Long-lasting CNS effects of a short-term chemical knockout of ornithine decarboxylase during development: nicotinic cholinergic receptor upregulation and subtle macromolecular changes in adulthood.
Ornithine decarboxylase (ODC) and the polyamines play an essential role in brain cell replication and differentiation and polyamines also regulate the function of nicotinic acetylcholine receptors (nAChRs). We administered alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to neonatal rats on postnatal days 5-12, during the mitotic peak of the cerebellum, a treatment regimen that achieves a chemical knockout of ODC activity and polyamine depletion limited to the treatment period. Although growth inhibition and gross dysmorphology were limited to the cerebellum, both alpha7 and alpha4beta2 nAChRs were upregulated in adulthood in the frontal cortex, hippocampus and thalamus, with the largest effect in the latter region, primarily in females. Receptor upregulation was accompanied by abnormalities in macromolecular indices of cell packing density and cell membrane surface area, but the generalized cellular alterations did not share the regional or sex selectivity shown by the effects on nAChRs. Elevated DNA concentration was most notable in the hippocampus and was associated with augmented levels of glial fibrillary acidic protein, thus implying gliosis as the cause of the increased number of cells. DFMO's effects on both nAChR expression and cellular biomarkers resembled those of developmental exposure to nicotine. Accordingly, some of the effects may represent a specific alteration in nAChR signaling evoked by polyamine depletion during a critical developmental window. Alterations in polyamine gating of cholinergic synaptic signaling may thus contribute to the adverse neurobehavioral effects of numerous neuroteratogens that directly or indirectly disrupt the ODC/polyamine pathway.


Numerical investigation of a novel spiral wound membrane sandwich design for an implantable bioartificial pancreas.
A novel spiral wound membrane sandwich (SWMS) design for an implantable bioartificial pancreas is presented and is numerically evaluated using a comprehensive model of the glucose-insulin kinetics within the device. The spiral blood flow pattern in this design induces a convective flow of blood ultrafiltrate directly through the islet chamber. Use of ultrafiltration in addition to diffusion allows rapid transmission of blood glucose changes to the islet chamber and efficient transport of insulin from the islet chamber back to the blood stream. Simulation results suggest that the implantable bioartificial pancreas design presented in this paper may offer a means of improving the control of blood glucose levels in type I diabetics.


A rare case of a recurrent atypical adenomyoepithelial tumor of the breast: Case report.
Adenomyoepithelial tumors of the breast are very rare tumors comprising of - fibroepithelial and myoepithelial components PRESENTATION OF THE CASE: We present the case of a 66 years old lady who presented with a right breast lump 5 cm in size, diagnosed as an atypical adenomyoepithelioma who underwent successful excision and returned two and half years later with a recurrence DISCUSSION: These tumors present a diagnostic dilemma needing histopathology for definitive diagnosis. Recurrence is not uncommon CONCLUSION: Adenomyoepitheliomas demand regular surveillance for early detection of any recurrence.


Verapamil and lithium in maintenance therapy of manic patients.
A year-long double-blind cross-over study was used to compare the long-term therapeutic effects of lithium versus verapamil in a group of 20 manic volunteers. Subjects received each medication for six months. Before cross-over, verapamil patients showed a significant improvement after 60 days, lithium-treated patients after 180 days. After cross-over, verapamil-treated subjects showed improvement at day 240. Lithium-treated patients showed no improvement after cross-over. The data indicate that verapamil may be effective as an agent in the maintenance treatment of manic patients.


[A case of chronic renal hemodialysis and intracranial hypertension--a study on CSF dynamics].
There are many reports on the disequilibrium syndrome due to dialysis in patients with chronic renal failure. However, they do not mention the findings of CT cisternography and MRI. We intend to investigate the mechanism of CSF dynamics in a patient with disequilibrium syndrome by means of these radiological examinations. A 31 year-old woman who had suffered from renal failure for 18 years was found to have prominent increase of serum creatinine (18.1 mg/dl) and BUN (127 mg/dl) 3 years ago. At that time, digital marking of the skull was already present by X-ray examination without other destruction in bone survey of the whole body. She was hemodialysed by the hollow fiber kidney three times weekly (dialysis time 4.5 hours, dialysate osmotic pressure 270 mOsm/kg H2O). Three months ago, she began to complain of severe headache, nausea and vomiting 2 hours after the beginning of dialysis, so that she was referred to Kosei Hospital. On admission, she showed exophthalmus, concentric narrowing of the visual field, optic atrophy and hyperreflexia in jaw and four extremities. After admission, she received hemodialysis therapy thrice weekly (dialysis time 5 hours, dialysate osmotic pressure 290 mOsm/kg H2O). At the same time, 200 ml of glycerol (contents of glycerin 10, fructose 5, NaCl 0.9%) was administered intravenously during dialysis, which ameliorated the symptoms of intracranial hypertension. Laboratory studies revealed marked decrease of serum creatinine, BUN and uric acid levels and osmotic pressure, and increase of blood pH at the time of postdialysis compared with predialysis. Manometric CSF pressure increased up to 310 mmH2O at the day without dialysis before the glycerol administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Premenstrual mood changes and gating of the auditory evoked potential.
To assess the effect of the menstrual cycle on a measure of brain physiology known to be affected in psychiatric illness, auditory-evoked electroencephalographic potentials were recorded from 12 women on the day prior to menstruation and nine days after the initiation of their cycle. Eight were normal college students, and four were patients in a premenstrual syndrome clinic. The women showed significant changes in self-ratings of mood between the two recordings. The P50 wave of the auditory-evoked response was evaluated in a conditioning-testing paradigm, in which stimuli were presented in pairs, allowing assessment of putative excitatory and inhibitory processes involved in the gating of central nervous system sensory responsiveness to auditory stimuli. The auditory-evoked potentials were unchanged between the two recording periods. There was also no difference between the women and age-matched male controls. The data suggest that these central nervous system functions are not responsive to hormonal fluxes in menstruation. Since inhibitory gating of the P50 wave is lost in the manic phase of manic-depressive illness, the data also suggest that premenstrual mood changes in normal women do not share electrophysiological properties of mania.


Collagen: a possible prediction mark for gastric cancer.
Considering the high mortality rates and the unfavorable prognosis of gastric cancer (GC), it is important to predict early GC canceration and the metastasis. Unfortunately, it has not been any clinical prediction mark sufficiently sensitive to GC yet. It is therefore important to investigate new sensitive and specific marks for GC prediction. Here, we review the evidence on gastric cancer and collagen, and discuss the sensitivity and the feasibility of collagens as potential prediction marks. Experiment researches and micro-array technology have shown that not only the biosynthesis and degradation of collagens but also collagen genes' expression are closely related to GC biological behaviour, especially canceration and metastasis and studies have proved some certain collagens might have ability to predict GC development. As outlined above, we hypothesize that collagens may be independent prediction marks of GC canceration and metastasis.


The Recent Rise of Suicide Mortality in the United States.
Suicide is a major public health concern in the United States. Between 2000 and 2018, US suicide rates increased by 35%, contributing to the stagnation and subsequent decrease in US life expectancy. During 2019, suicide declined modestly, mostly owing to slight reductions in suicides among Whites. Suicide rates, however, continued to increase or remained stable among all other racial/ethnic groups, and little is known about recent suicide trends among other vulnerable groups. This article (a) summarizes US suicide mortality trends over the twentieth and early twenty-first centuries, (b) reviews potential group-level causes of increased suicide risk among subpopulations characterized by markers of vulnerability to suicide, and (c) advocates for combining recent advances in population-based suicide prevention with a socially conscious perspective that captures the social, economic, and political contexts in which suicide risk unfolds over the life course of vulnerable individuals.


Absence of oesophageal mucosal folds in systemic sclerosis.
In a controlled study of barium swallow radiographs in systemic sclerosis, longitudinal oesophageal mucosal folds were absent in eight of 30 patients and in one of 30 control subjects (P less than 0.03). Patients without mucosal folds developed Raynaud's phenomenon at an earlier age than those who retained their mucosal folds (P less than 0.05). A loss of oesophageal mucosal folds did not necessarily signify more severe visceral or cutaneous disease.


Society's expectation of the role of the doctor in New Zealand: results of a national survey.
To describe the perceptions of the New Zealand public as to the role of the doctor in 2010. Telephone survey of 502 individuals throughout New Zealand during May 2010. The questions were based on a United Kingdom survey with added questions in respect of culture, equity and resource allocation. The data were weighted by gender and age according to the 2006 population census. Most respondents (82%) wanted to see a doctor first if they had a new concern about their health; 7% a nurse and 5% a pharmacist. Most respondents agreed (88%) that when visiting a doctor, getting an accurate diagnosis was their top priority. In respect of a doctor's personal qualities, integrity was expected (94%), as was compassion (89%). Most respondents (78%) agreed that they expected a doctor to be the leader of the healthcare team. Most agreed (70%) that there is limited money available and doctors must consider how best to use it for all patients and that doctors (82%) need to be involved in decisions about health spending. This comprehensive New Zealand survey provides important information about public perceptions of the role of the doctor and is a basis for workforce planning and future comparisons.


Dehydrogenase reductase 9 (SDR9C4) and related homologs recognize a broad spectrum of lipid mediator oxylipins as substrates.
Bioactive oxylipins play multiple roles during inflammation and in the immune response, with termination of their actions partly dependent on the activity of yet-to-be characterized dehydrogenases. Here, we report that human microsomal dehydrogenase reductase 9 (DHRS9, also known as SDR9C4 of the short-chain dehydrogenase/reductase (SDR) superfamily) exhibits a robust oxidative activity toward oxylipins with hydroxyl groups located at carbons C9 and C13 of octadecanoids, C12 and C15 carbons of eicosanoids, and C14 carbon of docosanoids. DHRS9/SDR9C4 is also active toward lipid inflammatory mediator dihydroxylated Leukotriene B4 and proresolving mediators such as tri-hydroxylated Resolvin D1 and Lipoxin A4, although notably, with lack of activity on the 15-hydroxyl of prostaglandins. We also found that the SDR enzymes phylogenetically related to DHRS9, i.e., human SDR9C8 (or retinol dehydrogenase 16), the rat SDR9C family member known as retinol dehydrogenase 7, and the mouse ortholog of human DHRS9 display similar activity toward oxylipin substrates. Mice deficient in DHRS9 protein are viable, fertile, and display no apparent phenotype under normal conditions. However, the oxidative activity of microsomal membranes from the skin, lung, and trachea of Dhrs9-/- mice toward 1 μM Leukotriene B4 is 1.7- to 6-fold lower than that of microsomes from wild-type littermates. In addition, the oxidative activity toward 1 μM Resolvin D1 is reduced by about 2.5-fold with DHRS9-null microsomes from the skin and trachea. These results strongly suggest that DHRS9 might play an important role in the metabolism of a wide range of bioactive oxylipins in vivo.


