Epidemiological Characteristics and Clinical Outcome of HIV-Related Tuberculosis in a Population of TB Patients in South-western Nigeria.
Tuberculosis (TB) is the second leading cause of death from infectious disease globally with its impact more dramatic in resource limited settings. Individuals with human immunodeficiency virus (HIV) infection who also develop tuberculosis represent a significant challenge to TB control. This study was carried out to determine the prevalence of TB-HIV coinfection and pattern of infection among TB patients. We also compared treatment outcome among coinfected patients with those not coinfected. A six-year retrospective review of records of patients managed at the Tuberculosis Treatment Center of the LAUTECH Teaching Hospital, South-Western Nigeria from January 2009 to December 2014 was carried out. One hundred and five (26.3%) of the 399 TB patients seen in the study period were coinfected with HIV. About 10% of the subjects had extrapulmonary tuberculosis. Treatment failure was significantly worse among patients who had both HIV and TB compared with those who had TB only (49.5% vs. 32%, p = 0.001). Death rate was also higher in the coinfected individuals implying a poorer clinical outcome. High prevalence of TB-HIV coinfection and poor treatment outcome in this group of individuals, though predictable, calls for a more concerted effort in the management of TB-HIV coinfection.


The gastrointestinal pharmacology of cannabinoids: focus on motility.
The marijuana plant Cannabis sp. and its derivatives and analogues, known as cannabinoids (CBs), induce many effects throughout the whole body. Herein we briefly review the gastrointestinal (GI) pharmacology of CBs, with special focus on motor function. Some drugs are available to treat nausea and emesis, and evidences in humans and animal models suggest that other GI motility alterations (gastro-oesophageal reflux, inflammatory bowel conditions or paralytic ileus) might benefit from modifications of the CB tone throughout the gut. However, central and peripheral (including GI) side effects may occur upon acute and chronic CB administration. Hopefully, the ongoing worldwide intense research on CBs will soon provide new, safer CB-based medicines.


Clinical Stroke prevention in atrial fibrillation.
Oral anticoagulation therapy has reduced the risk of ischaemic stroke and improved the outcomes for patients with atrial fibrillation considerably. The emergence of the non-vitamin K oral anticoagulants as alternatives to vitamin K antagonists has significantly changed the practice of stroke prevention in atrial fibrillation. As the main complication with antithrombotic therapy is bleeding, physicians should always balance the risk of ischaemic stroke against intracranial haemorrhage and intervene where appropriate to reduce both risks. Individual approach is often mandatory due to heterogeneity of the risks and patient preferences. The purpose of this review is to summarise the current knowledge of the oral anticoagulation therapy in atrial fibrillation patients and guide physicians with the management of anticoagulants based on data from clinical trials and systematic reviews.


Periadolescent Maturation of GABAergic Hyperpolarization at the Axon Initial Segment.
Neuronal chloride levels are developmentally regulated. Early in life, high intracellular concentrations support chloride efflux and depolarization at GABAergic synapses. In mouse, intracellular chloride decreases over the first postnatal week in the somatodendritic compartment, eventually supporting mature, hyperpolarizing GABAergic inhibition. In contrast to this dendritic switch, it is less clear how GABAergic signaling at the axon initial segment (AIS) functions in mature pyramidal cells, as reports of both depolarization and hyperpolarization have been reported in the AIS past the first postnatal week. Here, we show that GABAergic signaling at the AIS of prefrontal pyramidal cells, indeed, switches polarity from depolarizing to hyperpolarizing but does so over a protracted periadolescent period. This is the most delayed maturation in chloride reversal in any structure studied to date and suggests that chandelier cells, which mediate axo-axonic inhibition, play a unique role in the periadolescent maturation of prefrontal circuits.


Laparoendoscopic single-site repair of bladder rupture using a home-made single-port device: initial experience of treatment for a traumatic intraperitoneal bladder rupture.
We report our initial experience with a laparoendoscopic single-site (LESS) repair of a bladder rupture using a home-made single-port device. A 37-year-old man presented to the emergency department with complaints of voiding difficulty and gross hematuria after blunt trauma. Cystography and computed tomography revealed an intraperitoneal bladder rupture. The patient underwent LESS repair of a bladder rupture using the Alexis wound retractor, which was inserted through the umbilical incision. A home-made single-port device was made by fixing 6½ surgical gloves to the outer rim of the retractor and securing the glove finger to the end of 3 trocars with a tie. Using the flexible laparoscopic instruments and rigid instruments, LESS surgery was performed using a procedure similar to conventional laparoscopic surgery. The patient did not have any voiding problem after removal of the urethral Foley catheter on the 10th postoperative day. To our knowledge, this is the first published report of LESS repair of a traumatic bladder rupture using a home-made single-port device in the literature.


Local excision of large rectal villous adenomas: long-term results.
Transanal excision of rectal villous adenomas is a widely used surgical technique, because it is a one-step procedure, requiring no sophisticated instrumentation, and allowing complete histologic analysis of the excised tumor. Therefore, it ranks alongside radical surgery and palliative destructive procedures, but its results are highly variable in the published series. This discrepancy may be explained by the variable completeness of tumor excision because of potential dissection difficulties. Because intraoperative exposure may be a major limiting factor, one of us (JF) has developed a tractable cutaneomucous flap procedure to lower the rectal tumor to the anal verge, where control of the dissection line is easier. This retrospective review of consecutive patients operated on during ten-year period reports long-term results after transanal excision for large rectal villous adenomas with the tractable flap technique. From 1978 to 1988, 207 consecutive patients (100 males), mean age 68 (range, 24-90) years, were operated on for an apparently benign villous rectal adenoma. Twenty-one patients (10 percent) were referred after failure of previous treatments: 11 endoscopic, 8 surgical, 1 laser, 1 radiotherapy. Mean distance of lower tumor edge from anal margin was 5.6 (range, 0-13) cm and was <10 cm in 82 percent. Three patients (1.5 percent), including one with a Tis carcinoma, underwent a secondary treatment for immediate gross failure of resection: one further local excision and two palliative laser destructions. Immediate postoperative course was uneventful for 96 percent; there was one death from perineal gangrenous infection, four cases of hemorrhage, and three urinary retentions. Subsequently one case of transient fecal incontinence and 11 medically managed stenoses were noted. Mean size of resected tumor was 5.4 (range, 1-17) cm. Deep excision margins concerned the rectal muscular layers in 199 patients (96 percent) and perirectal fat in 8 (4 percent). Specimen margins were negative for cancer in 175 (85 percent) and positive or unknown in 32 cases. Histologic evaluation demonstrated in situ cancer in 28 (14 percent) and invasive carcinoma in 9 (4 percent). In three patients (1 percent), two abdominoperineal resections were immediately performed (one T2 with a mucinous contingent, one T3) and one adjuvant radiotherapy (one undifferentiated T2). Four patients (2 percent) did not return for postoperative evaluation. For the remaining 198 patients, mean follow-up was 74 +/- 34 (median, 75; range, 1-168) months. Forty-four died from unrelated causes. Recurrence occurred in seven (3.6 percent) and was malignant in two, who subsequently died. Specific recurrence-free probability was 99.5 percent at one year, 96 percent at five years, and 95 percent at ten years. A lesion size >6 cm (10 vs. 1 percent for smaller tumors) and the presence of an invasive carcinoma (20 vs. 3 percent without invasive carcinoma) were significantly associated with an increased probability of recurrence at five years. Providing that adequate intraoperative exposure is obtained and advanced malignant tumors receive immediate secondary treatment, transanal resection of clinically benign, large rectal villous adenomas is safe and effective. It is an alternative to rectal resection, which exposes the patient to potentially adverse effects, and also to destructive procedures, which preclude any histologic evaluation of the tumor.


Chloro(diethylenetriamine)copper(II) chloride: a disordered quasi-one-dimensional structure.
The title structure, [CuCl(C4H13N3)]Cl, consists of alternating [CuCl(dien)]+ (dien is diethylenetriamine) and Cl- ions arranged in quasi-one-dimensional stacks along the crystallographic a axis and forming tetragonally elongated octahedral coordination shells around each Cu atom [equatorial Cu-Cl = 2.2552 (8) A, and axial Cu-Cl = 2.831 (1) and 3.341 (1) A]. Crystallographic mirror planes bisect each stack vertically through the Cu, Cl and central N atoms, and horizontally through the [CuCl(dien)]+ cation. The horizontal mirrors lead to each atom in the puckered [CuCl(dien)]+ cations being disordered over two crystallographically equivalent sites. Comparison of the title structure with its Br and I analogues shows a growing influence of hydrogen bonding relative to coordination bonds on traversing the series I < Br < Cl.


Antibodies specific for human albumin function as blocking antibodies when attached to erythrocyte-bound albumin.
Albumin is shown to be firmly bound to human red blood cells using the techniques of flow cytometry, immunoblotting, and complement fixation. The interactions between antibodies attached to the cell bound albumin and the complement system are examined. Antibodies specific for human serum albumin bind to albumin on erythrocytes and activate both homologous and heterologous complement in the absence of hemolysis. Moreover, treatment of erythrocytes with anti-albumin antibodies renders the cells resistant to classical pathway mediated lysis initiated by a passive lysis system. Thus, erythrocyte-bound anti-albumin antibodies appear to function in a manner similar to "blocking" antibodies described in some bactericidal systems.


[Bridge between Total Synthesis of Bioactive Natural Products and Development of Drug Leads].
Although natural products are rich sources for drug discovery, only a small percentage of natural products themselves have been approved for clinical use, thus it is necessary to modulate various properties, such as efficacy, toxicity, and metabolic stability. A question in natural product drug discovery is how to logically design natural product derivatives with desired biological properties. This review describes our recent studies regarding the medicinal chemistry of tunicamycin. Tunicamycin inhibits bacterial phospho-N-acetylmuramic acid (MurNAc)-pentapeptide translocase (MraY), which is an essential enzyme in bacteria and a good target for antibacterial drug discovery. The usefulness of tunicamycin as antibacterial agents is limited by off-target inhibition of human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT). We positioned the total synthesis of tunicamycin as a starting point for the research and have accomplished the synthesis of tunicamycin V by using the Achmatowicz reaction, [3,3] sigmatropic rearrangement of allyl cyanate, and stereoselective glycosylation as key reactions. Next, the minimum structural requirements for tunicamycin V for MraY inhibition were established by systematic structure-activity relationship studies with truncated analogs of tunicamycin V. Our collaborative study elucidated a crystal structure of human GPT in complex with tunicamycin. This structural information was then exploited to rationally design an MraY-specific inhibitor of tunicamycin V in which the GlcNAc moiety was modified to a MurNAc amide. The analog was identified as a highly selective MraYAA inhibitor.


