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Polarimetric data is nowadays used to build recognition models for the characterization of organic tissues or the early detection of some diseases. Different Mueller matrix-derived polarimetric observables, which allow a physical interpretation of a specific characteristic of samples, are proposed in literature to feed the required recognition algorithms. However, they are obtained through mathematical transformations of the Mueller matrix and this process may loss relevant sample information in search of physical interpretation. In this work, we present a thorough comparative between 12 classification models based on different polarimetric datasets to find the ideal polarimetric framework to construct tissues classification models. The study is conducted on the experimental Mueller matrices images measured on different tissues: muscle, tendon, myotendinous junction and bone; from a collection of 165 ex-vivo chicken thighs. Three polarimetric datasets are analyzed: (A) a selection of most representative metrics presented in literature; (B) Mueller matrix elements; and (C) the combination of (A) and (B) sets. Results highlight the importance of using raw Mueller matrix elements for the design of classification models. | Myotendinous Junction |
We have identified and characterized a novel vascular endothelial growth factor (VEGF), VEGF-D, which is structurally related to vascular endothelial growth factor C. A full-length cDNA for human VEGF-D was cloned following the identification of an EST obtained through a TFASTA search of public EST databases. The murine VEGF-D was subsequently isolated from a mouse lung cDNA library. The human VEGF-D gene was mapped to human chromosome Xp22.31. Both human and mouse VEGF-D are strongly expressed in lung and encode the eight cysteine residues that are highly conserved among the members of this family. The high level of conservation between mouse and human VEGF-D may emphasize the biological importance of this gene. Recently the murine gene, FIGF, which is identical to mouse VEGF-D, was reported. | Endothelial Growth Factors |
OBJECTIVE: The purpose of this study was to evaluate the minimum amount of contrast material for coronary imaging with aortic root catheter-directed enhancement and 64-MDCT angiography (MDCTA). MATERIALS AND METHODS: A 64-MDCT scanner was used after animal institutional review board approval to study four swine (40-60 kg). Heart rate reduction to 65 beats per minute was achieved with atenolol by mouth and i.v. Cardizem. Common femoral artery access was obtained with a 5-French micropuncture kit and sonographic guidance. A diffusiontip (640 side holes), 5-French pigtail catheter was positioned in the aortic root on the CT table with a retrofitted C-arm fluoroscopy unit and connected to an arterial power injector. Aortic root MDCTA (retrospective ECG gating; collimation, 0.6 mm; tube rotation time, 0.33 second; scanning time, 10-12 seconds; tube voltage, 120 kVp; effective mAs, 850 mAs; pitch, 0.2; field of view, 109-123 mm; slice thickness and increment, 0.6 and 0.3 mm) was begun 1 second after the injection of 100 mL of various Visipaque (iodixanol) concentrations (10%, 20%, 30%, 40%) at 10 mL/s. Coronary mean and peak densities, 3D maximum intensity projections, and 4D projections were obtained. RESULTS: The mean pooled coronary attenuation values (H +/- SD) for the right (RCA), left anterior descending (LAD), and left circumflex (LCx) coronary arteries at various concentrations (10%, 20%, 30%, 40%) were as follows: 10% (RCA [232.6 +/- 64.0], LAD [180.4 +/- 45.1], and LCx [176.6 +/- 56.2]); 20% (RCA [383.0 +/- 98.7], LAD [324.3 +/- 60.1], and LCx [331.8 +/- 105.5]); 30% (RCA [441.8 +/- 137.6], LAD [401.3 +/- 125.8], and LCx [418.5 +/- 173.0]); and 40% (RCA [717.3 +/- 377.7], LAD [573.3 +/- 233.3], and LCx [584.8 +/- 189.0]). Coronary imaging with aortic root MDCTA was feasible at all concentrations, and the attenuation values were statistically significantly greater than 250 H at 20%, 30%, and 40% (p < 0.05). The attenuation values with aortic root MDCTA using one fifth of the volume of contrast material are comparable to those currently achieved both clinically and experimentally with peripheral i.v. MDCTA. CONCLUSION: Aortic root MDCTA can depict the coronary arteries with as little as 20 mL of contrast material. This may provide an alternative means of coronary evaluation in patients with renal insufficiency. | Aortography |
Neuroblastoma is the most common extracranial tumor of childhood. The clinical behavior is variable, ranging from spontaneous regression to fatal progression despite aggressive therapy. The most highly statistically significant and clinically relevant factors that are currently used for classification include stage, age, histopathologic category, MYCN oncogene status, chromosome 11q status and DNA ploidy. These genetic markers were analyzed separately by classical methods until recently: mainly fluorescence in situ hybridization or loss of heterozygosity. The development of genome-wide techniques such as comparative genomic hybridization, array comparative genomic hybridization and single nucleotide polymorphism allows the analysis of copy number variations through the whole genome in one step. This enabled the investigators to refine different genetic subtypes for the better comprehension of neuroblastoma tumor behavior and reach the conclusion that these data together with a genomic profile based on gene expression should be included in future treatment stratification. | Neuroblastoma |
INTRODUCTION: Despite the long experience of radiologists, pathologists and orthopaedists with aneurysmal bone cysts (ABC), there is limited knowledge regarding the cause of the lesion and the optimal treatment. The pathogenesis of ABC remains unclear with theories ranging from a post-traumatic, reactive vascular malformation to genetically predisposed bone tumours. Recent genetic and immunohistochemical studies proposed that primary ABC is a tumour and not a reactive tumour-simulating lesion. The chromosomal analyses and some reported familial cases of this osteolytic bone lesion propose a hereditary factor in a presumably multifactorial pathogenesis. MATERIALS AND METHODS: The imaging studies, even CT scan and MRI sometimes do not provide clearly diagnostic criteria for the diagnosis of ABC. The radiographically differential diagnosis between ABC and unicameral bone cyst (UBC) is sometimes not clear. Double density fluid level, septation, low signal on T1 images and high intensity on T2 images strongly suggest the bone cyst is an ABC, rather than a UBC. CONCLUSION: Common methods of treatment vary considerably in the literature. The usual methods of treatment are curettage, resection, intracystic injections and embolization. Biopsy is imperative before any treatment. Ethibloc treatment remains highly controversial. For some authors Ethibloc injection can be recommended as the first-choice treatment excluding spinal lesions. A minimally invasive method by introduction of demineralized bone and autogenous bone marrow is able to promote the self-healing of a primary ABC. | Bone Cysts, Aneurysmal |
We report the highest power operation of a resonantly cladding-pumped, holmium-doped silica fibre laser. The cladding pumped all-glass fibre utilises a fluorine doped glass layer to provide low loss cladding guidance of the 1.95 microm pump radiation. The operation of both single mode and large-mode area fibre lasers was demonstrated, with up to 140 W of output power achieved. A slope efficiency of 59% versus launched pump power was demonstrated. The free running emission was measured to be 2.12-2.15 microm demonstrating the potential of this architecture to address the long wavelength operation of silica based fibre lasers with high efficiency. | Holmium |
Aseptic loosening of the glenoid component is one of the main reasons for the high revision rates of reverse total shoulder arthroplasty (RTSA). It has been reported that the bulky implant designs may lead to stress shielding. However, it is uncertain whether the shielding effect is severe enough to lead to bone resorption and glenoid loosening. The purpose of this study was to evaluate the level of stress-shielding and assess whether bone resorption plays a role in aseptic glenoid loosening following RTSA. A cadaveric in vitro test model was used to validate a finite element model (FEM) of the scapula. The FEM of the scapula, incorporating adaptive bone remodeling algorithms, was used to predict changes in postoperative bone density after RTSA. Changes in bone strength after implantation were also analyzed. The strain values predicted from the FEM of the scapula were in agreement with the in vitro measurements. Analysis of postoperative bone adaptation revealed that strain-induced bone resorption began at the peg of the implant and around the resected bone surface and then gradually expended to the peripheral regions. The bone strength also reduced postoperatively and appeared particularly around the implant peg. Strain-induced bone resorption is a likely source of the bone loss commonly observed in RTSA. The finite element glenoid bone remodeling simulation may be used as a tool to evaluate glenoid implant design. | Prosthesis Failure |
THE RISK FACTORS, clinical manifestation, and preventive measures of Horner syndrome (HS) caused by internal jugular vein (IJV) catheterization were explored. Electronic databases were searched to identify all case reports of HS caused by IJV catheterization. Two authors independently extracted literature characteristics, IJV catheterization method, clinical manifestations, and prognosis data. Twenty case reports (22 patients in total) were included, 18 of which were written in English and the other 2 in Chinese. Patients were between 19 months to 65 years old, and clinical manifestations included ptosis (nâ¯=â¯22), miosis (nâ¯=â¯21), anhidrosis (nâ¯=â¯8), enophthalmos (nâ¯=â¯3), and hoarseness (nâ¯=â¯1). Onset of HS manifestation ranged from a few hours to 19 days after the procedure. Eight patients with ptosis, 6 patients with miosis, and 1 patient with hoarseness recovered during follow-up. Of the 22 patients, 8 underwent more than 1 attempt of IJV catheterization. Six patients experienced accidental carotid artery puncture or hematoma formation during or after IJV catheterization. Ultrasound guidance was applied in 4 patients and anatomic landmark technique was used in the other 18 patients. The left IJV was catheterized in 3 patients, and the right IJV was catheterized in 19 patients. Repeated attempts of puncture, anatomic landmark technique, accidental carotid artery puncture, or hematoma formation may increase the possibility of HS. Ptosis and miosis are the most common manifestations of HS caused by IJV catheterization. | Miosis |
Qualitative histopathology has been the gold standard for evaluation of morphological tissue changes in all organ systems, including the peripheral nervous system. However, the human eye is not sensitive enough to detect small changes in quantity or size. Peripheral nervous system toxicity can manifest as subtle changes in neuron size, neuron number, axon size, number of myelinated or unmyelinated axons, or number of nerve fibers. Detection of these changes may be beyond the sensitivity of the human eye alone, necessitating quantitative approaches in some cases. Although 2-dimensional (2D) histomorphometry can provide additional information and is more sensitive than qualitative evaluation alone, the results are not always representative of the entire tissue and assumptions about the tissue can lead to bias, or inaccuracies, in the data. Design-based stereology provides 3D estimates of number, volume, surface area, or length, and stereological principles can be applied to peripheral nervous system tissues to obtain accurate and precise estimates, such as neuron number and size, axon number, and total intraepidermal nerve fiber length. This review describes practical stereological approaches to 3 compartments of the peripheral nervous system: ganglia, peripheral nerves, and intraepidermal nerve fibers. | Peripheral Nervous System |
The zebrafish has proven to be a valuable vertebrate model in which to elucidate the molecular mechanisms of various diseases. A high degree of genetic and morphological similarity in hematopoiesis between the zebrafish and human indicates that zebrafish can provide valuable knowledge about the mechanisms behind pathogenesis of leukemia. To date, a small number of zebrafish leukemia models have been published and they have already provided some interesting information. However, the full potential of these models, especially the identification of contributing genetic factors and high-throughput drug screens, is yet to be fulfilled. Further transgenic or mutant animals are needed, especially for modeling high-risk leukemias, such as MLL rearranged infant leukemias." | Xenograft Model Antitumor Assays |
In a study comprising 116 patients at a hospital for general care, ofloxacin was tested in various doses and at various time intervals against pipemidic acid (for infections of the lower urinary tract) and co-trimoxazole forte (for infections of the upper urinary tract). Ofloxacin proved superior to the other drugs both clinically and, particularly, bacteriologically. Of 77 patients treated with ofloxacin, only one complained of diarrhoea as a side-effect of the drug. | Pipemidic Acid |
The effects of prolonged oral administration (21 days) of fumonisin B1 (FB1) and aflatoxin B1 (AFB1) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 microg AFB1 + 0 mg FB1/100g bw.; 2-72 microg AFB1+ 0 mg FB1/100 g bw; 3-0 microg AFB1 + 0.5 mg FB1 g bw; 4-0 microg AFB1 + 1.5 mg FB1/100 g bw; 5-72 microg AFB1 + 0.5 mg FB1/100g bw; 6-72 microgAFB1 + 1.5 mg FB1/100g bw. On day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB1 and FB1 gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 micro/l and 471.00 micro/l, respectively). Blood cholesterol increased in the groups treated with the highest dose of FB1 or FB1 associated with AFB1. Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB1. The association of aflatoxin B1 with fumonisin B1 at higher dose probably potentiated the effects of the higher dose of fumonisin B1 acting singly. | Aflatoxin B1 |
In conclusion, it is apparent that researchers are poised at the threshold of developing inhibitors of complement activation from the molecules in the RCA family. By creating soluble forms of these protective proteins for in vivo administration, or by making transgenic animals expressing these proteins or their derivatives, it may be possible to inhibit complement-mediated pathology stemming from autoimmune disease, reperfusion injuries, and physical trauma. This technology combined with current attempts to protect allografts from cellular rejection with monoclonal antibodies against members of the integrin family of adhesion molecules [52] makes it possible that the excessive mortality due to the severe shortage of human donor organs could be overcome by the use of xenografts." | Complement Inactivator Proteins |
The glutamine synthetase (EC 6.3.1.2) from the N2-fixing bacterium Azotobacter vinelandii was purified to homogeneity by heat treatment, ammonium sulfate precipitation and ion-exchange chromatography. The following molecular parameters were determined: molecular weight 640 000, subunit molecular weight 53 000, partial specific volume 0.710 cm3/g, isoelectric point 4.6, amino acid composition. Most of the molecules are composed of 12 identical subunits but active oligomers of other degrees of polymerization, apparently aggregates with 8, 10 and 24 subunits, were also detected to a lesser extent. The enzymatic activity is regulated via adenylylation-deadenylylation cycles: liberation of AMP was detected upon treatment of the adenylylated form with phosphodiesterase along with a change in the catalytic properties. Adenylylation in vivo is specifically induced by high extracellular ammonia levels. The Km values for the Mg2+-dependent formation of glutamine were independent of the degree of adenylylation for glutamate and ATP, but varied for ammonia. Furthermore the catalytic activity is regulated by several nitrogenous feedback inhibitors. The degree of inhibition in some cases was dependent on the substrate concentrations: the sensitivity towards glycine, alanine and serine decreased with a decreasing ammonia level, while the sensitivity towards ADP or AMP increased with a decreasing ATP concentration. Part of the enzyme (about 30%) seems to be attached to the plasma membrane while the main fraction is found in the cytosol. | Glutamate-Ammonia Ligase |