Testis-specific hnRNP is expressed in colorectal cancer cells and accelerates cell growth mediating ZDHHC11 mRNA stabilization.
Various heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be associated with cancer cell growth. However, it remains unclear whether hnRNP G-T, which is specifically expressed in the testis, is expressed in tumor cells, and whether hnRNP G-T expressed in colorectal cancer (CRC) cells is associated with tumor progression. We herein report that hnRNP G-T promoted cancer cell growth and stabilized mRNA of ZDHHC11 in CRC. The cell growth was inhibited by transfection of siRNA of hnRNP G-T in cancer cells, but not in non-cancerous epithelial cells. The tumor promotive effect of hnRNP G-T was confirmed in an HCT116 transplanted mouse model. RT-PCR and western blotting indicated the augmentation of hnRNP G-T in CRC in comparison to non-cancerous cells. The downregulation of hnRNP G-T inhibited cancer cell growth and promoted apoptosis in CRC. A transcriptome analysis combined with immunoprecipitation revealed that hnRNP G-T stabilized 174 mRNAs, including ZDHHC11 mRNA. The cell growth was also suppressed by the transfection of siRNA of ZDHHC11 and the mRNA and the protein expression were decreased by the transfection of siRNA of hnRNP G-T. These results suggested that hnRNP G-T promotes the cell growth of CRC by regulating the mRNA of ZDHHC11. Therefore, hnRNP G-T will be highlighted as an effective therapeutic target with less adverse effects in CRC therapy.


Diagnosis of obsessive-compulsive illness.
Obsessive-compulsive illness has long been subject to diagnostic neglect. Moreover, obsessive-compulsive features often underlie or are intercurrent with other symptom pictures and may be quite debilitating. Diagnostic dilemmas are discussed regarding obsessive-compulsive illness and its relation to eating disorders, generalized anxiety disorder, mood disorders, alcohol abuse, and adult attention deficit disorder. Some difficulties in eliciting and recognizing obsessive-compulsive illness are presented. These include patient secrecy, shame, and social and personality features of health professionals. Specific pharmacologic and therapeutic interventions are effective when directed at the intercurrent or underlying obsessive-compulsive illness.


Impaired liver regeneration in the analbuminemic rat.
Albumin has been implicated as both an inhibitor and a stimulator of liver regeneration. We examined the rate of liver regeneration following partial hepatectomy in rats which are genetically analbuminemic. Adult male analbuminemic and Sprague-Dawley control rats underwent either a 70% partial hepatectomy or a sham operation. Twenty-four hours postoperatively, rats were injected iv with tritiated thymidine and the liver remnants were resected 1 hr later. Liver weight, protein and DNA contents, and the rate of tritiated thymidine incorporation into DNA were determined. The rate of DNA synthesis in control sham-operated rats was greater (P less than 0.05) than that of analbuminemic rats. Following partial hepatectomy, there was a statistically significant (P less than 0.01) increase in DNA synthesis in control rats; no significant increase was noted in the analbuminemic rats. No significant differences in liver remnant weight or protein and DNA contents were noted between control and analbuminemic sham-operated or partially hepatectomized rats. Our data suggest that albumin plays a role in the regulation of DNA synthesis in both the resting and the regenerating liver and it may be essential in maintaining a normal rate of liver regeneration.


Biosensor development for low-level acetaldehyde gas detection using mesoporous carbon electrode printed on a porous polyimide film.
Acetaldehyde, which is an intermediate product of alcohol metabolism, is known to induce symptoms, including alcohol flushing, vomiting, and headaches in humans. Therefore, real-time monitoring of acetaldehyde levels is crucial to mitigating these health issues. However, current methods for detecting low-concentration gases necessitate the use of complex measurement equipment. In this study, we developed a low-cost, low-detection-limit, enzyme-based electrochemical biosensor for acetaldehyde gas detection that does not require sophisticated equipment. The sensor was constructed by screen-printing electrodes onto a porous polyimide film, using grafted MgO-templated carbon (GMgOC) as working electrode material, carbon for the counter electrode, and silver/silver chloride for the reference electrode. Pyrroloquinoline-quinone-dependent aldehyde dehydrogenase was immobilized on the working electrode, and a chamber was attached to the electrode chip and filled with 1-methoxy-5-methylphenazinium methyl sulfate solution. The sensor can be used to measure acetaldehyde gas concentrations from 0.02 to 0.1 ppm, making it suitable for monitoring human skin gas. This low detection limit was achieved by delivering the analyte through the porous polyimide film on which the electrodes were printed and accumulating acetaldehyde in the mesoporous GMgOC of the working electrode. This mechanism suggests that this sensor design can be adapted to develop other low-detection limit gas sensors, such as those for screening skin gas biomarkers.


Intravitreal triamcinolone acetonide for patients with macular edema due to branch retinal vein occlusion.
We designed a case series study to evaluate the outcome of intravitreal triamcinolone acetonide for the treatment of macular edema due to branch retinal vein occlusion (BRVO). The prospective comparative nonrandomized clinical interventional study included 27 patients (27 eyes) with macular edema due to BRVO. The study group consisted of 16 patients who had accepted an intravitreal injection (IVI) of 4 mg triamcinolone acetonide. The control group included 11 patients without IVI of triamcinolone acetonide. The mean follow-up was 103.00 +/- 36.24 days in the study group and 94.55 +/- 36.31 days in the control group. In the study group, visual acuity measurements improved significantly (p < 0.001) from 0.77 +/- 0.43 logarithm of minimal angle of resolution (logMAR) preoperatively to a best postoperative visual acuity of 0.44 +/- 0.43 logMAR. Fourteen eyes (87.5%) gained improvement in visual acuity, with 10 eyes (62.5%) showing an increase in visual acuity of at least two Snellen lines. All 16 patients showed significant macular edema resolution in optical coherence tomography examination (p < 0.001) and perivascular leakage decrease in fluorescein angiography post-IVI. In the control group, baseline best-corrected visual acuity and best-corrected visual acuity during the follow-up did not vary significantly (p = 0.294). In conclusion, IVI of triamcinolone acetonide can lead to an increase in visual acuity and a resolution of macular edema in patients with BRVO.


Propofol exhibits antiepileptic activity in hippocampal pyramidal neurons.
Propofol was reported to exhibit an antiepileptic activity. This study was performed to investigate the effect of propofol on evoked and spontaneous seizure-like activity induced by the convulsant veratridine. Studies were performed on rat brain slices using conventional electrophysiological intracellular techniques. The alteration of sodium channel function by veratridine (0.3 microM) induced an evoked and spontaneous seizure-like activity in the hippocampal CA1 pyramidal neurons. Therapeutic concentrations of propofol (10 microM) were ineffective in inhibiting veratridine-induced seizure-like activity. However, higher concentrations (50-100 microM, n=6) inhibited both evoked and spontaneous bursting, induced by veratridine. The inhibitory effect of propofol (100 microM) was associated with membrane hyperpolarization [after veratridine, -66+/-0.71 mV (mean+/-S.E.M.), and after propofol, -77+/-2.15 mV] and with an increase in input resistance [after veratridine (37.8+/-1.2 MOmega) and after propofol (43+/-1.3 MOmega)]. The drug also produced an increase in current threshold. Results from this study are valuable in solving critical questions regarding the antiepileptic activity of propofol and strengthen the validity of the veratridine model in testing for potential antiepileptic drugs.


Hierarchical NiCo2S4/ZnIn2S4 heterostructured prisms: High-efficient photocatalysts for hydrogen production under visible-light.
Exploring low-cost co-catalyst to ameliorate the photocatalytic activity of semiconductors sets a clear direction for solving energy crisis and achieving efficient solar-chemical energy conversion. In this work, a unique hierarchical hollow heterojunction was constructed by in-situ growing ZnIn2S4 nanosheets on the porous NiCo2S4 hollow prisms through a low temperature solvothermal method, in which NiCo2S4 with semi-metal property acted as non-noble metal co-catalyst. NiCo2S4 co-catalyst was innovatively encapsulated in ZnIn2S4, which not only relieved the light shielding effect caused by the large loading amount of co-catalyst, but also supplied abundant active sites for H2 evolution. The hierarchical hollow heterostructure of NiCo2S4/ZnIn2S4 provided a highly efficient channel for charge transfer. Combining these advantages, NiCo2S4/ZnIn2S4 composite demonstrated excellent photocatalytic activity. In the absence of sacrificial agent, the NiCo2S4/ZnIn2S4 photocatalyst achieved a remarkable improved H2 yield of 0.77 mmol g-1h-1 under visible light irradiation (λ > 400 nm), which is 6.6 times greater than that of ZnIn2S4. Besides, NiCo2S4 even exhibited better performance on the H2 evolution improvement of ZnIn2S4 than precious metal Pt. This work will offer novel insights into the reasonable design of non-noble metal photocatalysts with respectable activity for water splitting.


Combined targeting of TGF-β, EGFR and HER2 suppresses lymphangiogenesis and metastasis in a pancreatic cancer model.
Pancreatic ductal adenocarcinomas (PDACs) are aggressive with frequent lymphatic spread. By analysis of data from The Cancer Genome Atlas, we determined that ~35% of PDACs have a pro-angiogenic gene signature. We now show that the same PDACs exhibit increased expression of lymphangiogenic genes and lymphatic endothelial cell (LEC) markers, and that LEC abundance in human PDACs correlates with endothelial cell microvessel density. Lymphangiogenic genes and LECs are also elevated in murine PDACs arising in the KRC (mutated Kras; deleted RB) and KIC (mutated Kras; deleted INK4a) genetic models. Moreover, pancreatic cancer cells (PCCs) derived from KRC tumors express and secrete high levels of lymphangiogenic factors, including the EGF receptor ligand, amphiregulin. Importantly, TGF-β1 increases lymphangiogenic genes and amphiregulin expression in KRC PCCs but not in murine PCCs that lack SMAD4, and combinatorial targeting of the TGF-β type I receptor (TβRI) with LY2157299 and EGFR/HER2 with lapatinib suppresses tumor growth and metastasis in a syngeneic orthotopic model, and attenuates tumor lymphangiogenesis and angiogenesis while reducing lymphangiogenic genes and amphiregulin and enhancing apoptosis. Therefore, this combination could be beneficial in PDACs with lymphangiogenic or angiogenic gene signatures.


