An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis.
Rhinocerebral mucormycosis occurs in immunocompromised hosts with uncontrolled diabetes, solid organ transplants, and hematologic malignancies. Primary disease is in the paranasal sinuses but often progresses intracranially, via direct extension or angioinvasion. Rhinocerebral mucormycosis is rapidly fatal with a mortality rate of 85%, even when maximally treated with surgical debridement, antifungal therapy, and correction of underlying processes. We performed a retrospective chart review of patients with rhinocerebral mucormycosis from 2011 to 2014. These patients were analyzed for symptoms, surgical and medical management, and outcome. We found four patients who were diagnosed with rhinocerebral mucormycosis. All patients underwent rapid aggressive surgical debridement and were started on antifungal therapy on the day of diagnosis. Overall, we observed a mortality rate of 50%. An early aggressive multidisciplinary approach with surgical debridement, antifungal therapy, and correction of underlying disease have been shown to improve survivability in rhinocerebral mucormycosis. A multidisciplinary approach to rhinocerebral mucormycosis with otolaryngology, neurosurgery, and ophthalmology, infectious disease and medical intensivists can help reduce mortality in an otherwise largely fatal disease. Even despite these measures, outcomes remain poor, and a high index of suspicion must be maintained in at-risk populations, in order to rapidly execute a multifaceted approach.


Immunosuppressive Extracellular Vesicles as a Linking Factor in the Development of Tumor and Endometriotic Lesions in the Gynecologic Tract.
Both gynecological tumors and endometriosis require for their development a favorable environment, termed in the case of tumors a "pre-metastatic niche" and in case of endometriosis a "pro-endometriotic niche". This is characterized by chronic inflammation and immunosuppression that support the further progression of initial lesions. This microenvironment is established and shaped in the course of a vivid cross-talk between the tumor or endometrial cells with other stromal, endothelial and immune cells. There is emerging evidence that extracellular vesicles (EVs) play a key role in this cellular communication, mediating both in tumors and endometriosis similar immunosuppressive and pro-inflammatory mechanisms. In this review, we discuss the latest findings about EVs as immunosuppressive factors, highlighting the parallels between gynecological tumors and endometriosis. Furthermore, we outline their role as potential diagnostic or prognostic biomarkers as well as their future in therapeutic applications.


Choline acetyltransferase activity of the principal vestibular nuclei of rat, studied by micropunch technique.
We have assayed choline acetyltransferase (CAT) activity, as a specific marker for cholinergic neurons, in the vestibular nuclear complex (VNC) as a whole, and in the 4 individual principal vestibular nuclei, dissected by a micropunch technique. The VNC contains a significant amount of CAT activity, comparable to that of hippocampus and frontal cortex. CAT activity is relatively concentrated in the medial vestibular nucleus (MVN), which agrees with studies by others showing a greater concentration of muscarinic receptors in MVN. We conclude that cholinergic systems may play a role in central vestibular function, particularly within the MVN.


Evidence that blood group A antigen on lymphocytes is derived from the plasma.
Serum from group O volunteers, who had been injected with porcine A blood group substance, was used in lymphocytotoxicity tests. Positive reactions were obtained only with lymphocytes of group A secretors; the strongest reactors were Le(a--b--). The same group O sera reacted with group O lymphocytes which had been exposed to a glycosphingolipid fraction prepared from the plasma of A,Le(a--b--) secretors. These reactions were specifically inhibited by A substance. It is suggested that, unlike the A antigen on red cells, the A antigen detected in lymphocytotoxicity tests is entirely derived from the plasma.


Fractionation of follicle stimulating hormone charge isoforms in their native form by preparative electrophoresis technology.
Complex glycoprotein biopharmaceuticals, such as follicle stimulating hormone (FSH), erythropoietin and tissue plasminogen activator consist of a range of charge isoforms due to the extent of sialic acid capping of the glycoprotein glycans. Sialic acid occupies the terminal position on the oligosaccharide chain, masking the penultimate sugar residue, galactose from recognition and uptake by the hepatocyte asialoglycoprotein receptor. It is therefore well established that the more acidic charge isoforms of glycoprotein biopharmaceuticals have higher in vivo potencies than those of less acidic isoforms due to their longer serum half-life. Current strategies for manipulating glycoprotein charge isoform profile involve cell engineering or altering bioprocesss parameters to optimise expression of more acidic or basic isoforms, rather than downstream separation of isoforms. A method for the purification of a discrete range of bioactive recombinant human FSH (rhFSH) charge isoforms based on Gradiflowtrade mark preparative electrophoresis technology is described. Gradiflowtrade mark electrophoresis is scaleable, and incorporation into glycoprotein biopharmaceutical production bioprocesses as a potential final step facilitates the production of biopharmaceutical preparations of improved in vivo potency.