High levels of the anti-apoptotic BCL-2 family member MCL-1 are frequently found in breast cancer and, appropriately, BH3-mimetic drugs that specifically target MCL-1's function in apoptosis are in development as anti-cancer therapy. MCL-1 also has reported non-canonical roles that may be relevant in its tumour-promoting effect. Here we investigate the role of MCL-1 in clinically relevant breast cancer models and address whether the canonical role of MCL-1 in apoptosis, which can be targeted using BH3-mimetic drugs, is the major function for MCL-1 in breast cancer. We show that MCL-1 is essential in established tumours with genetic deletion inducing tumour regression and inhibition with the MCL-1-specific BH3-mimetic drug S63845 significantly impeding tumour growth. Importantly, we found that the anti-tumour functions achieved by MCL-1 deletion or inhibition were completely dependent on pro-apoptotic BAX/BAK. Interestingly, we find that MCL-1 is also critical for stem cell activity in human breast cancer cells and high MCL1 expression correlates with stemness markers in tumours. This strongly supports the idea that the key function of MCL-1 in breast cancer is through its anti-apoptotic function. This has important implications for the future use of MCL-1-specific BH3-mimetic drugs in breast cancer treatment." | Myeloid Cell Leukemia Sequence 1 Protein |
BACKGROUND AND AIMS: Incisional hernia development is a frequent long-term sequel after open abdomen treatment. This report describes a novel technique, the vacuum-assisted wound closure and permanent onlay mesh-mediated fascial traction for temporary and final closure of the open abdomen, with the intention to decrease incisional hernia rates. Primary aim was to evaluate incisional hernia development and secondary aims to describe short-term complications and patient-reported outcome. MATERIALS AND METHODS: The basics of the technique is an onlay mesh, applied early during open abdomen treatment by suturing to the fascia in two rows with a 3- to 4-cm overlap from the midline incision, used for traction and kept for reinforced permanent closure. A retrospective case series, including chart review, evaluation of computed tomography/ultrasound images, and an out-patient clinical examination were performed. The patients were asked to answer a modified version of the ventral hernia pain questionnaire. RESULTS: A total of 11 patients were treated with vacuum-assisted wound closure and permanent onlay mesh-mediated fascial traction with median follow-up of 467 days. Fascial closure rate was 100% and 30 day mortality 0%. Two of nine patients, eligible for incisional hernia follow-up, developed a hernia. Neither of the hernias were symptomatic nor clinically detectable. Six of 10 patients eligible for short-term follow-up had a prolonged wound-healing time exceeding 3 weeks. One of seven patients eligible for patient-reported outcome have had pain during the last week. CONCLUSION: The vacuum-assisted wound closure and permanent onlay mesh-mediated fascial traction is a promising new technique for open abdomen treatment and reinforced fascial closure. The results of the first 11 patients treated with this technique show a low incisional hernia rate with manageable short-term wound complications and few patient-reported disadvantages. | Open Abdomen Techniques |
PURPOSE OF REVIEW: Trauma-induced coagulopathy results from a complex interplay between shock resuscitation and impaired clotting protease function. A pathophysiological role of platelets in this condition remains as yet undefined. This review examines our current knowledge of platelet function in haemostasis, possible mechanisms for aberrant activity in trauma and the role of platelet transfusions in exsanguinating haemorrhage. RECENT FINDINGS: Platelet adhesion and aggregation enable a haemostatic plug to form at the site of vessel injury. As described within cell-based models of thrombin generation, platelet membranes provide a platform to amplify clot formation. There is evidence to suggest platelet activity may be of greater importance than platelet number for clot integrity. Analysis of platelet function is limited by currently available devices. Therefore, the precise role and triggers for platelet transfusion in trauma have yet to be fully characterized. Retrospective studies show that early high-volume platelet transfusion in trauma may be associated with similar outcome benefits observed in high ratio plasma: red blood cell replacement. SUMMARY: Platelets undoubtedly play a pivotal role in haemostasis and trauma-induced coagulopathy. However, their specific dysfunction in trauma remains to be elucidated. Further research to characterize the dysfunctional pathways of the platelet response is required, together with clinical trials of the optimal timing and dose of platelet transfusions. | Platelet Transfusion |
The versatile carbonyl reductases from Gluconobacter oxydans in the enantioselective reduction of ketones to the corresponding alcohols were exploited by genome search approach. All purified enzymes showed activities toward the tested ketoesters with different activities. In the reduction of 4-phenyl-2-butanone with in situ NAD(P)H regeneration system, (S)-alcohol was obtained with an e.e. of up to 100% catalyzed by Gox0644. Under the same experimental condition, all enzymes catalyzed ethyl 4-chloroacetoacetate to give chiral products with an excellent e.e. of up to 99%, except Gox0644. Gox2036 had a strict requirement for NADH as the cofactor and showed excellent enantiospecificity in the synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate. For the reduction of ethyl 2-oxo-4-phenylbutyrate, excellent e.e. (>99%) and high conversion (93.1%) were obtained by Gox0525, whereas the other enzymes showed relatively lower e.e. and conversions. Among them, Gox2036 and Gox0525 showed potentials in the synthesis of chiral alcohols as useful biocatalysts. | Gluconobacter oxydans |
Cesarean section (CS) is a surgical procedure used to deliver babies that is medically indicated to prevent maternal and neonatal mortality. However, it is associated with short- and long-term risks. CS rates have increased, and efforts are being made to ensure that CS is performed only when necessary. The Robson classification system is considered useful for studying, evaluating, monitoring, and comparing CS rates within and between healthcare facilities. In Brazil, there are few studies on this subject, and no large epidemiological studies on this topic utilizing the Robson classification have been reported. This study aimed to report and analyze CS rates in Brazil using the Robson classification system, and subsequently suggest possible measures to address it.Data were collected from the Brazilian Live Birth Information System (Sistema de Informacoes sobre Nascidos Vivos) that contains data of the entire obstetric population, from 2014 to 2017. All births in the country during this period were analyzed according to the Robson classification.A total of 11,774,665 live births were reported in Brazil during 2014 to 2017, most of which were mostly via CS (55.8%). Regions with high human development indexes had significantly higher CS rates than those with low human development indexes. The Robson group (RG) 1 to 4 accounts for 60.2% of live births and 47.1% of all CSs. RG5 was larger than all the other groups and contributed to the highest global rate of CS (31.3%), in addition to being the group who presented the largest growth.Although RG 1 to 4 present favorable initial conditions for vaginal delivery, CS accounted for almost half of births in these groups. The size of RG1 and RG2 in Brazil was comparable to that in countries with low CS rates; however, CS rates in these groups were 3 times higher in Brazil. Nulliparous women in RG1 and RG2 who undergo CS are subsequently categorized into RG5, increasing the global CS rate by 1% annually.We suggest the implementation of health policies to avoid the unnecessary performance of CS in RG1 and RG2 to decrease the CS rates in Brazil. | Obstetric Surgical Procedures |
During the three-year period 1978-1980, 2141 plasma samples from 1055 patients receiving therapy with amitriptyline (77%) or nortriptyline (23%) were analysed using GLC with nitrogen selective detection. Compared to the recommended therapeutic ranges, wild inter-individual differences were observed in plasma drug concentration, even when corrections for dosage were made. Concentrations ranged from below the limit of sensitivity of the assay (5 microgram.1(-1)) to greater than 1 mg.1(-1). The reporting of toxic symptoms subjective side-effects) was found not to reliably predict high drug concentrations. Serious complications, however, were associated with high plasma drug concentrations. Neither nortriptyline nor amitriptyline displayed dose-dependent pharmacokinetics over the concentration ranges studied. Treatment with either drug produced age-related increases in drug concentration, which were more pronounced in female patients. With amitriptyline therapy, there was an age-related decrease in the plasma nortriptyline:amitriptyline ratio, suggesting that demethylation may be more influenced by increasing age than hydroxylation. Plasma drug monitoring of tricyclic antidepressant therapy is the only reliable means of ensuring that all patients receive a fair opportunity to benefit from these drugs. | Benzocycloheptenes |
AIMS: To evaluate long-term patient satisfaction of sacral neuromodulation and to correlate satisfaction with incontinence parameters. METHODS: Patients at least 1-year remote from sacral neuromodulation were mailed a questionnaire to evaluate satisfaction and assess incontinence symptoms. RESULTS: Fifty-two patients were consecutively enrolled in the study. Forty-nine questionnaires (94.2%) were returned. The average interval between implantation and questionnaire completion was 27.2 (range 12-52) months. 83.7% of respondents were satisfied and 79.6% of patients would do it all over again." Compared to dissatisfied subjects during test stimulation, the satisfied patients had a significant decrease in 24-hr pad weight (84.5% vs. 60.6%, P = 0.002) but did not differ in daily pad usage (4.5 fewer pads per day vs. 3.4, P = 0.190). At long-term follow-up, satisfied patients noted significantly greater improvement in their Incontinence Impact Questionnaire score versus dissatisfied patients (mean improvement 53 vs. 10 points, P = 0.0003). Using multiple logistic regression, change in 24-hr pad weight, but not change in average daily pad usage, was correlated with long-term satisfaction. CONCLUSIONS: Eighty-four percent of patients were satisfied with sacral neuromodulation at a mean of 27 months. An 84.5% reduction in 24-hr pad weight correlated with long-term patient satisfaction. In addition to lack of efficacy, device pain was a contributing factor to dissatisfaction." | Incontinence Pads |
In recent years, starfish outbreaks occurred frequently in northern China, causing serious economic losses to marine aquaculture. The most common outbreak starfish species are Asterias amurensis and Asterina pectini-fera. We systematically reviewed the related studies by introducing the biological characteristics, current outbreaking status, and main impact of A. amurensis and A. pectinifera, and by discussing the causes, formation process, and migration pattern of starfish outbreaks in northern China. The early life history stage drives starfish outbreak. The increases of larval survival rate is the key leading to population outbreak. Population connectivity is the vital clue to reveal the source and dispersal of starfish populations. On this basis, we proposed several scientific and technical issues that should be addressed urgently, including the determination of the outbreak threshold, the traceability of starfish population, and the methods of monitoring, early warning and control. It would provide insight into the research on the mechanism of starfish outbreaks and the theoretical support for formulating prevention and treatment strategies for starfish outbreaks in northern China. | Disease Outbreaks |
Three calcium antagonists, diltiazem, flunarizine and verapamil stimulated human sperm motility in vitro. Among them, diltiazem induced the largest amplitude of motility increase. The concentration-response curve of diltiazem was similar in shape to those of calcium chelators. EGTA, a calcium chelator, potentiated the stimulatory effect of diltiazem while A23187, a calcium ionophore, antagonized it. These observations supported our previous hypothesis that an increased concentration of calcium ion was detrimental to human sperm motility. Whether calcium antagonists could be used in the treatment of subfertile patients awaits further investigation. | Prenylamine |
Selecting the optimal treatment for transposition of the great arteries with pulmonary stenosis is a challenge. The Rastelli procedure has long been the method of choice, but it carries the risk of subaortic obstruction. The dysplastic pulmonary valve, which cannot function under systemic pressure, can sometimes be recycled in the pulmonary position. "En bloc" rotation of the outflow tracts has been proposed for treatment of complex transposition of the great arteries and is demonstrated in the following videos. It is a technically demanding procedure and in this tutorial we provide a step-by-step presentation of its technique and the surgical options." | Transposition of Great Vessels |
Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17beta-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials. | Vitex |
Since their discovery almost two decades ago, interleukin-17-producing CD4(+) T cells (T(H)17 cells) have been implicated in the pathogenesis of multiple autoimmune and inflammatory disorders. In addition, T(H)17 cells have been found to play an important role in tissue homeostasis, especially in the intestinal mucosa. Recently, the use of single-cell technologies, along with fate mapping and various mutant mouse models, has led to substantial progress in the understanding of T(H)17 cell heterogeneity in tissues and of T(H)17 cell plasticity leading to alternative T cell states and differing functions. In this Review, we discuss the heterogeneity of T(H)17 cells and the role of this heterogeneity in diverse functions of T(H)17 cells from homeostasis to tissue inflammation. In addition, we discuss T(H)17 cell plasticity and its incorporation into the current understanding of T cell subsets and alternative views on the role of T(H)17 cells in autoimmune and inflammatory diseases. | T-Lymphocyte Subsets |
