 3.3 ± 0.54 for skin appearance. Adverse events observed after each treatment were moderate erythema, mild edema, erosions (two cases), and mild desquamation. No scarring or post-inflammatory pigmentary changes were observed. The clinical results were supported by histological changes observed in Yucatan pig studies in vivo and ex vivo. The 1540-nm fractional erbium glass laser in the non-contact mode is a safe and effective treatment for facial photodamage and AKs.
10.1007/s10103-012-1103-6
pubmed_683_1313
Autopsy studies of the heart of 221 subjects who suffered pre-hospital coronary sudden death were performed at the Paris Medico-Legal Institute over a period of 3 years to compare the lesions observed in subjects without known cardiovascular disease (Group A: n = 160; 72.4%) with those of subjects with known cardiovascular disease (Group B: n = 61). The proportion of men was greater in Group B (77%) that in Group A (62.5%). The average age of sudden death was the same in both groups: 65 years for men and 77 years for women. Sudden death usually occurred in the home (83%) at rest and, in one third of the cases, during sleep. Sudden death occurred in a context of severe coronary artery disease in both groups: significant triple vessel stenosis (> 75%) in 60% of subjects in both groups but thrombosis was found in only 13% of cases in Group A and 15% of cases in Group B. The mean weight of the heart was significantly greater than normal in both groups and in both sexes. In addition, the mean weight of the heart of subjects in Group B was significantly greater than that of subjects in Group A (p < 0.05). This autopsy study showed that prehospital coronary sudden death was the first sign of coronary disease in 70% of cases. Irrespective of whether the subject had known cardiovascular disease or not, sudden death occurred under similar circumstances and, in both cases, in the context of severe coronary artery disease.
pubmed_683_1313
pubmed_483_16900
Programs of gene transcription are controlled by cis-acting DNA elements, including enhancers, silencers, and promoters. Local accessibility of chromatin has proven to be a highly informative structural feature for identifying such regulatory elements, which tend to be relatively open due to their interactions with proteins. Recently, ATAC-seq (assay for transposase-accessible chromatin using sequencing) has emerged as one of the most powerful approaches for genome-wide chromatin accessibility profiling. This method assesses DNA accessibility using hyperactive Tn5 transposase, which simultaneously cuts DNA and inserts sequencing adaptors, preferentially in regions of open chromatin. ATAC-seq is a relatively simple procedure which can be applied to only a few thousand cells. It is well-suited to developing embryos of sea urchins and other echinoderms, which are a prominent experimental model for understanding the genomic control of animal development. In this chapter, we present a protocol for applying ATAC-seq to embryonic cells of sea urchins.
10.1016/bs.mcb.2018.11.002
pubmed_214_6838
Background and Aim Selecting the optimum nasal passage for nasotracheal intubation is quite important in the maxillofacial surgeries for the success of intubation and the reduction of potential complications such as nasal mucosal laceration, epistaxis, avulsion of the inferior and middle turbinates, and septal laceration. Materials and Methods The present study evaluates standard panoramic radiographs (PR) and posteroanterior cephalometric radiographs (PACR) to determine the optimal nasal passage for nasotracheal intubation and compares the results with those of routine anesthesiological occlusion and spatula tests (ST). The results of occlusion tests (OT), ST, and radiological assessments of 60 patients prior to nasotracheal intubation were compared with the nasal endoscopic assessment results, and complications were evaluated. Results There was no significant association between the OT and nasal endoscopy results (P = 0.075). A significant association was found between the ST and nasal endoscopy results (P = 0.000), and between the radiological assessments and the nasal endoscopy results (P = 0.000). Compatibility with nasal endoscopy was 54% when the occlusion and ST were evaluated together, 75% when the OT and radiological assessments were evaluated together, and 86% when the ST and radiological assessments were evaluated together. The highest level of compatibility was 92% when all the tests were evaluated together. Conclusion The simple tests alone were found to be inadequate for the selection of the optimal nasal passage. Evaluation of PR and PACR, which are commonly used in maxillofacial surgeries, together with simple anesthesiological examination tests would increase nasotracheal intubation success and decrease complications.
10.4103/njcp.njcp_1739_21
pubmed_357_7481
BACKGROUND Patients with American Thyroid Association (ATA) high-risk differentiated thyroid carcinoma (DTC) have poor clinical outcomes. This study aimed to evaluate the clinical implications of age and response to therapy classification in patients with ATA high-risk DTC. DESIGN AND PATIENTS This study included 222 patients with high-risk DTC who initially underwent therapy between 2000 and 2010 in a single tertiary center in Korea. We evaluated the prognostic parameters associated with progression-free survival (PFS) and disease-specific survival (DSS) with a focus on age and achieving an excellent response (ER). RESULTS During the median follow-up period of 11.3 years, disease progression was detected in 77 patients (34.7%), and disease-specific mortality was reported in 31 patients (14.0%). Older age (≥55 years) and not achieving ER (not-ER) were independent risk factors associated with PFS (age, p < .001; not-ER, p < .001) and DSS (age, p < .001; not-ER, p = .015). Of the 74 patients in the ER group, 7 (9.5%) displayed disease progression and 1 (1.4%) died from DTC. There were no significant differences in PFS and DSS according to age in the ER group. However, older patients had significantly worse PFS and DSS than younger patients in the not-ER group (p = .002 and p < .001, respectively). CONCLUSIONS Response to therapy classification is important for predicting PFS and DSS in patients with high-risk DTC. Patients in the ER group had a relatively good prognosis, but disease progression occurred in 9.5% of patients. Age was a key predictor of both PFS and DSS in high-risk patients who did not achieve ER.
10.1111/cen.14543
pubmed_707_3830
Obstructive sleep apnea (OSA) is characterized by repetitive partial/complete collapse of the pharynx during sleep, which results in apnea/hypopnea leading to arterial oxygen desaturations and arousals. Repetitive apnea/hypopnea-arousal episodes cause hypoxia/reoxygenation cycles, which increase free radical generation and oxidative stress that cause motor/sensory nerve impairments and muscle damage. We hypothesize that antioxidants may protect and/or reverse from oxidative stress-induced damage in OSA patients. To understand the acute protective effects of antioxidants on respiratory muscles, we studied the systemic effects of a membrane permeable superoxide dismutase mimetic, Tempol, on genioglossus (EMGGG) and diaphragmatic (EMGDIA) electro-myographic activities, hypoglossal motoneuron (HMN) nerve activity and cardiorespiratory parameters (mean arterial blood pressure, heart rate) in adult isoflurane-anesthetized obese Zucker rats (OZR) and age-matched lean Zucker rats (LZR). Tempol dose-dependently (1-100 mg/kg) increased EMGGG without changing EMGDIA in OZR and LZR. Tempol increased respiratory rate and tidal volume in OZR and LZR. Tempol (1-25 mg/kg) dose-dependently increased HMN nerve activity in healthy Sprague Dawley rats. Tempol (100 mg/kg) increased EMGGG output by 189% in OZR and 163% in LZR. With respect to mechanisms of effect, Tempol (100 mg/kg) did not augment EMGGG after bilateral HMN transection in Sprague Dawley rats. Although future studies are warranted, available data suggest that in addition to its antioxidant and antihypertensive properties, Tempol can selectively augment EMGGG through modulating HMN and this effect may prevent collapsibility and/or improve stability of the upper airway pharyngeal dilator muscles during episodes of partial and/or complete collapse of the upper airway in OSA human subjects.
10.3389/fphar.2022.814032
pubmed_1037_15578
BACKGROUND AND AIMS High plasma lipid/lipoprotein levels are risk factors for various metabolic diseases. We previously showed that circadian rhythms regulate plasma lipids and deregulation of these rhythms causes hyperlipidemia and atherosclerosis in mice. Here, we show that global and liver-specific brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1)-deficient mice maintained on a chow or Western diet developed hyperlipidemia, denoted by the presence of higher amounts of triglyceride-rich and apolipoprotein AIV (ApoAIV)-rich larger chylomicron and VLDL due to overproduction. APPROACH AND RESULTS Bmal1 deficiency decreased small heterodimer partner (Shp) and increased microsomal triglyceride transfer protein (MTP), a key protein that facilitates primordial lipoprotein assembly and secretion. Moreover, we show that Bmal1 regulates cAMP-responsive element-binding protein H (Crebh) to modulate ApoAIV expression and the assembly of larger lipoproteins. This is supported by the observation that Crebh-deficient and ApoAIV-deficient mice, along with Bmal1-deficient mice with knockdown of Crebh, had smaller lipoproteins. Further, overexpression of Bmal1 in Crebh-deficient mice had no effect on ApoAIV expression and lipoprotein size. CONCLUSIONS These studies indicate that regulation of ApoAIV and assembly of larger lipoproteins by Bmal1 requires Crebh. Mechanistic studies showed that Bmal1 regulates Crebh expression by two mechanisms. First, Bmal1 interacts with the Crebh promoter to control circadian regulation. Second, Bmal1 increases Rev-erbα expression, and nuclear receptor subfamily 1 group D member 1 (Nr1D1, Rev-erbα) interacts with the Crebh promoter to repress expression. In short, Bmal1 modulates both the synthesis of primordial lipoproteins and their subsequent expansion into larger lipoproteins by regulating two different proteins, MTP and ApoAIV, through two different transcription factors, Shp and Crebh. It is likely that disruptions in circadian mechanisms contribute to hyperlipidemia and that avoiding disruptions in circadian rhythms may limit/prevent hyperlipidemia and atherosclerosis.
10.1002/hep.32196
pubmed_1007_12324
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a high-risk infectious pathogen. In the proposed model of respiratory failure, SARS-CoV down-regulates its receptor, angiotensin-converting enzyme 2 (ACE2), but the mechanism involved is unknown. We found that the spike protein of SARS-CoV (SARS-S) induced TNF-alpha-converting enzyme (TACE)-dependent shedding of the ACE2 ectodomain. The modulation of TACE activity by SARS-S depended on the cytoplasmic domain of ACE2, because deletion mutants of ACE2 lacking the carboxyl-terminal region did not induce ACE2 shedding or TNF-alpha production. In contrast, the spike protein of HNL63-CoV (NL63-S), a CoV that uses ACE2 as a receptor and mainly induces the common cold, caused neither of these cellular responses. Intriguingly, viral infection, judged by real-time RT-PCR analysis of SARS-CoV mRNA expression, was significantly attenuated by deletion of the cytoplasmic tail of ACE2 or knock-down of TACE expression by siRNA. These data suggest that cellular signals triggered by the interaction of SARS-CoV with ACE2 are positively involved in viral entry but lead to tissue damage. These findings may lead to the development of anti-SARS-CoV agents.