A triple duplication of the alimentary tract.
Duplications of the alimentary tract occur infrequently, and are usually isolated anomalies. In the infant described below, a complex clinical picture was the result of three distinct duplication in widely separated portions of the alimentary tract (esophagus, duodenum, ileum). Details of the clinical course and technical management of an extremely long ileal duplication form the basis for this report.


Diagnostic flow chart for targeted detection of alpha1-antitrypsin deficiency.
Alpha1-antitrypsin (AAT) deficiency is under-recognized, probably because many individuals affected show no clinical impairment. The targeted detection is a tool to increase its recognition. We prospectively submitted to AAT serum levels determination, phenotyping and, if doubtful, genotyping: (i) patients with the early onset of emphysema, emphysema in absence of recognized risk or pneumothorax (path P), antineutrophil cytoplasm antibodies (ANCA) positive vasculitis (path V), cervical artery dissection (path A), Periodic acid-Schiff (PAS) positive bodies in the liver cell or unexplained abnormal transaminase level (Path L) [index cases: IC] and (ii) subjects with low-serum alpha1-globulin (path e) and close relatives of patients with AAT deficiency (path r) [non index cases: NIC]. We determined and compared gender, age, AAT serum levels values, the ratio between AAT deficiency subjects identified and all subjects examined (identified/examined). Receiver operating characteristic (ROC) curve was plotted to find the best threshold for AAT serum levels. Two hundred and eighty-five individuals were examined and 211 with AAT deficiency identified: 66 were IC and 145 NIC. The ratio identified/examined resulted 0.74. A serum level of 120 mg/dL was able to identify AAT deficiency with a specificity of 73% and a sensitivity of 97%. IC showed male prevalence (P=0.005), more advanced age (P=0.02), lower AAT serum levels (P=0.008). Our protocol is effective to detect AAT deficiency in a selected population. About 120 mg/dL (nephelometric method) is a reliable AAT serum level cut-off for selecting subjects/patients to submit to phenotype or genotype; as compared to NIC, IC are older, mostly male and with lower AAT serum levels.


Paediatric chronic suppurative lung disease: clinical characteristics and outcomes.
We describe the clinical, bronchoscopic, bronchoalveolar lavage (BAL) and radiographic characteristics of children whose chronic wet cough did not resolve with oral antibiotics and which led to their hospitalisation for intravenous antibiotics and airway clearance therapy. Between 2010 and 2014, medical chart review identified 22 such children. Their median cough duration was 26 weeks (interquartile range (IQR) 13-52). All received oral antibiotics immediately before their hospitalisation (median 4 weeks; IQR 4-6.5). On chest examination, seven (31 %) children had auscultatory crackles. At bronchoscopy, 9 (41 %) had tracheomalacia, 18 (86 %) demonstrated airway neutrophilia (>15 %) and 12 (57 %) grew Haemophilus influenzae from their BAL fluid. They received intravenous antibiotics (mostly cefotaxime or ceftriaxone) and airway clearance therapy as inpatients (median 12.5 days (IQR 10.8-14). All were cough-free at follow-up. The children's BAL characteristics are similar to those with protracted bacterial bronchitis and bronchiectasis, but their poor clinical response to oral antibiotics and non-specific chest CT findings differentiated them from these other two disorders. The findings are consistent with chronic suppurative lung disease. Intravenous antibiotics and airway clearance therapy should therefore be considered in children whose wet cough persists despite 4 weeks of oral antibiotics and where other causes of chronic wet cough are absent. What is known on this topic? • Chronic wet cough not resolving with appropriate antibiotics increases the likelihood of bronchiectasis. • Children with chronic suppurative lung disease (CSLD) have clinical features of bronchiectasis, but lack the radiographic evidence for this diagnosis. • Children with CSLD have airway neutrophilia and predominantly Haemophilus influenzae in lower airway cultures, similar to children with protracted bacterial bronchitis and bronchiectasis. • Chronic wet cough in CSLD, unresponsive to oral antibiotics, resolves with intravenous antibiotics and airway clearance therapy.


Vitamin E status in Sudanese children with protein-energy malnutrition.
Total tocopherols and alpha-tocopherols were estimated in the plasma of children with severe malnutrition (14 marasmus; 11 marasmic kwashiorkor; five kwashiorkor) and related to the total plasma lipids and different plasma lipid classes. If the mere plasma concentrations were taken as an index of the vitamin E status, five children with marasmus, five children with marasmic kwashiorkor, and two children with kwashiorkor would have been regarded as deficient (less than 500 micrograms/dl). However, if total tocopherols and alpha-tocopherols were related to the total plasma lipids, all malnourished children--except one--showed values within the limits found in healthy American children. The study shows that low tocopherol/lipid ratios are not a constant feature in severely malnourished children.