Backbone and side-chain ¹H, ¹⁵N, and ¹³C resonance assignments of the microtubule-binding domain of yeast cytoplasmic dynein in the high and low-affinity states.
Cytoplasmic dynein is a motor protein that walks toward the minus end of microtubules (MTs) by utilizing the energy of ATP hydrolysis. The heavy chain of cytoplasmic dynein contains the microtubule-binding domain (MTBD). Switching of MTBD between high and low affinity states for MTs is crucial for processive movement of cytoplasmic dynein. Previous biochemical studies demonstrated that the affinity of MTBD is regulated by the AAA+ family ATPase domain, which is separated by 15 nm long coiled-coil helix. In order to elucidate the structural basis of the affinity switching mechanism of MTBD, we designed two MTBD constructs, termed MTBD-High and MTBD-Low, which are locked in high and low affinity state for MTs, respectively, by introducing a disulfide bond between the coiled-coil helix. Here, we established the backbone and side-chain assignments of MTBD-High and MTBD-Low for further structural analyses.


[Features of the aggressive behavior of victorious mice in inter-male interactions].
Latency of the first attack, number of attacks and total attacking time in aggressive male C57BL/6J strain mice were studied during agonistic interactions with submissive mice which had a great defeat experience. Then, aggressive mice were placed together in order to find out which will be the winner in each pair. It has been shown that males with a shorter latency of the first attack and greater total attacking time gained the victory.


Lung transplantation in a Japanese patient with schizophrenia from brain-dead donor.
We herein report a case of lung transplantation in a patient with schizophrenia. The findings show that patients with schizophrenia can be considered for lung transplant after careful evaluation of psychiatric status and indications.


Navigating pneumococcal vaccination in adults.
With two nonequivalent vaccines available and different recommendations for different patient populations, vaccination against Streptococcus pneumoniae can be confusing. Here we try to clarify the situation.


Incisional hernia formation in hepatobiliary surgery using transverse and hybrid incisions: a systematic review and meta-analysis.
Evidence suggests that midline incisions should be closed with the small-bite technique to reduce IH formation. No recommendations exist for the closure of transverse incisions used in hepatobiliary surgery. This work systematically summarises rates of IH formation and associated technical factors for these transverse incisions. A systematic search was undertaken. Studies describing the incidence of IH were included. Incisions were classified as transverse (two incision types) or hybrid (transverse with midline extension, comprising five incision types). The primary outcome measure was the pooled proportion of IH. Subgroup analysis based on minimum follow-up of two years and a priori definition of IH with clinical and radiological diagnosis was undertaken. Thirteen studies were identified and included 5,427 patients; 1,427 patients (26.3%) underwent surgery for benign conditions, 3,465 (63.8%) for malignancy and 535 (9.9%) for conditions that were not stated or classified as 'other'. The pooled incidence of IH was 6.0% (2.0-10.0%) at a weighted mean follow-up of 17.5 months in the transverse group, compared with 15.0% (11.0-19.0%) at a weighted mean follow-up of 42.0 months in the hybrid group (p = 0.045). Subgroup analysis did not demonstrate a statistical difference in IH formation between the hybrid versus transverse groups. Owing to the limitations in study design and heterogeneity, there is limited evidence to guide incision choice and methods of closure in hepatopancreatobiliary surgery. There is an urgent need for a high-quality prospective cohort study to understand the techniques used and their outcomes, to inform future research.


Serotyping of Plesiomonas shigelloides strains with our own antigenic scheme. An attempted epidemiological study.
Thirty-four O and 19 H sera were used to test 169 strains of Plesiomonas shigelloides from several countries of three continents. The most frequent O serovar was O17 (O antigen identical with Shigella sonnei phase I) which occurred in the OH serovar combinations: O17:c, O17:d and O17:f. Some OH serovars were represented by a single strain; others, despite the small number of strains in hand, were evidently ubiquitous, having been isolated in mutually distant countries or at long time intervals. The source of our strains was most often human stools, diarrhoeal or collected at preventive examinations during epidemiological and ecological investigations, the droppings of animals (dogs, cats, pigs, sewer rats, water birds) and surface, sewer or aquarium water. The usefulness of serotyping in epidemiological investigation in the patients' environment was confirmed by a finding of two different serovars in one of our patients and her cat.


RELATIONSHIP between prandial drinking behavior and supersensitivity of salivary glands after superior salivatory nucleus lesions in RATS.
Prandial drinking, an increase in the number of drinking responses and secondary or non-homeostatic polydipsia in the presence of dry food, is typically associated with a deficit in salivary secretion. This study investigates the degree of salivary gland supersensitivity to pilocarpine administration after lesions to the superior salivatory nucleus (SSN), the site of origin of the parasympathetic preganglionic neurons that innervate the submandibular-sublingual (S-S) salivary glands. The main aim was to determine if there is a relationship between the degree of glandular supersensitivity, as an index of secretory deficit, and the development of prandial drinking in lesioned rats. Results showed that following SSN lesions two subgroups of rats were obtained. One subgroup exhibited prandial drinking but the other was similar to the control group. The SSN-lesioned prandial drinking subgroup presented significantly greater supersensitivity than the SSN-lesioned non-prandial drinking rats; the non-prandial drinking subgroup, in turn, presented significantly more supersensitivity than controls. Additionally, S-S supersensitivity observed in rats that exhibited prandial drinking due to the sectioning of chorda tympani efferent axons was compared to that observed in rats exhibiting prandial drinking due to SSN lesions. It was found that both groups presented the same S-S supersensitivity curve. These results indicate that SSN lesions produce a gradation of S-S supersensitivity values that appear to run parallel to the degree of glandular secretory deficit caused by the lesions. Thus, only the rats with greater secretory deficit (greater supersensitivity) develop prandial drinking. These data support the idea that there is in fact a functional link between the lateral reticular formation of the brainstem (the region associated with the SSN) and S-S salivary glands.


[Input of a laboratory in the management of patients with Ebola virus disease and in the training of health personnel: experience of the Forecariah Ebola treatment centre (Guinea) in 2015].
Ebola virus disease (EVD) is associated with a high lethality rate even when the afflicted are provided with good support in an Ebola treatment center (ETC). Basic laboratory tests can help to better understand the pathophysiology of the disease, to guide treatment and to establish simple protocols and procedures tailored to the practice of medicine in the context of such precarious environment for caregivers. Based on a few clinical cases of patients treated in the ETC of Forecariah, Guinea, run by the French Red Cross, this article describes the difficult conditions associated with the provision of medical practice in this challenging environment, aiming to minimize the casualties in the EVD patient and to train the health staff.


Investigation of the predictors of transition to persistent atrial fibrillation in patients with paroxysmal atrial fibrillation.
Until now, no clinically useful indicators have existed that predict the transition from paroxysmal to persistent atrial fibrillation (AF). The current prospective study was conducted for identifying predictors of progression to persistent AF over the long term. We studied 102 consecutive patients (mean age: 55 +/- 10 years: 75 men and 27 women) diagnosed with paroxysmal AF. Standard 12-lead electrocardiography, echocardiography, and P-wave-triggered signal-averaged electrocardiography (P-SAECG) were performed on all patients at the time of their entry into the study. The mean follow-up period was 61 +/- 13 months. Group 1 (n = 66) comprised patients in whom paroxysmal AF did not progress to persistent AF, and Group 2 (n = 36) comprised those who developed persistent AF. In Group 2 the patients were significantly older, and P-wave dispersion, filtered P-wave duration (FPD), and left atrial dimension were significantly higher than in Group 1 (p < 0.05). The root mean square voltage for the last 30 ms of the filtered P-wave was also significantly lower in Group 2 (p < 0.05). Multivariate logistic regression analysis using these five factors identified left atrial dimension (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.16-4.54; p = 0.02) and FPD (OR 2.71; 95% CI 1.78-4.13; p < 0.01) as independent predictors of transition to persistent AF. Left atrial dimension > or = 40 mm predicted progression to persistent AF with a sensitivity of 64%, specificity of 76%, positive predictive value of 59%, negative predictive value of 79%, and an accuracy of 71%. An FPD > or = 150 ms predicted persistent AF with a sensitivity of 81%, specificity of 91%, positive predictive value of 88%, negative predictive value of 90%, and an accuracy of 87%. Filtered P-wave duration was a significantly more sensitive and specific predictor than left atrial dimension (p < 0.05). We conclude that FPD is a clinically useful predictor of progression from paroxysmal to persistent AF over the long term.


DNA polymerase I gene of Saccharomyces cerevisiae: nucleotide sequence, mapping of a temperature-sensitive mutation, and protein homology with other DNA polymerases.
A 5600-base pair segment spanning the coding region of the Saccharomyces cerevisiae DNA polymerase I gene was sequenced and found to contain an open reading frame of 1468 codons, corresponding to a polypeptide of Mr 166,794. A pol1 temperature-sensitive mutation, encoding a DNA-polymerase-primase complex with altered stability, has a single base-pair substitution that changes the glycine at position 493 to a positively charged arginine. Protein sequence comparison with other prokaryotic and eukaryotic DNA polymerases reveals three major regions of homology. This observation suggests that certain DNA polymerases might require the conservation of critical amino acid residues for activity.


Transfer of experimental glomerulonephritis in chickens by mononuclear cells.
We have produced experimental autoimmune glomerulonephritis (EAG) in histocompatible SC chickens by immunization with different types of glomerular antigen. The development of EAG was time, but not antigen, dependent. Transfer of mononuclear cells from spleens and kidneys of nephritic animals resulted in EAG in naive recipients. Transferred EAG developed earlier than in immunized donors and was not associated with circulating or bound anti-GBM antibodies. Control recipients did not develop disease from control cells alone, soluble antigen, or antigen plus control cells. The cells which transferred EAG appeared morphologically by light and electron microscopy to be lymphocytes, sedimented as lymphocytes, were positive with anti-serum to thymocytes but negative with anti-bursa anti-serum, stained as T-cells with monoclonal antibodies and underwent blast transformation in response to mitogen and GBM antigen. Other organ specific diseases have been transferred by cells alone; to our knowledge this is the first description of glomerulonephritis transferred by cells alone. This new pathogenetic process may play an important role in the development of glomerulonephritis in other animal models as well as in humans.