10.1073/pnas.0711241105
pubmed_665_21894
The susceptibility to and the severity of Bordetella pertussis infections in infants and children varies widely, suggesting that genetic differences between individuals influence the course of infection. We have previously identified three novel loci that influence the severity of whooping cough by using recombinant congenic strains of mice: Bordetella pertussis susceptibility loci 1, 2, and 3 (Bps1, -2, and -3). Because these loci could not account for all genetic differences between mice, we extended our search for additional susceptibility loci. We therefore screened 11 inbred strains of mice for susceptibility to a pertussis infection after intranasal infection. Susceptibility was defined by the number of bacteria in the lungs, being indicative of the effect between the clearance and replication of bacteria. The most resistant (A/J) and the most susceptible (C3H/HeJ) strains were selected for further genetic and phenotypic characterization. The link between bacterial clearance and chromosomal location was investigated with 300 F2 mice, generated by crossing A/J and C3H/HeJ mice. We found a link between the delayed clearance of bacteria from the lung and a large part of chromosome 4 in F2 mice with a maximum log of the odds score of 33.6 at 65.4 Mb, which is the location of Tlr4. C3H/HeJ mice carry a functional mutation in the intracellular domain of Tlr4. This locus accounted for all detectable genetic differences between these strains. Compared to A/J mice, C3H/HeJ mice showed a delayed clearance of bacteria from the lung, a higher relative lung weight, and increased body weight loss. Splenocytes from infected C3H/HeJ mice produced almost no interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) upon ex vivo restimulation with B. pertussis compared to A/J mice and also showed a delayed gamma interferon (IFN-gamma) production. TNF-alpha expression in the lungs 3 days after infection was increased fivefold compared to uninfected controls in A/J mice and was not affected in C3H/HeJ mice. In conclusion, Tlr4 is a major host factor explaining the differences in the course of infection between these inbred strains of mice. Functional Tlr4 is essential for an efficient IL-1-beta, TNF-alpha, and IFN-gamma response; efficient clearance of bacteria from the lung; and reduced lung pathology.
10.1128/IAI.74.5.2596-2605.2006
pubmed_39_3646
BACKGROUND AND AIM Esophageal eosinophilia (EE) is the most important finding for the diagnosis of eosinophilic esophagitis. We conducted the present retrospective study to clarify the most suitable site of the esophagus to examine for EE detection. METHODS We enrolled 4999 subjects who underwent upper gastrointestinal endoscopy screening examinations as part of a detailed health check-up. When endoscopic esophageal abnormalities characteristic of eosinophilic esophagitis were observed, two or three biopsy specimens were obtained from the middle or lower esophagus, and endoscopic findings of fixed rings, exudates, furrows, edema, stricture, and crepe paper esophagus in biopsied sites were analyzed. RESULTS Thirty-five subjects underwent histological examination for EE, of whom 20 showed positive findings in biopsied specimens. Higher grade endoscopic findings of exudates, furrows, and edema were observed in cases with EE in comparison to the 15 without EE, whereas statistically significant higher grade endoscopic findings of exudates, furrows, and edema were also observed in biopsied sites with EE in comparison to those without EE. In addition, a positive finding of EE in biopsied specimens from the lower esophagus was significantly more frequently noted as compared to those from the middle esophagus. Multiple logistic regression analysis showed that a lower esophagus biopsy site and severe exudates were significant factors related to a positive EE finding in biopsied specimens. CONCLUSION The most suitable conditions for detection of EE are a lower esophagus biopsy site and the presence of exudates in cases suspicious of eosinophilic esophagitis shown by endoscopy.
10.1111/den.12555
pubmed_392_15286
BACKGROUND Coronavirus disease 2019 (COVID-19) continues to be a major global health burden. This study aims to estimate the all-cause excess mortality occurring in the COVID-19 outbreak in Japan, 2020, by sex and age group. METHODS Daily time series of mortality for the period January 2015-December 2020 in all 47 prefectures of Japan were obtained from the Ministry of Health, Labour and Welfare, Japan. A two-stage interrupted time-series design was used to calculate excess mortality. In the first stage, we estimated excess mortality by prefecture using quasi-Poisson regression models in combination with distributed lag non-linear models, adjusting for seasonal and long-term variations, weather conditions and influenza activity. In the second stage, we used a random-effects multivariate meta-analysis to synthesize prefecture-specific estimates at the nationwide level. RESULTS In 2020, we estimated an all-cause excess mortality of -20 982 deaths [95% empirical confidence intervals (eCI): -38 367 to -5472] in Japan, which corresponded to a percentage excess of -1.7% (95% eCI: -3.1 to -0.5) relative to the expected value. Reduced deaths were observed for both sexes and in all age groups except those aged <60 and 70-79 years. CONCLUSIONS All-cause mortality during the COVID-19 outbreak in Japan in 2020 was decreased compared with a historical baseline. Further evaluation of cause-specific excess mortality is warranted.
10.1093/ije/dyab216
pubmed_988_14691
The size and shape of the corpus callosum of twenty-seven normal young volunteers (age 18-31 years, 17 men and 10 women) were investigated using a superconducting high field (1.5 T) MRI unit. The length of the corpus callosum was 71.1 +/- 5.1 mm (mean +/- S.D.) and the height was 24.9 +/- 2.1 mm. The length ratio of the corpus callosum to the brain was 43.9 +/- 2.3% with the ratio of the height 25.0 +/- 2.3%. The callosal index (height/length) was 35.4 +/- 2.9%. The area of the corpus callosum in the midsagittal plane was 681.4 +/- 93.6 mm2 (min. 563 mm2 to max. 902 mm2). We divided the corpus callosum into three segments: rostrum and genu; anterior and posterior trunks; splenium. Each part accounts for one third of the total area of the corpus callosum. The genu and splenium were generally equal in thickness. The minimal thickness of the trunk was 3 mm with the maximal one 9 mm. The posterior trunk was never thicker than the anterior one. The posterior part of the posterior trunk showed thinning and concavity in almost all cases. So-called impressio corporis callosi was observed in 12 cases (44.4%). Thirteen cases (48.1%) showed a shallow concave configuration at the anterior dorsal surface of the corpus callosum. Six cases of these were thought to be due to compression by the pericallosal artery. This finding was not detected in the posterior portion of the corpus callosum. This concavity was also seen in infants. The thinning of the posterior part of the posterior trunk was seen after the development of the splenium, but the concave configuration at the anterior dorsal surface of the corpus callosum may be encountered before the full development of the genu and splenium.
pubmed_988_14691
pubmed_100_22213
The existence of handedness differences in the retrieval of episodic memories is well-documented, but virtually all have been obtained under conditions of intentional learning. Two experiments are reported that extend the presence of such handedness differences to memory retrieval under conditions of incidental learning. Experiment 1 used Craik and Tulving's (1975) classic levels-of-processing paradigm and obtained handedness differences under incidental and intentional conditions of deep processing, but not under conditions of shallow incidental processing. Experiment 2 looked at incidental memory for distracter items from a recognition memory task and again found a mixed-handed advantage. Results are discussed in terms of the relation between interhemispheric interaction, levels of processing, and episodic memory retrieval.
10.1016/j.bandc.2011.07.003
pubmed_86_17239
Antigenic variants resistant to eight neutralizing monoclonal antibodies were selected from wild (Mahoney) and attenuated (Sabin) type 1 infectious poliovirions. Cross-immunoprecipitation revealed interrelationships between epitopes which were not detected by cross-neutralization. Operational analysis of antigenic variants showed that seven of eight neutralization epitopes studied were interrelated. Only one neutralization epitope, named Kc, varied independently from all the others. This latter, recognized by C3 neutralizing monoclonal antibody, was present not only on infectious virions but also on heat-denatured (C-antigenic) particles and on isolated capsid protein VP1. Loss of the neutralization function of an epitope did not necessary result from the loss of its antibody-binding capacity. Such potential, but not functional, neutralization epitopes exist naturally on Mahoney and Sabin 1 viruses. Their antibody-binding property could be disrupted by isolating antigenic variants in the presence of the nonneutralizing monoclonal antibody and anti-mouse immunoglobulin antibodies. Single-point mutations responsible for the acquisition of resistance to neutralization in the antigenic variants were located by sequence analyses of their genomes. Mutants selected in the presence of C3 neutralizing monoclonal antibody always had the mutation located inside the antibody-binding site (residues 93 through 103 of VP1) at the amino acid position 100 of VP1. On the contrary, antigenic variants selected in the presence of neutralizing monoclonal antibodies reacting only with D-antigenic particles had mutations situated in VP3, outside the antibody-binding site (residues 93 through 103 of VP1). The complete conversion of the Mahoney to the Sabin 1 epitope map resulted from a threonine-to-lysine substitution at position 60 of VP3.
10.1128/JVI.57.1.81-90.1986
pubmed_374_17847
Respiratory syncytial virus (RSV) is primarily associated with respiratory disorders globally. Despite the availability of information, there is still no competitive vaccine available for RSV. Therefore, the present study has been designed to develop a multiepitope-based subunit vaccine (MEV) using a reverse vaccinology approach to curb RSV infections. Briefly, two highly antigenic and conserved proteins of RSV (glycoprotein and fusion protein) were selected and potential epitopes of different categories (B-cell and T-cell) were identified from them. Eminently antigenic and overlapping epitopes, which demonstrated strong associations with their respective human leukocyte antigen (HLA) alleles and depicted collective ~70% coverage of the world's populace, were shortlisted. Finally, 282 amino acids long MEV construct was established by connecting 13 major histocompatibility complex (MHC) class-I with two MHC class-II epitopes with appropriate adjuvant and linkers. Adjuvant and linkers were added to increase the immunogenic stimulation of the MEV. Developed MEV was stable, soluble, non-allergenic, non-toxic, flexible and highly antigenic. Furthermore, molecular docking and molecular dynamics (MD) simulations analyses were carried out. Results have shown a firm and robust binding affinity of MEV with human pathogenic toll-like receptor three (TLR3). The computationally mediated immune response of MEV demonstrated increased interferon-γ production, a significant abundance of immunoglobulin and activation of macrophages which are essential for immune-response against RSV. Moreover, MEV codons were optimized and in silico cloning was performed, to ensure its increased expression. These outcomes proposed that the MEV developed in this study will be a significant candidate against RSV to control and prevent RSV-related disorders if further investigated experimentally.