Increasing genetic variability in black oats using gamma irradiation.
The black oat (Avena strigosa Schreb) is commonly used for forage, soil cover, and green manure. Despite its importance, little improvement has been made to this species, leading to high levels of genotypic disuniformity within commercial cultivars. The objective of this study was to evaluate the efficiency of different doses of gamma rays [(60)Co] applied to black oat seeds on the increase of genetic variability of agronomic traits. We applied doses of 0, 10, 50, 100, and 200 Gy to the genotype ALPHA 94087 through exposure to [(60)Co]. Two experiments were conducted in the winter of 2008. The first aimed to test forage trait measurements such as plant height, dry matter yield, number of surviving tillers, and seedling stand. The second test assessed seed traits, such as yield and dormancy levels. Gamma irradiation seems not to increase seed yield in black oats, but it was effective in generating variability for the other traits. Tiller number and plant height are important selection traits to increase dry matter yield. Selection in advanced generations of mutant populations can increase the probability of identifying superior genotypes.


Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights.
To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath. Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present. BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.


Tumoral expression of IL-33 inhibits tumor growth and modifies the tumor microenvironment through CD8+ T and NK cells.
Cancer immunotherapy has shown great promise as a new standard cancer therapeutic modality. However, the response rates are limited for current approach that depends on enhancing spontaneous antitumor immune responses. Therefore, increasing tumor immunogenicity by expressing appropriate cytokines should further improve the current immunotherapy. IL-33 is a member of the IL-1 family of cytokines and is released by necrotic epithelial cells or activated innate immune cells and is thus considered a "danger" signal. The role of IL-33 in promoting type 2 immune responses and tissue inflammation has been well established. However, whether IL-33 drives antitumor immune responses is controversial. Our previous work established that IL-33 promoted the function of CD8(+) T cells. In this study, we showed that the expression of IL-33 in two types of cancer cells potently inhibited tumor growth and metastasis. Mechanistically, IL-33 increased numbers and IFN-γ production by CD8(+) T and NK cells in tumor tissues, thereby inducing a tumor microenvironment favoring tumor eradication. Importantly, IL-33 greatly increased tumor Ag-specific CD8(+) T cells. Furthermore, both NK and CD8(+) T cells were required for the antitumor effect of IL-33. Moreover, depletion of regulatory T cells worked synergistically with IL-33 expression for tumor elimination. Our studies established "alarmin" IL-33 as a promising new cytokine for tumor immunotherapy through promoting cancer-eradicating type 1 immune responses.


Topological characterization of the c, c', and c" subunits of the vacuolar ATPase from the yeast Saccharomyces cerevisiae.
The vacuolar ATPase (V-ATPase) is a multisubunit enzyme that acidifies intracellular organelles in eukaryotes. Similar to the F-type ATP synthase (FATPase), the V-ATPase is composed of two subcomplexes, V(1) and V(0). Hydrolysis of ATP in the V(1) subcomplex is tightly coupled to proton translocation accomplished by the V(0) subcomplex, which is composed of five unique subunits (a, d, c, c', and c"). Three of the subunits, subunit c (Vma3p), c' (Vma11p), and c" (Vma16p), are small highly hydrophobic integral membrane proteins called "proteolipids" that share sequence similarity to the F-ATPase subunit c. Whereas subunit c from the F-ATPase spans the membrane bilayer twice, the V-ATPase proteolipids have been modeled to have at least four transmembrane-spanning helices. Limited proteolysis experiments with epitope-tagged copies of the proteolipids have revealed that the N and the C termini of c (Vma3p) and c' (Vma11p) were in the lumen of the vacuole. Limited proteolysis of epitope-tagged c" (Vma16p) indicated that the N terminus is located on the cytoplasmic face of the vacuole, whereas the C terminus is located within the vacuole. Furthermore, a chimeric fusion between Vma16p and Vma3p, Vma16-Vma3p, was found to assemble into a fully functional V-ATPase complex, further supporting the conclusion that the C terminus of Vma16p resides within the lumen of the vacuole. These results indicate that subunits c and c' have four transmembrane segments with their N and C termini in the lumen and that c" has five transmembrane segments, with the N terminus exposed to the cytosol and the C terminus lumenal.


Central leptin gene therapy blocks high-fat diet-induced weight gain, hyperleptinemia, and hyperinsulinemia: increase in serum ghrelin levels.
Recombinant adeno-associated virus (rAAV), encoding either rat leptin (rAAV-lep) or green fluorescent protein (rAAV-GFP, control), was injected intracerebroventricularly in rats consuming a high-fat diet (HFD; 45 kcal%). Caloric consumption and body weight were monitored weekly until the rats were killed at 9 weeks. Untreated control rats consuming regular rat diet (RCD; 11 kcal%) were monitored in parallel. Body weight gain was accelerated in rAAV-GFP + HFD control rats relative to those consuming RCD, despite equivalent kcal consumption. At 9 weeks, serum leptin, free fatty acids, triglycerides, and insulin were elevated in HFD control rats. In contrast, rAAV-lep treatment reduced intake and blocked the HFD-induced increase in weight, adiposity, and metabolic variables. Blood glucose was slightly reduced but within the normal range, and serum ghrelin levels were significantly elevated in rAAV-lep + HFD rats. Uncoupling protein-1 (UCP1) mRNA in brown adipose tissue (BAT), an index of energy expenditure through nonshivering thermogenesis, was decreased in rats consuming HFD. Treatment with rAAV-lep significantly augmented BAT UCP1 mRNA expression, indicating increased thermogenic energy expenditure. These findings demonstrate that central leptin gene therapy efficiently prevents weight gain, increased adiposity, and hyperinsulinemia in rats consuming an HFD by decreasing energy intake and increasing thermogenic energy expenditure.


Transient occlusion of intracranial blood vessels. Presentation of one clinical and preliminary considerations.
The authors suggest that some cerebral ischaemic lesions depend upon a transient obstruction of intracranial blood vessels (particularly the trunk and the branches of the middle cerebral artery). This explains (as in the patient described here) the cases in which an ischaemic lesion does not correspond with the vascular lesions found on arteriography and/or at autopsy. Furthermore the authors indicate the importance of blood flow in the spontaneous relief of obstruction which is favoured by an undamaged vascular bed. Consequently they recommend, if possible, early surgical treatment of the carotid lesions, in order to reduce the risk of emboli and to improve cerebral blood flow in general.


[Use of the vena cava in renal transplantation. Extension of the right renal vein].
Vena cava is a providential material for the transplant surgeon. Prolongation of the right renal vein using vena cava is a simple and effective procedure. Consequently the inferior vena cava must be harvested with the right and not the left kidney for which it is unnecessary. The use of a long segment of vena cava makes the renal transplantation and easy, well-defined procedure without interfering with the requirements of multiorgan donation.


Gonadal hormone fluctuations do not affect the expression or extinction of fear-potentiated startle in female rats.
Prior studies suggest that levels of ovarian hormones may affect learning and memory in rats, including studies of fear conditioning and extinction. We previously showed that female rats show reduced retention of extinction compared to males when measuring fear-potentiated startle, but not when measuring freezing behavior. One commonly reported observation in studies of freezing behavior is that rats with increased levels of estradiol during extinction learning show better retention of extinction than rats given extinction training when levels of estradiol are low. Here, we tested the hypothesis that fear extinction retention in a fear-potentiated startle paradigm in females is influenced by levels gonadal hormones, which we had not accounted for in our original report. We used the fear-potentiated startle paradigm to test if extinction learning was affected by estrous phase, ovariectomy, or acute systemic injections of estradiol in ovariectomized rats. We report that neither the expression nor extinction of fear-potentiated startle differed in rats given extinction training in proestrus compared to those in metestrus. Removal of the ovaries had no effect on fear acquisition or extinction learning as assessed by fear-potentiated startle. Finally, systemic injections of estradiol given to ovariectomized rats before extinction training had no effect on the expression of fear or the retention of extinction. Our findings suggest that the effect of female gonadal hormones on fear conditioning and extinction may depend on the measure of fear employed or by the parameters used to study fear learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


The Mediterranean diet and health: a comprehensive overview.
The Mediterranean diet (MedDiet), one of the most studied and well-known dietary patterns worldwide, has been associated with a wide range of benefits for health. In the present narrative review, we aimed to provide a comprehensive overview of the current knowledge on the relation of the MedDiet to important health outcomes, considering both observational and intervention studies with both risk factors and clinical diseases as outcomes. In addition, we considered the clinical and public health impacts of the MedDiet on both human and planetary health. Earlier research confirmed by recent studies has provided strong evidence for the benefits of the MedDiet on cardiovascular health, including reduction in the incidence of cardiovascular outcomes as well as risk factors including obesity, hypertension, metabolic syndrome, and dyslipidaemia. There is also evidence that MedDiet is associated with lower rates of incident diabetes, and better glycaemic control in diabetic patients compared to control diets. In prospective studies, adherence to the MedDiet reduced mortality, especially cardiovascular mortality, hence increased longevity. In addition, it has been associated with less age-related cognitive dysfunction and lower incidence of neurodegenerative disorders, particularly Alzheimer's disease. Furthermore, the relatively low environmental impacts (water, nitrogen and carbon footprint) of the MedDiet is an additional positive aspect of the Mediterranean dietary model. It is likely that the combination of a healthy diet with social behaviours and the way of life of Mediterranean regions makes the MedDiet a sustainable lifestyle model that could likely be followed in other regions with country-specific and culturally appropriate variations.