Physiological resolution of periodic breath holding during heavy-intensity Fartlek exercise.
The purpose was to compare the singular and combined effects of 5 s breath holds (BH) and 5 s sprints, every 30 s, during continuous high-intensity exercise, on ventilation ([Formula: see text]), oxygen uptake ([Formula: see text]O2) and associated kinetics (τ), carbon dioxide production ([Formula: see text]CO2), and arterialized-capillary lactate concentration ([La-]). Ten men (24 ± 3 years) performed 4-6 min ergometer protocols that included a step-transition from 20 W to a power output of 50% of the difference between lactate threshold and [Formula: see text]O2 peak (Δ50%) including: (1) a continuous protocol (CONT) with free breathing, (2) an intermittent BH protocol (CONT-BH); repeated cycles of 5 s BH: 25 s free breathing, (3) a Fartlek protocol (Fartlek); repeated 5 s at peak aerobic power output: 25 s at Δ50%; (4) combining the 5 s Fartlek and CONT-BH protocol (Fartlek-BH). Breath-by-breath gas exchange, measured by mass spectrometry and turbine, was recorded. [Formula: see text] E (L min-1) was greater (p < 0.05) than CONT (90 ± 7) in all conditions CONT-BH (98 ± 16), Fartlek (105 ± 10), and Fartlek-BH (101 ± 19). [Formula: see text]O2 and [Formula: see text]CO2 (L min-1) were unchanged in CONT-BH (2.73 ± 0.14 and 3.16 ± 0.38) and greater in Fartlek (2.85 ± 0.12 and 3.43 ± 0.16), compared to CONT (2.71 ± 0.12 and 3.12 ± 0.13). Whereas, [Formula: see text]CO2 during Fartlek-BH was higher (3.28 ± 0.35) and [Formula: see text]O2 was unchanged (2.73 ± 0.14). Fartlek-BH resulted in slower [Formula: see text]O2 kinetics (62.2 ± 19 s) and greater blood lactate concentrations (11.5 ± 2.7 mM), compared to CONT (48.8 ± 12 s; 9.0 ± 2.3 mM, respectively). It was demonstrated that the CONT-BH resulted in increased ventilation that sustained [Formula: see text]O2. However, [Formula: see text]O2 was restricted when an additional work was combined with the BH condition.


Heterogeneous reaction of peroxyacetyl nitrate (PAN) on soot.
The interaction between photochemical oxidants and aerosol particles has been examined in previous atmospheric pollution studies. The heterogeneous reaction can affect the concentration of gases and free radicals, as well as the morphology and properties of particles. In this report, the interaction between the photochemical oxidant peroxyacetyl nitrate (PAN) and soot particles was investigated using a flow tube system. We used real-time online monitoring equipment to track changes in PAN concentrations. Substances on the soot surface were detected using ion chromatography (IC), x-ray photoelectron spectroscopy (XPS), and other surface analysis methods. At 295 K, the upper and lower limits of the initial uptake coefficients were 1.28 × 10-5 and 9.16 × 10-9, respectively. The heterogeneous reaction of PAN on soot was a first-order reaction to PAN under both dry and wet conditions. The products formed on soot included CH3COO-, HCOO-, NO2-, and NO3-. With an increase in relative humidity, the production of all species decreased and the relative amounts changed.


Stress2TF: a manually curated database of TF regulation in plant response to stress.
Considerable studies demonstrate that plant transcription factors (TFs) play key regulatory roles in abiotic/biotic stress conditions, such as drought and pathogen attack. However, there is no effort dedicated to curate experimentally validated stress-TF regulatory relationships from these individual reports into a central database, which put an obstacle in the exploration of stress-TF regulations in plants. To address this issue, we presented a literature-curated database 'Stress2TF' that currently documented 1533 regulatory relationships between 71 abiotic/biotic stresses and 558 TFs in 47 plant species. Each entry in Stress2TF contains detailed information about a stress-TF relationship such as plant name, stress name, TF and brief description of stress-TF relationship. Stress2TF provided a user-friendly interface for entry browse, search and download. In addition, a submission page and several useful tools (e.g., BLAST, network visualization) were integrated. Stress2TF may be a valuable resource for the research of stress-TF regulatory mechanisms in plants. Stress2TF is available at http://csgenomics.ahau.edu.cn/Stress2TF.


Guidelines for minimal report in gynaecologic sonography: Are they useful for emergency department resident physicians?
This study aimed to evaluate the impact of Collège National des Gynécologues et Obstétriciens Français (CNGOF) guidelines on the minimal sonographic reports generated by emergency department resident physicians. This prospective observational study was conducted in the gynaecologic emergency unit of a teaching hospital from November 2016 to May 2017. We analysed sonographic reports generated by residents during gynaecological emergencies before and after training on the minimal report standards. An analysis of the evaluated items was carried out. We also compared residents according to their specialities and seniority. A total of 240 reports were analysed, 120 before and 120 after the training. Half of the reports concerned women with an early pregnancy while the others concerned women with negative hCG. All residents significantly improved their practice after the training, as shown by the increase in ratings of the evaluated items (38 % before training vs 44.8 % after, p < 0.01). General practitioners had greater improvement (48.1 % of evaluated items), whereas older residents reported fewer items before or after the training (43.5 %) than younger residents. Finally, all residents improved their practice with a conclusion that followed the guidelines in 92.5 % of cases (versus 68.3 % before the training; p < 0.01). Training on the CNGOF minimal sonographic report guidelines significantly improved the emergency sonographic reports generated by residents. Wider dissemination of this training, particularly to young residents, would probably improve the quality of sonographic reports performed at gynaecological emergencies.


A Prospective Randomized Study Comparing Bupivacaine Hydrochloride Versus Bupivacaine Liposome for Pain Management After Distal Radius Fracture Repair Surgery.
To compare pain experience and opioid use after distal radius fracture repair surgery performed with perioperative infiltration of the local anesthesia bupivacaine hydrochloride (Marcaine; Pfizer, New York, NY) or bupivacaine liposome (Exparel; Pacira, Parsippany, NJ). We conducted a prospective comparison of consecutive patients scheduled to undergo distal radius fracture repair surgery. Patients were randomized to either Marcaine or Exparel. Patients in the Marcaine group received 20 mL 0.5% bupivacaine without epinephrine into the incision and surgical site before incision. Patients in the Exparel group first received 10 mL 0.5% Marcaine with no epinephrine into the incision and surgical site before incision; then, upon completion of the surgery and wound closure, they also received 10 mL Exparel into the same site that had been preinjected with Marcaine. All operations were performed with the same surgical technique. Daily opioid pill consumption, pain levels, and any adverse reactions were recorded from postoperative days 0 to 5. On the day of surgery, patients in the Exparel group reported significantly lower pain levels (3.9 vs 5.8) and consumed significantly fewer prescribed opioid pills (1.2 vs 2.0) compared with patients in the Marcaine group. However, there were no other significant differences between the Exparel and Marcaine groups on any subsequent days or in the total number of pills consumed at the end of the study period (7.5 vs 8.9 pills, respectively). No major adverse reactions were noted in either group. Exparel use was found to result in decreased pain and opioid consumption only on the day of surgery and not thereafter. Therapeutic II.


Overuse injuries.
Stress injuries common to running athletes are always associated with a breakdown of the protective mechanisms normally inherent in healthy posture and gait. It is more important to identify and treat these breakdowns of the motor process than the resulting injury itself. Simple motor screening of athletes can identify functional abnormalities that lead to stress injuries. This screen includes assessment of flexibility of all major joints, responsiveness of primary postural muscles, posture, balance, and gait. Present definitions of physical fitness are focused on cardiorespiratory function and strength and do not properly determine the ability of an athlete to run or walk. The basic motor screen outlined in this article has been shown to be of value in correcting this shortcoming.


Tolerability and safety of early enteral nutrition in children after percutaneous endoscopic gastrostomy placement: A multicentre randomised controlled trial.
We assessed the tolerability and safety of implementing early enteral nutrition in children at 3 h after percutaneous endoscopic gastrostomy (PEG) placement to establish an optimum feeding mode in paediatric patients that reduced the fasting period, the inadequate nutritional support interval, and the hospitalisation time. Children with clinical indications for PEG placement were recruited from six medical centres in Poland to participate in the study. The patients were centrally randomised to receive the first bolus feed, which comprised a polymeric diet (1 kcal/mL), via a feeding tube at 3 h (group 1) or 8 h (group 2) after PEG placement. The pre-procedural preparation, the post-operative care, and the resumption of feeding were performed on all of the patients in accordance with the study's protocol. The primary endpoint was the number of patients who consumed a full feed, which contained their total fluid and caloric requirements, within 48 h of the first bolus feed. The secondary endpoints were the number of complications and the duration of hospitalisation after PEG placement. Of the 97 randomised patients, 49 were assigned to group 1 and 48 were assigned to group 2. There were no differences between the groups regarding feeding tolerability (81.6% vs. 91.6%), the number of complications (25.5% vs. 37.5%), or the duration of hospitalisation after PEG placement (p > 0.05). Full feed post PEG placement was achieved within 24-48 h in most cases (74% vs. 82%). Most of the complications were mild. Two patients in group 2 due to dislocation of the PEG were qualified for laparotomy (at 6 days post-PEG placement in one case and at 14 days post-PEG placement in the other case). One patient in group 2 died at 7 days post-PEG placement; the death was unrelated to the investigation. Introducing feeding at 3 h post-PEG placement in children appears to be well tolerated. The early initiation of post-PEG feeding was not associated with an increase in the number of complications and it had no impact on the duration of hospitalisation. CLINICAL TRIAL REGISTRY: www.clinicaltrials.gov (NCT02777541; registration date: 18/05/2016).


Papillomaviruses and human oncogenesis.
During the past year, significant advances have been made in understanding the functions of the oncoproteins, E6 and E7, of human papillomaviruses that are associated with malignant genital tumors. In addition, important new information is now available on the responses of both the keratinocyte and of the individual following papillomavirus infection.


QuadBase: genome-wide database of G4 DNA--occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes.
Emerging evidence indicates the importance of G-quadruplex motifs as drug targets. [Stuart A. Borman, Ascent of quadruplexes-nucleic acid structures become promising drug targets. Chem. Eng. News, 2007;85, 12-17], which stems from the fact that these motifs are present in a surprising number of promoters wherein their role in controlling gene expression has been demonstrated for a few. We present a compendium of quadruplex motifs, with particular focus on their occurrence and conservation in promoters-QuadBase. It is composed of two parts (EuQuad and ProQuad). EuQuad gives information on quadruplex motifs present within 10 kb of transcription starts sites in 99 980 human, chimpanzee, rat and mouse genes. ProQuad contains quadruplex information of 146 prokaryotes. Apart from gene-specific searches for quadruplex motifs, QuadBase has a number of other modules. 'Orthologs Analysis' queries for conserved motifs across species based on a selected reference organism; 'Pattern Search' can be used to fetch specific motifs of interest from a selected organism using user-defined criteria for quadruplex motifs, i.e. stem, loop size, etc. 'Pattern Finder' tool can search for motifs in any given sequence. QuadBase is freely available to users from non-profit organization at http://quadbase.igib.res.in/.