10.3390/vaccines8020288
pubmed_40_22148
Deserts and arid regions are generally perceived as bare and rather homogeneous areas of low diversity. The Sahara is the largest warm desert in the world and together with the arid Sahel displays high topographical and climatic heterogeneity, and has experienced recent and strong climatic oscillations that have greatly shifted biodiversity distribution and community composition. The large size, remoteness and long-term political instability of the Sahara-Sahel, have limited knowledge on its biodiversity. However, over the last decade, there have been an increasing number of published scientific studies based on modern geomatic and molecular tools, and broad sampling of taxa of these regions. This review tracks trends in knowledge about biodiversity patterns, processes and threats across the Sahara-Sahel, and anticipates needs for biodiversity research and conservation. Recent studies are changing completely the perception of regional biodiversity patterns. Instead of relatively low species diversity with distribution covering most of the region, studies now suggest a high rate of endemism and larger number of species, with much narrower and fragmented ranges, frequently limited to micro-hotspots of biodiversity. Molecular-based studies are also unravelling cryptic diversity associated with mountains, which together with recent distribution atlases, allows identifying integrative biogeographic patterns in biodiversity distribution. Mapping of multivariate environmental variation (at 1 km × 1 km resolution) of the region illustrates main biogeographical features of the Sahara-Sahel and supports recently hypothesised dispersal corridors and refugia. Micro-scale water-features present mostly in mountains have been associated with local biodiversity hotspots. However, the distribution of available data on vertebrates highlights current knowledge gaps that still apply to a large proportion of the Sahara-Sahel. Current research is providing insights into key evolutionary and ecological processes, including causes and timing of radiation and divergence for multiple taxa, and associating the onset of the Sahara with diversification processes for low-mobility vertebrates. Examples of phylogeographic patterns are showing the importance of allopatric speciation in the Sahara-Sahel, and this review presents a synthetic overview of the most commonly hypothesised diversification mechanisms. Studies are also stressing that biodiversity is threatened by increasing human activities in the region, including overhunting and natural resources prospection, and in the future by predicted global warming. A representation of areas of conflict, landmines, and natural resources extraction illustrates how human activities and regional insecurity are hampering biodiversity research and conservation. Although there are still numerous knowledge gaps for the optimised conservation of biodiversity in the region, a set of research priorities is provided to identify the framework data needed to support regional conservation planning.
10.1111/brv.12049
pubmed_829_2397
BACKGROUND Mass, free distribution (Catch-up) of insecticide-treated bednets (ITNs) during measles vaccination campaigns achieves immediate, high and equitable coverage for both ITNs and measles vaccine. Maintaining high coverage over time requires long-term, routine access to new nets (Keep-up). In many settings, only one approach--either campaign or routine delivery--has been available and have been seen as competing methods. Relying only on campaigns achieves high coverage at the cost of lack of later access. Relying solely on routine coverage builds a delivery infrastructure but may lead to slower rates of coverage and inequities. A combined Catch-up/Keep-up approach has been a common feature of vaccination programs for many years. We assessed the 3-year effects of a one-time Catch-up campaign followed by clinic-based social marketing for routine Keep-up on ITN coverage and use. METHODS In December 2002, ITNs were distributed to all children attending a measles vaccination campaign in a rural district of Ghana. In the 3 years following that campaign, the district began offering ITNs at a subsidized price to pregnant women attending ante-natal clinics. This Keep-up scheme did not become fully operational until 2 years after the campaign. A coverage survey was conducted 38-month post-campaign using a standard two-stage cluster sampling method. RESULTS Coverage of nets was high due to the combined contributions of both Catch-up and Keep-up. There were 475 households in the survey with at least one child less than 5 years of age. Among these households, coverage was 95.6% with any net, 83.8% with a campaign net, and 73.9% with an ITN. Of all children, 95.7% slept in a household that had a net, 86.1% slept in a household that had a campaign net. Not all available nets were used as only 59.6% of children slept under an ITN. The source of the nets was 77.7% from the campaign and 20% from routine clinics. Compared to households that participated in the campaign, households with children born after the campaign had higher rates of net ownership (75.1% vs. 67.7%, P=0.04). Equity was high as the ratio of coverage in the lowest wealth quintile to that in the highest was 0.95 for ITN ownership and 1.08 for ITN use. These coverage and use rates were similar to those previously reported 5-month post-campaign, suggesting no decrease over 3 years. CONCLUSION A high level of ITN coverage and use was achieved and sustained by sequential community-based mass campaign Catch-up and clinic-based Keep-up distribution. The campaign nets covered virtually all extant households while clinic-based distribution provided nets for the new sleeping spaces created post-campaign. Because nets can be shared, and most children are born into families that already have a net, the number of new nets needed to sustain high coverage is substantially lower than the number of newborn children. A Catch-up/Keep-up strategy combining mass campaigns for children and clinic-based distribution to pregnant women is an efficient strategy for achieving and sustaining high net coverage. Assuring proper use of nets is a remaining challenge.
10.1111/j.1365-3156.2007.01862.x
pubmed_935_11516
Dearterialization of the liver causes necrosis of primary liver tumors or metastases, because their blood supply is largely arterial. The normal liver tissue remains vital after a period of ischemia if the portal vein is intact. A patient with a carcinoid syndrome due to liver metastases is described. It was found that it is difficult to achieve complete dearterialization of the liver. Rather, preoperative and particularly peroperative angiograms are required to ensure the best possible degree of dearterialization.
10.1002/jso.2930130303
pubmed_181_13949
Parents-offspring bonding is critical for development of offspring in mammals. While it is known that pups stimuli provide rewarding effects on their parents, few studies have assessed whether parental stimuli serve as a reinforcing agent to their pups, and what the neural mechanisms underlying this reward process may be. In addition to maternal care, male ICR mice display pairmate-dependent parental behavior. Using the conditioned place preference (CPP) paradigm, we examined the effects of maternal and paternal conditioning on the postnatal day 17-21 female ICR mice pups, and compared the expression of oxytocin (OT)- and tyrosine hydroxylase (TH)- immunoreactive (IR) neurons. We found that the pups established dam- or sire- induced CPP when using mother conditioning (MC) or father conditioning (FC) alone. However, the pups failed to show any preference when using mother versus father conditioning (MFC). Compared to the control group, the MC and MFC groups displayed more OT-IR neurons in the supraoptic nucleus and more TH-IR neurons in the ventral tegmental area (VTA). The FC group showed more TH-IR neurons in the VTA compared to the control group, but there were no significant differences in OT-IR neurons. These findings indicate that female ICR mice pups may establish mother- or father- induced CPP. The underpinnings of preference for parents are associated with the activity of VTA dopaminergic neurons, and the preference of pups for mother in particular appears to be associated with OT levels.
10.1016/j.bbr.2016.10.021
pubmed_1082_20349
A trimeric enzyme chloramphenicol acetyltransferase (CATI) has been synthesized in the Zubay system genetically depleted from DnaK and DnaJ. Most of CAT formed in the system fail to assemble into an active trimer. Instead CAT is accumulated in either a GroEL-bound complex or as an inactive monomer. Addition of purified DnaK and DnaJ to the system prior to the start of protein synthesis leads to the increase of the specific activity of formed CAT. A portion of exogenous DnaK and DnaJ added to the system associate with nascent polypeptide chains in the ribosomes. DnaK also comigrates with 50S-ribosomal subunits.
10.1016/0014-5793(95)01213-x
pubmed_402_7441
AIM To study effect of protein synthesis inhibitor cicloheximide (Cic) on the apoptosis induced by alpha-anordrin (Ano) in leukemia K562 cells. METHODS Morphological changes were observed by fluorescent microscopy. DNA content was measured by flow cytometry. DNA fragmentation was analyzed by agarose gel electrophoresis. RESULTS Exposure of K562 cells to Ano 50 mumol.L-1 for 24 h induced apoptotic cell death. Cic 1 mumol.L-1 did not abrogate or delay this effect. Indeed, Ano-induced apoptosis was augmented by Cic. Cic 100 mumol.L-1 itself stimulated 25% K562 cell apoptosis after 24-h culture. CONCLUSION Ano-induced apoptosis was independent of de novo protein synthesis.
pubmed_402_7441
pubmed_773_3237
A system for the isolation and functional evaluation of fetal liver erythroblasts is described. Isolated erythroblasts were prepared from 14-day embryonic avian livers and incubated at various oxygen tension (0, 5, 12, and 95%). The concentration of ATP in erythroblasts remained constant for at least 4 hr at 37degree, but was rapidly reduced by incubation in nitrogen. Protein synthesis as measured by L-[14C]leucine incorporation into cell protein occurred at a linear rate in 5%, 12%, and 95% oxygen, whereas little protein synthesis occurred at 0% oxygen. The effect of hypoxia on the type of hemoglobin synthesized was studied in this system by isolating the hemoglobin A, hemoglobin D, and hemoglobin H fractions and determining the incorporation of L-[14C]leucine. The major fraction, hemoglobin A, contained most of the radioactivity; smaller amounts were present in hemoglobin D and hemoglobin H, respectively. The relative proportion of each hemoglobin synthesized was not altered by oxygen from 5% to 95%. These results argue against a direct effect of oxygen on the type of hemoglobin synthesized at this stage of development.
10.1203/00006450-197609000-00007
pubmed_1082_16280
In this study 104 adult patients with chronic conjunctival irritation without obvious diagnosis were investigated by conjunctival scrapings. The smears were stained with May-Grünwald-Giemsa or fluorescein-conjugated monoclonal antibodies prepared against Chlamydiae. In 45 cases it was possible to make a correct diagnosis of Chlamydia infection (29%) or allergy (20%).
pubmed_1082_16280
pubmed_970_9523
BACKGROUND Cervical cancer during pregnancy is rare. The management for stage IB3 during pregnancy remains unclear and challenging. We report a successful preserved pregnancy in a stage IB3 patient who was treated with neoadjuvant chemotherapy (NACT) plus radical surgery. CASE PRESENTATION A 36-year-old pregnant woman was diagnosed with a 5-cm-diameter stage IB3 squamous cell carcinoma of the uterine cervix at 13 gestational weeks. The patient received 5 courses of systemic chemotherapy with carboplatin and paclitaxel every 3 weeks, followed by caesarean section and radical hysterectomy. Both the mother and infant are in good general condition. CONCLUSION This case suggests that NACT plus radical surgery could be one method to maintain pregnancy in stage IB3 cervical cancer diagnosed as early as 13 gestational weeks.