BACKGROUND: Electronic health records (EHRs) are increasingly available and this was expected to reduce healthcare costs and medical errors. This promise has not been realized because healthcare professionals are unable to use EHRs in a manner that contributes to significant improvements in care, i.e. meaningful. Policymakers now acknowledge that training healthcare professionals in meaningful use is essential for successful EHR implementation. To help educators and policymakers design evidence based educational interventions (i.e. interventions that involve educational activities but no practical lessons) and training (i.e. interventions that involve practical components), we summarized all evidence regarding the efficacy of different educational interventions to improve meaningful use of EHRs. METHODS: We used a predefined search filter to search eight databases for studies that considered an educational intervention to promote meaningful use of EHRs by healthcare professionals. RESULTS: Seven of the 4507 reviewed articles met the in- and exclusion criteria. CONCLUSIONS: These studies suggest that a combination of classroom training, computer-based training and feedback is most effective to improve meaningful use. In addition, the training should be tailored to the needs of the trainees and they should be able to practice in their own time. However, the evidence is very limited and we recommend that governments, hospitals and other policymakers invest more in the development of evidence based educational interventions to improve meaningful use of EHRs. | Meaningful Use |
Despite progress in modern surgery, the choice of the surgical procedure of rectal prolapse is regarded with controversy. Selection criteria between the abdominal or perineal approach or between rectopexy and resection rectopexy are not yet proven. This article gives a review of the literature about rectal prolapse and an analysis of the outcome of posterior rectopexy and resection rectopexy--partly conventionally and partly laparoscopically--in 25 patients with rectal prolapse III degrees and IV degrees. All except for one patient were examined during a mean follow-up of 5.5 (3.1) years for the rectopexy group and 2.1 (0.7) years for the resection rectopexy group. Recurrence occurred in one patient in each group respectively. There was no significant difference concerning the continence function (p = 0.32) and constipation (p = 0.36) between both groups. No mesh-related complications such as infection, fistula or rectum stenosis were observed. According to the review of the literature and our data, we believe that the choice of the operative procedure for rectal prolapse should be based on individual criteria. Fit patients should be offered laparoscopic procedures such as resection rectopexy and rectopexy without colonic resection. | Rectal Prolapse |
BACKGROUND: Hemispheric disconnection represents a challenging and major epilepsy surgical procedure. This procedure in experienced hands offers excellent results in terms of seizure outcomes, especially for hemispheric pathologies such as Rasmussen's encephalitis, hemispheric dysplasias, hemimegalencephaly. The technique of hemispherotomy has witnessed various modifications over the years, beginning from anatomical hemispherectomy to the current era of minimally invasive functional hemispheric disconnections. OBJECTIVE: This study aimed to describe the technique of performing endoscopic vertical hemispherotomy using interhemispheric corridor developed by the senior author. MATERIALS AND METHODS: A 12-year-old girl with seizure onset at the age of 10 years presented with an aura of fear and nausea followed by tonic deviation of eyes to the right and blinking with speech arrest. There were tonic-clonic movements of the right-sided limbs along with ictal spitting and occasional deviation of the angle of mouth to the right. The patient had loss of awareness for the event along with postictal confusion lasting few minutes. RESULTS: Video electroencephalography (VEEG) revealed left parietocentral and left temporal localization. Serial magnetic resonance imaging (MRI) brain over 3 years revealed progressive left hemispheric changes suggestive of Rasmussen's encephalitis. The patient underwent left-sided endoscopic hemispherotomy. At 2 years follow-up, the patient is seizure-free (ILAE [International League Against Epilepsy] Class 1). CONCLUSION: Endoscopic hemispherotomy using the interhemispheric approach is an elegant, minimally invasive, reproducible, safe, and efficacious technique. | Hemimegalencephaly |
The porphyrias are a group of inherited disorders that result in defects in the enzymes of the haem biosynthetic pathway, causing photosensitive bullous skin eruptions or abdominal and neurological attacks. Enzymatic defects result in specific porphyrin excretory patterns that are diagnosed biochemically and can be confirmed by genetic testing. Defects in the coproporphyrinogen oxidase (CPOX) enzyme result in the autosomal dominant hereditary coproporphyria. Multiple mutations have been identified in the CPOX gene and incomplete penetrance is noted. Latent carriers without clinical evidence of disease are at risk of life-threatening attacks. Porphyria cutanea tarda may be inherited, but is more commonly acquired. Occasionally two forms of porphyria may co-exist. The importance of genetic testing is discussed. | Coproporphyria, Hereditary |
In this study we have investigated the features of the glass transition relaxation of indomethacin using Differential Scanning Calorimetry (DSC). The purpose of this work is to provide an estimation of the activation energy at the glass transition temperature, as well as of the fragility index, of amorphous indomethacin from DSC data. To do so, the glass transition temperature region of amorphous indomethacin was characterized in both cooling and heating regimes. The activation energy for structural relaxation (directly related to glass fragility) was estimated from the heating and cooling rate dependence of the location of the DSC profile of the glass transition. The obtained results were similar in the heating and in the cooling modes. The results on the fragility index of indomethacin obtained in the present study, m = 60 in the cooling mode and m = 56 in the heating mode, are compared with other values previously published in the literature." | Calorimetry, Differential Scanning |
Lentiviruses are known to encode factors which trans activate expression from the viral long terminal repeat (LTR); the primary trans activator is the tat gene product. One of the putative accessory genes (tat) of the bovine immunodeficiency-like virus (BIV) bears sequence similarity to other lentivirus tat genes. This finding suggests that BIV may encode a trans-activating protein capable of stimulating LTR-directed gene expression. To test this hypothesis in vitro, BIV LTR-chloramphenicol acetyltransferase (CAT) reporter gene plasmids were constructed and transfected into three cell lines established from canine, bovine, or lapine tissues that are susceptible to BIV infection. The level of BIV LTR-directed CAT gene expression was significantly elevated in BIV-infected cells compared with uninfected cells. The relatively high basal-level expression of BIV LTR-CAT in uninfected canine and bovine cell lines suggests that cellular factors play a role in regulating BIV LTR-directed gene expression. Additionally, by using a clonal canine cell line in which the BIV LTR-CAT plasmid is stably expressed, BIV LTR-directed CAT expression is elevated 15- to 80-fold by cocultivation with BIV-infected cells, supporting the notion that BIV encodes a trans activator. The relative specificity of this viral activation was assessed by coculturing the clonal BIV LTR-CAT cell line with bovine leukemia virus- or bovine syncytial virus-infected cells; these bovine retroviruses increased expression from the BIV LTR only two- to threefold. Thus, BIV LTR regulatory elements in infected cells, like those of human immunodeficiency virus type 1 and other lentiviruses, are trans activated, presumably through the action of a Tat-like protein and cellular factors. | Lentiviruses, Bovine |
The interhemispheric subdural hematomas (ISHs) are located along the whole interhemispheric scissure. The ISHs are a rare complication of head traumas. Possible predisposing factors such as coagulopathies, alcohol abuse or anticoagulant therapy are favouring factors. ISHs are rarely accompanied by changes in consciousness and it usually manifests itself with signs of "Falx Syndrome" (controlateral monoparesis of lower extremity or controlateral hemiparesis with lower limb weakness predominating). The treatment can consist of conservative observation or craniotomy and is dictated by the neurological evolution. In literature are described 140 cases since 1940 including our two conservatively managed patients. The salient aspects of ISHs are discussed in an analysis of the pertinent literature." | Hematoma, Subdural, Intracranial |
Fungi produce pigments and acids, generating particular local conditions which modify the physicochemical properties of materials. The aims of this work are (i) to investigate bioadhesion, foxing production and biofilm formation by Scopulariopsis sp. and Fusarium sp. isolated from document collections under laboratory conditions; (ii) to verify attack on cellulose fibres and (iii) to study the possibility of reducing fungal growth using natural products. Biofilm formation and extracellular polymeric substance (EPS) production by fungi were demonstrated in laboratory assays and by scanning electron microscopy (SEM) observations. The biocidal activity of two essential oils of Origanum vulgare L. and Thymus vulgaris L. was evaluated using the microatmosphere method. SEM observations showed that these strains were able to attach to paper and form biofilms, causing damage on them, which demonstrates the biodeterioration ability of these microorganisms. Scopulariopsis sp. and Fusarium sp. isolated from paper books showed the formation of fox-like reddish-brown colour spots, attack to the paper structure and pigment production on aged paper samples. The strains tested produced a decrease in the pH of one unit. This would substantiate the effect of the strains in paper biodeterioration. The microatmosphere method showed that volatile compounds of the essential oils have antifungal activity. | Scopulariopsis |
The Gram-positive bacterium Rhodococcus sp. strain RHA1, naturally containing the biphenyl pathway, was electroporated with a broad host range plasmid containing the 4-chlorobenzoate (4-CBA) degradation operon (fcb) isolated from Arthrobacter globiformis strain KZT1. The recombinant strain grew in medium containing 4-CBA and 4-chlorobiphenyl (4-CB) as the only source of carbon, with stoichiometric release of chloride and a molar growth yield on 4-CB that suggested utilization of both biphenyl rings. In resting cell assays, similar rates of degradation were observed for wild-type and recombinant strains for the most common eight congeners from the anaerobic dechlorination of Aroclor 1242, but the recombinant strain accumulated lower amounts of chlorinated meta-cleavage products and no 4-CBA. Recombinant cells inoculated at 10(4) cells/g into nonsterile soil amended with 4-CB grew to 6-10(5) cells/g, a density consistent with the 4-CB consumed. 4-CB was removed only in the inoculated soil, and the recombinant strain did not grow in the same soil when it was not amended with 4-CB. The fcb operon remained stable in the recombinant strain reisolated from soil after 60 days. This work provides proof of concept that a Rhodococcus strain constructed to grow on a PCB would grow in nonsterile soil if the appropriate chlorobiphenyl is available. | Chlorobenzoates |
The selectivity of synovial fluid protein adsorption onto ultra-high molecular weight polyethylene (UHMWPE) and alumina (Al(2)O(3)), and in particular the ability of glycoproteins to adsorb in the presence of all the other synovial fluid proteins, was investigated by means of fluorescence microscopy and gel electrophoresis (SDS-PAGE). The non-specific nature of protein adsorption from synovial fluid indicated that the lubrication of artificial hip-joint materials may not be attributable to a single protein as has been frequently suggested. The friction behavior of polyethylene (PE) sliding against Al(2)O(3) in solutions of bovine serum albumin (BSA), alpha-1-acid glycoprotein (AGP) and alpha-1-antitrypsin (A1AT) was investigated by means of colloidal probe atomic force microscopy. BSA was shown to be a poorer boundary lubricant than the phosphate buffered saline used as a control. This was attributed to denaturation of the BSA upon adsorption, which provided a high-shear-strength layer at the interface, impairing the lubrication. Interestingly, both the glycoproteins AGP and A1AT, despite their low concentrations, improved lubrication. The lubricating properties of AGP and A1AT were attributed to adsorption via the hydrophobic backbone, allowing the hydrophilic carbohydrate moieties to be exposed to the aqueous solution, thus providing a low-shear-strength fluid film that lubricated the system. The amount of glycoprotein adsorbed on hydrophobic surfaces was determined by means of optical waveguide lightmode spectroscopy (OWLS), allowing conclusions to be drawn about the conformation of the glycan residues following adsorption. | Synovial Fluid |
Single and ternary solute gas phase adsorption isotherms were conducted in this study to evaluate the effectiveness of a simple constant volume method, which was utilized by using Tedlar gas sampling bags as a constant volume batch reactor. For this purpose, gas phase adsorption of toluene, methyl ethyl ketone (MEK), and methyl isobutyl ketone (MIBK) on two types of activated carbons, BPL-bituminous base and OVC--coconut base, were investigated. For the single solute adsorption, the experimental adsorption data were found to be well correlated with Freundlich and Myers adsorption equations. The pore size distribution of adsorbents was found to affect their adsorption capacities; its effect was dependant on the solute concentration. The ternary adsorption experimental isotherms were accurately predicted by using the well-known model, i.e., ideal adsorbed solution theory (IAST). | Methyl n-Butyl Ketone |
Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. We studied the activation state of classical and alternative pathways of complement during the acute phase of Shiga toxin-associated HUS by performing a prospective study of 18 patients and 17 age-matched healthy controls to evaluate C3, C3c, C4, C4d, Bb and SC5b-9 levels. SC5b-9 levels were increased significantly in all patients at admission compared to healthy and end-stage renal disease controls, but were significantly higher in patients presenting with oliguria compared to those with preserved diuresis. C3 and C4 levels were elevated significantly at admission in the non-oliguric group when compared to controls. No significant differences were found for C4d values, whereas factor Bb was elevated in all patients and significantly higher in oliguric patients when compared to both controls and non-oliguric individuals. A positive and significant association was detected when Bb formation was plotted as a function of plasma SC5b-9 at admission. Bb levels declined rapidly during the first week, with values not significantly different from controls by days 3 and 5 for non-oligurics and oligurics, respectively. Our data demonstrate the activation of the alternative pathway of complement during the acute phase of Stx-associated HUS. This finding suggests that complement activation may represent an important trigger for the cell damage that occurs during the syndrome." | Complement C3-C5 Convertases, Alternative Pathway |