Introduction of the MASH1 gene into mouse embryonic stem cells leads to differentiation of motoneuron precursors lacking Nogo receptor expression that can be applicable for transplantation to spinal cord injury.
ES cells transfected with the MASH1 gene yielded purified spinal motoneuron precursors expressing HB9 and Islet1. The cells lacked the expression of Nogo receptor that was of great advantage for axon growth after transplantation to an injured spinal cord. After transplantation, mice with the complete transection of spinal cord exhibited excellent improvement of the motor functions. Electrophysiological assessment confirmed the quantitative recovery of motor-evoked potential in the transplanted spinal cord. In the grafted spinal cord, gliosis was inhibited and Nogo receptor expression was scarcely detected. The transplanted cells labeled with GFP showed extensive outgrowth of axons positive for neurofilament middle chain, connected to each other and expressed Synaptophysin, Lim1/2 and Islet1. Thus, the in vivo differentiation into mature spinal motoneurons and the reconstitution of neuronal pathways were suggested. The grafted cell population was purified for neurons and was free from teratoma development. These therapeutic strategies may contribute to a potent treatment for spinal cord injury in future.


Effectiveness of 'motivational interviewing' on sick leave: a randomized controlled trial in a social insurance setting.
This study aimed to evaluate the effectiveness of motivational interviewing (MI) - a counselling approach offered by caseworkers at the Norwegian Labor and Welfare Administration (NAV) - on return to work (RTW) for individuals sick-listed for ≥8 weeks due to any diagnoses. MI was compared to usual case management and an active control during 12 months of follow-up. In a randomized clinical trial with three parallel arms, participants were randomized to MI (N=257), usual case management (N=266), or an active control group (N=252). MI consisted of two MI sessions while the active control involved two sessions without MI, both were offered in addition to usual case management. The primary outcome was number of sickness absence days based on registry data. Secondary outcomes included time to sustainable RTW, defined as four consecutive weeks without medical benefits. The median number of sickness absence days for the MI group was 73 days [interquartile range (IQR) 31-147], 76 days (35-134) for usual care, and 75 days (34-155) for active control. In total 89%, 88% and 86% of the participants, respectively, achieved sustainable RTW. The adjusted hazard ratio (HR) for time to sustainable RTW was 1.12 (95% CI 0.90-1.40) for MI compared to usual case management and HR 1.16 (95% CI 0.93-1.44) compared to the active control. This study did not provide evidence that MI offered by NAV caseworkers to sick-listed individuals was more effective on RTW than usual case management or an active control. Providing MI in this context could be challenging as only half of the MI group received the intervention.


Prospective Cross-Sectional Evaluation of Penile Helicine Circulation by Power Doppler During Dynamic Ultrasound in Veno-Occlusive Erectile Dysfunction.
To evaluate the usefulness of Power Doppler to improve the diagnostic work up of veno-occlusive erectile dysfunction patients. Patients affected by erectile dysfunction, mean IIEF 5 = 13.5 (12-17) for at least 6 months, were enrolled in a prospective cross-sectional study. All patients underwent Dynamic Power Doppler after intracavernous injection of vasoactive drugs (PGE1 20 mcg and Papaverine 6 mg). Poor responders' patients subsequently underwent to cavernosometry to get a full assessment of the vascular framework. 202 patients (mean age 46 years), were included in the study. 96 subjects (47.5%) who did not adequately respond to the intracavernous injection -test, subsequently underwent to cavernosometry. In 42 of 96 patients (43.7%) cavernosometry was positive for veno-occlusive dysfunction. In a total of 160 patients who did not have veno-occlusive dysfunction (54 with negative cavernosometry + 106 intracavernous injection-test responders), the Power Doppler was normal in 126 (78.8%) and pathological in 34 (21.3%) in terms of steric conformation of "low flow" vessels corresponding to the Cavernosal Terminal Unit. The diagnostic sensitivity of Power Doppler towards veno-occlusive dysfunction was found to be 52.4% (Positive Predictive Value: 39.3%), the specificity was 78.8% (Negative Predictive Value: 86.3%) and the total diagnostic accuracy was equal to 73.3%. Collected data evidenced that patients who reported altered morphological features of the Cavernosal Terminal Unit had an approximately 4-fold greater risk of having veno-occlusive dysfunction compared to patients who had normal Power Doppler features (OR = 4.076; 95% CI: 1.996-8.327).