10.1186/s12884-020-02895-y
pubmed_112_13496
This paper examines the notion of risk assessment in relation to nursing patients with HIV infection or AIDS. Risk assessment consists in examining three features of a given hazard; its magnitude, its probability, and its acceptability. In relation to the last of these, an 'acceptability threshold' can be identified. If contact with HIV-infected patients is perceived to pass this threshold, nurses may seek to abrogate the usual 'duty to treat'. Rather than endeavour to pinpoint this threshold, the paper explores some of the factors which may either raise or lower it, and their ethical implications. In particular, the consequences of setting a high threshold, and thereby limiting or avoiding contact with patients infected with HIV, are examined. In this debate, the burden of proof is seen as resting firmly on nurses themselves, not on the patients at risk of being deprived of care.
10.1111/j.1365-2648.1992.tb02834.x
pubmed_363_16159
Human macrophages (Mphi) respond to Mycobacterium tuberculosis (Mtb) infection by undergoing apoptosis, a cornerstone of effective antimycobacterial host defense. Virulent mycobacteria override this reaction by inducing necrosis leading to uncontrolled Mtb replication. Accordingly, Mphi death induced by inoculation with Mtb had the characteristics of apoptosis and necrosis and correlated with moderate increase of mitochondrial permeability transition (MPT), mitochondrial cytochrome c release, and caspase-9 and -3 activation. We hypothesized that changes in intramitochondrial Ca(2+) concentration ([Ca(2+)](m)) determine whether Mphi undergo either apoptosis or necrosis. Therefore, we induced mechanism(s) leading to predominant apoptosis or necrosis by modulating [Ca(2+)](m) and examined their physiological consequences. Adding calcium ionophore A23187 to Mphi inoculated with Mtb further increased calcium flux into the cells which is thought to lead to increased [Ca(2+)](m), blocked necrosis, stabilized MPT, decreased mitochondrial cytochrome c release, lowered caspase activation, and accompanied effective antimycobacterial activity. In contrast, Mphi infected with Mtb in presence of the mitochondrial calcium uniporter inhibitor ruthenium red showed increased mitochondrial swelling and cytochrome c release and decreased MPT and antimycobacterial activity. Thus, in Mtb-infected Mphi, high levels of mitochondrial membrane integrity, low levels of caspase activation, and diminished mitochondrial cytochrome c release are hallmarks of apoptosis and effective antimycobacterial activity. In contrast, breakdown of mitochondrial membrane integrity and increased caspase activation are characteristic of necrosis and uncontrolled Mtb replication.
10.4049/jimmunol.169.9.5181
pubmed_407_24605
OBJECTIVE To evaluate the frequency, severity, and risk factors for restless legs syndrome (RLS) in healthcare personnel. METHODS This cross-sectional study was performed at the Outpatient Family Medicine Clinic of Meram Medical Faculty in Konya, Turkey and included 354 healthcare personnel who were working at the Meram Medical Faculty Hospital between October 2010 and June 2011. The International RLS (IRLS) rating scale was used to calculate RLS severity. The RLS symptoms positive patients were investigated for neurological examination. RESULTS Of all the participants, 277 (78.2%) were female. The overall prevalence of RLS according to the 4 essential criteria in the participating healthcare personnel was 15% (n=53) (16.9% male, 14.4% female). Gender (p=0.726) and age (p=0.197) were not significantly related to RLS. According to the International Restless Legs Syndrome Study Group (IRLSSG) the severity scale for RLS, of the RLS positive patients, 16% were classified as mild (n=8), 40% as moderate (n=21), and 44% as severe (n=24). Approximately, 54.7% of 53 RLS patients had a positive family history of the disorder. CONCLUSION Restless leg syndrome is a treatable disorder; however, it is still widely misdiagnosed by physicians. The history of the patient and family is very important in the diagnosis of RLS.
pubmed_407_24605
pubmed_349_21913
Minocycline hydrochloride (MH), a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema. This review discusses the potential mechanisms of the multifaceted actions of MH. Its anti-inflammatory and neuroprotective effects are partially achieved through conserved mechanisms such as modulation of p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways as well as inhibition of matrix metalloproteinases (MMPs). Additionally, MH can directly inhibit calcium influx through the N-methyl-D-aspartate (NMDA) receptors, mitochondrial calcium uptake, poly(ADP-ribose) polymerase-1 (PARP-1) enzymatic activity, and iron toxicity. It can also directly scavenge free radicals. Because it can target many secondary injury mechanisms, MH treatment holds great promise for reducing tissue damage and promoting functional recovery following spinal cord injury.
10.4103/1673-5374.206633
pubmed_268_8353
On materials of 45 biopsies dissected at the time of antiglaucomatous operations and 10 eyes of newborns, a detailed morphologic analysis of the state of the drainage apparatus of the in norm and at relatively early stages of hydrophthalmos simplex is presented, and considering results of clinical investigations (105 eyes, of them 45 eyes mentioned) a foundation of modern surgery of congenital glaucoma is given. It is shown that the basis of congenital pathology of retinocorneal angle is disturbance of anatomotopographic relationships of its structures as well as expressed trabeculodysgenesis and dysgenesis of scleral sinus. The paper describes three main variants of combinations of pathologic changes in the drainage apparatus, characterized by a common gonioscopic picture and reflecting the degree of severity of congenital pathology (3 degrees of goniodysgenesis). It is noted that the presence of a coarse congenital pathology of trabecular plexus in hydrophthalmus, incompatible with the possibility of its functioning, and at the same time a satisfactory enough state of the "scleral sinus-emissary" link allow to consider the basic element of surgical reconstruction of anterior outflow passage to be trabeculotomy from outside. Indications in the choice of adequate surgical intervention and its volume are shown (the degree of goniodysgenesis and the state of functional preservation of scleral sinus and emissaries). The approved, within 15 years, system of operations in case of hydrophthalmos simplex and their results are presented.
pubmed_268_8353
pubmed_149_20286
This study assesses the quality of the SIM and SINASC information systems in coverage, incompleteness and consistency aspects, as well as the contribution of the linkage for data retrieval. It includes all live births and infant deaths in Rio Grande do Sul from 2000 to 2014. The records were paired by deterministic linkage through the DNV number and, in its absence, by probabilistic linkage. SINASC's coverage rose from 72.2% in 2000 to 98.9%, namely a 37% increase in the number of matched records. All variables in SINASC presented excellent incompleteness throughout the period, except for the number of dead children and maternal occupation. SIM presented poor or very poor incompleteness for most of the variables until 2003. Although it improved, in 2014, six variables still presented regular or poor incompleteness. The linkage procedure greatly reduced the incompleteness for most variables. There was a great variability in terms of consistency: while for gender this percentage was over 97% throughout the period, for another five variables it was still less than 75% in 2014. SINASC presented high coverage level and excellent incompleteness. Problems related to consistency persist. This study shows the linkage technic efficiency to retrieve missing information.
10.1590/1413-81232018245.19632017
pubmed_1109_25843
The goal of this study is to determine optimal conditions of optically pumped atomic magnetometers using a hybrid cell of potassium and rubidium atoms. We theoretically investigated the properties of the magnetometers and considered the optimal density ratio of potassium and rubidium atoms. We found that the experimental results agreed well with the theoretical estimations and the density ratio of potassium and rubidium atoms should be around 200 to achieve the highest sensitivity.
10.1109/EMBC.2013.6610235
pubmed_1075_6803
In the title compound, C(21)H(21)FO(2)S, the cyclo-hexyl ring adopts a chair conformation. The 3-fluoro-phenyl ring makes a dihedral angle of 38.38 (6)° with the mean plane [r.m.s. deviation = 0.010 (1) Å] of the benzofuran fragment. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds.
10.1107/S1600536812008343
pubmed_743_22603
BACKGROUND Adenosine is a purine nucleoside involved in regulating bone homeostasis through binding to A1, A2A, A2B, and A3 adenosine receptors (A1R, A2AR, A2BR, and A3R, respectively). However, the underlying mechanisms by which adenosine and receptor subtypes regulate osteoclast differentiation remain uncertain. This study aims to assess the role of exogenous adenosine and receptor subtypes in receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation and explore the underlying molecular mechanisms. METHODS AND RESULTS The nanofibrous mats incorporated with adenosine exhibited robust ability to facilitate rat critical-size calvarial defect healing with decreased number of osteoclasts. Moreover, exogenous adenosine substantially enhanced the expression of A2AR and suppressed tartrate-resistant acid phosphatase-positive osteoclast formation and expression of osteoclast-related genes Ctsk, NFATc1, MMP9, and ACP5. This enhancement and suppression could be reversed by adding an A2AR antagonist, ZM241385, in RAW264.7 cells. Finally, RNA sequencing showed that the expression of Fos-related antigen 2 (Fra2) was distinctly downregulated through stimulation of adenosine in RAW264.7 cells treated with RANKL. This downregulation was reversed by ZM241385 according to real-time PCR, Western blot, and immunofluorescence analyses. CONCLUSIONS These findings demonstrated that exogenous adenosine binding to A2AR attenuated osteoclast differentiation via the inhibition of activating protein-1 (AP-1, including Fra2 subunit) pathway both in vitro and in vivo.
10.1007/s11033-021-07017-1
pubmed_39_6550
PURPOSE This study was an attempt to verify the utility of complete dentures modified as a mandibular advancement device (MAD) in effecting expansion in pharyngeal volume to treat obstructive sleep apnea (OSA) in edentulous patients. MATERIALS AND METHODS The sample consisted of 17 patients (12 male, 5 female, average age 61 ± 4 years; BMI, 22 ± 5; apnea hypopnea index [AHI] 15 to 30). All patients had worn complete dentures for at least 1 year; all patients had the dentures modified to a MAD. Five variables were assessed preoperatively and 6 months after wearing the modified MADs. These variables were: sleep efficiency, AHI, oxygen desaturation events/hr., mean oxygen saturation, snoring index, and airway volume. This assessment was done by subjecting the patients to all-night polysomnography. RESULTS Without any prosthesis or device in the edentulous patients, the mean velopharyngeal volume was 8.05 ± 0.58 cm(3) , oropharyngeal volume was 2.14 ± 0.38 cm(3) , and hypopharyngeal volume was 3.26 ± 0.78 cm(3) . With complete dentures (unaltered) in the edentulous patients, the mean velopharyngeal, oropharyngeal, and hypopharyngeal volumes were 10.73 ± 0.98 cm(3) , 2.60 ± 0.48 cm(3) , and 4.31 ± 0.89 cm(3) , respectively. There was a statistically significant change in the airway volume following insertion of the complete dentures modified as MADs with velopharyngeal, oropharyngeal, and hypopharyngeal volume recorded as 11.76 ± 1.07 cm(3) , 3.33 ± 0.51 cm(3) , and 4.94 ± 0.83 cm(3) , respectively. CONCLUSION From the results obtained in this limited small sample study, it was inferred that the pharyngeal expansion induced by complete dentures modified as MADs effectively reduced symptoms of OSA. Increased volume was most pronounced in the velopharynx region followed by hypopharynx and oropharynx.