Sterol methenyl transferase inhibitors alter the ultrastructure and function of the Leishmania amazonensis mitochondrion leading to potent growth inhibition.
We describe here the effects of Delta(24(25)) sterol methenyl transferase inhibitors (SMTI) on promastigote and axenic amastigote forms of Leishmania amazonensis. When these cells were exposed to 20-piperidin-2-yl-5alpha-pregnan-3beta-20-diol (22,26-azasterol; AZA), hydrazone-imidazol-2-yl-5alpha-pregnan-3beta-ol (IMI), 20-hydrazone-pyridin-2-yl-5alpha-pregnan-3beta-ol (PYR) or 24(R,S),25-epiiminolanosterol (EIL), a concentration- and time-dependent inhibition of growth was observed, with IC(50) values in the sub-micromolar range. Ultrastructural alterations in treated cells were mainly observed in the mitochondrion, which displayed an intense swelling and a reduction of the electron density of the matrix with remarkable changes in the inner mitochondrial membranes. Mitochondrial transmembrane electric potential (DeltaPsi) was measured using spectrophotometric methods in control and treated promastigotes permeabilized with digitonin. After energization with the substrates for complexes I, II or IV of the respiratory chain, it was possible to detect marked changes of DeltaPsi in promastigotes treated with 1 microM of the SMTI for 48 or 72 h when compared with normal cells, indicating that these compounds led to the loss of the energy-transducing properties of the mitochondrial inner membrane, probably related to the alteration of its lipid composition. The present study confirms these findings, showing that in Leishmania amazonensis the mitochondrial complex appears to be the first organelle affected after treatment with different SMTI.


The effects of postnatal lead exposure on Purkinje cell dendritic development in the rat.
Rat pups, suckled by mothers maintained after parturition on a diet containing 4% lead acetate, were killed at 30 days and their cerebella examined. The blood lead was greatly increased in these animals (258.20 +/- 6.72 micrograms/100 ml) as compared with controls (4.75 +/- 0.75 micrograms/100 ml) and their mean body weight was reduced by 28%. Cerebellar weight, however, remained unchanged. Histologically the vermis showed vacuolation of the white matter and an increase in the size of Purkinje cell bodies. The total number of Purkinje and granule cells and their densities were unchanged except in animals with encephalopathy when these parameters were reduced. Network analysis of the dendritic trees of Purkinje cells indicated a 34.8% reduction in total dendritic length, due to reduction in total segment number and in the length of distal segments. Dendritic density and the frequency of trichotomous branching were unchanged by the experimental treatment. The density of dendritic spines over the periphery of the network was normal. The topology of the dendritic trees of Purkinje cells was abnormal in that branching patterns deviated from the normal pattern generated by random terminal growth. These results suggest that lead causes changes in Purkinje cell metabolism which reduce the rate of dendritic growth and cause abnormal branching. It remains to be determined whether these are direct effects or secondary to the vascular changes known to occur in the cerebellum during lead intoxication.


[Trabeculectomy in uveitis associated with juvenile idiopathic arthritis: long-term results in pediatric secondary glaucoma].
Secondary uveitic glaucoma in children can only be controlled in many cases by surgery. The aim of this study was to evaluate the outcome of trabeculectomy (TE) with administration of mitomycin C in children with secondary uveitis associated with juvenile idiopathic arthritis (JIA). This study was a retrospective chart review of 21 children with uveitic glaucoma who underwent TE with administration of mitomycin C including analysis of complications, further interventions, additional surgical procedures to control intraocular pressure (IOP) and of the success rates after a mean follow-up of 5 years. Defining success as an IOP ≤ 15 mmHg, the surgical success rate after TE was 55 % after 1 year and 38 % after 5 years but 43 % of the children required further IOP controlling operations in the long-term follow-up. An IOP ≤ 15 mmHg was observed in 70 % of the children after 1 year and in 62 % after 5 years. In regard to the overall success (with topical antiglaucomatous medication) the success rate increased to 71.4 % after 5 years. The results show that TE is a suitable surgical procedure to control IOP in secondary uveitic glaucoma of JIA patients. In the long-term follow up additional postoperative adjustments are necessary to control the IOP.


CD105+CD90+CD13+ identifies a clonogenic subset of adventitial lung fibroblasts.
Mesenchymal cells are important components of specified niches in the lung, and can mediate a wide range of processes including tissue regeneration and repair. Dysregulation of these processes can lead to improper remodeling of tissue as observed in several lung diseases. The mesenchymal cells responsible remain poorly described, partially due to the heterogenic nature of the mesenchymal compartment and the absence of appropriate markers. Here, we describe that CD105+CD90+ mesenchymal cells can be divided into two populations based on their expression of CD13/aminopeptidase N (CD105+CD90+CD13- and CD105+CD90+CD13+). By prospective isolation using FACS, we show that both these populations give rise to clonogenic fibroblast-like cells, but with an increased clonogenic and proliferative capacity of CD105+CD90+CD13+ cells. Transcriptomic and spatial analysis pinpoints an adventitial fibroblast subset as the origin of CD105+CD90+CD13+ clonogenic mesenchymal cells in human lung.


Biphasic entry of glucocorticoids into cultured human skin keratinocytes and fibroblasts.
The uptake of glucocorticoids by cultured human skin keratinocytes and fibroblasts was found to be a rapid, temperature-sensitive process. All glucocorticoids tested accumulated in the cells, and the ratio between the intracellular and extracellular concentrations (ci/co ratio) was higher than 1. For most of the glucocorticoids under study there was good correlation between the lipophilicity and the rate of uptake. Since the uptake of glucocorticoids seems to be unsaturable in the concentration range used and no competition was observed between these compounds for entry into the cells, it may be assumed that the uptake of glucocorticoids is essentially a simple diffusion process based on a distribution of glucocorticoids between a lipid-rich phase and water. The analysis of the uptake process revealed that the entry of glucocorticoids into cultured human skin fibroblasts and keratinocytes is a non-mediated passive diffusion process that involves two distinct steps: a rapid, non-specific, high-capacity association to the cell membrane followed by a slower internalization process associated with a stronger binding of glucocorticoids within the cell.


Violence in emergency departments: under-reported, unconstrained, and unconscionable.
Violence in emergency departments (EDs) has reached a level that requires concerted action and a shift in attitude - to eradicate a socially and professionally unacceptable peril. In some EDs, violence is a daily occurrence, with nursing staff reporting several episodes each week. Increased societal violence results in an increase in presentations for injury. Anger and pain and the influence of alcohol and drugs contribute to violence spilling over into the ED. The well known "system blockers" to reporting adverse events in hospitals result in under-reporting of violence episodes. Violence in EDs is different from other forms of violence - the aggressor has no overt dominance or power status and, in a setting of care, victims are likely to excuse the behaviour. Strategies to curb violence in EDs include modifying building design, providing security systems and personnel, and training staff in aggression management. The key to successful intervention is a strong preventive orientation that looks for high-risk indicators, and may extend to active physical and behavioural screening.


Synthesis, ligand-receptor modeling studies and pharmacological evaluation of novel 4-modified-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives as potent and selective human A3 adenosine receptor antagonists.
The study of some 4-substituted-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives, designed as hA(3) adenosine receptor antagonists, is reported. The new compounds bear on the four-position different acylamino, sulfonylamino, benzylureido and benzyloxy moieties, which have also been combined with a para-methoxy group on the 2-phenyl ring or with a nitro residue at the six-position. Many derivatives show high hA(3) adenosine receptor affinities and selectivities both versus hA(1) and hA(2A) receptors. The observed structure-affinity relationships of this class of antagonists have been exhaustively rationalized using the recently published ligand-based homology modeling (LBHM) approach. The selected 4-bismethanesulfonylamino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (13), which shows high hA(3) affinity (K(i)=5.5nM) and selectivity versus hA(1), hA(2A) (both selectivity ratios>1800) and hA(2B) (cAMP assay, IC(50)>10,000nM) receptors, was tested in an in vitro rat model of cerebral ischemia, proving to be effective in preventing the failure of synaptic activity, induced by oxygen and glucose deprivation in the hippocampus, and in delaying the occurrence of anoxic depolarization.


Influence of nerve transsections and combined bladder filling on intravesical electrostimulation-induced bladder contraction in the rat.
The exact mechanisms of action of intravesical electrical stimulation (IVES) are not yet fully understood. To gain more insight into the underlying mechanism(s) of the direct detrusor response during IVES by transsecting the dorsal roots and the pelvic nerve consecutively at different levels and to determine whether the efficiency of IVES to induce contraction could be enhanced by simultaneous bladder filling and IVES and by changing the bladder-filling grade. Eighteen Sprague-Dawley rats underwent IVES (square-wave pulses at 10 Hz, 20-ms pulse duration). In seven rats, IVES-induced bladder-pressure development was studied after the bladder nerves were consecutively sectioned bilaterally at four different levels: no lesion, L6 dorsal roots, L6 ventral roots, pelvic nerve, and major pelvic ganglion with surrounding nerves. Bladder-pressure development induced by IVES with simultaneous bladder filling, by bladder filling alone, and by IVES alone was recorded in seven other rats, and bladder-pressure development induced by IVES with different grades of bladder filling was recorded in four rats. Contraction during IVES was significantly weaker after consecutive section of more nerves (all p<0.001), but a small contraction (19+/-17% of baseline) could be elicited even after total decentralization. In the neurologically intact rats, separate stimulation and bladder filling gave contraction strengths similar to those of simultaneous bladder filling and stimulation, but the latter gave contraction after a significantly shorter stimulation time (both p<0.015). IVES-induced contraction is, for the major part, a nerve-mediated process. However, a small bladder-pressure rise was induced by direct bladder-wall stimulation after all nerves were cut. Simultaneous electrical stimulation and bladder filling needed much shorter stimulation times than bladder filling alone or stimulation alone. If confirmed in humans, this could shorten IVES sessions substantially without altering the contractile results and could indicate that summation of afferent potentials from different triggers is possible.


Human rectal adenocarcinoma: demonstration of 1H-MR spectra in vivo at 1.5 T.
This study was designed to determine whether 1H-MR spectra of locally advanced human rectal adenocarcinoma could be acquired in vivo at 1.5 T. Despite the relatively large size of these neoplasms, only six out of 21 tumors accommodated a voxel size of 8 cm3. This was due to air pockets within the tumor mass, which limited voxel positioning. Localized proton spectra were acquired at short (20 ms) and long (135 ms) echo times (TEs) using a single-voxel technique. The most commonly detected metabolites were choline and lipid.