BACKGROUND: Reindeer herding and husbandry is a traditional and important livelihood in Fennoscandia, and about 200,000 semi-domesticated reindeer are herded in Finland. Climatic changes, leading to ice-locked winter pastures, and encroachment of pasture-land have led to changes in reindeer husbandry, increasing the extent of supplementary or full ration feeding, which has become very common in Finland. Keeping reindeer in corrals or gathering them at permanent feeding sites will increase nose-to-nose contact between animals and they may be exposed to poor hygienic conditions. This may impact the epidemiology of infectious diseases, such as viral infections. The aim of this study was to investigate Finnish semi-domesticated reindeer for exposure to viral pathogens. Blood samples were collected from 596 reindeer (358 calves, 238 adults) in 2015, from nine reindeer slaughterhouses, representing most of the reindeer herding regions in Finland. Plasma samples were investigated for antibodies against a selection of known and potential reindeer viral pathogens by using enzyme linked immunosorbent assays (ELISA). RESULTS: The screening suggested that alphaherpesvirus and gammaherpesvirus (malignant catarrhal fever virus group; MCFV) were enzootic in the reindeer population, with a seroprevalence of 46.5% (range at slaughterhouse level 28.6-64.3%) and 29.0% (range 3.5-62.2%), respectively. Whereas the seroprevalence was significantly higher for alphaherpesvirus among adult reindeer (91.2%) as compared to calves (16.8%), no age difference was revealed for antibodies against gammaherpesvirus. For alphaherpesvirus, the seroprevalence in the northernmost region, having the highest animal density (animals/km(2)), was significantly higher (55.6%) as compared to the southernmost region (36.2%), whereas the seroprevalence pattern for gammaherpesvirus indicated the opposite, with 8.1% in the north and 50.0% in the south. Four reindeer (0.7%) had antibodies against Pestivirus, whereas no antibodies were detected against Bluetongue virus or Schmallenbergvirus. CONCLUSIONS: Alphaherpesvirus and gammaherpesvirus (MCFV) seems to be enzootic in the Finnish reindeer population, similar to other reindeer herds in Fennoscandia, whereas the exposure to Pestivirus was low compared to findings in Norway and Sweden. The ongoing changes in the reindeer herding industry necessitate knowledge on reindeer health and diseases that may impact animal welfare and health of reindeer as well as the economy of the reindeer herding industry. | Tundra |
Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the intermediate filament network, cytolysis of the basal layer of the epidermis, or attenuation of hemidesmosomal/desmosomal components. Mutations in keratins 5/14 or in other genes that encode associated proteins induce structural disarrangements of different strengths depending on their locations in the genes. Keratin aggregates display impaired dynamics of assembly and diminished solubility and appear to be the trigger for endoplasmic reticulum (ER) stress upon being phosphorylated by MAPKs. Global changes in cellular signaling mainly occur in cases of severe dominant EBS mutations. The spectrum of changes initiated by phosphorylation includes the inhibition of proteasome degradation, TNF-alpha signaling activation, deregulated proliferation, abnormal cell migration, and impaired adherence of keratinocytes. ER stress also leads to the release of proinflammatory danger-associated molecular pattern (DAMP) molecules, which enhance avalanche-like inflammation. Many instances of positive feedback in the course of cellular stress and the development of sterile inflammation led to systemic chronic inflammation in EBS. This highlights the role of keratin in the maintenance of epidermal and immune homeostasis. | Keratin-5 |
PURPOSE: Bladder exstrophy and epispadias complex is a rare congenital malformation that may have detrimental effects on sexual function. We evaluated sexual function of patients with bladder exstrophy and epispadias complex using validated questionnaires and compared the results with age matched controls. MATERIALS AND METHODS: Patients with bladder exstrophy and epispadias complex treated between 1956 and 1992 were identified from our hospital operative database. A total of 63 patients were mailed questionnaires up to 3 times, resulting in 32 replies (51%). Men were mailed the International Index of Erectile Function-15 questionnaire and women were mailed the Female Sexual Function Index questionnaire, and all patients were asked auxiliary questions regarding children, satisfaction with external genitalia and urinary continence. RESULTS: There were no differences in sexual function between sexually active men with bladder exstrophy and epispadias complex and age matched controls on different erectile function domain scores according to the International Index of Erectile Function-15 questionnaire. The Female Sexual Function Index questionnaire among women yielded comparable results on different domain scores, except for median total score, which was higher in patients (33.6, IQR 29.4 to 34.9) than in controls (30.1, IQR 26.4 to 32.4, p = 0.049), suggesting better sexual function in patients with bladder exstrophy and epispadias complex. A greater proportion of patients with bladder exstrophy and epispadias complex had not become sexually active, compared to controls (35% vs 11%, p = 0.008). Patients with bladder exstrophy and epispadias complex were less likely to have children than controls (22% vs 45%, p = 0.021). CONCLUSIONS: Men and women with bladder exstrophy and epispadias complex had good long-term outcomes on erectile and general sexual function tests. However, there is a likelihood that these individuals start their sexual life later than the general population, and fewer have children compared to controls. | Bladder Exstrophy |
Clinical and arteriographic features of 12 patients with external iliac artery fibrodysplasia are reviewed. These lesions usually occur in patients having arterial fibrodysplasia elsewhere, attesting to the fact that they represent a generalized arteriopathy. Occasionally they occur in association with severe atherosclerosis. External iliac artery fibrodysplasia exhibits the classic corrugated string-of-beads" angiographic appearance in the majority of patients. The pattern of aneurysmal dilatation of the external iliac arteries in one patient and the aorta and common iliac and internal iliac arteries in another with diffuse arterial fibrodysplasia has not been previously reported. Three patients had symptoms directly referable to external iliac artery fibrodysplasia. The lesions may be symptomatic when the arterial lumen is sufficiently compromised to reduce blood flow or when superimposed thrombosis and/or embolization occurs." | Fibromuscular Dysplasia |
The light and electron microscopic characteristics of an adenofibroma of the rete testis in a 51-year-old man are described. The tumor was 5.5 cm in greatest diameter and situated in the anterior superior portion of the right testis. It was composed mainly of mesenchymal and secondary epithelial proliferation. Long slit-like spaces and short tubules lined by a layer of epithelial cells were seen in the mesenchymal tissue. The epithelium was histochemically and ultrastructurally similar to that of the rete testis, and the tumor was considered to be of rete testis origin. | Adenofibroma |
Nearly all recurrent microdeletion/duplication syndromes described to date are characterized by the presence of flanking low copy repeats that act as substrates for non-allelic homologous recombination (NAHR) leading to the loss, gain or disruption of dosage sensitive genes. We describe an identical 1.11 Mb heterozygous deletion of 14q32.2 including the DLK1/GTL2 imprinted gene cluster in two unrelated patients. In both patients, the deleted chromosome 14 was of paternal origin, and consistent with this both exhibit clinical features compatible with uniparental disomy (UPD) (14)mat. Using a high-resolution oligonucleotide array, we mapped the breakpoints of this recurrent deletion to large flanking (TGG)(n) tandem repeats, each approximately 500 bp in size and sharing > or =88% homology. These expanded (TGG)(n) motifs share features with known fragile sites and are predicted to form strong guanine quadruplex secondary structures. We suggest that this recurrent deletion is mediated either by NAHR between the TGG repeats, or alternatively results from their inherent instability and/or strong secondary structure. Our results define a recurrent microdeletion of the 14q32.2 imprinted gene cluster mediated by flanking (TGG)(n) repeats, identifying a novel mechanism of recurrent genomic rearrangement. Our observation that expanded repeats can act as catalysts for genomic rearrangement extends the role of triplet repeats in human disease, raising the possibility that similar repeat structures may act as substrates for pathogenic rearrangements genome-wide." | Trinucleotide Repeat Expansion |
The 15 human kallikrein-related peptidases (KLKs) are clinically important biomarkers and therapeutic targets of interest in inflammation, cancer, and neurodegenerative disease. KLKs are secreted as inactive pro-forms (pro-KLKs) that are activated extracellularly by specific proteolytic release of their amino-terminal pro-peptide, and this is a key step in their functional regulation. Physiologically relevant KLK regulatory cascades of activation have been described in skin desquamation and semen liquefaction, and work by a large number of investigators has elucidated pairwise and autolytic activation relationships among the KLKs with the potential for more extensive activation cascades. More recent work has asked whether functional intersection of KLKs with other types of regulatory proteases exists. Such studies show a capacity for members of the thrombostasis axis to act as broad activators of pro-KLKs. In the present report, we ask whether such functional intersection is possible between the KLKs and the members of the matrix metalloproteinase (MMP) family by evaluating the ability of the MMPs to activate pro-KLKs. The results identify MMP-20 as a broad activator of pro-KLKs, suggesting the potential for intersection of the KLK and MMP axes under pathological dysregulation of MMP-20 expression. | Matrix Metalloproteinase 20 |
Infectious laryngotracheitis (ILT), fowlpox (FP), and reticuloendotheliosis are important poultry diseases caused by gallid herpesvirus 1 (ILTV), fowlpox virus (FWPV), and reticuloendotheliosis virus (REV), respectively. Coinfections with ILTV and FWPV occur naturally in chickens, and FP in its more virulent wet form is characterized by diphtheritic lesions and easily confused with ILT. Moreover, the insertion of only partial REV-LTR or a nearly full-length REV into the FWPV genome, located between the ORF 201 and ORF 203, has increased recently in wild-type field FWPV isolates. Therefore, it is critical to detect ILTV, FWPV, REV-integrated FWPV, and REV early and accurately. In this study, we successfully developed a multiplex PCR assay for the simultaneous detection of ILTV, FWPV, REV-integrated FWPV, and REV, and the detection limits was 1 x 5(4) copies/tube. When used to test clinical samples, the results of the multiplex PCR were in 100% agreement with singleplex PCRs and sequencing. This new multiplex PCR is a simple, rapid, sensitive, speci fi c, and cost-effective method for detection of 4 viruses in clinical specimens. | Fowlpox virus |
Nutritional needs are defined as the amount and chemical form of a nutrient needed to support normal health, growth and development without disturbing the metabolism of other nutrients. Nutrient intake recommendations are based on the estimated average requirement (EAR) of a population group. Enteral and parenteral needs differ for many nutrients because of differences in bioavailability and utilization. Assuming a near-normal distribution of nutrient needs, the reference nutrient intake (RNI--also called population reference intake or recommended dietary allowance) is equal to the EAR plus two standard deviations of the distribution, with the exception of energy intake where the reference intake is equal to the EAR. The upper level (UL) is the highest level of intake where no untoward effects can be detected in virtually all individuals in a specific population group. The acceptable range of intakes (AR) is the range from the EAR to the UL that is considered safe, however preterm infants are not a homogeneous population thus intake often needs to be individualized based on clinical condition and developmental stage." | Recommended Dietary Allowances |
BACKGROUND: This study provides a comprehensive analysis of total hip arthroplasty (THA) revisions in the U.S. from 2007 to 2013. METHODS: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify all THA revisions in the Nationwide Inpatient Sample (NIS) from 2007 to 2013. The diagnoses leading to the revisions, types of revisions, major inpatient complications, and hospital and patient characteristics were compared between 2007 and 2013. Multivariable logistic regression models were used to calculate adjusted odds ratios (ORs) for complications in 2013 versus 2007. RESULTS: This study identified 320,496 THA revisions performed between 2007 and 2013. From 2007 to 2013, the THA revision rate adjusted for U.S. population growth increased by 30.4% in patients between 45 and 64 years of age and decreased in all other age groups. The rate of surgically treated THA dislocations decreased by 14.3% from 2007 to 2013 (p < 0.0001). The mean length of the hospital stay and hospital costs for THA revision were significantly lower in 2013 than in 2007 (4.6 versus 5.8 days and $20,463 versus $25,401 both p < 0.0001). A multivariable model showed that the odds of a patient undergoing THA revision having the following inpatient complications were significantly lower in 2013 than in 2007: deep vein thrombosis (OR = 0.57, p = 0.004), pulmonary embolism (OR = 0.45, p = 0.047), myocardial infarction (OR = 0.52, p = 0.003), transfusion (OR = 0.64, p < 0.0001), pneumonia (OR = 0.56, p < 0.0001), urinary tract infection (OR = 0.66, p < 0.0001), and mortality (OR = 0.50, p = 0.0009). Notably, the odds of being discharged to a skilled nursing facility were also lower in 2013 than in 2007 (OR = 0.71, p < 0.0001). CONCLUSIONS: The THA revision rate has significantly increased in patients between 45 and 64 years of age. However, the rate of surgically treated THA dislocations has decreased significantly. This may indicate that evolving techniques and implants are improving stability. The rate of inpatient complications following THA revision also decreased significantly from 2007 to 2013. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence." | Procedures and Techniques Utilization |
To guarantee an adequate food supply for the world's growing population, intensive agriculture is necessary to ensure efficient food production. The use of pesticides helps maintain maximum productivity in intensive agriculture by minimizing crop losses due to pests. However, pesticide contamination of surface waters constitutes a major problem as they are resistant to degradation and soluble enough to be transported in water. In recent years, all groups of pesticides defined by the World Health Organization have increased their use and, therefore, their prevalence in the different environmental compartments that can have harmful effects. Despite this effort, there is no rigorous monitoring program that quantifies and controls the toxic effects of each pesticide. However, multiple scientific studies have been published by specialized research groups in which this information is disseminated. Therefore, any attempt to systematize this information is relevant. This review offers a current overview of the presence and distribution of the most widely-used pesticides (insecticides, herbicides, and fungicides) by crop type and an evaluation of the relationships between their uses and environmental implications in Spain. The data demonstrated that there are correlations between the presence of specific pesticides used in the main crops and their presence in the environmental compartments. We have found preliminary data pointing to existing associations between specific pesticides used in the main crops and their presence in environmental compartments within different geographical areas of Spain; this should be the subject of further investigation. | Agrochemicals |