10.1111/jopr.12335
pubmed_256_9951
We examine the relationship of childhood living arrangements to adult child-parent relations. Compared with adult children raised in intact families, adult children whose parents divorced have less frequent contact with their parents and report a lower-quality relationship with their parents. We observe these negative effects for both custodial and noncustodial parents, although the effects are larger for noncustodial parents. Remarriage of the custodial parent tends to offset the negative impacts of divorce on relations with the custodial parent and to amplify the negative impacts on relations with noncustodial parents. Further, the longer the adult child lived apart from the parent, the weaker the relations with noncustodial parents.
pubmed_256_9951
pubmed_628_1736
Oxidation of a mixture of diketene and a 1,1-diarylethene 1 with manganese(III) acetate dihydrate gave an equilibrium mixture of 5-hydroxy-2-pentanone 2 and a tetrahydrofuran-2-ol, which was subsequently dehydrated in glacial acetic acid to yield 4-penten-2-one 4 in good yield. A similar reaction in the presence of alcohols or amines afforded 2-alkoxy-2-methyltetrahydrofurans 5 or 3-acetyl-2-aminodihydrofurans 9 in moderate yields. Diketene reacted with manganese(III) acetate in the presence of nucleophiles, such as water and alcohols, to give a mixture of unconjugated manganese(III) enolate A and conjugated manganese(III) enolate B. Major products 4 and 5 were formed by the oxidation of the conjugated manganese(III) enolate B. Tetrahydrofurylideneacetates 3 and 7 derived from the unstable unconjugated enolate A were also obtained as minor products. The reaction pathways are discussed.
10.1021/jo960939w
pubmed_666_21617
BACKGROUND Gastric cancer (GC) is a major health issue in the Western world. Current clinical imperatives for this disease include the identification of more effective biomarkers to detect GC at early stages and enhance the prevention and treatment of metastatic and chemoresistant GC. The advent of non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long-non coding RNAs (lncRNAs), has led to a better understanding of the mechanisms by which GC cells acquire features of therapy resistance. ncRNAs play critical roles in normal physiology, but their dysregulation has been detected in a variety of cancers, including GC. A subset of ncRNAs is GC-specific, implying their potential application as biomarkers and/or therapeutic targets. Hence, evaluating the specific functions of ncRNAs will help to expand novel treatment options for GC. CONCLUSIONS In this review, we summarize some of the well-known ncRNAs that play a role in the development and progression of GC. We also review the application of such ncRNAs in clinical diagnostics and trials as potential biomarkers. Obviously, a deeper understanding of the biology and function of ncRNAs underlying chemoresistance can broaden horizons toward the development of personalized therapy against GC.
10.1007/s13402-020-00528-2
pubmed_284_10568
An inexpensive and minimally restrictive restraint system for cats is described which protects any temporary connections to chronic physiological implants during recording sessions and permits free movement of the head and extremities for behavioral studies. Procedures for constructing and implanting a chronic indwelling venous catheter device are also described which allows, directly with a syringe of via a connector system, for intravenous drug infusions in cats. These catheters have remained intact and relatively free of infection for a period of months before tissue rejection begins at the site of the subcutaneous implant.
10.1016/0091-3057(75)90199-9
pubmed_93_1859
BACKGROUND Postreperfusion syndrome (PRS) is a state of significant hemodynamic instability following graft reperfusion during orthotopic liver transplantation (OLTx). We aimed to investigate its risk factors and influence on patient outcome based on a single centre's experience. MATERIAL/METHODS A retrospective study on a group of 340 patients undergoing OLTx during the period 2005-2008 was conducted. Piggy-back technique was employed in 266 cases and classical technique in 64. PRS was defined as a decrease in mean arterial pressure greater than 30% below the baseline for a minimum of 1 minute during first 5 minutes of the reperfusion. Logistic regression analysis, Mann-Whitney test and 2-sample proportion test were used. P<0.05 was considered statistically significant. RESULTS PRS occurred in 12.1% of patients. We observed correlations between PRS and the following: longer cold ischemia time, operation with classical technique, longer duration of the operation, higher intraoperative erythrocytal mass (EM) and fresh frozen plasma (FFP) requirements, more frequent early post-operative complications, and lower 1-year survival. Retransplantation was needed nearly twice as often in the PRS-group, but the correlation was not statistically significant (the group was very small, as only 8 patients requested re-OLTx). The study did not demonstrate any statistically significant relationship between PRS and donors' age, recipients' age or sex, duration of the hospitalization, and occurrence of complications after discharge. CONCLUSIONS PRS occurrence seems to be associated with higher mortality rate and worse patient outcome. The study revealed a few risk factors that could be relevant in the prevention of PRS.
10.12659/aot.881861
pubmed_219_22484
BACKGROUND Listeria monocytogenes (LM) is a gram-positive intracellular bacillus that in immunodeficient patients, children, geriatric patients, pregnant women, and even in healthy individuals can cause central nervous system infection, bacteremia, and other clinical manifestations, becoming a relevant pathogen. MATERIALS AND METHODS From the Microbiology Service data of 'Gregorio Marañón' Hospital, we selected all positive biological sample cultures for LM from inflammatory bowel disease (IBD) patients, from January 1986 until January 2011. These cases were included in an SPSS database, analyzing several basal clinical characteristics and factors related to the infection. RESULTS Three patients diagnosed with IBD had positive cultures for LM during this period. All of them were male, and also all of them had a diagnosis of Crohn's disease. Every patient had a corticosteroid cumulated dose of more than 400 mg (equivalency in methylprednisolone doses), adding anti-tumor necrosis factor-α treatment (certolizumab) in one patient. Prior colonoscopy with biopsy was performed in two patients. Clinical presentation of the infection was bacteremia in two patients, accompanied by central nervous system infection in one patient. One patient had isolated meningoencephalitis. Despite correct empiric treatment, one patient died from a cause related to the infection, that is, rombencephalitis. Increased incidence of LM bacteremia was found in IBD patients, compared with the general population (12.2 bacteremias/100 000 IBD patient-years, compared with 1.6 bacteremias/100 000 person-years), with an odds ratio of 7.4. CONCLUSION IBD patients may be at risk for more frequent and serious LM infection compared with the general population.
10.1097/MEG.0000000000000188
pubmed_300_24413
OBJECTIVE To report the oncological outcome of 106 patients who had locally advanced prostate cancer with microscopic bladder neck invasion, identified in a series of 1129 patients surgically treated with retropubic radical prostatectomy over a 12-year period. PATIENTS AND METHODS All specimens were reviewed. Microscopic bladder neck invasion was defined as the presence of neoplastic cells within the smooth muscle bundles of the bladder neck, with no accompanying prostatic glandular tissue on the corresponding slide. Survival was analysed for different subgroups in relation to several variables. RESULTS The follow-up (median 7.2 years, mean 6.68, range 0.3-14) was available for 106 patients with microscopic bladder neck invasion. Seminal vesicle invasion was present in 69.8% of the cases, lymph node involvement in 29.2%, apex infiltration in 31.8%, and positive surgical margins in 23.6%. Biochemical progression occurred in 61 (57.5%) patients, and 25 of them died from cancer. The mean (sd) biochemical progression-free survival was 0.68 (0.05), 0.59 (0.05), 0.40 (0.05) and 0.38 (0.05) at 1, 2, 5 and 10 years, respectively. Age, Gleason score and lymph node invasion were independent prognostic factors on multivariate analysis. Overall and cancer-specific survival rates were 0.75 (0.04) and 0.80 (0.04) at 5 years and 0.57 (0.04) and 0.75 (0.04) at 10 years, respectively. Univariate analysis showed that seminal vesicle invasion, lymph node involvement and surgical Gleason score > or =8 significantly increased the risk of death. On multivariate analysis only the surgical Gleason score had an independent prognostic role with regard to overall survival (P = 0.01; odds ratio 2.82, 95% confidence interval 1.2-6.4) and cancer-specific survival (P < 0.001; 8.6, 2.5-28.8). CONCLUSIONS In this series, overall and cancer-specific survival rates were comparable to those reported for surgically treated cT3 prostate cancers. The lack of need for external urinary diversion during the entire follow-up significantly contributed to the patients' quality of life.
10.1111/j.1464-410X.2009.08914.x
pubmed_489_9867
BACKGROUND Data suggest that prolonged Emergency Department length of stay (EDLOS) has a detrimental effect on outcomes in some critically ill patients. However, the relationship between EDLOS and outcomes in traumatic brain injury (TBI) has not been examined. OBJECTIVE Our objective was to determine the effect of EDLOS on neurologic outcomes in TBI patients. METHODS We performed a retrospective analysis of a prospectively identified cohort of patients with moderate (Glasgow Coma Scale [GCS] score 9-13) and severe (GCS ≤ 8) TBI who presented to a Level 1 trauma center (2006-2010). Inclusion criteria were transfer to the intensive care unit (ICU) or operating room (OR) from the ED. Primary outcome was Glasgow Outcome Scale (GOS) score, a measure of neurologic function, at discharge. We used a proportional odds model to control for significant predictors of GOS in univariate analysis. RESULTS Two hundred and twenty-four patients were included in the analysis, 77 (34%) of which were transferred to the OR. Median EDLOS was 3.3 h and 81.2% of patients had a GOS score ≤3 (e.g., severe disability, vegetative, or deceased). In multivariable analyses, EDLOS was not associated with GOS score in either ICU bound (p = 0.57) or OR bound (p = 0.11) patients. Younger age, pupil reactivity, and absence of intubation were independent predictors of good outcomes in the ICU group. In OR patients, predictors of higher GOS score included presence of an epidural hemorrhage, absence of midline shift, and pupil reactivity. CONCLUSIONS Our study demonstrates that EDLOS was not associated with poor outcomes in patients with moderate to severe TBI who required intensive care or early operative intervention in an academic Level 1 trauma center.
pubmed_489_9867
pubmed_663_5518
Mycobacterium tuberculosis isolates with identical IS6110 restriction fragment length polymorphism (RFLP) patterns are considered to be clonally related. The presence of IS6110 in the dnaA-dnaN intergenic region, one preferential locus for the integration of IS6110, was evaluated in 125 M. tuberculosis isolates. Five isolates had IS6110 inserted in this region, and two consisted of a mix of isogenic strains that putatively have evolved during a single infection. Strains from the same isolate had identical spoligo and mycobacterial interspersed repetitive unit-variable-number tandem repeat profiles, but had slight variations in IS6110 RFLP patterns, due to the presence of IS6110 in the dnaA-dnaN intergenic region. Duplication of the dnaA-dnaN intergenic region was found in one isogenic strain.