Incidence, morbidity and 5-year survival of colorectal cancer patients in the Kujawsko-Pomorskie voivodship in 2005-2011, based on data from the National Health Fund.
The incidence, morbidity and 5-year survival rates illustrate the epidemiological situation of colorectal cancer and assess the effectiveness of the treatment. In Poland, the National Health Fund is the payer of benefits. The data related to morbidity, incidence, and 5-year survival may be supplementary to the epidemiological data of the National Cancer Registry. Analysis of benefits granted by NHF in Bydgoszcz to persons with diagnosed colorectal cancer in 2006-2011 including the assessment of incidence, morbidity and 5-year survival of the population in the Kujawsko-Pomorskie province. The study analyzed the benefits recorded in the database of the National Health Fund in Bydgoszcz in 2006-2011 given to patients with colorectal cancer. The Kaplan-Meier method and the gambling rate were used to determine the probability of survival. In 2006-2011 men were offered 10.1% more benefits than women. The most frequent benefits were colorectal cancer (48.9%), rectal cancer (43.8%) and esophageal cancer (7.2%). In total, 50410 benefits were provided. Despite the increase in the number of women in the population, 388 more men died than women. The probability of survival was 46.8 %% and 42.6% for men and women, respectively, and 41.8%, 44.2% and 48.9% for colon cancer, esophageal and rectal folds, respectively. In the Kujawsko-Pomorskie province during the period of 2006-2011 the number of diagnosed colorectal cancers increased as did the overall number of benefits provided.There was also a downward trend for the total number of benefits granted in relation to the trend of the increase in the number of new diagnosed cases. Incidence and morbidity rates were variable, gradually increasing in subsequent years and amounted to 59/100000 and 67/100000, 355/100000 and 408/100000 in 2010 and 2011, respectively. The probability of 5-year survival was 45.2%. Diagnosis of a disease in patients above 69 years of age increased the likelihood of death.


Characterization of UGPase from Aureobasidium pullulans NRRL Y-12974 and Application in Enhanced Pullulan Production.
UDPG pyrophosphatase (UGPase) plays an important role in carbohydrate metabolism, catalyzing a reversible production of uridine diphosphate glucose (UDPG) and pyrophosphate (PPi) from Glc-1-P and UTP. UGPase gene from Aureobasidium pullulans NRRL Y-12974 was cloned, overexpressed in Escherichia coli. The recombinant UGPase possess molecular mass of 55 KDa and specific activity of 7.33 U/mg protein. The K m values of rUGPase were 5.045 μM against UTP and 3.333 μM against Glc-1-P. The V max values of rUGPase were 3.467 μM min(-1)against UTP and 2.817 μM min(-1) against Glc-1-P. And, it does not catalyze Glc-1-P and ATP, nor galactose-1-P and UTP. Homolgous expression of UGPase in native organism can improve the intracellular UDPG concentration by 4.7-fold time. The yield of pullulan in engineering strain A4 was improved to 18.2 g g(-1) cell dry weight which is 1.3-fold time of parent strain. No obvious change of growth was found between engineering strain and parent strain. To the best of our knowledge, this is the first report of improving pullulan yield in A. pullulans using metabolic engineering technique.


The postnatal development of rat dentate gyrus and the effect of early thyroid hormone treatment.
The postnatal development of the dentate gyrus and the effect of 5 microgram/day triiodothyronine treatment was examined by means of tritiated thymidine autoradiography. The polymorph layer of the dentate gyrus is a secondary germinal layer and forms cells for the granular layer. The cell formation in the dentate gyrus was found to be nearly completed on the 21st day, but development ended only in adulthood. Thyroid-hormone treatment did not affect significantly the postnatal cell formation of the dentate gyrus, but resulted in the appearance of a great number of pycnotic cells in the granular layer.


Uninsurance, underinsurance, and health care utilization in Mexico by US border residents.
Using data from the 2008 Cross-Border Utilization of Health Care Survey, we examined the relationship between United States (US) health insurance coverage plans and the use of health care services in Mexico by US residents of the US-Mexico border region. We found immigrants were far more likely to be uninsured than their native-born counterparts (63 vs. 27.8 %). Adults without health insurance coverage were more likely to purchase medications or visit physicians in Mexico compared to insured adults. However, adults with Medicaid coverage were more likely to visit dentists in Mexico compared to uninsured adults. Improving health care access for US residents in the southwestern border region of the country will require initiatives that target not only providing coverage to the large uninsured population but also improving access to health care services for the large underinsured population.


The effect of compliance with a perioperative goal-directed therapy protocol on outcomes after high-risk surgery: a before-after study.
Perioperative goal-directed therapy is considered to improve patient outcomes after high-risk surgery. The association of compliance with perioperative goal-directed therapy protocols and postoperative outcomes is unclear. The purpose of this study is to determine the effect of protocol compliance on postoperative outcomes following high-risk surgery, after implementation of a perioperative goal-directed therapy protocol. Through a before-after study design, patients undergoing elective high-risk surgery before (before-group) and after implementation of a perioperative goal-directed therapy protocol (after-group) were included. Perioperative goal-directed therapy in the after-group consisted of optimized stroke volume variation or stroke volume index and optimized cardiac index. Additionally, the association of protocol compliance with postoperative complications when using perioperative goal-directed therapy was assessed. High protocol compliance was defined as ≥ 85% of the procedure time spent within the individual targets. The difference in complications during the first 30 postoperative days before and after implementation of the protocol was assessed. In the before-group, 214 patients were included and 193 patients in the after-group. The number of complications was higher in the before-group compared to the after-group (n = 414 vs. 282; p = 0.031). In the after-group, patients with high protocol compliance for stroke volume variation or stroke volume index had less complications compared to patients with low protocol compliance for stroke volume variation or stroke volume index (n = 187 vs. 90; p = 0.01). Protocol compliance by the attending clinicians is essential and should be monitored to facilitate an improvement in postoperative outcomes desired by the implementation of perioperative goal-directed therapy protocols.


The Effects of Pre-conditioning on Exercise-Induced Muscle Damage: A Systematic Review and Meta-analysis.
Several studies have utilised isometric, eccentric and downhill walking pre-conditioning as a strategy for alleviating the signs and symptoms of exercise-induced muscle damage (EIMD) following a bout of damaging physical activity. This systematic review and meta-analysis examined the effects of pre-conditioning strategies on indices of muscle damage and physical performance measures following a second bout of strenuous physical activity. PubMed, CINAHL and Scopus. Studies meeting the PICO (population, intervention/exposure, comparison, and outcome) criteria were included in this review: (1) general population or "untrained" participants with no contraindications affecting physical performance; (2) studies with a parallel design to examine the prevention and severity of muscle-damaging contractions; (3) outcome measures were compared using baseline and post-intervention measures; and (4) outcome measures included any markers of indirect muscle damage and muscular contractility measures. Individuals with no resistance training experiences in the previous 6 or more months. A single bout of pre-conditioning exercises consisting of eccentric or isometric contractions performed a minimum of 24 h prior to a bout of damaging physical activity were compared to control interventions that did not perform pre-conditioning prior to damaging physical activity. Kmet appraisal system. Quantitative analysis was conducted using forest plots to examine standardised mean differences (SMD, i.e. effect size), test statistics for statistical significance (i.e. Z-values) and between-study heterogeneity by inspecting I2. Following abstract and full-text screening, 23 articles were included in this paper. Based on the meta-analysis, the pre-conditioning group exhibited lower levels of creatine kinase at 24 h (SMD = - 1.64; Z = 8.39; p = 0.00001), 48 h (SMD = - 2.65; Z = 7.78; p = 0.00001), 72 h (SMD = - 2.39; Z = 5.71; p = 0.00001) and 96 h post-exercise (SMD = - 3.52; Z = 7.39; p = 0.00001) than the control group. Delayed-onset muscle soreness was also lower for the pre-conditioning group at 24 h (SMD = - 1.89; Z = 6.17; p = 0.00001), 48 h (SMD = - 2.50; Z = 7.99; p = 0.00001), 72 h (SMD = - 2.73; Z = 7.86; p = 0.00001) and 96 h post-exercise (SMD = - 3.30; Z = 8.47; p = 0.00001). Maximal voluntary contraction force was maintained and returned to normal sooner in the pre-conditioning group than in the control group, 24 h (SMD = 1.46; Z = 5.49; p = 0.00001), 48 h (SMD = 1.59; Z = 6.04; p = 0.00001), 72 h (SMD = 2.02; Z = 6.09; p = 0.00001) and 96 h post-exercise (SMD = 2.16; Z = 5.69; p = 0.00001). Range of motion was better maintained by the pre-conditioning group compared with the control group at 24 h (SMD = 1.48; Z = 4.30; p = 0.00001), 48 h (SMD = 2.20; Z = 5.64; p = 0.00001), 72 h (SMD = 2.66; Z = 5.42; p = 0.00001) and 96 h post-exercise (SMD = 2.5; Z = 5.46; p = 0.00001). Based on qualitative analyses, pre-conditioning activities were more effective when performed at 2-4 days before the muscle-damaging protocol compared with immediately prior to the muscle-damaging protocol, or 1-3 weeks prior to the muscle-damaging protocol. Furthermore, pre-conditioning activities performed using eccentric contractions over isometric contractions, with higher volumes, greater intensity and more lengthened muscle contractions provided greater protection from EIMD. Several outcome measures showed high inter-study heterogeneity. The inability to account for differences in durations between pre-conditioning and the second bout of damaging physical activity was also limiting. Pre-conditioning significantly reduced the severity of creatine kinase release, delayed-onset muscle soreness, loss of maximal voluntary contraction force and the range of motion decrease. Pre-conditioning may prevent severe EIMD and accelerate recovery of muscle force generation capacity.


2D materials-based nanomedicine: From discovery to applications.
Due to their unique physicochemical characteristics, 2D materials have attracted more and more attention in the biomedicine field. Currently, 2D materials-based nanomedicines have been extensively applied in various diseases including cancer, bacterial infection, tissue engineering, biological protection, neurodegenerative diseases, and cardiovascular disease. Depending on their various characteristics, these 2D nanomedicines exert their therapeutic effect in different ways, showing great clinical application prospects. Herein, we focus on the various biomedical applications of 2D materials-based nanomedicine. The structures and characteristics of several typical 2D nanomaterials with different configurations and their corresponding biomedical applications are first introduced. Then, the potential of 2D nanomedicines on therapeutic and imaging and their biological functionalization are discussed. Furthermore, the therapeutic potentials of 2D nanomedicines in various diseases are also comprehensively summarized. At last, the challenges and perspectives for the advancement of 2D nanomedicines in clinical transformation are outlooks.