Genetic variability of Leishmania infantum in naturally infected dogs in the state of Bahia, Brazil.
In Brazil, Leishmania infantum mainly affects humans and dogs. The state of Bahia presents many dogs that are positive for this parasite. Despite the importance of epidemiology in this region, there are still very few studies that have assessed the genetic characteristics of L. infantum. The aim of this study is to investigate the genetic variability of L. infantum isolated identified in naturally infected dogs, in order to verify occurrence of subpopulation of this parasite in the different biomes existing in the state of Bahia. Thirty-two samples of L. infantum were analyzed, which were obtained isolated in dogs from the Mata Atlântica (rainforest), Caatinga (semi-arid scrub forest), and Cerrado (a vast tropical savannah eco-region) Bahia municipalities' biomes. All animals presented with clinical changes suggestive of Leishmania spp. and they exhibited positive reactions to serological tests. kDNA analysis with RFLP markers revealed the presence of genetic variability and gene flow in subpopulations of L. infantum; samples from the Mata Atlântica areas were genetically more similar to those from the areas of Caatinga and they were less likely to resemble those of the Cerrado. This data may be used to investigate the dissemination of parasite in the canine population of state of Bahia.


Development and validation of an HPLC-UV method for the simultaneous determination of the antipsychotics clozapine, olanzapine and quetiapine, several beta-blockers and their metabolites.
A simple, accurate and selective column-switching high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous quantification of six beta-blockers (metoprolol, timolol, bisoprolol, propranolol, carvedilol and nebivolol), three of their metabolites (α-hydroxy metoprolol, N-desisopropyl propranolol and 4'-hydroxy carvedilol 4-HCAR), three antipsychotics (olanzapine, clozapine and quetiapine) and three of their metabolites (N-desmethyl olanzapine, N-desmethyl clozapine and N-desalkyl quetiapine) in human serum. After pretreatment on a Merck LiChrospher RP-4 ADS column (25 μm), drugs were separated on a Phenomenex Gemini Phenyl Hexyl 110 A column (250 × 4.6 mm, 5 μm) using a gradient mixture of acetonitrile and potassium dihydrogen phosphate buffer pH 3.1 (containing 10% methanol) as a mobile phase at a flow rate of 1 mL/min. The total analysis time was 40 min. For detection of the analytes, four different UV wavelengths were used: 215, 226, 242 and 299 nm. The method was validated according to the guidelines of the Society of Toxicology and Forensic Chemistry in terms of selectivity, linearity, accuracy, precision and stability and successfully applied for the analysis of the 15 described analytes in human serum.


Hospitalizations for infectious diseases in Jewish and Bedouin children in southern Israel.
Two different population groups reside in the Negev region of southern Israel and have equal, and free from financial barrier, access to tertiary care at a single regional hospital. The Jewish population has a largely urban and industrialized lifestyle, while the Moslem Bedouins are in transition from their traditional nomadic life to settlement. To examine the differences in morbidity patterns reflected in hospitalizations, the computerized hospitalization records of children <15 years of age, for 1989-1991 were used (n=15,947). Rates of hospitalizations for infectious diseases were significantly higher for Bedouins in comparison to Jews (250 and 121/10,000 child years, respectively, odds ratio (OR): 2.1, 95% confidence interval (CI): 2.0-2.2, p < 0.001). Rates of hospitalization per 10,000 child years in Bedouins and Jews for diarrhea were 114 and 32 (OR: 3.7, 95% CI: 3.3-4.0, p < 0.001), respectively, and for pneumonia 55 and 19 (OR: 2.9, 95% CI: 2.6-3.3, p < 0.001), respectively. In infants the differences were even more pronounced, especially for diarrheal diseases. In Bedouin children infectious diseases were associated with longer hospital stay, more pediatric Intensive Care hospitalizations (OR: 2.7, 95% CI: 1.7-4.5,p < 0.001), and higher in-hospital mortality (OR: 5.7, 95% CI: 2.8-12.2, p < 0.001). Thus, Bedouin children are at higher risks of hospitalizations for infectious diseases in early childhood, as compared to Jewish children. This may reflect the differences in lifestyle, environmental and social conditions of the two populations.


Novel Collaborative Weighted Non-negative Matrix Factorization Improves Prediction of Disease-Associated Human Microbes.
Extensive clinical and biomedical studies have shown that microbiome plays a prominent role in human health. Identifying potential microbe-disease associations (MDAs) can help reveal the pathological mechanism of human diseases and be useful for the prevention, diagnosis, and treatment of human diseases. Therefore, it is necessary to develop effective computational models and reduce the cost and time of biological experiments. Here, we developed a novel machine learning-based joint framework called CWNMF-GLapRLS for human MDA prediction using the proposed collaborative weighted non-negative matrix factorization (CWNMF) technique and graph Laplacian regularized least squares. Especially, to fuse more similarity information, we calculated the functional similarity of microbes. To deal with missing values and effectively overcome the data sparsity problem, we proposed a collaborative weighted NMF technique to reconstruct the original association matrix. In addition, we developed a graph Laplacian regularized least-squares method for prediction. The experimental results of fivefold and leave-one-out cross-validation demonstrated that our method achieved the best performance by comparing it with 5 state-of-the-art methods on the benchmark dataset. Case studies further showed that the proposed method is an effective tool to predict potential MDAs and can provide more help for biomedical researchers.


Matrix-mediated formation of hierarchically structured SnO crystals as intermediates between single crystals and polycrystalline aggregates.
Crystalline SnO grown in a Sn 6O 4(OH) 4 matrix exhibited hierarchical architectures, such as stepped bipyramids, stacked meshes, and rosettes, which were not categorized into the classical assortment of crystal morphologies. The complex architectures consisting of small building units were found to be produced through stacking and/or branching growth accompanied with a decrease in the unit size and degradation of the crystallographic symmetry in their assembly. This particular morphological evolution is presumed to be achieved by increasing the driving force of crystallization in the presence of abundant precursor species supplied from the matrix.


Perception of barriers to postoperative pain management in elderly patients in Polish hospitals with and without a "Hospital Without Pain" Certificate - a multi-center study.
In 2005-2050, the global population of elderly people will increase by 12%. This will lead to increased demand for such healthcare services as hospital care or surgical interventions. Pain in elderly patients is a substantial problem. Insufficiently controlled postoperative pain continues to be a widespread phenomenon. Pain management in Poland is usually based on nursing care supervised by an anesthesiologist or surgeon. The aim of the study was to identify barriers to effective nurse-controlled analgesia in postoperative pain management in elderly patients in hospitals with and without a Hospital Without Pain certificate. The study was conducted after the approval of the study protocol by the Independent Bioethics Committee for Scientific Research of the Medical University of Gdansk. The study project was multicenter and was conducted from July 2012 to December 2013. The research was questionnaire-based and used the Polish version of the Nurses' Perceived Obstacles to Pain Assessment and Management Practices questionnaire. The project included 676 nurses from hospitals awarded the Hospital Without Pain Certificate and 926 respondents from hospitals without the certificate. After calculating the overall average result in particular groups, healthcare system-related problems were first among the barriers hindering pain management in elderly patients M = (C = 3.81, N/C = 3.87). Patient-related barriers were second (M = 3.77). Physician- and nurse-related barriers took the subsequent positions, with very similar scores M = (C = 3.47, N/C = 3.44) and M = (C = 3.46, N/C = 3.44), respectively. The greatest barriers to pain management in elderly patients are related to the healthcare system. Nurses from Hospital Without Pain certified hospitals devoted significantly more time to relieving pain through non-pharmacological methods.


Tumour area infiltration and cell count in endoscopic biopsies of therapy-naive upper GI tract carcinomas by QuPath analysis: implications for predictive biomarker testing.
Guidelines regulate how many (tumour-bearing) tissue particles should be sampled during gastric cancer biopsy to obtain representative results in predictive biomarker testing. Little is known about how well these guidelines are applied, how the number of tissue particles correlates with the actual tumour-infiltrated area and how many absolute tumour cells are captured. The study included endoscopic biopsies of untreated carcinomas of the upper gastrointestinal (GI)-tract during the 2016-2020 review period. Archival (H&E)-stained histological sections were digitised and the tumour areas were manually annotated. The tumour-bearing tissue area and absolute carcinoma cell count per case were determined by image analysis and compared with a reference primary surgical specimen. Biopsies from 253 patients were analysed. The following mean values were determined: (a) tumour tissue particle number: 6.5 (range: 1-25, standard deviation (SD) = 3.33), (b) number of tumour-bearing tissue particles: 4.7 (range: 1-20, SD = 2.80), (c) tumour-infiltrated area: 7.5 mm2 (range: 0.18-59.46 mm2, SD = 6.67 mm2), (d) absolute tumour cell count: 13,492 (range: 193-92,834, SD = 14,185) and (e) tumour cell count in a primary surgical specimen (tumour size: 6.7 cm): 105,200,176. The guideline-recommended tissue particle count of 10 was not achieved in 208 patients (82.2%) and the required tumour-bearing tissue particle count of 5 was not achieved in 133 patients (52.6%). Tissue particle count, tumour-infiltrated area and tumour cell count were only weakly correlated. Most cases featured an infiltrated area ≥ 4.5 mm2 (156, 61.7%). Cases with more tissue particles showed only a moderate increase in infiltrated area and tumour cells compared to cases with fewer particles. Biopsies are often used to determine predictive biomarkers, particularly Her2/neu and PD-L1. Diagnostic standards to ensure representative material have been suggested in guidelines to reduce false-negative predictions. However, the real-world practice seems to substantially deviate from recommended standards. To the best of our knowledge, this is the first systematic study describing the relationships between endoscopic tissue fragment number, actual infiltrated tumour area and carcinoma cell number. The data question the tissue particle number as a quality assessment parameter. We advocate histopathological reports indicating on which basis statements on therapy-relevant biomarkers were made. Digital pathology has the potential to objectively quantify the tissue for documentation, quality assessment and future clinical studies.


Atrophie blanche examined with thermography.
Atrophie blanche developed in a 25-year-old man with systemic lupus erythematosus is reported. A thermographic examination was applied to estimate skin temperature, and the temperature was low on areas where lesions were distributed.