10.1111/j.1469-0691.2008.02107.x
pubmed_742_24905
INTRODUCTION Abnormal ventricular repolarization has been proposed as a marker of arrhythmogenesis, and cardiovascular morbidity and mortality. However, little is known about the influence of the interval between the peak and the end of the T wave (Tp-Te) on the inducibility of sustained ventricular arrhythmias (VA) in patients with Chagas disease (CD). METHODS Using a case-control design, chagasics undergoing electrophysiological study (EPS) in the last three years were matched by age and sex. Cases represented those with positive EPS and controls those with no inducible VA. Tp-Te>100 ms was considered abnormal. Logistic regression analysis was performed to assess the association between Tp-Te and a positive EPS, after adjusting for confounders. RESULTS A total of 105 patients (mean age 56 years, 52.4% male) were included: 41 (39%) had a positive EPS; 85.4% with inducible VA (n=35) had non-sustained ventricular tachycardia on the Holter monitoring, compared to 62.5% with negative EPS (n=40, p<0.001). While ventricular aneurysm (adjusted OR=5.3, 95% CI: 1.11-24.96, p=0.03) and coronary artery disease (adjusted OR=8.8, 95% CI: 1.45-53.15, p=0.01) were associated with an increased risk of malignant arrhythmias, a greater ejection fraction (adjusted OR=0.96, 95% CI: 0.93-0.99, p<0.01) was associated with a lower risk of VA. Prolonged Tp-Te trended to be associated with an increased risk of induced VA (p=0.07). CONCLUSIONS Ventricular aneurysm, coronary artery disease, and ejection fraction are associated with inducible VA. Prolonged TP-Te may have a modest role in the identification of patients with CD who are at high risk for VA. Further studies are warranted to validate our results and to correlate them with clinical outcomes.
pubmed_742_24905
pubmed_21_14171
OBJECTIVES The objective was to assess whether testicular torsion is associated with low testicular tissue saturation of oxygen (StO2 ) as measured by transscrotal near-infrared spectroscopy (NIRS) and to compare the differences in NIRS values between testicles of the same patient, both in patients with testicular torsion and in healthy controls. METHODS This was an observational study of healthy controls and patients with surgically confirmed testicular torsion who were recruited from males under 30 years of age presenting to the emergency department (ED). The hypothesis was that the difference in NIRS values for the control's two testicles would be zero, and that the difference between the torsed and healthy testicles on an individual patient would not be zero. Based on animal data, the study was powered to detect an absolute difference of StO2 of 47%. RESULTS The mean StO2 for the left control patients' testicles was 73.6% (95% confidence interval [CI] = 68.0% to 79.1%) and the mean StO2 for the right controls' testicles for controls was 73.6% (95% CI = 66.9% to 80.4%; n = 17). The absolute difference in NIRS StO2 for left minus right for each individual was 3.5% (95% CI = 1.8% to 5.4%), which was significantly different (p = 0.0007), and refuted the hypothesis that there was no significant difference in StO2 between left and right testes in healthy patients. In the testicular torsion group, the torsed side had a mean StO2 of 82.8% (95% CI = 68.7% to 96.9%), and the contralateral nontorsed testes had a mean of 85.8% (95% CI = 72.3% to 99.3%). The mean StO2 difference, nontorsed minus torsed was 3.0% (range = -1% to 9%, 95% CI = -2% to 8%; p = 0.174), refuting the hypothesis that torsed testes would demonstrate significantly lower values for StO2 . CONCLUSIONS While pilot animal investigations support a potential role for transscrotal NIRS for the detection of testicular torsion, this first clinical translation of animal findings reveals that the investigated, transcutaneous, reflectance geometry NIRS device failed to demonstrate symmetric oxygenation of left and right testes in healthy controls and also failed to demonstrate depressed tissue saturation of oxygen values in patients with confirmed testicular torsion. While limited by a small sample size, other problems such as inability to calibrate depth of measurement of StO2 may have led to falsely elevated readings in patients with torsion.
10.1111/acem.12233
pubmed_206_15241
Attention-deficit/hyperactivity disorder (ADHD) is more common in boys than in girls. It has been hypothesized that this sex difference might be related to genes on the X-chromosome, like Monoamine Oxidase A (MAOA). Almost all studies on the role of MAOA in ADHD have focused predominantly on boys, making it unknown whether MAOA also has an effect on ADHD in girls, and few studies have investigated the relationship between MAOA and neuropsychological functioning, yet this may provide insight into the pathways leading from genotype to phenotype. The current study set out to examine the relationship between MAOA, ADHD, and neuropsychological functioning in both boys (265 boys with ADHD and 89 male non-affected siblings) and girls (85 girls with ADHD and 106 female non-affected siblings). A haplotype was used based on three single nucleotide polymorphisms (SNPs) (rs12843268, rs3027400, and rs1137070). Two haplotypes (GGC and ATT) captured 97% of the genetic variance in the investigated MAOA SNPs. The ATT haplotype was more common in non-affected siblings (P = 0.025), conferring a protective effect for ADHD in both boys and girls. The target and direction of the MAOA effect on neuropsychological functioning was different in boys and girls: The ATT haplotype was associated with poorer motor control in boys (P = 0.002), but with better visuo-spatial working memory in girls (P = 0.01). These findings suggest that the genetic and neuropsychological mechanisms underlying ADHD may be different in boys and girls and underline the importance of taking into account sex effects when studying ADHD.
10.1002/ajmg.b.30845
pubmed_414_16242
Injection sclerotherapy has a prominent role in the treatment of bleeding hemorrhoids. The commonly used sclerosants are not available or very expensive in Nigeria. We prospectively evaluated 50% dextrose water, used as a nonallergenic sclerosant, in the treatment of bleeding internal hemorrhoids. Forty consenting adult patients (median age 50 years [range 35-67]; 22 women) with bleeding hemorrhoids, seen over a 2-year period, were offered injection sclerotherapy with 50% dextrose water. They were assessed for response, tolerance and complications. The duration of symptoms before presentation was 3 months to 15 years. The bleeding stopped after the injection in all patients. No patient needed a repeat procedure. No complication was recorded during follow up which ranged from 2 months to 12 months. We conclude that endoscopic hemorrhoidal sclerotherapy using 50% dextrose water offers a simple, safe and effective modality of treatment if properly utilized.
10.1007/s12664-009-0007-2
pubmed_457_10032
Muscle stem cells, named satellite cells, are quiescent in resting skeletal muscle. Following injury, satellite cells are activated and become proliferating myoblasts that either self-renew or differentiate. Several markers are used to identify the different myogenic populations, such as Pax7 (quiescent and activated satellite cells), MyoD (proliferating myoblasts), and myogenin (differentiating myoblasts). Immunodetection of these markers is a very useful tool to analyze myogenic cells and muscle regeneration. Here, we describe a method for immunodetection of satellite cells and their myogenic progeny in resting and regenerating skeletal muscles.
10.1007/978-1-4939-6788-9_12
pubmed_73_1517
OBJECTIVES There is no universally accepted instrument to measure sexual function (SF) in men. We compare validated SF measures in a single cohort. METHODS We compare the Sexual Health Inventory for Men (SHIM), Expanded Prostate Cancer Index Composite SF domain (EPIC-SF), and a reconstructed University of California Los Angeles Prostate Cancer Index SF domain (PCI-SF) in 856 men scheduled for radical prostatectomy. We define potency thresholds for the PCI-SF and EPIC-SF. RESULTS Mean age, body mass index, Gleason sum, and PSA were 57 years, 26.7 kg/m(2), 6.3, and 5.9 ng/mL, respectively. Mean instrument scores were as follows: SHIM 20.1; EPIC-SF 65; PCI-SF 71. All instruments were significantly intercorrelated (r = 0.99 for EPIC-SF vs PCI-SF, r = 0.75 for SHIM vs EPIC-SF, r = 0.77 for SHIM vs PCI-SF, all P < .001). The SHIM had the greatest negative skew and ceiling effect (P < .001). Although high scores on either the EPIC-SF or PCI-SF translated reliably to high SHIM scores, the reverse was not true. Subjects who reported no erectile dysfunction (ED) on the SHIM (>or=22) had diverse overall SF, whereas those who scored highly on the EPIC-SF or PCI-SF had both excellent erectile function (potency) and overall SF (including orgasmic function, erectile function, and sexual desire). EPIC-SF scores >or=65 and PCI-SF scores >or=75 define men that are both potent and have good SF. CONCLUSIONS The SHIM is intended as an instrument to assess ED. It is, however, inadequate as a measure of overall SF. The EPIC-SF and PCI-SF capture gradations of both sexual and erectile function and may also be used to define potency more comprehensively.
10.1016/j.urology.2010.04.033
pubmed_835_16447
INTRODUCTION Pharmacists are frequent users of mobile medical apps (MMA) for drug information (DI) and clinical decision-making purposes. However, the wide range of available MMA may be of variable credibility and results in heterogeneous recommendations. The need for subscription may also influence choice of apps. OBJECTIVE The objective of this study was to determine the usage pattern of MMA among hospital pharmacists, including their perceptions and factors affecting their choice of apps. METHODS This cross-sectional study required respondents to fill in an online questionnaire. The questionnaire included sections on respondents' demographic data, MMA usage pattern, perceived usefulness and opinion on subscription fees. Items were adapted from available literature and validated locally. It was made accessible for 6 weeks starting November 2019 for all pharmacists working in the 23 public hospitals in Sarawak to response (universal sampling). Collected data were analysed using descriptive and inferential statistics. RESULTS A response rate of 37.2% was achieved (n = 162). Respondents were heavily reliant on MMA, with 78.4% accessing them multiple times daily. The majority also agreed that MMA contain correct and up-to-date information. A median of 5 apps were downloaded, suggesting an ultimate app catering for all DI needs was lacking. The Malaysian Drug Formulary was the most downloaded app (88.3%), whereas Lexicomp® was the most "well-rounded" in terms of functionality. Clinical pharmacists were significantly more likely to purchase MMA, in particular UpToDate® (p < 0.01) due to their need to access clinical updates. Respondents highly recommended institutional access for either UpToDate® or Lexicomp® be made available. Pre-registration pharmacists should be guided on judicious MMA usage, as they downloaded significantly more apps and were more likely to indicate not knowing which DI recommendation to follow (both p < 0.01). CONCLUSION MMA has become an indispensable tool for hospital pharmacists, however there was a tendency to download multiple apps for DI needs. Institutional access can be considered for credible apps identified to ensure accuracy and uniformity of DI recommendations, with purchase decision made after surveying the needs and preferences of end users.