Plasma adrenocorticotropic hormone (ACTH) concentration is used in the diagnosis of pituitary pars intermedia dysfunction (PPID) in horses. We enrolled 10 horses, 5 PPID-positive and 5 PPID-negative, in our study, September 20-22, 2016. On day 0, 5 mL of whole blood was collected into each of 6 EDTA tubes and immediately placed in a refrigerator at 7 degrees C. One tube was centrifuged within 15 min of collection, followed by centrifugation of one tube from each horse at 4, 8, 12, 24, and 36 h following collection. At each time, centrifuged plasma was pipetted into 1.5-mL polypropylene tubes and stored at -80 degrees C. None of the plasma samples were turbid, hemolyzed, or icteric. Plasma was shipped frozen with cold packs overnight to the Animal Health Diagnostic Center of Cornell University (Ithaca, NY) for analysis. The percent change from baseline (PCFB) was reported to standardize the data given that baseline values differed. The mean PCFB was 2.8 (95% confidence interval: -2.9%, 7.0%). Neither refrigeration of whole blood for up to 36 h prior to centrifugation nor freezing affected plasma ACTH concentrations significantly. | Pituitary Gland, Intermediate |
N-(2,2-Dimethyl-3,4-dihydro-2H-1-benzopyran-4-yl)-4H-1,2,4-benzothiadiazine-3-carboxamides 1,1-dioxides were prepared and evaluated on rat uterus, rat aortic rings and rat pancreatic beta-cells. Pharmacological studies conducted on rat uterus indicated that several of these original hybrid compounds displayed a strong myorelaxant activity. The most active compounds hold a bromine atom at the 6-position of the dihydrobenzopyran ring. Moreover, the compounds failed to display a marked inhibitory effect on insulin secretion and vascular myogenic activity. These features suggest that the 6-bromo compounds could be relatively selective towards the uterine smooth muscle. | Benzothiadiazines |
BACKGROUND: Bifidobacterium breve represents a common member of the infant gut microbiota and its presence in the gut has been associated with host well being. For this reason it is relevant to investigate and understand the molecular mechanisms underlying the establishment, persistence and activities of this gut commensal in the host environment. RESULTS: The assessment of vegetative promoters in the bifidobacterial prototype Bifidobacterium breve UCC2003 was performed employing a combination of RNA tiling array analysis and cDNA sequencing. Canonical -10 (TATAAT) and -35 (TTGACA) sequences were identified upstream of transcribed genes or operons, where deviations from this consensus correspond to transcription level variations. A Random Forest analysis assigned the -10 region of B. breve promoters as the element most impacting on the level of transcription, followed by the spacer length and the 5'-UTR length of transcripts. Furthermore, our transcriptome study also identified rho-independent termination as the most common and effective termination signal of highly and moderately transcribed operons in B. breve. CONCLUSION: The present study allowed us to identify genes and operons that are actively transcribed in this organism during logarithmic growth, and link promoter elements with levels of transcription of essential genes in this organism. As homologs of many of our identified genes are present across the whole genus Bifidobacterium, our dataset constitutes a transcriptomic reference to be used for future investigations of gene expression in members of this genus. | Bifidobacterium breve |
Genetic parameters for ewes were estimated for stayability (STAY) and productive life (Prodlife). Records from 658,871 animals from 241 seed stock or ram breeder flocks and one research flock were used to estimate parameters for ram breeder flock STAY and Prodlife. These flocks would have a culling policy based on criteria typical of a commercial enterprise, but including culls based on knowledge such as estimated breeding values. A subset of 35,688 of these animals from 4 ram breeder and one research flock was used to infer the animals that might be culled based on the perspective of a commercial flock as these flocks recorded reasons for culling. These data were used to estimate parameters for commercial flock STAY and Prodlife. Heritability for ram breeder flock STAY until age 3 to 6 yr ranged from 0.07 to 0.09. The heritability of commercial flock STAY was similar in yr 5 and 6, but lower at 0.05 (age 3) and 0.07 (age 4). Heritability of Prodlife for ram breeder flock and commercial flock was respectively 0.10 and 0.13. The genetic correlations between ram breeder flock STAY and commercial flock STAY ranged from 0.20 to 0.99. Both STAY and Prodlife were most correlated genetically with the trait number of lambs born, at about 0.4, and to a lesser degree, live weight up to the age of 12 mo for the traits analyzed with lower genetic correlations estimated for the commercial flocks. Live weight at 18 mo and fleece weight had little or no correlation with STAY and Prodlife. From the data set used to estimate genetic parameters from a ram breeder flock, 4,330 animals were genotyped with the Illumina OvineSNP50 BeadChip and the genotypes used to develop genomic predictions via genomic best linear unbiased prediction. The animals used in the training data set were multibreed, but were heavily Romney breed based. The genomic prediction accuracy for ram breeder flock STAY, according to breed, was dependent on sample size and ranged from 0.4 to 0.44 for Romney and 0.26 to 0.4 for Coopworth. Accuracies for Perendale and Composites, for which sample sizes were less, were more variable. This study has derived genetic parameters for STAY and Prodlife and investigated genomic predictions for these traits. As these traits are of low heritability, sex limited and expressed late in life genomic selection will be useful. | Animal Culling |
Catholic healthcare's mission is keeping people healthy, and providers must listen closely to determine their needs in these fast-paced, stressful times. In a society preoccupied with technology and acute care, which has the least overall impact on people's health, providers must implement more preventive strategies. The shift to promoting community health will require diverse, creative approaches. Catholic facilities must offer holistic healing, becoming community resources for children and the elderly. Religious institutes also must prepare for the laity's increasing role in the ministry. Providers must develop initiatives that define Catholic healthcare, such as the Welfare-to-Work Program in St. Louis, which offers women employment opportunities and benefits as a starting point to gain control of their lives. With increased school collaboration, nurses can help children develop good health habits. The guiding vision must be the health of the whole person and the community. Catholic providers must restore public trust and confidence by emphasizing person-centered healthcare. Only by becoming an integral part of the community can Catholic healthcare make a difference in people's lives. | Hospitals, Religious |
Anaplastic thyroid carcinoma is an aggressive form of cancer with no treatment. Angiogenesis inhibitors, such as TNP-470, a synthetic derivative of fumagillin, have been shown to reduce tumor size and increase survival in heterotopic animal models of thyroid cancer. Our goals were to determine the effect of TNP-470 on anaplastic thyroid cancer using an orthotopic murine model, to identify the molecular pathways of TNP-470 actions on endothelial cells, and to determine the non-endothelial tumor effects of TNP-470. We injected human anaplastic thyroid carcinoma cells (DRO'90) into the thyroid glands of nude mice. Mice received TNP-470 (30 mg/kg) s.c. for 6 weeks. TNP-470 prolonged survival and reduced liver metastases. TNP-470 had direct cytotoxic effects on anaplastic thyroid carcinoma cells in vitro and in vivo. Paradoxically, TNP-470 increased vascular endothelial growth factor secretion from tumor cells in vitro and in vivo. However, there was no associated increase in tumor microvessel density. In endothelial cells, TNP-470 prevented vascular endothelial growth factor-induced endothelial permeability, intercellular gap formation, and ruffle formation by preventing Rac1 activation." | O-(Chloroacetylcarbamoyl)fumagillol |
The objective of this work was to quantify the heat loss by cutaneous evaporation of goats in an equatorial semi-arid environment. The latent heat loss from the body surfaces of these ten undefined breed goats was measured using a ventilated capsule in sun and shade and in the three body regions (neck, flank and hindquarters). Skin samples from these three regions were histologically analyzed to relate the quantity of sweat glands, the area of sweat glands and the epithelium thickness of each of these regions to the heat loss by cutaneous evaporation of the examined goats. The epithelium thickness that was measured varied significantly for body regions with different quantities and areas of sweat glands (P < 0.01). Among the body regions that were examined, the samples from the neck demonstrated the highest epithelium thickness (16.23 +/- 0.13 mum). However, the samples of sweat glands from the flank had the biggest area (43330.51 +/- 778.71 mum(2)) and quantity per square centimeter (390 +/- 9 cm(-2)). After the animals were exposed to sun, the flanks lost the greatest amount of heat by cutaneous evaporation (73.03 +/- 1.75 W m(-2)) and possessed the highest surface temperatures (39.47 +/- 0.18 degrees C). The histological characteristics may have influenced the heat loss by cutaneous evaporation that was observed in the flank region after the animals were exposed to sun. | Cutaneous Elimination |
Hepatic artery aneurysms are a rare phenomenon but their diagnosis and prompt treatment are imperative due to a high risk of mortality and complications. Appropriate management depends on patient characteristics, anatomical location of the aneurysm, operative risk and collateral arterial supply. Management options include surgical and endovascular approaches. The endovascular approach has gained popularity over recent years as it is an effective and less invasive alternative to surgical management. In this case report, we present a giant common hepatic artery aneurysm and its successful endovascular management. The patient had a complete resolution of symptoms after the procedure and remained well 8 months postprocedure. | Hepatic Artery |
The disciplines of medicine, law and ethics frequently impinge upon each other in clinical practice but are seldom given the opportunity to come together in dialogue. It was with this aim that senior professionals from law and medicine met at the fifth Northern Region Paediatric Colloquium. An added dimension to the ethical viewpoint was brought to the meeting by the attendance of local religious leaders for the first time. We report the proceedings of the Colloquium, which adopted the usual format of clinical case presentation followed by discussion. | Pediatrics |
Although the evolutionary causes and consequences of pathogen avoidance have been gaining increasing interest, there has been less attention paid to the proximate neurobiological mechanisms. Animals gauge the infection status of conspecifics and the threat they represent on the basis of various sensory and social cues. Here, we consider the neurobiology of pathogen detection and avoidance from a cognitive, motivational and affective state (disgust) perspective, focusing on the mechanisms associated with activating and directing parasite/pathogen avoidance. Drawing upon studies with laboratory rodents, we briefly discuss aspects of (i) olfactory-mediated recognition and avoidance of infected conspecifics; (ii) relationships between pathogen avoidance and various social factors (e.g. social vigilance, social distancing (approach/avoidance), social salience and social reward); (iii) the roles of various brain regions (in particular the amygdala and insular cortex) and neuromodulators (neurotransmitters, neuropeptides, steroidal hormones and immune components) in the regulation of pathogen avoidance. We propose that understanding the proximate neurobiological mechanisms can provide insights into the ecological and evolutionary consequences of the non-consumptive effects of pathogens and how, when and why females and males engage in pathogen avoidance. | Avoidance Learning |
The Department of Neurosurgery at Seoul National University College of Medicine is one of the oldest neurosurgical departments in Korea, and it is a center of academic leadership in neurosurgery. In September 1957, the department was established by Bo Sung Sim, and it has produced many leaders of neurosurgery in Korea. Chairmen Bo Sung Sim, Kil Soo Choi, Dae Hee Han, and Byung-Kyu Cho each brought special skills and talents to the development of the department. The current and fifth chair, Hyun Jib Kim, assumed the chairmanship in July 2000. The department comprises 11 full-time faculty members, 5 fellows, and 14 residents. More than 1,700 neurosurgical procedures are performed annually in four operating theaters. A gamma knife was installed in 1997, and approximately 200 gamma knife procedures are performed each year. In addition to clinical activities, research and education for graduate and postgraduate students are also particular strengths of the department. This article traces the clinical, academic, and scientific development of the department, its present activities, and its future direction. | Surgery Department, Hospital |
BACKGROUND: Bilateral facial palsy is a rare clinical entity caused by myriad disparate conditions requiring different treatment paradigms. Lyme disease, Guillain-Barre syndrome, and leukemia are several examples. In this article, the authors describe the cause, the initial diagnostic approach, and the management of long-term sequelae of bilateral paralysis that has evolved in the authors' center over the past 13 years. METHODS: A chart review was performed to identify all patients diagnosed with bilateral paralysis at the authors' center between January of 2002 and January of 2015. Demographics, signs and symptoms, diagnosis, initial medical treatment, interventions for facial reanimation, and outcomes were reviewed. RESULTS: Of the 2471 patients seen at the authors' center, 68 patients (3 percent) with bilateral facial paralysis were identified. Ten patients (15 percent) presented with bilateral facial paralysis caused by Lyme disease, nine (13 percent) with Mobius syndrome, nine (13 percent) with neurofibromatosis type 2, five (7 percent) with bilateral facial palsy caused by brain tumor, four (6 percent) with Melkersson-Rosenthal syndrome, three (4 percent) with bilateral temporal bone fractures, two (3 percent) with Guillain-Barre syndrome, one (2 percent) with central nervous system lymphoma, one (2 percent) with human immunodeficiency virus infection, and 24 (35 percent) with presumed Bell palsy. Treatment included pharmacologic therapy, physical therapy, chemodenervation, and surgical interventions. CONCLUSIONS: Bilateral facial palsy is a rare medical condition, and treatment often requires a multidisciplinary approach. The authors outline diagnostic and therapeutic algorithms of a tertiary care center to provide clinicians with a systematic approach to managing these complicated patients. | Facial Paralysis |
A bacterial strain designated 11N27(T) was isolated from an agricultural soil sample. Cells of this strain were Gram-reaction-variable, facultatively anaerobic, endospore-forming, white-pigmented, peritrichously flagellated and hydrolysed xanthine. The major fatty acids of strain 11N27(T) were anteiso-C15 : 0, iso-C16 : 0 and C16 : 0. The polar lipid profile contained phosphatidylethanolamine, two unknown phospholipids, two unknown aminolipids, one unknown aminophospholipid and two unknown polar lipids. The G+C content of the genomic DNA of strain 11N27(T) was 50.3 mol%. MK-7 was the predominant respiratory quinone. meso-Diaminopimelic acid was the diagnostic diamino acid in the peptidoglycan. 16S rRNA gene sequence analysis showed that strain 11N27(T) was phylogenetically related to Paenibacillus mendelii C/2(T) (96.2% sequence similarity) and Paenibacillus sepulcri CMM 7311(T) (96.0%). The genotypic and phenotypic data showed that strain 11N27(T) could be distinguished from phylogenetically related species and that this strain represents a novel species of the genus Paenibacillus. The name Paenibacillus xanthinilyticus sp. nov. is proposed with the type strain 11N27(T)( = KACC 17935(T) = NBRC 109108(T)). | Paenibacillus |