Sahel nutrition survey, 1974.
In time of food shortage, accurate assessment of nutrition status is important so that effective aid may be directed to those in greatest need and, in the future, the impact of this aid on the nutritional situation may be assessed. Using a population proportional sampling method and the index weight for height (which is relatively independent of sex, race, and age) as a criterion of nutritional status, CDC investigators determined that about 10% of the sampled population (aged about 6 months through 6 years) in Mali, Mauritania, Niger, and Upper Volta and over 20% in the sampled population in Chad were severely and acutely undernourished. Apparently younger children were affected first, but as the food shortage became more severe the prevalence of undernourished older children increased. This method of nutrition surveillance has proven itself during a stressful period and should be considered a fundamental tool when rapid assessment of acute undernutrition in children in developing nations is required.


Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease prevalent worldwide, with an increasing incidence associated with obesity, diabetes, and metabolic syndrome. The progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH) poses a pressing health concern, highlighting the significance of accurately identifying MASLD and its progression to MASH as a primary challenge in the field. In this study, a systematic integration of 66 immune cell types was conducted. Comprehensive analyses were performed on bulk, single-cell RNA-Seq, and clinical data to investigate the immune cell types implicated in MASLD progression thoroughly. Multiple approaches, including immune infiltration, gene expression trend analysis, weighted gene coexpression network analysis, and 4 machine learning algorithms, were used to examine the dynamic changes in genes and immune cells during MASLD progression. C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 have been identified as potential diagnostic biomarkers for MASLD progression. Furthermore, cell communication analysis at the single-cell level revealed that the involvement of C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 in MASLD progression is mediated through their influence on T cells. Overall, our study identified vital immune cells and a 2-gene diagnostic signature for the progression of MASLD, providing a new perspective on the diagnosis and immune-related molecular mechanisms of MASLD. These findings have important implications for developing innovative diagnostic tools and therapies for MASLD.


Impact of Anxiety and Depression on Physical Health Condition and Disability in an Elderly Korean Population.
This study aimed to investigate the longitudinal effects of anxiety, depression, and their comorbidity on physical disorders and disability in an elderly Korean population. In total, 1,204 community-dwelling elders were evaluated at baseline, and of these 909 (75%) were re-assessed two years later. Anxiety and depression were identified at baseline using questions from the community version of the Geriatric Mental State diagnostic schedule (GMS-B3). Participants were assessed for functional disability and for 11 physical disorders both at baseline and at follow-up. Anxiety alone was associated with the incidence of heart disease, depression alone with the incidence of asthma, and comorbid anxiety and depression with incidence of eyesight problem, persistent cough, asthma, hypertension, heart disease, and gastrointestinal problems. Comorbid anxiety and depression were associated with an increase in the number of physical disorders and the degree of disability during the two-year follow-up, compared to anxiety or depression alone or the absence of anxiety or depression. Anxiety, depression, and particularly their comorbidity should be assessed in the elderly population considering their longitudinal effects on physical disorders and disability. Future study is required to determine whether interventions aimed at these disorders can mitigate their impacts.


Cerebrovascular accidents (strokes) in children with sickle cell disease residing at high and low altitudes of Saudi Arabia.
In a 3-year period, eight cases of cerebrovascular accident were seen out of 400 patients with sickle cell disease residing at high and low altitudes of Asir Province of Saudi Arabia. They were all Saudi nationals and comprised five boys and three girls of ages ranging from 3.5 to 9 years. They had varied clinical presentations of their cerebrovascular accident. Cranial computed tomography in seven of them showed abnormality in the region of the middle cerebral circulation. Management and some suggested factors contributing to the occurrence of the cerebrovascular accident are discussed.


Pulsed reduced dose-rate radiotherapy as re-irradiation for brain metastasis in a patient with lung squamous-celled carcinoma.
The recurrence and progression of brain metastases after brain irradiation are a major cause of mortality and morbidity in patients with cancer. The risk of radiation-induced neurotoxicity and efficacy probably leads oncologists to not consider re-irradiation. We report the case of a 48-year-old Asian male diagnosed with squamous cell lung cancer and multiple brain metastases initially treated with 40 Gy whole-brain radiotherapy and 20 Gy partial brain boost. Fourteen gray stereotactic radiosurgery as salvage for brain metastases in the left occipital lobe was performed after initial irradiation. The recurrence of brain metastases in the left occipital lobe was demonstrated on magnetic resonance imaging at 9 months after initial radiotherapy. He received the second course of 28 Gy stereotactic radiosurgery for the recurrent brain metastases in the left occipital lobe. The third relapse of brain metastases was demonstrated by a magnetic resonance imaging scan at 7 months after the second radiotherapy. The third course of irradiation was performed because he refused to undergo surgical resection of the recurrent brain metastases. The third course of irradiation used a pulsed reduced dose-rate radiotherapy technique. It was delivered in a series of 0.2 Gy pulses separated by 3-min intervals. The recurrent brain metastases were treated with a dose of 60 Gy using 30 daily fractions of 2 Gy. Despite the brain metastases receiving 162 Gy irradiation, this patient had no apparent acute or late neurologic toxicities and showed clinical improvement. This is the first report of the pulsed reduced dose-rate radiotherapy technique being used as the third course of radiotherapy for recurrent brain metastases.


DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma.
Dual specificity protein phosphatase (DUSP)12 is an atypical member of the protein tyrosine phosphatase family, which are overexpressed in multiple types of malignant tumors. This protein family protect cells from apoptosis and promotes the proliferation and motility of cells. However, the pathological role of DUSP12 in hepatocellular carcinoma (HCC) is incompletely understood. We analyzed mRNA expression of DUSP12 between HCC and normal liver tissues using multiple online databases, and explored the status of DUSP12 mutants using the cBioPortal database. The correlation between DUSP12 expression and tumor-infiltrating immune cells was demonstrated using the Tumor Immune Estimation Resource database and the Tumor and Immune System Interaction Database. Loss of function assay was utilized to evaluate the role of DUSP12 in HCC progression. DUSP12 had higher expression along with mRNA amplification in HCC tissues compared with those in normal liver tissues, which suggested that higher DUSP12 expression predicted shorter overall survival. Analyses of functional enrichment of differentially expressed genes suggested that DUSP12 regulated HCC tumorigenesis, and that knockdown of DUSP12 expression by short hairpin (sh)RNA decreased the proliferation and migration of HCC cells. Besides, DUSP12 expression was positively associated with the infiltration of cluster of differentiation (CD)4+ T cells (especially CD4+ regulatory T cells), macrophages, neutrophils and dendritic cells. DUSP12 expression was positively associated with immune-checkpoint moieties, and was downregulated in a C3 immune-subgroup of HCC (which had the longest survival). These data suggest that DUSP12 may have a critical role in the tumorigenesis, infiltration of immune cells, and prognosis of HCC.


Multiple Responsive Fluids Based on Vesicle to Wormlike Micelle Transitions by Single-Tailed Pyrrolidone Surfactants.
We report a new family of multiple responsive fluids based on the single-tailed pyrrolidone surfactants, N-ethyl-2-pyrrolidone N-alkyl amine (C(m)NP, where m = 10, 12, 14, 16, and 18). These surfactants are highly sensitive to solution pH as a result of the presence of the N-amino group in the molecules. Equilibrium surface tension results indicate that both the surface activity and micellization ability of C(m)NPs decrease with the increase of the protonation degree; i.e., they exhibit a higher critical micelle concentration (cmc) and higher surface tension at the cmc (γ(cmc)) at the acidic conditions than those at the basic conditions. The cmc values of C(m)NPs follow the well-known Klevens equation, which decrease linearly with the increase of the hydrocarbon chain length m at a given pH. More importantly, the self-assemblies of C(m)NPs are highly sensitive to pH, CO2, and CuCl2, as identified by turbidity and viscosity. The transitions between vesicles and wormlike micelles are further confirmed by rheology, static and dynamic light scattering (SLS and DLS), cryogenic transmission electron microscopy (cryo-TEM), and nuclear magnetic resonance (NMR) techniques systematically. Although the aggregate transitions induced by different factors are similar, however, the mechanisms are different. The pH- and CO2-induced transitions are attributed to variation in the protonation degree of the N-amino group; however, CuCl2-induced transitions are a result of the formation of C(m)NP and CuCl2 coordination complexes as revealed by two-dimensional (2D) nuclear Overhauser effect spectrometry (NOESY) NMR and ultraviolet-visible (UV-vis) spectra.


Building on Synthetic Immunology and T Cell Engineering: A Brief Journey Through the History of Chimeric Antigen Receptors.
Advancement in our understanding of immune cell recognition and emerging cellular engineering technologies during the last decades made active manipulation of the T cell response possible. Synthetic immunology is providing us with an expanding set of composite receptor molecules capable to reprogram immune cell function in a predefined fashion. Since the first prototypes in the late 1980s, the design of chimeric antigen receptors (CARs; T-bodies, immunoreceptors), has followed a clear line of stepwise improvements from antigen-redirected targeting to designed "living factories" delivering transgenic products on demand. Building on basic research and creative clinical exploration, CAR T cell therapy has been achieving spectacular success in the treatment of hematologic malignancies, now beginning to improve the outcome of cancer patients. In this study, we briefly review the history of CARs and outline how the progress in the basic understanding of T cell recognition and of cell engineering technologies made novel therapies possible.


The organization and content of informatics doctoral dissertations.
This article offers suggested guidelines for graduate students who are embarking on informatics doctoral studies and anticipating the dissertation research and its documentation. Much of the guidance is pertinent for writing dissertations in other disciplines as well. The messages are largely directed at doctoral students, but some elements are also pertinent for master's students. All are relevant for faculty research advisors. The value of the dissertation is often underestimated. Too often it is seen as a hurdle to be overcome rather than an opportunity to gain insight into one's own research and to learn how to communicate effectively about it. Ideas that have been ill-formed often do not gel effectively until one tries to write about them. The main lesson is that the preparation of a carefully crafted, rigorous, logically evidence-based, and influential dissertation can be remarkably rewarding, both personally and professionally.