10.1186/s12911-022-01949-9
pubmed_325_25026
A grand challenge in materials research is to understand complex electronic correlation and non-equilibrium atomic interactions, and how such intrinsic properties and dynamic processes affect energy transfer and defect evolution in irradiated materials. Here we report that chemical disorder, with an increasing number of principal elements and/or altered concentrations of specific elements, in single-phase concentrated solid solution alloys can lead to substantial reduction in electron mean free path and orders of magnitude decrease in electrical and thermal conductivity. The subsequently slow energy dissipation affects defect dynamics at the early stages, and consequentially may result in less deleterious defects. Suppressed damage accumulation with increasing chemical disorder from pure nickel to binary and to more complex quaternary solid solutions is observed. Understanding and controlling energy dissipation and defect dynamics by altering alloy complexity may pave the way for new design principles of radiation-tolerant structural alloys for energy applications.
10.1038/ncomms9736
pubmed_1028_7022
The enzymes used in the identification of Gram negative bacteria belonging to the families of Enterobacteriaceae, Vibrionaceae, Parvobacteriaceae, Pseudomonadaceae and to the genera Alteromonas, Xanthomonas, Alkaligenes, Flavobacterium are classified arbitrarily by the author into enzymes essential for the diagnosis of the family (oxidase, nitratase), enzymes useful in the diagnosis of the genus or the species (ONPG-hydrolase, urease, oxidative desaminase, lysine decarboxylase and ornithine, arginine dihydrolase, thiosulphate reductase, pectinase), and into enzymes sought to confirm the diagnosis (tetrathionate reductase, gelatinase, lipase, DNase, amylase, beta-xylosidase, lecithinase). The technics permitting their identification are described and their distribution in the species and genera studied is reported.
pubmed_1028_7022
pubmed_48_25945
PURPOSE To evaluate the influence of prior abdominal surgery on the outcomes after robotic-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS We retrospectively analyzed patients with prostate cancer who underwent RALP between June 2012 and February 2015 at our institution. Patients with prior abdominal surgery were compared with those without prior surgery while considering the mean total operating, console, and port-insertion times; mean estimated blood loss; positive surgical margin rate; mean duration of catheterization; and rate of complications. RESULTS A total of 203 patients who underwent RALP during the study period were included in this study. In all, 65 patients (32%) had a prior history of abdominal surgery, whereas 138 patients (68%) had no prior history. The total operating, console, and port-insertion times were 328 and 308 (P=0.06), 252 and 242 (P=0.28), and 22 and 17 minutes (P=0.01), respectively, for patients with prior and no prior surgery. The estimated blood losses, positive surgical margin rates, mean durations of catheterization, and complication rates were 197 and 170 mL (P=0.29), 26.2% and 20.2% (P=0.32), 7.1 and 6.8 days (P=0.74), and 12.3% and 8.7% (P=0.42), respectively. Furthermore, whether prior abdominal surgery was performed above or below the umbilicus or whether single or multiple surgeries were performed did not further affect the perioperative outcomes. CONCLUSIONS Our results suggest that RALP can be performed safely in patients with prior abdominal surgery, without increasing the risk of complications.
10.1590/S1677-5538.IBJU.2015.0607
pubmed_454_934
Bacterial cells interact extensively within and between species. These interactions can be divided into those that rely on diffusible factors and those that depend on direct cell-to-cell contacts. An example of a contact-dependent interaction is the transfer of lipoproteins between Myxococcus xanthus cells that leads to transient stimulation of motility in certain motility mutants. In this issue of Molecular Microbiology, Wei et al. (2011) provide mechanistic insights into this contact-dependent transfer of lipoproteins. Briefly, a heterologous protein fused to a type II (lipoprotein) signal sequence that targets the protein to the outer membrane is required and sufficient for transfer. Moreover, evidence is provided that transfer may depend on specific contacts between donor and recipient cells. The data demonstrate that lipoprotein transfer in M. xanthus is not restricted to a few odd motility proteins but could be a wide-spread phenomenon in M. xanthus and possibly other bacteria. Recent years have been fruitful in identifying contact-dependent interactions between bacterial cells. These interactions can be grouped into those that involve delivery of cargo to a recipient and those that seem to be involved in cell-to-cell signalling. Several contact-dependent interactions involve widely conserved proteins, suggesting that cell contact-dependent processes may be widespread among bacteria.
10.1111/j.1365-2958.2011.07711.x
pubmed_50_18497
Although the technique of pars plana vitrectomy (PPV) develops rapidly, scleral buckling (SB) has several advantages over PPV for rhegmatogenous retinal detachment (RRD), including early visual rehabilitation and prevention of cataract progression. It is recommended to select the primary procedure for RRD by considering the advantages and disadvantages of each procedure based on the patient status. The vitreous body status affects the features of RRD. Vitreous liquefaction is an age-dependent process, resulting in the development of posterior vitreous detachment (PVD). RRD is usually associated with PVD, typically presenting with a retinal tear, strong vitreoretinal traction, and bullous detachment. In contrast, RRD may develop without PVD, and typically presents with a small atrophic hole, shallow detachment, and slow progression. RRD with less liquefied vitreous and no PVD can be managed successfully with SB alone even in the presence of subretinal strand as less liquefied vitreous acts as bio-tamponade blocking fluid passage. The strong traction induced by PVD and bullous detachment in an eye with extensively liquefied vitreous reduces the success rate of SB. PPV is gaining popularity as the primary procedure for RRD, especially in eyes with retinal tears, PVD, or pseudophakia. Nevertheless, SB remains the preferred procedure in young phakic patients without PVD.
10.2147/OPTH.S153717
pubmed_720_19855
BACKGROUND Porcine circovirus 3 (PCV3) is an emerging etiological agent to the swine industry. However, its circulating status and genetic characteristics were still unclear in Henan, central China. Here, 318 porcine oral fluid specimens were collected from asymptomatic pigs in five farms and tested by PCR . RESULTS The results showed that the positive rate of PCV3 was 12.3% (39/318) for the total samples, and 15.06% (25/166) in the stall-based samples, 9.21% (14/152) in the pen-based samples. Of the PCV3-positive samples, 41.0% were also positive for porcine circovirus 2 (PCV2). Nucleotide sequence comparison indicated that the 10 complete genomes and 34 capsid (cap) genes in this study shared 98.7-99.9% and 98-100% pairwise identities to each other, respectively. According to phylogenetic analysis and sequence alignment of cap gene, all the isolated sequences were clustered into 3 clades, including subgroup 1 (21/39, 61.8%), subgroup 2 (5/39, 14.7%) and subgroup 3 (8/39, 23.5%). Similar to previous reports, four amino acids (V24A, K27R, S77 T and I150L) in cap protein were identified as a conserved subgroup specific molecular marker. CONCLUSION Our research provided new insights into the epidemiology surveillance and genetic characteristics of PCV3 in China.
10.1186/s12917-019-1952-3
pubmed_1074_14082
AIMS/HYPOTHESIS Recent studies have provided evidence that intrauterine exposure to maternal diabetes has lifelong effects on adult offspring, including increased risks of obesity, type 2 diabetes and cardiovascular disease. The aim of this study was to assess the relationship between exposure to maternal diabetes in utero and cardiovascular risk factors in healthy children and to investigate whether these associations are independent of maternal prepregnancy BMI and offspring attained BMI. METHODS Data were from a retrospective cohort of children aged 6-13 years born during 1994-2002. Multiple linear regression was used to examine the associations between exposure and cardiovascular risk factors with adjustment for demographic factors and pubertal stage and additionally for maternal prepregnancy BMI and offspring attained BMI. RESULTS Ninety-nine offspring of diabetic pregnancies had significantly increased E-selectin, vascular adhesion molecule 1 (VCAM1), leptin, waist circumference, BMI and systolic blood pressure and decreased adiponectin levels compared with 422 offspring of non-diabetic pregnancies after adjustment for age, sex and race/ethnicity (p < 0.05 for each risk factor). Additional adjustment for maternal prepregnancy BMI substantially attenuated group differences in the risk factors except for E-selectin, VCAM1 and waist circumference, which remained significantly higher in exposed children. CONCLUSIONS/INTERPRETATION Compared with unexposed children, healthy offspring exposed to maternal diabetes in utero have a worse cardiovascular risk profile. In particular, offspring have substantially increased levels of circulating cellular adhesion molecules, which are biomarkers of adverse endothelium perturbation and may be related to the earliest preclinical stages of atherosclerosis and diabetes.
10.1007/s00125-010-2008-1
pubmed_414_6138
BACKGROUND Leiomyoma is the most common benign esophageal neoplasm. Different open and minimally invasive approaches have been described. We describe a right thoracoscopic enucleation with the patient in the prone position. METHOD A 49-year-old woman consulted us about solid-diet dysphagia without other symptoms. Preoperative work-up showed the presence of 50 x 28-mm leiomyoma of the middle esophagus, without satellite lymph nodes. The patient underwent general anesthesia with a double-lumen endotracheal tube, and subsequently was placed in the prone position. A 30 degrees scope was introduced in the right 7th intercostal space on the posterior axillary line. Perioperative gastroscopy permitted localization of the lesion, which appeared to be situated at the level of the azygos vein. Two 5-mm trocars were inserted in the right 5th and 9th intercostal spaces on one line with the first one. The azygos vein was ligated. The muscular layer of the mid-esophagus was opened by coagulating hook. Due to a 2-mm trocarless Cadière's forceps (Microfrance, France), introduced into the right 7th intercostal space, the operative field was well exposed and the lesion was enucleated without mucosal perforation. The muscular layer was closed by interrupted silk 2/0 stitches. A drain was left in the chest cavity. RESULTS Total operative time was 85 min and blood loss was less than 20 ml. The gastrograffin swallow on postoperative day 2 showed good clearance of the esophagus and absence of leak, hence the patient was allowed a liquid diet. The patient was discharged on postoperative day 3. Benign pathology was confirmed. CONCLUSION Thoracoscopy in the prone position permits the surgeon to reach the esophagus under excellent working conditions, despite an only partially deflated lung. Gravity displaces blood loss eventually, which allows good visualization, and the surgeon can operate in an ergonomic position. This approach allows for fewer trocars which favorably influences the patient's comfort and reduces the length of hospital stay.