Theophylline is a bronchodilator and respiratory stimulant that is effective in the treatment of acute and chronic asthma, Cheyne-Stokes respirations, and apnea/bradycardia episodes in newborns. It is also used as an adjunct in the treatment of congestive heart failure and acute pulmonary edema, but it has no established efficacy in patients with chronic irreversible airways obstruction. Benefits and risks from theophylline relate directly to serum concentration, which is a function of both dose and elimination characteristics of the drug in an individual patient. When used to treat acute symptoms, an initial loading dose based on a mean volume of distribution is required to rapidly obtain maximum bronchodilator effect. Because of large interpatient differences in elimination, constant intravenous infusion rates for continued therapy must be guided by monitoring serum theophylline concentration at intervals until a steady-state serum concentration is reached within the 10-20 micrograms/ml therapeutic range. Intravenous, oral or rectal solutions and plain uncoated tablets are appropriate for acute therapy, while reliably absorbed slow-release formulations offer therapeutic advantages for the management of chronic asthma, particularly in patients with rapid elimination. Dosage for long-term therapy is determined by starting with low doses that allow virtually complete acceptance of the medication followed by gradual increases, if tolerated, at three day intervals until mean age-specific doses are reached. Subsequent adjustment in dosage regimens are then based upon serum concentration measurements. Most clinical laboratories now measure theophylline, and newer systems have been developed to provide emergency results within minutes at a reasonable cost. In cases of theophylline poisoning, the drug must be rapidly removed to prevent life-threatening toxicity. When serum concentrations are in excess of 60 micrograms/ml charcoal hemoperfusion dialysis may be indicated, even in the absence of obvious signs of toxicity. | Theophylline |
This article describes acetylcholinesterase (AChE), an enzyme involved in parasympathetic neurotransmission, its activity, and how its inhibition can be pharmacologically useful for treating dementia, caused by Alzheimer's disease, or as a warfare method due to the action of nerve agents. The chemical concepts related to the irreversible inhibition of AChE, its reactivation, and aging are discussed, along with a relationship to the current international legislation on chemical weapons. | GPI-Linked Proteins |
Transcription factors (TFs) are proteins that bind to specific DNA sequences, thereby playing crucial roles in gene-expression regulation through controlling the transcription of genetic information from DNA to RNA. Transcription cofactors and chromatin remodeling factors are also essential in the gene transcriptional regulation. Identifying and annotating all the TFs are primary and crucial steps for illustrating their functions and understanding the transcriptional regulation. In this study, based on manual literature reviews, we collected and curated 72 TF families for animals, which is currently the most complete list of TF families in animals. Then, we systematically characterized all the TFs in 50 animal species and constructed a comprehensive animal TF database, AnimalTFDB. To better serve the community, we provided detailed annotations for each TF, including basic information, gene structure, functional domain, 3D structure hit, Gene Ontology, pathway, protein-protein interaction, paralogs, orthologs, potential TF-binding sites and targets. In addition, we collected and annotated transcription cofactors and chromatin remodeling factors. AnimalTFDB has a user-friendly web interface with multiple browse and search functions, as well as data downloading. It is freely available at http://www.bioguo.org/AnimalTFDB/. | Transcription Factors |
Nature has us wired instinctively to be cautious of things that are unknown or unfamiliar. Children may fear the dark, but even as adults we remain afraid of things that go bump in the night. | Ebola Vaccines |
Copolymers were synthesized by ring opening polymerization of l- or d-lactide in the presence of dihydroxyl PEG with molar mass of 6000, 12,000 and 20,000, using zinc lactate as catalyst. Bioresorbable hydrogels were obtained by mixing PLLA-PEG-PLLA and PDLA-PEG-PDLA aqueous solutions due to stereocomplexation between PLLA and PDLA chains. Rheological measurements show that the hydrogels present typical viscoelastic behaviors, although degradation could occur during the gelation process. Thymopentin was taken as a model drug to evaluate the potential of PLA-PEG-PLA hydrogels as carrier of hydrophilic drugs. Various parameters such as copolymer concentration, drug load, copolymer composition and the difference between sol and gel were considered. The release profiles are characterized by an initial burst followed by slower release. Higher copolymer concentration leads to slower release rate and less burst effect due to more compact structure which disfavors drug diffusion. Similarly, higher molar mass of the copolymers disfavors the release of TP5, and hydrogels composed of both PLLA/PEG and PDLA/PEG present slower release rates than single copolymer solutions. In contrast, drug load exhibits little influence on the release profiles due to the high water solubility of TP5. In all cases, nearly 80% of TP5 is released. In vivo studies proved the potential of TP5 containing hydrogels, especially those with a concentration of 25%. Both the CD4(+)/CD8(+) ratio and the morphology of thymus indicate the immunization efficacy of the TP5 release systems based on PLA/PEG hydrogels. | Thymopentin |
Next-generation sequencing (NGS) is transforming clinical research and diagnostics, vastly enhancing our ability to identify novel disease-causing genetic mutations and perform comprehensive diagnostic testing in the clinic. Whole-exome sequencing (WES) is a commonly used method which captures the majority of coding regions of the genome for sequencing, as these regions contain the majority of disease-causing mutations. The clinical applications of WES are not limited to diagnosis; the technique can be employed to help determine an optimal therapeutic strategy for a patient considering their mutation profile. WES may also be used to predict a patient's risk of developing a disease, e.g., type 2 diabetes (T2D), and can therefore be used to tailor advice for the patient about lifestyle choices that could mitigate those risks. Thus, genome sequencing strategies, such as WES, underpin the emerging field of personalized medicine. Initiatives also exist for sharing WES data in public repositories, e.g., the Exome Aggregation Consortium (ExAC) database. In time, by mining these valuable data resources, we will acquire a better understanding of the roles of both single rare mutations and specific combinations of common mutations (mutation signatures) in the pathology of complex diseases such as diabetes.Herein, we describe a protocol for performing WES on genomic DNA extracted from blood or saliva. Starting with gDNA extraction, we document preparation of a library for sequencing on Illumina instruments and the enrichment of the protein-coding regions from the library using the Roche NimbleGen SeqCap EZ Exome v3 kit; a solution-based capture method. We include details of how to efficiently purify the products of each step using the AMPure XP System and describe how to use qPCR to test the efficiency of capture, and thus determine finished library quality. | Exome Sequencing |
Understanding the nutrient composition of kiwifruit is central to discussions of the nutritional value and potential health benefits of kiwifruit. Until recently, there were only limited validated data providing extensive compositional information available as reference values for common commercial cultivars. As a genus, Actinidia is diverse in both form and composition; however, there are several notable compounds that, within the context of fruit, are the signature of Actinidia: vitamin C, actinidin, fiber, vitamin E, and for selected cultivars, the persistence of chlorophyll in the mature fruit. Kiwifruit is also known as a nutritionally dense fruit, based on the level of nutrients present. The high amount of vitamin C in kiwifruit is the primary driver of such nutritional scores. Recently, a new approach to estimating the true energy value of kiwifruit has shown that kiwifruit delivers less available energy relative to other foods than is assumed based on traditional measures of food energy content. This, together with the key nutritional elements of kiwifruit, supports its position as a highly nutritious, low-calorie fruit with the potential to deliver a range of health benefits. | Actinidia |
Post-chemotherapy cognitive impairment, also known as 'chemobrain,' is a neurological condition in which cognitive function is impaired as a result of cancer chemotherapy treatment. In this work, we used fast-scan cyclic voltammetry (FSCV) to measure electrically evoked dopamine release and uptake in whole brain preparations from zebrafish that have been treated with carboplatin, an agent associated with chemobrain. We administered carboplatin by addition to the fish's tank water or their food. One week of treatment with 100 muM carboplatin in the water was needed to significantly impair dopamine release ( approximately 40 % of control); however, only one day of treatment through the zebrafish's food was needed to cause a similar impairment. Atomic absorption spectroscopy measurements suggested that administration through food resulted in higher initial levels of carboplatin compared to water administration, but water administration resulted in an increase over time. Uptake, determined by modeling stimulated release plots, was unaffected. These results are consistent with our previous findings of diminished neurotransmitter release in rats and support a role for zebrafish in chemobrain-related studies. | Carboplatin |
The prevalence of drinking behavior and sex differences were examined. A possible relationship between drinking behavior and drinking refusal self-efficacy (DRSE) also was investigated among a convenience sample of 582 Korean college students (309 men, 273 women). A drinking habit scale (from AUDIT-K) and drinking refusal self-efficacy questionnaire (DRSEQ-R) were administered. Results indicated 74.4% of the students drank alcohol and 80.1% of the students were regular drinkers (> 2 to 4 times per month). There were significant differences in drinking behavior by sex and in the DRSE constructs for current drinking statuses. Drinking behavior was significantly associated with sex and DRSE. The present study offers more information about practical interventions aimed at reasonably controlling the drinking behavior of Korean college students in a university setting. The findings may provide better understanding of Korean students' drinking behavior. | Temperance |
Eight patients sustained a combination of clival epidural hematoma, traumatic sixth cranial nerve palsy (6 NP), and occipitocervical injury. This combination of features has been sparsely described. Whether the hematoma, which represents tectorial membrane injury, is merely a marker for 6 NP and occipitocervical injury or is causative is unresolved, but this imaging finding should alert examiners who note traumatic 6 NP to the need for detailed cervical imaging, as surgical stabilization of this region may be critical to prevent future spinal cord dysfunction. | Abducens Nerve Injury |
The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems. Experimental animal models that recapitulate schistosomiasis immunology, disease progression, and pathology observed in humans are important in testing and validation of control interventions. We discuss the pivotal value of these models in contributing to elimination of schistosomiasis. Treatment of schistosomiasis relies heavily on mass drug administration of praziquantel whose efficacy is comprised due to re-infections and experimental systems have revealed the inability to kill juvenile schistosomes. In terms of diagnosis, nonhuman primate models have demonstrated the low sensitivity of the gold standard Kato Katz smear technique. Antibody assays are valuable tools for evaluating efficacy of candidate vaccines, and sera from graded infection experiments are useful for evaluating diagnostic sensitivity of different targets. Lastly, the presence of Schistosomes can compromise the efficacy of vaccines to other infectious diseases and its elimination will benefit control programs of the other diseases. As the focus moves towards schistosomiasis elimination, it will be critical to integrate treatment, diagnostics, novel research tools such as sequencing, improved understanding of disease pathogenesis and utilization of experimental models to assist with evaluating performance of new approaches. | Neglected Diseases |
The extracellular matrix (ECM) imparts critical mechanical and biochemical information to cells in the lungs. Proteoglycans are essential constituents of the ECM and play a crucial role in controlling numerous biological processes, including regulating cellular phenotype and function. Versican, a chondroitin sulfate proteoglycan required for embryonic development, is almost absent from mature, healthy lungs and is reexpressed and accumulates in acute and chronic lung disease. Studies using genetically engineered mice show that the versican-enriched matrix can be pro- or anti-inflammatory depending on the cellular source or disease process studied. The mechanisms whereby versican develops a contextual ECM remain largely unknown. The primary goal of this review is to provide an overview of the interaction of versican with its many binding partners, the versican interactome," and how through these interactions, versican is an integrator of complex extracellular information. Hopefully, the information provided in this review will be used to develop future studies to determine how versican and its binding partners can develop contextual ECMs that control select biological processes. Although this review focuses on versican and the lungs, what is described can be extended to other proteoglycans, tissues, and organs." | Versicans |
Long non-coding RNAs (lncRNAs) play important roles in plant growth and stress responses. As a dominant abiotic stress factor in soil, boron (B) deficiency stress has impacted the growth and development of citrus in the red soil region of southern China. In the present work, we performed a genome-wide identification and characterization of lncRNAs in response to B deficiency stress in the leaves of trifoliate orange (Poncirus trifoliata), an important rootstock of citrus. A total of 2101 unique lncRNAs and 24,534 mRNAs were predicted. Quantitative real-time polymerase chain reaction (qRT-PCR) experiments were performed for a total of 16 random mRNAs and lncRNAs to validate their existence and expression patterns. Expression profiling of the leaves of trifoliate orange under B deficiency stress identified 729 up-regulated and 721 down-regulated lncRNAs, and 8419 up-regulated and 8395 down-regulated mRNAs. Further analysis showed that a total of 84 differentially expressed lncRNAs (DELs) were up-regulated and 31 were down-regulated, where the number of up-regulated DELs was 2.71-fold that of down-regulated. A similar trend was also observed in differentially expressed mRNAs (DEMs, 4.21-fold). Functional annotation of these DEMs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and the results demonstrated an enrichment of the categories of the biosynthesis of secondary metabolites (including phenylpropanoid biosynthesis/lignin biosynthesis), plant hormone signal transduction and the calcium signaling pathway. LncRNA target gene enrichment identified several target genes that were involved in plant hormones, and the expression of lncRNAs and their target genes was significantly influenced. Therefore, our results suggest that lncRNAs can regulate the metabolism and signal transduction of plant hormones, which play an important role in the responses of citrus plants to B deficiency stress. Co-expression network analysis indicated that 468 significantly differentially expressed genes may be potential targets of 90 lncRNAs, and a total of 838 matched lncRNA-mRNA pairs were identified. In summary, our data provides a rich resource of candidate lncRNAs and mRNAs, as well as their related pathways, thereby improving our understanding of the role of lncRNAs in response to B deficiency stress, and in symptom formation caused by B deficiency in the leaves of trifoliate orange. | Poncirus |