Formation of Avenacein Y by Fusarium avenaceum Fries Sacc. isolates from Germany and pathogenicity of the isolates to cereal seedlings.
Twelve isolates ofFusarium avenaceum Fries Sacc. originating from diseased corn plants from Germany produced Avenacein Y in amounts ranging from 0.001 to 1.6 g/kg of wheat grain. The isolates proved most pathogenic to triticale seedlings, less pathogenic to rye seedlings and least to wheat. Pathogenicity of the isolates was not correlated with their ability to produce Avenacein Y.


[How should hormone therapy for castration-resistant prostate cancer be continued?].
After an average of 18-36 months under androgen suppression therapy by surgical castration, LHRH, and steroidal or non-steroidal antiandrogens, almost all patients with metastatic prostate cancer show PSA progression as a sign of androgen-independent but still androgen-sensitive tumor growth. Our understanding and the treatment of such castration-resistant prostate cancer has changed markedly. The introduction of new drugs like abiraterone and MDV3100 has shown that prostate cancer progression even in the"hormone-refractory" stage is driven by androgen receptor signaling. Based on this information the question of whether androgen deprivation therapy in castration-resistant prostate cancer should be continued or not is still of relevance. This review gives a critical overview of the literature and current guideline recommendations.


Holding it all together? Candidate proteins for the plant Golgi matrix.
A combination of electron microscopy and fluorescence microscopy has provided us with a global picture of the structure of the plant Golgi apparatus. However, the components that shape this structure remain elusive. In other organisms, members of the golgin family of coiled-coil proteins are essential for Golgi structure and organisation. Putative Arabidopsis and rice homologues of some golgin family members can be identified using database searches. Likewise, the heterogeneous group of multi-subunit-tethering complexes is responsible for crucial transport steps that affect Golgi structure and cisternal organisation in animals and yeasts. The Arabidopsis genome harbours possible homologues for the majority of the subunits of these complexes, suggesting that they also operate in the plant kingdom.


Drinking habits and water sources with the incidence of cognitive impairment in Chinese elderly population: The Chinese Longitudinal Healthy Longevity Survey.
Little was known on whether drinking habits and water sources affected cognitive function. This study aimed to examine the associations of drinking habits and water sources with the incidence of cognitive impairment in the Chinese elderly population. Data were drawn from the Chinese Longitudinal Healthy Longevity Survey. All participants aged ≥ 60 years at baseline were potential eligible. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (CMMSE). Participants with the CMMSE score ≤ 24 were identified as cognitive impairment. Drinking habits included preferring to drink boiled water or un-boiled water. Water sources included well, surface water, spring, and tap water. This study included 18034 participants. Participants drinking un- boiled water were more likely to develop cognitive impairment than those drinking boiled water (P< 0.001; HR: 1.269; and 95% CI: 1.128-1.427). Compared to drinking from a well, drinking from tap water at childhood, around aged 60 years, and present was associated with a lower incidence of cognitive impairment (all P< 0.001; HR: 0.672, 0.735, and 0.765; and 95% CI: 0.540-0.836, 0.686-0.788, and 0.723-0.810, respectively). The underline mechanisms behind the associations of drinking habits and water sources with the incidence of cognitive impairment were not fully explained. Participants drinking un- boiled water were more likely to develop cognitive impairment. Meanwhile, compared to drinking from a well, drinking from tap water was associated with a lower incidence of cognitive impairment.


Reasons and predictors for early termination of pediatric polysomnography: one children's hospital's experience.
We sought to identify reasons for early polysomnography termination in pediatric patients. We retrospectively reviewed all studies conducted at the Pediatric Sleep Center at UT Southwestern Medical Center from January 1, 2017, through December 31, 2019, that were terminated before study completion. We investigated reasons for early termination and gathered characteristics such as age, sex, presence of neurocognitive impairment, payor status, seasonal variability, and testing site location. There were 137 patients who terminated their studies before completion, comprising 1.05% of all patients who arrived for their scheduled polysomnographies during that time frame. The 3 main categories of reasons were equipment intolerance (47%), acute illness (33%), and parental refusal (20%). Parental refusal reasons included the patient's becoming combative, a lack of specialized equipment, patient's inability to fall asleep, forgetting the patient's nighttime medications, and the parent's inability to stay the night. Males represented a greater proportion of those who terminated due to intolerance of equipment (75%). Patients who terminated early due to equipment intolerance consisted of more neurologically impaired patients compared with those who terminated due to acute illness (56% vs 24%). Termination due to acute illness occurred more during the wintertime (44%) than in the summer (7%). In those who terminated due to parental refusal, there was a greater proportion of children under 6 years of age (75%). Determining factors that are associated with early polysomnography termination is an important step to help identify at-risk groups and implement strategies to improve study completion. Luong S, Culp M, McCreary M, Wani A, Caraballo M. Reasons and predictors for early termination of pediatric polysomnography: one children's hospital's experience. J Clin Sleep Med. 2023;19(10):1711-1716.


Guidelines for pre-manipulative testing of the cervical spine - an appraisal.
Are the guidelines valid? It is not clear if recommendations were derived from evidence of high quality or from evidence that is much more liable to error. The majority of evidence is based on low level evidence; that is, physiology, bench research, or "first principles" (Sackett et al 2000). Studies of moderate level evidence, where inappropriate sampling and a narrow spectrum of study individuals was used, revealed vertebrobasilar insufficiency tests to be invalid. Information on the validity of the diagnostic studies, their accuracy, and detailed instruction for applying that evidence to our patients (Sackett et al 2000) was not reported in the guidelines.


Enterocutaneous fistula: a complication of posterior iliac bone graft harvesting not previously described.
A case of enterocutaneous fistula at the donor site is presented. A patient underwent posterior C5-C6 wire fusion with autologous bone graft taken from the posterior superior iliac crest for degenerative C5-C6 spondylolisthesis. The tip of the osteotome slipped anteriorly during the procurement but neither neurovascular nor peritoneal injury were observed. Spillage of formed faecal material was observed from the donor site on the 12th postoperative day. Fistulogram showed an enterocutaneous fistula to descending colon. The fistula closed spontaneously in a week. Enterocutaneous fistula after bone harvesting has never been reported in the literature as far as we know. Congenital malformations and acquired causes may create a vulnerable peritoneal area. Small bowel or descending colon may show a close relationship or even an adhesion to peritoneum in the presence of local peritonitis. A small lesion in this area may play a role in the occurrence of a fistula, and a low flow pseudofistulous tract may appear. The thermal injury and possible ischaemic necrosis due to cauterisation may be predisposing factors in the aetiology of this kind of fistula. The lack of foreign material and spontaneous closure were against an infectious origin. The aims of this report are to present and analyse the reasons of this complication, not previously described.


Utilization of insecticide-treated nets and associated factors among childbearing women in Northern Nigeria.
Studies have explored the correlates of insecticide-treated nets in Nigeria. The few studies that focused on Northern Nigeria mostly examined individual correlates, but largely ignored the community correlates. Also, the persistence of armed insurgencies in the region calls for more research attention. This study examines the utilization and the associated individual and community factors of insecticide-treated nets in Northern Nigeria. The study adopted a cross-sectional design. Data were extracted from the 2021 Nigeria Malaria Indicator Survey (NMIS). A weighted sample size of 6873 women was analysed. The outcome variable was the utilization of insecticide-treated nets. The explanatory variables selected at the individual/household level were maternal age, maternal education, parity, religion, sex of head of household, household wealth, and household size. The variables selected at the community level were the type of place of residence, geo-political zone of residence, the proportion of children under five who slept under a bed net, the proportion of women aged 15-49 who heard malaria media messages, and the community literacy level. Two variables, namely, the number of mosquito bed nets in the household, and the number of rooms used for sleeping were included for statistical control. Three multilevel mixed-effect regression models were fitted. The majority of childbearing women (71.8%) utilized insecticide-treated nets. Parity and household size were the significant individual/household characteristics associated with the utilization of insecticide-treated nets. The proportion of under-five children in the community who slept under mosquito bed nets, and the geopolitical zone of residence were significant community correlates of the use of insecticide-treated nets. In addition, the number of rooms for sleeping, and the number of mosquito bed nets in the households were significantly associated with the utilization of insecticide-treated nets. Parity, household size, number of sleeping rooms, number of treated bed nets, geo-political zone of residence, and proportion of under-five children sleeping under bed nets are important associated factors of the utilization of insecticide-treated nets in Northern Nigeria. Existing malaria preventive initiatives should be strengthened to target these characteristics.


Economics and outcomes of sotalol in-patient dosing approaches in patients with atrial fibrillation.
There exists variability in the administration of in-patient sotalol therapy for symptomatic atrial fibrillation (AF). The impact of this variability on patient in-hospital and 30-day posthospitalization costs and outcomes is not known. Also, the cost impact of intravenous sotalol, which can accelerate drug loading to therapeutic levels, is unknown. One hundred and thirty-three AF patients admitted for oral sotalol initiation at an Intermountain Healthcare Hospital from January 2017 to December 2018 were included. Patient and dosing characteristics were described descriptively and the impact of dosing schedule was correlated with daily hospital costs/clinical outcomes during the index hospitalization and for 30 days. The Centers for Medicare and Medicaid Services reimbursement for 3-day sotalol initiation is $9263.51. Projections of cost savings were made considering a 1-day load using intravenous sotalol that costs $2500.00 to administer. The average age was 70.3 ± 12.3 years and 60.2% were male with comorbidities of hypertension (83%), diabetes (36%), and coronary artery disease (53%). The mean ejection fraction was 59.9 ± 7.8% and the median corrected QT interval was 453.7 ± 37.6 ms before sotalol dosing. No ventricular arrhythmias developed, but bradycardia (<60 bpm) was observed in 37.6% of patients. The average length of stay was 3.9 ± 4.6 (median: 2.2) days. Postdischarge outcomes and rehospitalization rates stratified by length of stay were similar. The cost per day was estimated at $2931.55 (1. $2931.55, 2. $5863.10, 3. $8794.65, 4. $11 726.20). In-patient oral sotalol dosing is markedly variable and results in the potential of both cost gain and loss to a hospital. In consideration of estimated costs, there is the potential for $871.55 cost savings compared to a 2-day oral load and $3803.10 compared to a 3-day oral load.