10.1007/s00464-009-0514-3
pubmed_146_7071
In this study, a quasi-experimental design with repeated measures was used to compare anxious (n = 129) and nonanxious (n = 186) older adults on the cortisol secretion rate attributable to an experimental stressor. Our results support the hypothesis that a first-order longitudinal factor model appropriately describes the cortisol concentration in three saliva samples collected at two experimental times. The model tested explained between 82.6 and 98.0% of the variance in cortisol concentration of the respondent's saliva samples at T1, and between 55.4% and 78.4% at T2. In the nonanxious group ((State-Trait Anxiety Inventory) STAI < 42), the magnitude of the experiment-related cortisol reactivity was, respectively 51 and 33% higher than the respondent's baseline reactivity level at both T1 and T2. By contrast, in the anxious group (STAI >or= 42), our results showed no significant gradient in the magnitude of the cortisol reactivity at either time. This result was interpreted to be in agreement with the helplessness reaction hypothesis. These results suggest that salivary cortisol is a valid measure that is sensitive to experimental stress, and may therefore, be useful in examining physiological response to stress.
10.1080/13607860701616499
pubmed_510_1525
Sudden Infant Death Syndrome (SIDS), the leading cause of infant death from one to six months in the developed world, strikes approximately two infants per 1000 live births in the U.S. The characteristics of the infants who die suddenly and unexpectedly are non-specific; none are universal except for the age distribution. Therefore, an infant is recognized to have died from SIDS only after thorough examination fails to demonstrate any other cause for the death. It is the purpose of this paper to review the most populat hypotheses of the causes of SIDS and try to explain through published scientific findings how breastfed infants appear to be protected from this condition. Many hypotheses have been proposed to explain SIDS. Some deficiencies/problems are related to the infant, such as a defect in sleep and/or breathing control, severe infant botulism, infections, reactions to immunizations, hypersensitivity to cow's milk, "maternal deprivation syndrome." Other causes are attributed to maternal circumstances, such as lower socioeconomic status, prenatal health, smoking, and the winter season. Additional suggestions of potential causes of SIDS include baby's thiamine deficiency, and hormonal and/or biochemical imbalance. The occurrence of most of these circumstances can be associated with a lack of breastfeeding. Because SIDS occurs much less frequently in breastfed infants, it is speculated that breastfeeding protects infants against SIDS. However, scientific literature lacks uniformity in the definitions of breastfeeding (whether partial and exclusive). This specification is necessary to select control infants to elucidate the well documented substantial lower rate of incidence of SIDS in breastfed babies.
10.1177/089033449100700227
pubmed_546_11508
The chemical structures, mechanisms of actions, bioavailabilities, insulinotrophic and hypoglycemic actions, and clinical trials of three novel oral hypoglycemic agents, NN-623, A-4166 and KAD-1229 are overviewed. They are non-SU insulin secretagogues and they induce quicker and shorter hypoglycemia than sulphonylureas do, presumably because they are rapidly absorbed into (Tmax: < 30 min) and excreted from blood (T 1/2: < 60 min). They bind to the SU-receptors and suppress K-ATP channels like sulphonylureas do. They stimulate mainly the initial phase of insulin release and evoke a decrease in postprandial rises in plasma glucose in several animals and humans. Clinical trials demonstrated they are efficacious and safe in the treatment of NIDDM subjects. They are useful as a first choice drug for the early stage of NIDDM.
pubmed_546_11508
pubmed_470_124
Comparative sequence analysis has been used to study specific questions about the structure and function of proteins for many years. Here we propose a knowledge-based framework in which the maximum likelihood rate of evolution is used to quantify the level of constraint on the identity of a site. We demonstrate that site-rate mapping on 3D structures using datasets of rhodopsin-like G-protein receptors and alpha- and beta-tubulins provides an excellent tool for pinpointing the functional features shared between orthologous and paralogous proteins. In addition, functional divergence within protein families can be inferred by examining the differences in the site rates, the differences in the chemical properties of the side chains or amino acid usage between aligned sites. Two novel analytical methods are introduced to characterize rate- independent functional divergence. These are tested using a dataset of two classes of HMG-CoA reductases for which only one class can perform both the forward and reverse reaction. We show that functionally divergent sites occur in a cluster of sites interacting with the catalytic residues and that this information should facilitate the design of experimental strategies to directly test functional properties of residues.
10.1093/nar/gkg151
pubmed_520_14697
This manuscript provides the description of the bacterial strain A621T characterized by Gram negative motile rods, presenting green circular colonies on TCBS. It was obtained from the skin of the sharpnose pufferfish Canthigaster figueredoi (Tetraodontidae Family), collected in Arraial do Cabo, located in the Rio de Janeiro region, Brazil. Optimum growth occurs at 20-28 °C in the presence of 3% NaCl. The Genome sequence of the novel isolate consisted of 4.224 Mb, 4431 coding genes and G + C content of 44.5%. Genomic taxonomy analysis based on average amino acid (AAI), genome-to-genome-distance (GGDH) and phylogenetic reconstruction placed (A621T= CBAS 741T = CAIM 1945T = CCMR 150T) into a new species of the genus Vibrio (Vibrio fluminensis sp. nov). The genome of the novel species contains four gene clusters (~ 56.17 Kbp in total) coding for different types of bioactive compounds that hint to several possible ecological roles in the sharpnose pufferfish host.
10.1007/s00203-022-03266-1
pubmed_58_17545
Use of stem cell-based therapies in tissue engineering and regenerative medicine is hindered by efficient means of directed differentiation. For pluripotent stem cells, an initial critical differentiation event is specification to one of three germ lineages: endoderm, mesoderm, and ectoderm. Differentiation is known to be regulated by numerous extracellular and intracellular factors, but the role of the cytoskeleton during specification, or early differentiation, is still unknown. In these studies, we used agonists and antagonists to modulate actin polymerization and the actin-myosin molecular motor during spontaneous differentiation of embryonic stem cells in embryoid bodies. We found that inhibiting either actin polymerization or actin-myosin interactions led to a decrease in differentiation to the mesodermal lineage and an increase in differentiation to the endodermal lineage. Thus, targeting processes that regulate cytoskeletal tension may be effective in enhancing or inhibiting differentiation towards cells of the endodermal or mesodermal lineages, which include hepatocytes, islets, cardiomyocytes, endothelial cells, and osteocytes. Therefore, these fundamental findings demonstrate that modulation of the cytoskeleton may be useful in production for a range of cell-based therapies, including for liver, pancreatic, cardiac, vascular, and orthopedic applications.
10.1371/journal.pone.0195588
pubmed_290_389
Transcatheter mitral valve implantation (TMVI) is an emerging field in structural cardiology. A particularly difficult group to treat is high-risk patients requiring valve in mitral annular calcification (ViMAC) intervention, with overall poor procedural success and outcomes in recent registries. This case highlights an unusual complication of paravalvular regurgitation (PVL) through the uncovered stent frame of a balloon expandable transcatheter heart valve (THV) on the left ventricular side of the prosthesis, leading to mechanical hemolysis and subsequent anuric renal failure post a ViMAC procedure. Attempts to treat the PVL with an occlusion plug device were unsuccessful and led to left circumflex coronary occlusion secondary to mechanical compression of the vessel in the posterior mitral valve annulus, a previously unreported phenomenon. A repeat valve-in-valve procedure was performed to treat the PVL, and immediate angioplasty resolved the left circumflex occlusion. High-risk patients requiring TMVI pose multiple challenges to Heart Teams in the treatment of valve pathology. Optimal procedural planning, multimodality imaging, improved THVs, and the awareness of potential complications are fundamental in overcoming the learning curve of TMVI and improved outcome for patients requiring ViMAC.
10.1002/ccd.28573
pubmed_869_13883
Depressive insomnia and diurnal fluctuations of mood and activity are core clinical features of mood disorders. Here we studied the effect of CLOCK 3111 T/C SNP (rs1801260) on the actimetric recorded diurnal activity and nocturnal sleep of 39 bipolar depressed inpatients. Compared to T/T homozygotes, carriers of the C allele had a similar degree of severity of depression, but showed higher activity levels in the evening, a delayed sleep onset (mean 79 min later), and a reduced amount of sleep during the night (mean 75 min less). Ongoing lithium treatment significantly interacted with rs1801260 by enhancing activity levels in the evening and reducing the differences among genotype groups. Individual characteristics of the molecular clock can influence sleep symptoms in mood disorders.
10.1002/ajmg.b.30475
pubmed_492_17981
Phocomelia is a developmental abnormality which occurs during pregnancy and results in congenital ectromelia (developmental arrest of one or more limbs), with characteristically atrophied limbs that look as if they were directly implanted on the trunk, that is, like seal (phocid) flippers. The authors report the case of a Cameroonian neonate. Abnormalities were limited to the upper limbs. The lack of useful causal information and especially the difficulties in therapeutic management in this context are highlighted.
10.1684/san.2010.0203
pubmed_225_17266
Patients with disseminated intraperitoneal malignant neoplasms were given intra-abdominal photodynamic therapy. Patients received dihematoporphyrin ethers intravenously 48 to 72 hours before laparotomy at doses of 1.5 to 3.0 mg/kg. At operation, as much tumor as possible was resected. Red light (630 nm) was delivered to all peritoneal surfaces from an argon-pumped dye laser at doses ranging from 0.2 to 3.0 J/cm2 in an escalating fashion. Viscera and peritoneal surfaces were anatomically isolated and exposed to light for intervals calculated to deliver the prescribed energy. Light was delivered to mesentery and bowel by a flat-cut optical fiber, while other areas, including diaphragm, viscera, omental bursa, gutters, and pelvis, were delivered light through a diffusing wand. Twenty-three patients (13 with ovarian cancer, eight with sarcoma, and two with pseudomyxoma peritoneii) underwent photodynamic therapy. Five of eight patients cleared positive peritoneal cytologies after treatment. Six patients remained clinically free of disease for up to 18 months, and five patients had treatment-related complications. Intraperitoneal phototherapy is technically feasible and deserving of clinical evaluation.
10.1001/archsurg.1991.01410270062011