OBJECTIVE: Corneal allograft rejection is an immunological hypersensitive reaction caused by the antigenicity of the donor cornea. This study aimed to explore the effects of RMT1-10 on the prevention of corneal graft rejection by modifying immunological characteristics of dendritic cells (DCs). MATERIALS AND METHODS: DCs and CD4+T cells were sorted using flow cytometry and used for in vitro mixed lymphocyte culture. The cultured cells were prepared for the characterization of the DC cell phenotypes using the markers CD11c, CD80, MHC II, CD54, and TIM-4. Cytokine concentrations of IL-4, IL-12, and IL-10 of supernatants were measured by the enzyme-linked immunosorbent assay. CD4+T cells were examined by flow cytometry for apoptosis and proliferation. We also investigated the effect of RMT1-10 in the prevention and treatment of high-risk corneal graft rejection using a mouse model of corneal transplantation. RESULTS: DCs were identified as the CD11c+MHC-II-expressing subset. RMT1-10 suppressed the expression of CD11c, CD80, MHC II, CD54, and TIM-4 of DCs using the blockade of TIM-1 signaling. Moreover, TIM-1 blockade inhibited the production of IL-12 and IL-10 in a mixed lymphocyte culture system. However, a TIM-1 blockade had no effect on the apoptosis of CD4+T cells. RMT1-10 suppressed DC maturation, inhibiting the proliferation of CD4+T cells. CONCLUSIONS: RMT1-10 significantly improved the survival rate of the corneal allografts in mice compared with saline-injected controls. This clinical improvement from RMT1-10 occurred through the inhibition of CD4+T cell proliferation. Moreover, RMT1-10 induced antigen-specific detection of receptor immune tolerance. The cross-linking of TIM-1 on CD4+T cells with the agonist mAb provided a costimulatory inhibition signal for T cell activation or proliferation." | Hepatitis A Virus Cellular Receptor 1 |
Alzheimer disease (AD) is the most common form of dementia and characterized by deposition of amyloid-beta (Abeta) plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, atrophy, and progressive neurodegeneration. While the familial, early onset form of AD is known to be caused by specific mutations in genes encoding presenilin 1, presenilin 2, or amyloid-beta protein precursor, the underlying mechanisms leading to the development of sporadic AD are still not known. The major risk factors are, however, aging and APOE epsilon4. Here we review the latest evidence for the involvement of malfunctioning insulin signaling, dysfunction of mitochondria-associated membranes, cerebrovascular changes, increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic dysfunction in early stages of AD. We focus on whether the changes in these processes precede or succeed the earliest symptoms in AD patients, i.e., minimal cognitive impairment. Since changes in Abeta processing are probably a key event in AD we also highlight the relationship of the above mentioned processes with the formation, secretion, aggregation, and toxicity of Abeta. Based on our literature findings we propose a model in which insulin dysfunction, pathological cerebrovascular changes, dysfunction of mitochondria-associated membranes, and/or synaptic changes are likely to interact with each other, thereby initiating and facilitating the development of AD pathology by accelerating the production and deposition of Abeta. Increased oxidative stress and free radical formation, DNA damage, disturbed energy metabolism, and synaptic loss follow these events, but still occur very early in AD. | Plaque, Amyloid |
Plasminogen activator inhibitor type-2 (PAI-2), a member of the serpin family, is dramatically upregulated during pregnancy and in response to inflammation. Although PAI-2 exists in glycosylated and non-glycosylated forms in vivo, the majority of in vitro studies of PAI-2 have exclusively involved the intracellular non-glycosylated form. This study shows that exposure to inflammation-associated hypochlorite induces the oligomerisation of PAI-2 via a mechanism involving dityrosine formation. Compared to plasminogen activator inhibitor type-1 (PAI-1), both forms of PAI-2 are more resistant to hypochlorite-induced inactivation of its protease inhibitory activity. Holdase-type extracellular chaperone activity plays a putative non-canonical role for PAI-2. Our data demonstrate that glycosylated PAI-2 more efficiently inhibits the aggregation of Alzheimer's disease and preeclampsia-associated amyloid beta peptide (Abeta), compared to non-glycosylated PAI-2 in vitro. However, hypochlorite-induced modification of non-glycosylated PAI-2 dramatically enhances its holdase activity by promoting the formation of very high-molecular-mass chaperone-active PAI-2 oligomers. Both PAI-2 forms protect against Abeta-induced cytotoxicity in the SH-SY5Y neuroblastoma cell line in vitro. In the villous placenta, PAI-2 is localised primarily to syncytiotrophoblast with wide interpersonal variation in women with preeclampsia and in gestational-age-matched controls. Although intracellular PAI-2 and Abeta staining localised to different placental cell types, some PAI-2 co-localised with Abeta in the extracellular plaque-like aggregated deposits abundant in preeclamptic placenta. Thus, PAI-2 potentially contributes to controlling aberrant fibrinolysis and the accumulation of misfolded proteins in states characterised by oxidative and proteostasis stress, such as in Alzheimer's disease and preeclampsia." | Plasminogen Activator Inhibitor 2 |
Five carvotacetone derivatives, including two known ones, 3,5-diangeloyloxy-7-hydroxycarvotacetone (1) and 3-angeloyloxy-5-[2'',3''-epoxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone (2), along with three new compounds, 3-angeloyloxy-5-[3''-chloro-2''-hydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone (3), 5-angeloyloxy-7-hydroxy-3-tigloyloxycarvotacetone (4), and 3-angeloyloxy-5,7-dihydroxycarvotacetone (5), were isolated from the aerial parts of Sphaeranthus africanus collected in Vietnam. Bioassay-guided fractionation was monitored by the antiproliferative activity on CCRF-CEM human cancer cells. The structures of compounds 1-5 were determined on the basis of NMR spectroscopic and mass spectrometric data. Activities of compounds 1-5 were evaluated in vitro against the human cancer cell lines CCRF-CEM, MDA-MB-231, U-251, and HCT-116. All compounds exhibited significant antiproliferative activity against all four cancer cell lines. CCRF-CEM was most sensitive to the compounds, with IC(50) values ranging from 0.6 to 1.5 muM. Compounds 3 and 4 possessed the highest activity, with IC(50) values in the four cell lines ranging from 0.6 to 2.9 muM and 1.3 to 2.5 muM, respectively. These compounds also showed inhibitory activity toward the HEK-293 human embryonic kidney cells with IC(50) values ranging from 2.5 to 5.5 muM. This is the first time that antiproliferative activity of S. africanus has been reported, and 1-5 are the most cytotoxic carvotacetone derivatives reported so far. | Cyclohexanones |
Dental implant alloys made from titanium and zirconium are known for their high mechanical strength, fracture toughness and corrosion resistance in comparison with commercially pure titanium. The aim of the study was to investigate possible differences in the surface chemistry and/or surface topography of titanium and titanium-zirconium surfaces after sand blasting and acid etching. The two surfaces were compared by X-ray photoelectron spectroscopy, secondary ion mass spectroscopy, scanning electron microscopy and profilometry. The 1.9 times greater surface hydrogen concentration of titanium zirconium compared to titanium was found to be the major difference between the two materials. Zirconium appeared to enhance hydride formation on titanium alloys when etched in acid. Surface topography revealed significant differences on the micro and nanoscale. Surface roughness was increased significantly (p<0.01) on the titanium-zirconium alloy. High-resolution images showed nanostructures only present on titanium zirconium. | Zirconium |
Minor structural variations of benzomorphans opiates are associated with striking, unpredictable shifts in the relative extent of agonist or antagonist properties in vivo. The relative abilities of a number of benzomorphans in inhibit 3H-naloxone binding in the absence and presence of sodium in vitro show some correlations with their pharmacologic properties in vivo, although distinct exceptions exist. The ability of opiate agonists to inhibit 3H-naloxone binding is greatly reduced by sodium, while pure antagonists are affected very little, if at all, and mixed agonist-antagonist benzomorphans display an intermediate response. | Morphinans |
Idiopathic is the most common etiology for acute onset of facial neuropathy in dogs with limited number of studies describing MRI characteristics. A retrospective, observational study was performed using archived records, aiming to describe the MRI features of the caudal portion of the digastric muscle in dogs diagnosed with idiopathic facial neuropathy and to determine correlation with prognosis. Client-owned dogs presented to a referral hospital between 2009 and 2019, diagnosed with unilateral idiopathic facial neuropathy and having undergone MRI, with images including the caudal portion of the digastric muscle, were included (n = 19). MRI appearance of the affected muscle, including degree of muscle atrophy, signal intensity, enhancement post-contrast, and enhancement characteristics of the affected facial nerve, was described and compared to the contralateral, clinically unaffected caudal portion of the digastric muscle. Correlation between MRI appearance and outcome at 1-month and 3-months following onset of clinical signs was investigated. The majority of patients demonstrated some degree of muscle atrophy (n = 17, 89%), hyperintensity in T2W (n = 17, 89%), and pre-contrast T1W (n = 15, 79%) images, as well as contrast enhancement of the affected muscle (n = 14, 74%) and affected facial nerve (n = 9, 47%). There was no statistically significant correlation between atrophy or enhancement of the affected caudal portion of the digastric muscle nor between enhancement of the affected facial nerve and outcome. Hyperintensity both in T2W images and pre-contrast T1W images was significantly correlated with a worse prognosis. Ensuring inclusion and evaluation of this muscle in MRI may therefore be indicated in canine idiopathic facial neuropathy. | Facial Nerve Diseases |
A group of 24 sows selected from herds affected by atrophic rhinitis was subjected to the study of the therapeutic effect of the administration of wide-spectrum antibiotics combined with an improvement of the zoohygienic conditions and with full-value nutrition in the pre-partal period and during lactation. It was found that the mentioned measures in sows before parturition and their housing in a sanitized farrowing house during treatment generally improved the health of the sows and enabled the rearing of healthy piglets. The mortality rate during rearing up to the age of 28 days was 12.5%. In the control group of piglets and sows the losses amounted to 29%; the clinical symptoms of rhinitis were found in 11% of the piglets already at the age of 28 days. | Rhinitis, Atrophic |
BACKGROUND/AIM: Adult T-cell leukemia (ATL) is a peripheral T-lymphocytic malignancy influenced by human T-cell leukemia virus type 1 (HTLV-1) infection. Aggressive ATL has a poor prognosis, therefore newer agents are desperately needed. We revealed that dimethyl fumarate (DMF) causes ATL cell death via inhibition of nuclear factor-kappa B (NF-B) and signal transducer and activator of transcription 3 signaling. Here, we evaluated the specific mechanism of DMF effects on NF-B signaling in MT-2 HTLV-1-infected T-cells. MATERIALS AND METHODS: We examined the effects of DMF on the caspase recruitment domain family member 11 (CARD11)-BCL10 immune signaling adaptor (BCL10)-mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (CBM) complex and upstream signaling molecules which are critical for NF-B signaling in MT-2 cells by immunoblotting. We also explored its effects on cell-cycle distribution. Furthermore, we assessed whether the BCL2 apoptosis regulator (BCL2)/BCL2-like 1 (BCL-xL) inhibitor navitoclax promoted the inhibitory effect of DMF on cell proliferation and apoptosis-associated proteins by trypan blue exclusion test and immunoblotting, respectively. RESULTS: DMF inhibited constitutive phosphorylation of CARD11 followed by suppression of inhibitory-B kinase alpha/beta phosphorylation at serine in a dose-dependent fashion in MT-2 cells. Furthermore, DMF inhibited MALT1 and BCL10 expression in the same fashion. However, DMF did not prevent the phosphorylation of protein kinase C-beta, an upstream signaling molecule of CARD11. Cell-cycle analysis highlighted that DMF treatment at 75 muM resulted in the accumulation of cells at the sub-G(1) and G(2)/M phases. Navitoclax modestly promoted DMF-induced suppression of MT-2 cells via inhibition of cellular inhibitor of apoptosis protein-2 expression and c-JUN N-terminal kinase phosphorylation. CONCLUSION: The suppression of MT-2 cell proliferation by DMF makes its further evaluation as an innovative agent for therapy of ATL worthwhile. | Dimethyl Fumarate |
Quantitative morphological analysis of the number of granule cell dendritic spines, as well as total dendritic length and dendritic branching of neurons in the dentate gyrus and the nucleus of Meynert was done in 11-day-old rats after passive avoidance training in the neonatal period. Learning improved stepwise and its neuromorphological sequels were characterized by a statistically significant enhanced number of dendritic spines, due to an increase of thin spines, enhanced dendritic branching in both structures, and increased total dendritic length in the dentate gyrus compared with the controls. | Substantia Innominata |
During the COVID-19 pandemic, justification for orders to shelter in place have emphasized the vulnerability of older people. Although other at-risk groups were sometimes mentioned, the emphasis on older people could have effects on attitudes about aging and older people for decades to come. This essay provides a comprehensive biopsychosocial description of ageism and discusses the pandemic as a focusing event" that exemplifies the extreme social consequence of ageism for the entire older population. It suggests revisions to the Elder Justice Act and utilization of programs such as the Reframing Aging, Age-Friendly University, and Ageism First Aid initiatives to reduce ageism in the wake of the pandemic." | Ageism |