Electroencephalographic correlates of prism adaptation in mentally retarded individuals.
Sensorimotor adaptation was studied in 23 institutionalized, mentally retarded individuals. This was achieved by recording the pattern of off-target pointing errors resulting from viewing through a 20-diopter prism. The results showed a wide range of individual differences in prism adaptation. The electroencephalogram (EEG) was also recorded from four scalp locations and analyzed by computer to determine EEG intensity, coherence, and phase angle. Correlations between EEG and behavioral scores of prism adaptation revealed a number of significant relationships, especially negative correlations between alpha intensity and prismatic adaptation. These results indicate that patterns of central nervous system activity are meaningful related to sensorimotor capabilities in retarded individuals.


Preparation and sterilization by filtration of Renacidin irrigation.
A method for the sterilizing filtration of Renacidin, a urologic irrigating solution, was evaluated. Renacidin irrigation was prepared and sterilized by microporous membrane filtration. A sterilizing membrane filtration apparatus was challenged by inoculating a batch of irrigation solution with Escherichia coli. The sterility of both intentionally contaminated and routinely prepared batches was evaluated. The stability of the solution was monitored by pH measurement, visual examination, maintenance of a vacuum, and absorbance spectrum of a 1:100 dilution in deionized water over a wavelength range from 400 to 200 nm. The time required to prepare three one-liter units was about two hours. No microbial growth was detected in any of the samples. The predicted minimum shelf-life at 10 degrees C was six months. Because the prepared solution contains some unreacted citric acid and bicarbonates, storage at room temperature could produce excessive pressure inside the container from carbon dioxide gas evolution. Refrigerated storage is recommended. This method for the preparation and sterilization of Renacidin irrigation is reasonably expedient, economical, and reliable.


Increasing uptake time in FDG-PET: standardized uptake values in normal tissues at 1 versus 3 h.
Positron emission tomography (PET) imaging at more than 1 h after 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) administration may result in less blood pool activity and possibly decreased normal FDG uptake in tissues such as liver. Lower normal background activity could be an important component of improved image contrast on delayed imaging. Increasing FDG uptake in normal organs, however, may mitigate the beneficial effects of blood pool clearance. The purpose of this study is to determine the normal tissue and blood pool FDG uptake at 1 and 3 h after injection. Ninety-nine patients with known or suspected malignancy referred for FDG-PET-computed tomography (CT) were retrospectively evaluated. PET imaging was performed at either 1 h (60 +/- 15 min; n = 50) or at 3 h (180 +/- 15 min; n = 49) after FDG administration. Normal tissue FDG uptake without involvement by malignancy or influenced by artifact (misregistration, "brown fat," focal muscle uptake, focal atherosclerotic disease) was confirmed by inspection of both the PET and CT scans. Aortic blood pool, adipose tissue, bone marrow, cerebellum, liver, lungs, muscle, and spleen were quantitatively evaluated by CT-guided region of interest analysis in three contiguous slices. Mean standardized uptake values (SUVs) were analyzed using one-way analysis of variance. Mean SUVs on the 3- versus 1-h images were significantly lower for aortic blood pool 13% (p < 0.0001) and adipose tissue 20% (p < 0.008). FDG uptake showed significant increases at 3 h compared to 1-h imaging in the cerebellum 40% (p < 0.0001), bone marrow 25% (p = 0.003), muscle 21% (p = 0.0004), and spleen 13% (p = 0.01). The liver and lung showed no significant differences (1%, p = 0.85; -2%, p = 0.62, respectively). On FDG imaging at 3 h compared to 1 h, significant changes were apparent, but the magnitude of changes was modest overall. Three-hour delayed imaging demonstrated significantly lower aortic blood pool and adipose tissue activity and significantly higher cerebellum, muscle, spleen, and bone marrow activity. Hepatic and lung activities were not significantly different. These results suggest that previously reported improvements in tumor image contrast with delayed imaging may be primarily due to cumulative FDG uptake within the tumor rather than reduction in normal background activity.


[Infant breastfeeding prevalence in the city of São Paulo, Brazil, 2008].
This cross-sectional epidemiological study based on AMAMUNIC aimed to evaluate infant breastfeeding (BF) prevalence and duration in São Paulo, Brazil. Sample size was based on a cluster calculation, selecting 35 primary care units and 35 infants (< 1 year of age) per unit. A total of 1,424 interviews with mothers were performed (56 items on feeding in the previous 24 hours) in August 2008, subsequently analyzed according to residential areas: Central West, East, North, Southeast, and South. Prevalence of exclusive breastfeeding (EBF) was 52% up to three months and 39% up to six months, as follows: 44% (Central West), 57% (East), 62% (North), 43% (Southeast), and 48% (South) up to three months and 36% (Central West), 46% (East), 39% (North), 36% (Southeast), and 33% (South) up to six months. Prevalence of EBF according to infant age was 58% in the first month, 50% in the second and third, and 13% in the sixth. In conclusion, EBF prevalence up to six months is still heterogeneous in the city, suggesting the need for programs to encourage BF that are differentiated according to region.


Recognizing Single Collisions of PtCl6(2-) at Femtomolar Concentrations on Ultramicroelectrodes by Nucleating Electrocatalytic Clusters.
We report the electrodeposition of electrocatalytic clusters of platinum from femtomolar platinate solutions. An inert carbon fiber ultramicroelectrode (UME) was held at a potential where proton reduction was unfavorable on carbon but favorable on platinum in a 1 M sulfuric acid solution. Upon addition of femtomolar amounts of hexachloroplatinic acid, which will also reduce to Pt(0) at the applied potential on the carbon fiber UME, cathodic blips were observed in the amperometric i-t response. These blips correspond to the reduction of protons to molecular hydrogen at the small platinum clusters followed by a rapid deactivation likely due to hydrogen bubble formation. On average, these current spikes occur when five platinum atoms have been formed on the electrode, as determined by a comparative analysis of experimental cathodic blips and calculated hexachloroplatinate molecule collision frequencies.


Anal sac mast cell tumor in a dog.
An 11-year-old castrated mixed-breed dog was diagnosed with a unilateral anal sac mass. Anal sacculectomy was performed without complication. Histopathology of the mass was consistent with a well-differentiated mast cell tumor. Analyses for the Ki-67 protein, KIT expression pattern, and the presence of c-kit mutations were done. Recovery from surgery was unremarkable and repeat staging revealed no evidence of mast cell disease at 4, 8, and 12 mo after surgery. To the authors' knowledge, primary mast cell neoplasia of the anal sac has not previously been reported in the veterinary literature. Key clinical message: Although mast cell tumors of the perineal region are commonly encountered in veterinary practice, the anal sac represents a novel location for this disease. Cytology of anal sac masses can be a useful diagnostic tool to confirm the diagnosis, guide staging, and assist in treatment decisions.


Recognising, assessing and managing offending behaviour in persons with intellectual disability.
The association between intellectual disability and offending is complex. Recent evidence would suggest that the received wisdom of intellectually disabled persons being more prone to offending is either incorrect or only tells part of the story. Those within the 'borderline' intellectual disability range may be more prone to committing sexual and criminal damage offences but those with an IQ less than 50 rarely offend. The offender with intellectual disability shares characteristics with his counterpart from the general population. As with the general population as a whole, offending in this group is often unreported and its recognition is complicated by issues of competence. The lack of validated forensic assessment schedules for this population poses a further challenge. Some general approaches to assessment in this population are discussed. This case report illustrates the difficulties of assessing and managing offending behaviour in an individual with moderate intellectual disability. The challenge of treating offenders with an intellectual disability is immense and requires specialist expertise. Managing such cases in a generic setting is inappropriate and the need for a forensic learning disability service in Ireland is highlighted.


Radiology of perinephric fluid collections.
The perinephric spaces consist of the subcapsular, perirenal, anterior and posterior pararenal spaces. Fluid may collect in one or more of these compartments; this can be readily demonstrated by cross-sectional imaging, particularly computed tomography (CT). This pictorial review illustrates the radiological manifestations of perinephric fluid collections with their differential diagnosis including perinephric abscess, perirenal urine collection, subcapsular and perirenal hematoma, renal lymphangiomatosis, pancreatic pararenal fluid collections and transudate fluid associated with nephropathies.


Aberrant temporal growth pattern and morphology of root and shoot caused by a defective circadian clock in Arabidopsis thaliana.
Circadian clocks synchronized with the environment allow plants to anticipate recurring daily changes and give a fitness advantage. Here, we mapped the dynamic growth phenotype of leaves and roots in two lines of Arabidopsis thaliana with a disrupted circadian clock: the CCA1 over-expressing line (CCA1ox) and the prr9 prr7 prr5 (prr975) mutant. We demonstrate leaf growth defects due to a disrupted circadian clock over a 24 h time scale. Both lines showed enhanced leaf growth compared with the wild-type during the diurnal period, suggesting increased partitioning of photosynthates for leaf growth. Nocturnal leaf growth was reduced and growth inhibition occurred by dawn, which may be explained by ineffective starch degradation in the leaves of the mutants. However, this growth inhibition was not caused by starch exhaustion. Overall, these results are consistent with the notion that the defective clock affects carbon and energy allocation, thereby reducing growth capacity during the night. Furthermore, rosette morphology and size as well as root architecture were strikingly altered by the defective clock control. Separate analysis of the primary root and lateral roots revealed strong suppression of lateral root formation in both CCA1ox and prr975, accompanied by unusual changes in lateral root growth direction under light-dark cycles and increased lateral extension of the root system. We conclude that growth of the whole plant is severely affected by improper clock regulation in A. thaliana, resulting not only in altered timing and capacity for growth but also aberrant development of shoot and root architecture.


Intravitreal injection of vancomycin in experimental staphylococcal endophthalmitis.
Toxicity, clearance, and therapeutic effectiveness of intravitreal vancomycin hydrochloride injection in experimentally induced staphylococcal endophthalmitis were evaluated. Vancomycin was found to be nontoxic in a single, 1 mg/0.1 ml intravitreal dose. Therapeutic levels of vancomycin were present in the vitreous for over 72 hours and in the aqueous during a period from 6 to 48 hours after injection. Injection of a methicillin-resistant Staphylococcus aureus produced a panophthalmitis in our systemically treated controls, whereas in the rabbits treated by intraocular injection, the course of the infection was significantly altered.