The in vivo degradation, absorption and excretion of PCL-based implant.
The in vivo degradation of poly (epsilon-caprolactone)(PCL) was observed for 3 years in rats. The distribution, absorption and excretion of PCL were traced in rats by radioactive labeling. The results showed that PCL capsules with initial molecular weight (Mw) of 66000 remained intact in shape during 2-year implantation. It broke into low molecular weight (Mw=8000) pieces at the end of 30 months. The Mw of PCL deceased with time and followed a linear relationship between logMw and time. Tritium-labeled PCL (Mw 3000) was subcutaneous implanted in rats to investigate its absorption and excretion. The radioactive tracer was first detected in plasma 15 days after implantation. At the same time radioactive excreta was recovered from feces and urine. An accumulative 92% of the implanted radioactive tracer was excreted from feces and urine by 135 days after implantation. In the mean while, the plasma radioactivity dropped to the background level. Radioactivity in the organs was all close to the background level confirming that the material did not cumulate in body tissue and could be completely excreted.


The potential therapeutic impact of a topical bacteriophage preparation in treating Pseudomonas aeruginosa-infected burn wounds in mice.
This study compared a topical formulation containing lytic phages with a routine antibiotic in the murine model of burn/Pseudomonas aeruginosa infected wound healing. Isolated and purified lytic bacteriophages from hospital sewage were added to the polyethylene glycol (PEG) based ointment. A second-degree burned wound on the back of twenty-four adult female mice was created. The wounds were infected subcutaneously with 100 μL of 1 × 102-3 CFU/mL P. aeruginosa. After 24 h, mice were randomly assigned to one of four groups: mice received a standard antibiotic (antibiotic-treated group), mice received an ointment without bacteriophage (PEG-based group), mice received a PEG-ointment with bacteriophage (bacteriophage-treated group), or mice received no treatment (untreated-control group). Every two days, the contraction of burned wounds, physical activity, and rectal body temperature were recorded. On day 10, mice were sacrificed, and the wounds were cut off and evaluated histopathologically. In ointments containing PEG, bacteriophages were active and stable. The mice receiving bacteriophage and PEG-based ointment had substantially different wound contraction in primary wound healing (P = 0.001). When compared to the control group, the bacteriophage-treated group showed significant variations in wound contraction (P = 0.001). The wound contraction changed significantly between the antibiotic and PEG-based groups (P = 0.002). In all groups, physical activity in mice improved over time, with significant differences (P = 0.001). When the 8th day was compared to the days 2, 4, and 6, significant changes were found (P = 0.001, P = 0.02, and P = 0.02, respectively). Both the positive control and bacteriophage-treated groups showed perfect wound healing histopathologically. However, no significant variations in microscopic histopathological criteria were found between the groups. Formulated phage ointment could be a promising approach for treating infected burn wounds infected by P. aeruginosa in mice with no allergic reactions.


Role of platelets in the in vivo removal of T. cruzi from circulation.
The possible role of platelets in the clearance of Trypanosoma cruzi was studied in vivo in A/sn female mice. Platelet depletion achieved by anti-platelet IgG antibodies induced a significant, though not total, reduction in the rate of removal of T. cruzi bloodstream trypomastigotes (BTRYS) from the circulation. Furthermore, during removal of T. cruzi BTRYS from the circulation of normal mice there was a simultaneous decrease in the number of platelets. These results suggest that platelets play a role in the in vivo mechanism of defense against T. cruzi infection.


Comparison of four dosage schedules in the treatment of giardiasis with metronidazole.
Sixty patients with parasitologically confirmed giardiasis were treated with metronidazole using four different regimens administered to four groups of 15 patients each. A seven-day course of 200 mg thrice daily successfully eliminated the organism in 11 patients. A repetition of the seven-day course after an interval of one week was successful in 14 patients, a single dose of 2400 mg in nine patients, and two 2400 mg doses on successive days in 12 patients. Late relapses, detected more than one month after therapy, were relatively common in the single-dose groups. Side-effects associated with the 2400 mg dosages were frequent but tolerable.


Cytotoxic and Antitumor Activity of some Coumarin Derivatives.
Several natural and synthetic coumarins were assayed against different cancer cell lines. Four of them have shown cytotoxicity against a panel of three human solid tumor cell lines (HeLa, T-47D, and WiDr) and a clearly activity/hydrophobicity relationship. Compound 13 proved to be the most active product in all cell lines tested, with values of 8.0 (±0.38) μM against HeLa cells and also able to inhibit Taq DNA polymerase. This dual activity of 13 makes it a candidate to be considered as a "lead" compound in the search for novel antitumor drugs.


Dopaminergic mediation of the discriminative stimulus functions of modafinil in rats.
Modafinil is a wake-promoting drug with FDA approval for the treatment of excessive daytime sleepiness that has been prescribed for ADHD and recently assessed as a potential treatment for psychostimulant dependence. Previous research indicates that modafinil modestly increases locomotor activity and produces similar discriminative stimulus effects to psychostimulants in rodents, although the subjective effects of modafinil are reportedly distinct from those of cocaine or amphetamine in humans with a history of psychostimulant abuse. The current study employed drug discrimination procedures in rats to examine the pharmacological actions contributing to modafinil's discriminative stimulus functions. Eight male Sprague-Dawley rats were trained to discriminate intragastric administration of 256 mg/kg modafinil from vehicle (5% arabic gum) under a FR 20 schedule of food reinforcement. Substitution tests were conducted with various dopaminergic agents (d-amphetamine, cocaine, PNU-91356A, GBR 12909, methylphenidate) and nondopaminergic agents (nicotine, ethanol). Antagonist tests were conducted with the selective D1 antagonist, SCH 39166, and the nonselective D2 antagonist, haloperidol. Rats trained to discriminate modafinil displayed complete stimulus generalization to cocaine, methylphenidate, and GBR 12909 and the discrimination was completely blocked by both SCH 39166 and haloperidol. Evidence for significant partial substitution was obtained with d-amphetamine, PNU-91356A, and nicotine. Results strongly support the role of dopaminergic mechanisms in the discriminative stimulus functions of modafinil, although further evaluation regarding the contribution of other neurotransmitter systems to these effects should be continued. The findings are discussed in light of clinical research efforts with modafinil as a treatment for psychostimulant dependence.


Copper-mediated DNA photocleavage by a tetrapyridoacridine (tpac) ligand.
We have focused our interest on the tetrapyridoacridine ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h: 2''',3'''-j]acridine (tpac), as a model system for the preparation of novel copper-based artificial nucleases. The complex of copper(II)-tpac cleaves supercoiled pUC18 plasmid DNA in an oxidative manner by photoactivation with visible light, exhibiting maximum cleaving efficiency at 1:2 metal-ligand stoichiometric ratio. We propose an interaction of the copper-tpac complex with DNA through both major and minor grooves and a photocleavage mechanism via the formation of hydroxyl radicals and singlet oxygen or singlet oxygen-like species.


Measuring parent proxy-reported quality of life of 11 rare diseases in children in Zhejiang, China.
It has become increasingly important to measure the health-related quality of life (HRQoL) of rare diseases in children and adolescents in recent decades. Much attention has been paid to investigate the HROoL of a specific rare disease by self-report in previous studies. This study aimed to evaluate and compare the HROoL of 11 rare diseases in Chinese children by parent proxy-report, to explore the factors associated with HROoL of patients, and to understand the problems of most concern. A total of 651 children aged from 2 to 18 were enrolled from the Children's Hospital Affiliated Zhejiang University in 2018. Their parents completed the parent proxy-report version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0). Independent samples t-test, one-way ANOVA, or Kruskal-Wallis H test was used to compare HROoL scores between groups. Multilevel linear regression models with random intercept were applied to analyze the relationship between socioeconomic variables and both the total score and subdomain scores. The total PedsQL scores of Patent ductus arteriosus (PDA), Infantile agranulocytosis, Autoimmune thrombocytopenia (ITP), Polysyndactyly, Hirschsprung disease, Cleft lip and palate, Tetralogy of fallot, Myasthenia gravis, Guillain-barre syndrome, Glycogen storage disease, and Langerhans cell histiocytosis children were 79.65 ± 5.46, 95.88 ± 3.48, 71.39 ± 3.27, 91.77 ± 6.35, 76.18 ± 6.92, 96.33 ± 4.22, 77.85 ± 8.90, 95.99 ± 3.31, 85.77 ± 4.56, 82.97 ± 4.13 and 77.6 ± 5.15, respectively. Age was significantly associated with physical functioning, school functioning, and psychosocial health scores. The household registration place was significantly related to the total score. The most urgent desire of patients was to reduce the overall medical costs. This study showed that patients with PDA had the lowest physical functioning score, while patients with ITP scored the lowest in the emotional functioning, social functioning, school functioning, psychosocial health, and total scores. Incentive policies should be further adopted to improve orphan drug availability and reduce the economic burden of rare diseases.


Harnack's inequality for doubly nonlinear equations of slow diffusion type.
In this article we prove a Harnack inequality for non-negative weak solutions to doubly nonlinear parabolic equations of the form ∂ t u - div A ( x , t , u , D u m ) = div F , where the vector field A fulfills p-ellipticity and growth conditions. We treat the slow diffusion case in its full range, i.e. all exponents m > 0 and p > 1 with m ( p - 1 ) > 1 are included in our considerations.


Encouraging vegetable intake as a snack among children: the influence of portion and unit size.
People eat more unhealthy foods when served more (portion size effect) and when the food is served in larger units (unit size effect). The present study aimed to examine whether these effects can be used for the good: to increase vegetable consumption among children. A 2×2 between-subjects experiment was conducted at two schools. Pupils were presented in class with cucumber that varied both in unit size (one piece v. pre-sliced) and portion size (one-third v. two-thirds of a cucumber). Children ate ad libitum during the morning break and filled in a survey. Primary schools in the centre of the Netherlands. Primary-school pupils (n 255) aged 8-13 years. Children ate 54 % more cucumber when served a large compared with a smaller portion (difference of 49 g; P<0·001). Large units did not impact consumption (P=0·58), but were considered as less convenient to eat than small units (P=0·001). Findings suggest that children's vegetable intake can be improved by serving larger portions in smaller-sized pieces.


Management of complications with flap procedures and replantation.
Replantation and flap procedures employ microvascular techniques to salvage or reconstruct a severely damaged limb or digit. The most devastating complications include complete or partial flap loss, or replantation failure due to vascular complications. Often, these complications can be prevented by appropriate patient selection, careful surgical planning, meticulous technique, and proper postoperative management. This article discusses complications related to replantation and flap procedures in the upper limb, focusing on preventing and managing these complications.