BACKGROUND: Recently, a novel systemic immune-inflammation index (SII) based on peripheral lymphocytes, neutrophils, and platelets has been reported to be correlated with patient prognosis in several malignancies, including gastric cancer. However, the prognostic value of the SII for gastric cancer patients with a signet-ring cell (SRC) component has not yet been reported. In this study, we aimed to assess the prognostic value of the SII in gastric cancer patients with an SRC component after curative resection. METHODS: This study was a retrospective analysis of 512 GC patients with an SRC component who underwent curative resection. The prognostic value of the SII was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: In our study cohort, an optimal cut-off value for the SII of 527 was used to stratify patients with gastric cancer (GC) into low (<527) and high SII (>/=527) groups. Our study indicated that a high SII (>/=527) was significantly correlated with a large tumor size (p < 0.001), infiltration of serosa (p < 0.001), lymph node metastasis (p < 0.001), and advanced TNM stage (p < 0.001). Univariate and multivariate analyses further demonstrated that a low SII was correlated with better clinical outcome and was an independent prognostic predictor in GC patients with an SRC component. Furthermore, the SII retained prognostic value in the subgroup analysis, including subgroup of different TNM stages and pure or mixed signet-ring cell carcinomas (SRCCs). CONCLUSION: The SII is a simple, promising, and practical prognostic biomarker for patients with surgically resected mixed SRCC and pure SRCC. The SII could complement current prognostic tools for better treatment planning and stratification of patients. | Carcinoma, Signet Ring Cell |
The neurotransmitter glutamate is the primary excitatory neurotransmitter in mammalian brain and is responsible for most corticocortical and corticofugal neurotransmission. Disturbances in glutamatergic function have been implicated in the pathophysiology of several neuropsychiatric disorders-including schizophrenia, drug abuse and addiction, autism, and depression-that were until recently poorly understood. Nevertheless, improvements in basic information regarding these disorders have yet to translate into Food and Drug Administration-approved treatments. Barriers to translation include the need not only for improved compounds but also for improved biomarkers sensitive to both structural and functional target engagement and for improved translational models. Overcoming these barriers will require unique collaborative arrangements between pharma, government, and academia. Here, we review a recent Institute of Medicine-sponsored meeting, highlighting advances in glutamatergic theories of neuropsychiatric illness as well as remaining barriers to treatment development. | Glutamic Acid |
Muscle stem cells (MuSCs) exhibit different metabolic profiles depending on their activity, however the mechanisms by which mitochondria affect MuSC fate has been understudied. In this issue of Cell Stem Cell, Hong et al. (2022) and Baker et al. (2022) demonstrate that defects in mitochondrial dynamics hinder proper MuSC activation and impair muscle regeneration. | Myoblasts |
Drug delivery requires precise intradermal and subcutaneous injections of formulations to clinically relevant penetration depths. However, penetration depth is confounded by skin deflection, which occurs prior to and during penetration as the skin surface deforms axially with the needle, and which varies profoundly due to differing intrinsic mechanical (e.g. viscoelastic) tissue properties, disease state, aging, and ethnicity. Herein, an ex vivo model was utilized to study factors that affect skin deflection and the efficacy of injection, including prestress applied at the tissue surface, needle gauge, velocity, and actuation depth. The application of prestress minimized skin deflection during needle penetration and allowed for needle actuation to the targeted penetration depths with minimum variability. The force required to achieve target penetration depths was found to increase with prestress and decrease with needle gauge. Our findings emphasize the need for prestress applied to the skin surface to minimize variation in skin properties and administer formulations for intradermal and subcutaneous treatments with maximum precision. | Injections |
Central diabetes insipidus (CDI) is characterized by hypotonic polyuria due to impairment of AVP secretion from the posterior pituitary. In clinical practice, it needs to be distinguished from renal resistance to the antidiuretic effects of AVP (nephrogenic DI), and abnormalities of thirst appreciation (primary polydipsia). As nephrogenic diabetes insipidus is rare in adults, unless they are treated with lithium salts, the practical challenge is how to differentiate between CDI and clinical disorders of excess thirst. The differential diagnosis is usually straight forward, but the recommended gold standard test, the water deprivation test, is not without interpretative pitfalls. The addition of the measurement of plasma AVP concentrations improves diagnostic accuracy, but the radioimmunoassay for AVP is technically difficult, and is only available in a few specialized centres. More recently, the measurement of plasma copeptin concentrations has been claimed to provide a reliable alternative to measurement of plasma AVP, without the sampling handling challenges. In addition, the measurement of thirst ratings can help the differentiation between CDI and primary polydipsia. Once the diagnosis of CDI is biochemically certain, investigations to determine the cause of AVP deficiency are needed. In this review, we will outline the diagnostic approach to polyuria, revisit the caveats of the water deprivation test and review recent data on value of adding AVP/copeptin measurement. We will also discuss treatment strategies for CDI, with analysis of potential complications of treatment. | Polydipsia, Psychogenic |
The last half of the 20th Century witnessed an increase in the occurrence and recognition of urban zoonoses caused by members of the genera Bartonella, Coxiella, Ehrlichia, and Rickettsia, all traditionally considered to be members of the family Rickettsiaceae. In recent years, new human pathogens (Bartonella elizabethae, Bartonella henselae, and Rickettsia felis) have been recognized in urban environments. Other newly recognized pathogens (Ehrlichia chaffeensis and Ehrlichia phagocytophila in the United States) have sylvan zoonotic cycles but are present in urban areas because their vertebrate hosts and associated ectoparasitic arthropod vectors are able to survive in cities. Still other agents, which were primarily of historical importance (Bartonella quintana) or have not traditionally been associated with urban environments (Rickettsia rickettsii), have been recognized as causes of human disease in urban areas. Some diseases that have traditionally been associated with urban environments, such as rickettsialpox (caused by Rickettsia akari) and murine typhus (caused by Rickettsia typhi), still occur in large cities at low or undetermined frequencies and often go undetected, despite the availability of effective measures to diagnose and control them. In addition, alternate transmission cycles have been discovered for Coxiella burnetii, Rickettsia prowazekii, and R. typhi that differ substantially from their established, classic cycles, indicating that the epidemiology of these agents is more complex than originally thought and may be changing. Factors leading to an increase in the incidence of illnesses caused by these bacteria in urban areas include societal changes as well as intrinsic components of the natural history of these organisms that favor their survival in cities. Transovarial and transstadial transmission of many of the agents in their arthropod hosts contributes to the highly focal nature of many of the diseases they cause by allowing the pathogens to persist in areas during adverse times when vertebrate amplifying hosts may be scarce or absent. Domesticated animals (primarily cats, dogs, and livestock) or commensal rodents [primarily Norway rats (Rattus norvegicus) and house mice (Mus musculus)] can serve as vertebrate amplifying hosts and bring these agents and their ectoparasitic arthropod vectors into direct association with humans and help maintain transmission cycles in densely populated urban areas. The reasons for the increase in these urban zoonoses are complex. Increasing population density worldwide, shifts in populations from rural areas to cities, increased domestic and international mobility, an increase in homelessness, the decline of inner-city neighborhoods, and an increase in the population of immunosuppressed individuals all contribute to the emergence and recognition of human diseases caused by these groups of agents. Due to the focal nature of infections in urban areas, control or prevention of these diseases is possible. Increased physician awareness and public health surveillance support will be required to detect and treat existing urban infections caused by these agents, to determine the disease burden caused by them, to design and implement control programs to combat and prevent their spread, and to recognize emerging or resurging infections caused by members of these genera as they occur. | Coxiella |
Polygalae Radix has long been used in China for calming the mind, promoting intelligence, communicating the heart and kidney, eliminating phlegm, and reducing swelling. At present, it is used to treat amnesia, insomnia, and malaise. Modern research has revealed that Polygalae Radix mainly contains triterpenoid saponins, xanthone, oligosaccharide esters, etc., with the activities of improving memory, resisting dementia, protecting the brain, relieving cough, and removing phlegm, as well as sedation and hypnosis. The present study reviews the research progress on chemical composition, pharmacological action, quality control, and metabolism of Polygalae Radix in the past 30 years, to provide a theoretical basis for further research and development. | Polygala |
NIS-mediated aminoamidiniumation has been developed for the syntheses of bicyclic imidazolidinium salts, which could be readily converted into cyclic vicinal diamines. | Imidazolines |
Today, the increasing use of chemical preservatives in foods is considered one of the main problems in food industries. This study aimed to produce the pasteurised Doogh (Iranian yogurt drink) containing a nanoemulsion of essential oil (EO) with appropriate quality. A factorial test based on a completely randomised design with two treatments in three levels, including EO type (pennyroyal, Gijavash, and their equal combination) and a control sample was applied to assess the physicochemical and sensory properties of Doogh. The highest negative zeta potential and antioxidant activity percentage were observed in the sample containing the nanoemulsion of pennyroyal and enriched with a combination of two essential oils. The microbial evaluation results indicated that the total microorganism count was minimised in the Doogh containing the nanoemulsion of Gijavash. The nanoemulsions of pennyroyal and Gijavash can be added into Doogh formulation to produce a new product with maximum sensory acceptability. | Mentha pulegium |
Dental implants have shown great success in recent years. However, in certain circumstances they can suffer from complications. It usually results from a combination of infection and host inflammatory responses or a lack thereof. This report documents an extra-oral cutaneous fistula associated with an osseointegrated dentoalveolar implant. | Periapical Abscess |
Human epithelial keratin is an intermediate filament protein that serves as a backbone to maintain the stability of the cell nucleus and mechanical stability of the whole cells. The present study focused on two point mutations, F231L and S233L, of the 1B domain of keratin K 1/10 related to the rare genetic skin disease palmoplantar keratoderma (PPK). We used molecular dynamics simulation to study the effects of the mutations on various hierarchical structures, including heterodimers, tetramers, and octamers of the K1/10 1B domain at the atomic scale. The initial results demonstrated that the wild type and mutant proteins were highly similar at the dimer level but had different microstructures and mechanics at a higher-level assembly. A decrease in the hydrophobic interactions and hydrogen bonds at the terminus resulted in weakened mechanical properties of the tetramer and octamer of the F231L mutant. The asymmetrical structure of the S233L tetramer with an uneven distribution of the hydrogen bonds decreased its mechanical properties. However, the S233L mutation provided extra hydrophobic interactions between these mutated amino acid residues in the octamer, leading to improved mechanical properties. The results of the present study provided a deeper understanding of how the differences in point mutations induced the changes in the configuration and mechanical properties at the molecular scale. The differences in these properties may influence keratin assembly at the microscopic scale and ultimately cause diseases at the macroscopic scale." | Intermediate Filament Proteins |
Carbapenemase-producing Enterobacteriaceae (CPE) infections are increasingly reported in Australian hospitals, but prevalence is unknown. In 2016, Victorian hospitals conducted CPE point-prevalence surveys in high-risk wards (intensive care, haematology, transplant). Forty-three hospitals performed 134 surveys, with 1839/2342 (79%) high-risk patients screened. Twenty-four surveys were also performed in other wards. Inability to obtain patient consent was the leading reason for non-participation. In high-risk wards, no CPE cases were detected; three cases were identified in other wards. Since there is low prevalence in high-risk wards, continuous screening is not recommended. Targeted screening may be enhanced by review of patient consent processes. | Enterobacteriaceae Infections |
'Masked hypertension' is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15-30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared with sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustained hypertension (elevated clinic and ambulatory BP). The confluence of increased cardiovascular risk and a failure to be diagnosed by the conventional approach of clinic BP measurement makes masked hypertension a significant public health concern. However, many important questions remain. First, the definition of masked hypertension varies across studies. Further, the best approach in the clinical setting to exclude masked hypertension also remains unknown. It is unclear whether home BP monitoring is an adequate substitute for ambulatory BP monitoring in identifying masked hypertension. Few studies have examined the mechanistic pathways that may explain masked hypertension. Finally, scarce data are available on the best approach to treating individuals with masked hypertension. Herein, we review the current literature on masked hypertension including definition, prevalence, clinical implications, special patient populations, correlates, issues related to diagnosis, treatment and areas for future research. | Masked Hypertension |
This article aimed to reflect about the importance of the role nurses perform in strategies of health education to lay caregivers, who are important actors in the health/disease process. It is a thematic reflection, built through bibliographic review, which discusses the role of lay caregivers in different stages of the life cycle. Considering the participation of lay caregivers in the Brazilian reality, strategies have been sought to include them in the health care, given the little attention Public Policies have given to them. Therefore, the nurses as health educators, must offer support to the lay caregivers helping them to choose among available alternatives, while delivering care, to not harm their own health. Concluding, health education can be an alternative to offer attention to the lay caregivers, while the nurse has important role in the development of alternatives. | Patient Escort Service |
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