Specific viral RNA drives the SARS CoV-2 nucleocapsid to phase separate.
A mechanistic understanding of the SARS-CoV-2 viral replication cycle is essential to develop new therapies for the COVID-19 global health crisis. In this study, we show that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with the viral genome, and propose a model of viral packaging through LLPS. N-protein condenses with specific RNA sequences in the first 1000 nts (5'-End) under physiological conditions and is enhanced at human upper airway temperatures. N-protein condensates exclude non-packaged RNA sequences. We comprehensively map sites bound by N-protein in the 5'-End and find preferences for single-stranded RNA flanked by stable structured elements. Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules thus presenting screenable processes for identifying antiviral compounds effective against SARS-CoV-2.


Epidemiology and Comorbidity of Patients with Alopecia Areata in Germany - Analysis of Longitudinal Claims Data.
Alopecia areata (AA) is a chronic, immune-mediated disease characterised by acute onset hair loss. The hair loss can range from small, circumscribed hairless areas on the scalp to complete loss of head and body hair. However, data on the epidemiology of AA are limited. Current evaluations are lacking in Germany. The aim of this study was to evaluate the epidemiology and comorbidity of AA in Germany based on claims data. A representative 40% sample of all adults who were insured with a German statutory health insurance (DAK-G) between 2016 and 2020 was evaluated (n = 2.88 million). Based on at least one relevant outpatient or inpatient diagnosis of ICD-10 L63, the annual AA prevalence and incidence (ICD-10 L63) were calculated for 2016 to 2020. Different case definitions were used for diagnosis validation. In addition, the occurrence of comorbidities in AA patients was investigated. In 2020, AA prevalence was 210 per 100,000 and incidence 72 per 100,000. Compared to persons without AA, those with AA significantly more often had atopic dermatitis (rate ratio (RR) 2.9), pruritus (RR 2.7), lupus erythematosus (RR 2.4), urticaria (RR 2.3) and psoriasis (RR 2.2). Women were affected slightly more often than men (0.2% vs. 0.1%). On a regional level, higher prevalence and incidence rates were found in Brandenburg (prevalence: 332; incidence: 116 per 100,000), Hesse (344 and 124 per 100,000, respectively) and Mecklenburg-Western Pomerania (303 and 111 per 100,000, respectively). AA is a common immune-mediated skin condition with a relevant prevalence and marked regional variations in Germany. For a complete understanding of epidemiology, complementary population-based exams including clinical characteristics of AA are useful.


Factor structure of the levels of attribution and change (LAC) scale in samples of psychotherapists and smokers.
Investigated the factor structure of the Levels of Attribution and Change (LAC) Scale, a 60-item, Likert-format instrument designed to assess the levels and loci of causal attributions about a problem behavior. Principal component analyses were performed on two samples, 194 adult smokers and 140 professional psychotherapists. In both cases, nine distinct and interpretable components were retained, which accounted for 63% and 68% of the total variance, respectively. Coefficients of congruence indicated that the two component patterns were quite similar. Item cross-classification revealed that the nine components closely resemble the 10 theoretical scales, with 2 scales (Familial Conflicts, Interpersonal Conflicts) represented by one component. Estimates of internal consistency averaged .84 and .87 for the two samples. The LAC theoretical scales and the scoring system have considerable empirical justification. The LAC Scale appears to be an internally consistent, multidimensional inventory with a robust factor structure.


Qualification of ship doctors: a German approach.
While a steady growth of cruise tourism since the 1970s created an increasing demand for ship doctors medical postgraduate specialty training did not sufficiently reflect the scope of skills and knowledge required from a physician being left to himself at sea. The German Maritime Health Association therefore tasked a working group with analysing the situation and coming up with suggestions for an adequate postgraduate training for ship doctors. The working group consisted of 19 experts with various backgrounds in maritime medicine. A literature review was done on cruise ship epidemiology as well as an assessment of tasks and environmental factors influencing medical care on board of cruise ships. Necessary knowledge and skills were derived and compared with those imparted by standard German medical education. Mandatory knowledge and skills were identified as well as elements of standard medical education contributing to these goals. Those aspects that would or could not be adequately covered by German standard education were catalogued and summarised in a course curriculum. In 2013 after approval by its board of directors the German Maritime Health Association published a qualification and training recommendation addressing colleagues planning to muster as ship doctors.


Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC).
The treatment of unresectable "non-early" (according to the BCLC classification) hepatocellular carcinoma (HCC) in cirrhotic patients with transcatheter arterial chemoembolization (TACE) followed by radiofrequency ablation (RFA) is retrospectively evaluated and possible prognostic factors of this combined therapy are investigated. Forty-six consecutive cirrhotic patients (Child-Pugh class A or B) with solitary or oligonodular HCC underwent RFA after TACE. The treated lesions were 51 overall (size 30-80 mm, mean 48.9). RFA was performed by a multitined expandable electrodes device after one TACE administration. Local efficacy was evaluated with multiphasic computed tomography (CT) performed an average of 2 months after treatment and then during follow-up. Patient survival rate was also evaluated (follow-up time 1-51 months, mean 15 months). Technical success (defined as complete devascularization during the arterial phase) was achieved in 34/51 lesions (66.7%) at the first CT check and in 29/51 (56.9%) during the succeeding follow-up. Among the considered prognostic factors, only lesion diameter (< or > = 50 mm) was statistically significant in the Fisher's exact test in terms of local control (85.2 vs. 45.8% at first CT, p=.0065; 70.4 vs. 41.7% during follow-up, p=.051). There were two major complications (6.5%): one hepatic failure and one death. A Kaplan-Meier analysis showed survival rates of 89.7% at 12 months and 67.1% at 24 months. Combined therapy for non-early HCC shows a relatively high complete local response (especially in lesions less than 5 cm in diameter) and promising mid-term clinical success. Its overall usefulness has yet to be established by a larger series and risk-benefit analysis.


[The cloning and expression of the gene for Staphylococcus aureus beta-hemolysin].
The gene coding the synthesis of beta-hemolysin (phospholipase C) has been cloned from S.aureus strain 126/89. A highly active Escherichia coli producer has been obtained, its capacity of synthesizing phospholipase C exceeding that of the natural strain 37-fold. Phospholipase C (beta-hemolysin) obtained from the natural and gene-engineering producers have been found to be identical in their enzymatic and molecular characteristics. The nucleotide sequence of the full plc gene which codes peptide consisting of 333 acid radicals has been established. In S.aureus strains of different origin this gene has been found to have a conservative character.


The irreducible needs of children for development: a frame of reference to health care.
A comprehensive health care to children implies in caring for their development, by perceiving the needs based on a suitable reference to children's specificities. This theoretical study aimed to analyze the "irreducible needs of children" frame of reference, based on a child development theory. We performed a comparative analysis between the contents of children's irreducible needs and the components of the Bioecological Theory of Human Development. An extensive correspondence was verified among the components of the Bioecological Theory and the following essential needs: ongoing nurturing relationships; experiences tailored to individual differences; developmentally appropriate experiences; limit setting, structure and expectations; stable, supportive communities and cultural continuity. The need for physical protection, safety, and regulation is not explicit in the elements of the theory, although it is also verified in their definitions. We concluded that the irreducible needs' reference can support nurses in health care and in child development promotion.


Cost-effective downstream processing of recombinantly produced pexiganan peptide and its antimicrobial activity.
Antimicrobial peptides (AMPs) have significant potential as alternatives to classical antibiotics. However, AMPs are currently prepared using processes which are often laborious, expensive and of low-yield, thus hindering their research and application. Large-scale methods for production of AMPs using a cost-effective approach is urgently required. In this study, we report a scalable, chromatography-free downstream processing method for producing an antimicrobial peptide, pexiganan, using recombinant Escherichia coli (E. coli). The four helix bundle structure of the unique carrier protein DAMP4 was used to facilitate a simple and cheap purification process based on a selective thermochemical precipitation. Highly pure fusion protein DAMP4var-pexiganan was obtained at high yield (around 24 mg per 800 mL cell culture with a final cultivation OD600 ~ 2). The purification yield of DAMP4var-pexiganan protein is increased twofold with a 72.9% of the protein recovery in this study as compared to the previous purification processes (Dwyer in Chem Eng Sci 105:12-21, 2014). The antimicrobial peptide pexiganan was released and activated from the fusion protein by a simple acid-cleavage. Isoelectric precipitation was then applied to separate the pexiganan peptide from the DAMP4var protein carrier. The final yield of pure bio-produced pexiganan was 1.6 mg from 800 mL of bacterial cell culture (final cultivation OD600 ~ 2). The minimum bactericidal concentration (MBC) test demonstrated that the bio-produced pexiganan has the same antimicrobial activity as chemically synthesized counterpart. This novel downstream process provides a new strategy for simple and probable economic production of antimicrobial peptides.


Model simulations of the Arctic atmospheric boundary-layer from the SHEBA year.
We present Arctic atmospheric boundary-layer modeling with a regional model COAMPS, for the Surface Heat Budget of the Arctic Ocean (SHEBA) experiment. Model results are compared to soundings, near-surface measurements and forecasts from the ECMWF model. The near-surface temperature is often too high in winter, except in shorter periods when the boundary layer was cloud-capped and well-mixed due to cloud-top cooling. Temperatures are slightly too high also during the summer melt season. Effects are too high boundary-layer moisture and formation of too dense stratocumulus, generating a too deep well-mixed boundary layer with a cold bias at the simulated boundary-layer top. Errors in temperature and therefore moisture are responsible for large errors in heat flux, in particular in solar radiation, by forming these clouds. We conclude that the main problems lie in the surface energy balance and the treatment of the heat conduction through the ice and snow and in how low-level clouds are treated.


Safety assessment and antioxidant activity of Lantana montevidensis leaves: Contribution to its phytochemical and pharmacological activity.
Lantana camara, the widely studied species, and L. montevidensis, the less studied species of the genus Lantana are both used in traditional medicine for the same purpose (anti-asthma, anti-ulcer, anti-tumor, etc). However, little is known about the toxicity of L. montevidensis and there is limited information on its chemical constituents. Here, we investigated for the first time the genotoxicity and cytotoxicity of the ethanolic (EtOH) and aqueous extracts from the leaves of Lantana montevidensis in human leukocytes, as well as their possible interaction with human erythrocyte membranes in vitro. The antioxidant activities of both extracts were also investigated in chemical and biological models. Treatment of leukocytes with EtOH or aqueous extracts (1-480 µg/mL) did not affect DNA damage index, but promoted cytotoxicity at higher concentrations (240-480 µg/mL). Both extracts did not modify the osmotic fragility of human erythrocytes. The extracts scavenged DPPH radical and prevented Fe2+-induced lipid peroxidation in rat's brain and liver homogenates, and this was likely not attributed to Fe (II) chelation. The HPLC analysis of the extracts showed different amounts of polyphenolic compounds (isoquercitrin, gallic acid, catechin, ellagic acid, apigenin, kaempferol, caffeic acid, rutin, quercitrin, quercetin, chlorogenic acid, luteolin) that may have contributed to these effects. These results supported information on the functional use of L. montevidensis in folk medicine.


Strike fast, strike hard: the red-throated caracara exploits absconding behavior of social wasps during nest predation.
Red-throated Caracaras Ibycter americanus (Falconidae) are specialist predators of social wasps in the Neotropics. It had been proposed that these caracaras possess chemical repellents that allow them to take the brood of wasp nests without being attacked by worker wasps. To determine how caracaras exploit nests of social wasps and whether chemical repellents facilitate predation, we: (1) video recorded the birds attacking wasp nests; (2) analyzed surface extracts of the birds' faces, feet, and feathers for potential chemical repellents; and (3) inflicted mechanical damage on wasp nests to determine the defensive behavior of wasps in response to varying levels of disturbance. During caracara predation events, two species of large-bodied wasps mounted stinging attacks on caracaras, whereas three smaller-bodied wasp species did not. The "hit-and-run" predation tactic of caracaras when they attacked nests of large and aggressive wasps reduced the risk of getting stung. Our data reveal that the predation strategy of caracaras is based on mechanical disturbance of, and damage to, target wasp nests. Caracara attacks and severe experimental disturbance of nests invariably caused wasps to abscond (abandon their nests). Two compounds in caracara foot extracts [sulcatone and iridodial] elicited electrophysiological responses from wasp antennae, and were also present in defensive secretions of sympatric arboreal-nesting Azteca ants. These compounds appear not to be wasp repellents but to be acquired coincidentally by caracaras when they perch on trees inhabited with Azteca ants. We conclude that caracara predation success does not depend on wasp repellents but relies on the absconding response that is typical of swarm-founding polistine wasps. Our study highlights the potential importance of vertebrate predators in the ecology and evolution of social wasps.


Ca2CuTe4O10Cl2, a new synthetic tellurium(IV) oxochloride.
Single crystals of dicalcium copper tetratellurium decaoxide dichloride, Ca2CuTe4O10Cl2, were synthesized via a transport reaction in sealed evacuated quartz glass tubes. The building units of the structure are irregular CaO7 polyhedra, centrosymmetric CuO4Cl2 octahedra and two crystallographically distinct TeO4E distorted bipyramids (E being the 5s2 lone pair of TeIV). The TeO4E and CuO4Cl2 polyhedra together form planes that are connected by the Ca atoms. The CuO4Cl2 octahedra are isolated from each other by the other building units.


Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post-transcriptional changes in PKC epsilon.
PKC isozymes are the major binding proteins for tumor-promoting phorbol esters, and PKC activity is abnormal in a number of different human cancers. Less is known about putative structural and functional changes of specific PKC isozymes in human neoplasms. A single-point mutation of PKCalpha at position 881 of the coding sequence has been observed in human pituitary adenomas and up to 50% of thyroid follicular neoplasms, and a rearrangement of PKCepsilon was reported in a thyroid follicular carcinoma cell line, suggesting that these signaling proteins may play a role in thyroid tumorigenesis. To explore this possibility, we examined thyroid neoplasms for mutations and changes in expression levels of PKCepsilon or alpha. None of the 57 follicular adenomas, 26 papillary carcinomas (PCs), 7 follicular carcinomas, or the anaplastic carcinoma harbored the PKCalpha 881A>G mutation. Moreover, none of 15 PCs, 10 follicular adenomas, or 6 follicular carcinomas showed evidence of mutations of PKCepsilon. However, 8 of 11 PCs had major isozyme-specific reductions of the PKCepsilon protein, which occurred through either translational or posttranslational mechanisms. These data indicate that post-transcriptional changes in PKCepsilon are highly prevalent in thyroid tumors and may play a significant role in their development.


Anti-Müllerian hormone (AMH) receptor type II expression and AMH activity in bovine granulosa cells.
Anti-Müllerian hormone (AMH) produced by granulosa cells has previously been proposed to play a role in regulating granulosa cell differentiation and follicle selection. Although AMH receptor type II (AMHR2) dimerizes with a type I receptor to initiate AMH signaling, little is known about the regulation of AMHR2 expression in bovine granulosa cells and the role of AMH in follicle development. The primary objectives of this study were to: (1) characterize AMHR2 expression in granulosa cells during follicle development; (2) identify factors that regulate AMHR2 mRNA expression in granulosa cells; and (3) examine the role of AMH signaling in granulosa cell differentiation and proliferation. Bovine granulosa cells were isolated from 5- to 8-mm follicles before selection and deviation, as well as from 9- to 12-mm and 13- to 24-mm follicles after selection. Analyses revealed that expression of AMHR2 was greater in 5- to 8-mm follicles compared with 13- to 24-mm follicles (P < 0.05). Granulosa cells treated with bone morphogenetic protein 6 (BMP6) or BMP15, but not BMP2, significantly increased AMHR2 expression when compared with control cultured cells (P < 0.05). In addition, expression of AMH was greater in granulosa cells cultured with BMP2, BMP6, or BMP15 when compared with controls (P < 0.05). Finally, treatment with recombinant human AMH, in vitro, inhibited CYP19A1 expression in a dose-related (10-100 ng/mL) fashion, and reduced granulosa cell proliferation at 48 and 72 hours (P < 0.05). Results from these studies indicate that AMH signaling plays a role in both regulating granulosa cell proliferation and preventing granulosa cells from 5- to 8-mm follicles from undergoing premature differentiation before follicle selection.


A Study of Young Chinese Intentions to Purchase "Online Paid Knowledge": An Extended Technological Acceptance Model.
Under the catalysis of knowledge anxiety and cognitive surplus, knowledge sharing platforms has experienced rapid growth, which has accelerated the integration of knowledge resources online. As with all new successful and sustainable business products, the consumers will play an important role in the future development of online paid knowledge. Therefore, we constructed an extended technological acceptance model by examining factors that influence young Chinese people's willingness to pay for online paid knowledge. The study surveyed 405 young Chinese participants, in which the extended technological acceptance model was tested by using structural equation modeling. Findings indicate that perceived ease of use is positively associated with perceived usefulness and associated attitudes, whereas perceived usefulness and attitude is positively associated with purchase intention. Perceived risk and group conformity are found to indirectly affect consumers' willingness to pay. The study advances the current body of knowledge by empirically testing the impact of perceived risk and the role of cultural influence (group conformity) on purchasing intention. Finally, theoretical and practical implications are discussed.


Taxonomic revision of a darkling beetles genus Anaxius (Tenebrionidae: Pedinini: Helopinina).
The genus Anaxius Fåhraeus, 1870 (Tenebrionidae: Helopinina) is revised to include seven Southern African species, four of which are new. A taxonomic treatment of the genus is provided including a morphological study, new species descriptions, keys, illustrations, and notes on species distributions. The following species are treated: Anaxius bloubergensis sp. nov., A. campbellae Koch, 1958, A. limpopoensis sp. nov., A. meletsensis sp. nov., A. obesus Fåhraeus, 1870, A. prozeskyi Koch, 1958, and A. pseudoloensus sp. nov. A lectotype is designated for Anaxius obesus Fåhraeus, 1870 to fix the taxonomic status of this species. Anaxius montiscaerulei Koch, 1958 is considered as a synonym of A. campbellae.


Pan-Cancer Analysis Based on EPOR Expression With Potential Value in Prognosis and Tumor Immunity in 33 Tumors.
Erythropoietin receptor (EPOR), a member of the cytokine class I receptor family, mediates erythropoietin (EPO)-induced erythroblast proliferation and differentiation, but its significance goes beyond that. The expression and prognosis of EPOR in cancer remain unclear. This study intended to perform a pan-cancer analysis of EPOR by bioinformatics methods. Several databases such as GTEx, TCGA, CCLE, and others were used to explore the overall situation of EPOR expression, and the correlation of EPOR expression with prognosis, microRNAs (miRNAs), immune infiltration, tumor microenvironment, immune checkpoint genes, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), methyltransferases, and DNA mismatch repair (MMR) genes in 33 tumors was analyzed. In addition, we compared the promoter methylation levels of EPOR in cancer tissues with those in normal tissues and performed protein-protein interaction network, gene-disease network, and genetic alteration analyses of EPOR, and finally enrichment analysis of EPOR-interacting proteins, co-expressed genes, and differentially expressed genes. The TCGA database showed that EPOR expression was upregulated in BLCA, CHOL, HNSC, KIRC, LIHC, STAD, and THCA and downregulated in LUAD and LUSC. After combining the GTEx database, EPOR expression was found to be downregulated in 18 cancer tissues and upregulated in 6 cancer tissues. The CCLE database showed that EPOR expression was highest in LAML cell lines and lowest in HNSC cell lines. Survival analysis showed that high EPOR expression was positively correlated with OS in LUAD and PAAD and negatively correlated with OS in COAD, KIRC, and MESO. Moreover, EPOR had a good prognostic ability for COAD, LUAD, MESO, and PAAD and also influenced progression-free survival, disease-specific survival, disease-free survival, and progression-free interval in specific tumors. Further, EPOR was found to play a non-negligible role in tumor immunity, and a correlation of EPOR with miRNAs, TMB, MSI, and MMR genes and methyltransferases was confirmed to some extent. In addition, the enrichment analysis revealed that EPOR is involved in multiple cancer-related pathways. The general situation of EPOR expression in cancer provided a valuable clinical reference. EPOR may be target gene of hsa-miR-575, etc. A pan-cancer analysis of panoramic schema revealed that EPOR not only may play an important role in mediating EPO-induced erythroblast proliferation and differentiation but also has potential value in tumor immunity and is expected to be a prognostic marker for specific cancers.


The Patient Concerns Inventory integrated as part of routine head and neck cancer follow-up consultations: frequency, case-mix, and items initiated by the patient.
Introduction The National Institute for Health and Care Excellence guidance Improving Supportive and Palliative Care for Adults with Cancer (2004) and the Cancer Reform Strategy (2007) support the premise that assessment and discussion of patients' needs for physical, social, psychological, and spiritual wellbeing should be undertaken during oncology follow-up. We report the use of the Patient Concerns Inventory in a routine head and neck cancer clinic setting over a seven-year period, summarising the number of available clinics, the number of patients completing the inventory within a clinic, the range of clinical characteristics and the concerns they wanted to discuss. Methods The data were analysed from oncology follow-up clinics between 1 August 2007 and 10 December 2014. Audit approval was given by the Clinical Audit Department, University Hospital Aintree. Results There were 386 patients with 1198 inventories completed at 220 clinics, median 6 (range 4-7) per clinic. The most common concerns raised by patients across all the clinic consultations were dry mouth (34%), fear of recurrence (33%), sore mouth (26%), dental health (25%), chewing (22%) and fatigue/tiredness (21%). Conclusions The incorporation of the Patient Concerns Inventory as part of routine oncology clinics allows for a more patient initiated and focused consultation available to the majority of patients throughout their follow-up. The inventory allows for greater opportunity to provide holistic targeted multiprofessional intervention and support.


A novel selective GABA(A) alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents.
In our pursuit to identify selective ligands for Bz/GABA(A) receptor subtypes, a novel pyrazolo[1,5-a]pyrimidine derivative (4), the azaisostere of zolpidem, was synthesized and evaluated in vitro on bovine brain homogenate and on recombinant benzodiazepine receptors (alphaxbeta2/3gamma2, x = 1-3, 5) expressed in HEK293 cells. Compound 4 displayed affinity only for alpha1beta2gamma2 subtype (K(i) = 31 nM), and in an in-depth, in vivo study it revealed sedative and anxiolytic-like properties without any amnesic and myorelaxant effects in rodents.


Suicide in adolescence: attempt to cure a crisis, but also the fatal outcome of certain pathologies.
Teen suicide is an alarming public health issue. The purpose of this paper is to better understand the reasons behind attempting/committing suicide. Our research focuses on adolescent psychopathology and on pathologies that are considered as adolescent suicide risk factors. We conducted literature-based research. The first part of this research was based on adolescent psychopathological traits, whilst the second concentrated on the most frequently made diagnoses in the case of adolescents who had attempted suicide. Adolescence is a period of life characterized by great instability, where everything is called into question. We can observe a high propensity towards taking action, which allows the adolescent to bypass certain questions that they cannot answer. This takes place against a background where the body, which is undergoing change, becomes the scene, the means and the purpose to answer these questions, once and for all, through suicide. Notwithstanding, the studies also show that, setting aside these psychopathological considerations that characterize every adolescent, certain diagnoses are commonly related to adolescent suicide and, as such, constitute risk factors. These pathologies are as follows: depression, adjustment disorder and personality disorder. We can, however, include some precisions as regards the frequency of these diagnoses, given that adolescence is inherently a period of life characterized by depression and that the future adult is obliged to adjust. Teen suicide is, therefore, conditioned by pathological behaviour, which is part of a necessary and normal transition, but one which is occasionally stimulated by certain pathological instabilities.


Adenosquamous carcinoma of the esophagogastric junction. Case report.
Adenosquamous carcinoma is a rare tumor with coexisting elements of infiltrating squamous cell carcinoma and adenocarcinoma. This tumor is reported to arise in different organs but rarely in the oesophagus. In most cases, it shows highly aggressive biological behaviour with high propensity to regional lymph-node metastasis and poor prognosis. We describe the management of a patient with an aggressive adenosquamous carcinoma of the esophagogastric junction.


Sulfonyl-containing aldophosphamide analogues as novel anticancer prodrugs targeted against cyclophosphamide-resistant tumor cell lines.
A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via beta-elimination, a nonenzymatic activation mechanism. Kinetic studies demonstrated that all these compounds spontaneously liberate phosphoramide mustards with half-lives in the range of 0.08-15.2 h under model physiological conditions in 0.08 M phosphate buffer at pH 7.4 and 37 degrees C. Analogous to Aldo, the rates of beta-elimination in all compounds was enhanced in reconstituted human plasma under same conditions. The compounds were more potent than the corresponding phosphoramide mustards against V-79 Chinese hamster lung fibroblasts in vitro (IC(50) = 1.8-69.1 microM). Several compounds showed excellent in vivo antitumor activity in CD2F1 mice against both P388/0 (Wild) and P388/CPA (CP-resistant) tumor cell lines.


Congenital thoracic lordosis and scoliosis in a cat.
A 10-week-old domestic shorthair kitten was referred for intermittent episodes of dyspnea, cyanosis and a suspected congenital thoracic anomaly. Physical examination showed an obvious palpable concavity in the caudal thoracic spine. Thoracic radiographs showed severe caudal thoracic lordosis from T5 to T13 with a Cobb angle of -77°, a centroid lordosis angle of -68°, a vertebral index of 6.3 and a flattened sternum. Severe loss of vital capacity was suspected and surgical correction of the thoracic deformity was to be performed in two separate stages, the first being surgical ventral distraction on the sternum to increase thoracic volume and rigid fixation with an external splint. The second stage, if required, would be surgical correction of the spinal deformity to also increase thoracic volume. The initial stage of surgery was performed and postoperative radiographs showed a vertebral index of 10.3. The kitten suffered a left sided pneumothorax in recovery and died from cardiorespiratory arrest despite immediate pleural drainage and cardiopulmonary resuscitation. Treatment recommendations that may benefit future case management are discussed.


The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: a review with emphasis on a reanalysis of previous studies.
This article evaluates the suitability of low frequency (LF) heart rate variability (HRV) as an index of sympathetic cardiac control and the LF/high frequency (HF) ratio as an index of autonomic balance. It includes a comprehensive literature review and a reanalysis of some previous studies on autonomic cardiovascular regulation. The following sources of evidence are addressed: effects of manipulations affecting sympathetic and vagal activity on HRV, predictions of group differences in cardiac autonomic regulation from HRV, relationships between HRV and other cardiac parameters, and the theoretical and mathematical bases of the concept of autonomic balance. Available data challenge the interpretation of the LF and LF/HF ratio as indices of sympathetic cardiac control and autonomic balance, respectively, and suggest that the HRV power spectrum, including its LF component, is mainly determined by the parasympathetic system.


[Operative guidelines for the shoe industry: risk assessment and environmental hygiene].
Considering the most relevant factors for occupational safety and health, the Safety Check application in the footwear industry makes little and medium size factories employers able to carry out risk assessment. However, in specific cases, it is necessary to achieve an in-depth evaluation.


Vanillin biosynthetic pathways in plants.
The present review compiles the up-to-date knowledge on vanillin biosynthesis in plant systems to focus principally on the enzymatic reactions of in planta vanillin biosynthetic pathway and to find out its impact and prospect in future research in this field. Vanillin, a very popular flavouring compound, is widely used throughout the world. The principal natural resource of vanillin is the cured vanilla pods. Due to the high demand of vanillin as a flavouring agent, it is necessary to explore its biosynthetic enzymes and genes, so that improvement in its commercial production can be achieved through metabolic engineering. In spite of significant advancement in elucidating vanillin biosynthetic pathway in the last two decades, no conclusive demonstration had been reported yet for plant system. Several biosynthetic enzymes have been worked upon but divergences in published reports, particularly in characterizing the crucial biochemical steps of vanillin biosynthesis, such as side-chain shortening, methylation, and glucoside formation and have created a space for discussion. Recently, published reviews on vanillin biosynthesis have focused mainly on the biotechnological approaches and bioconversion in microbial systems. This review, however, aims to compile in brief the overall vanillin biosynthetic route and present a comparative as well as comprehensive description of enzymes involved in the pathway in Vanilla planifolia and other plants. Special emphasis has been given on the key enzymatic biochemical reactions that have been investigated extensively. Finally, the present standpoint and future prospects have been highlighted.


Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease.
Mutations in the SCO2 gene have been associated with fatal cardioencephalomyopathy. To report a novel SCO2 mutation with prominent spinal cord involvement mimicking spinal muscular atrophy (Werdnig-Hoffmann disease). An infant girl presented at birth with generalized weakness, hypotonia, and lactic acidosis. At 1 month of age she developed hypertrophic cardiomyopathy and died of heart failure 1 month later. Neuroradiological studies were unremarkable. Muscle biopsy specimens showed groups of atrophic and hypertrophic fibers, but mutation screening of the SMN gene was negative. Histochemical and biochemical studies of respiratory chain complexes were performed, and the whole coding region of the SCO2 gene was sequenced. Findings from muscle histochemistry studies showed virtually undetectable cytochrome c oxidase activity, but normal succinate dehydrogenase reaction. Biochemical analysis in muscle confirmed a severe isolated cytochrome c oxidase deficiency. Pathologic findings of the brain were unremarkable, but the ventral horns of the spinal cord showed moderate-to-severe loss of motor neurons and astrocytosis. Sequencing of the SCO2 gene showed the common E140K mutation, and a novel 10 base-pair duplication of nucleotides 1302 to 1311, which disrupts the reading frame of the messenger RNA and gives rise to a truncated protein. The SCO2 mutations should be considered in the differential diagnosis of children with spinal muscular atrophy without mutations in the SMN gene.