Administration of tranexamic acid during total shoulder arthroplasty is not associated with increased risk of complications in patients with a history of thrombotic events.
Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion risk in various orthopedic surgeries including shoulder arthroplasty. However, concerns still exist regarding its use in patients with a history of thrombotic events. Using national claims data, we aimed to study the safety of TXA administration in shoulder arthroplasty patients with a history of thrombotic events. We used retrospective national claims data (Premier Healthcare) on 71,174 patients who underwent a total or reverse shoulder arthroplasty between 2010 and 2016. TXA use was evaluated specifically within a subgroup of patients with a history of thrombotic events such as myocardial infarction, deep venous thrombosis, pulmonary embolism, transient ischemic attack, or ischemic stroke. Studied outcomes were blood transfusion need, complications (including acute renal failure, new onset myocardial infarction, deep venous thrombosis, pulmonary embolism, transient ischemic attack, or ischemic stroke), and cost and length of hospitalization. Mixed-effects models measured the association between TXA use and outcomes, separately in patients with and without a history of thrombotic events. Odds ratios (OR) or percent change for continuous outcomes with 95% confidence intervals (CI) were reported. Overall, TXA was used in 13.7% (n = 9735) of patients, whereas 10.5% (n = 7475) of patients had a history of a thrombotic event. After adjustment for relevant covariates, TXA use (compared with no TXA use) in patients without a history of thrombotic events was associated with decreased odds of blood transfusions (OR, 0.48; CI, 0.24-0.98; P = .0444), whereas no increased odds for complications were observed (OR, 0.83; CI, 0.40-1.76; P = .6354). Similar results were observed in patients with a history of thrombotic events. Moreover, in this subgroup, TXA use was associated with a slight reduction in hospitalization cost (-8.9% CI: -13.1%; -4.6%; P < .0001; group median $18,830). Among shoulder arthroplasty patients, TXA use was not associated with increased complication odds, independent of a history of thrombotic events. These findings are in support of wider TXA use.


Does Kin-Selection Theory Help to Explain Support Networks among Farmers in South-Central Ethiopia?
Social support networks play a key role in human livelihood security, especially in vulnerable communities. Here we explore how evolutionary ideas of kin selection and intrahousehold resource competition can explain individual variation in daily support network size and composition in a south-central Ethiopian agricultural community. We consider both domestic and agricultural help across two generations with different wealth-transfer norms that yield different contexts for sibling competition. For farmers who inherited land rights from family, firstborns were more likely to report daily support from parents and to have larger nonparental kin networks (n = 180). Compared with other farmers, firstborns were also more likely to reciprocate their parents' support, and to help nonparental kin without reciprocity. For farmers who received land rights from the government (n = 151), middle-born farmers reported more nonparental kin in their support networks compared with other farmers; nonreciprocal interactions were particularly common in both directions. This suggests a diversification of adult support networks to nonparental kin, possibly in response to a long-term parental investment disadvantage of being middle-born sons. In all instances, regardless of inheritance, lastborn farmers were the most disadvantaged in terms of kin support. Overall, we found that nonreciprocal interactions among farmers followed kin selection predictions. Direct reciprocity explained a substantial part of the support received from kin, suggesting the importance of the combined effects of kin selection and reciprocity for investment from kin.


The prognostic significance of preoperative nutritional/inflammatory markers and clinicopathological features in resectable esophagectomy patients: possibility of nutritional intervention.
Preoperative inflammatory or nutritional biomarkers and clinicopathological features may be survival predictors in resectable esophageal squamous cell carcinoma. We included 118 patients with resectable squamous esophageal carcinoma (stages I-IV), assessing preoperative CRP- and albumin-based modified Glasgow prognostic score, the modified controlling nutritional status score, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, pathologic stage, and tumor location(s), looking for correlation with overall survival and relapse-free survival. Using univariate and Cox analysis, we selected the most reliable prognostic factors. Five-year overall survival and recurrence-free survival were 54.9% and 48.5%, respectively. C-reactive protein values correlated negatively with hypoalbuminemia (P = 0.0036). On univariate analysis, tumor stage, invasion depth, location, nodal involvement, albumin, and modified Glasgow prognostic score were significant prognostic factors for overall and recurrence-free survival. Preoperative C-reactive protein was prognostic factor for overall survival, but not for relapse-free survival (P = 0.017, 0.063, respectively). The Cox proportional hazards model showed the modified Glasgow prognostic score to be an independent prognostic factor for relapse-free survival and overall survival after using the stepwise variable selection procedure. Cox analysis including clinicopathological factors and modified Glasgow prognostic scores showed that only tumor location(s) and pathologic stage were independent prognostic factors for overall survival and recurrence-free survival. Although the modified Glasgow prognostic score is not superior to pathologic stage and tumor location as a biomarker of preoperative nutrition/inflammation and clinicopathological factors, it remains an important prognostic marker in resectable esophageal cancers. Preoperative decreased inflammatory response and improved nutritional status may contribute to prognosis in patients with esophageal cancer.


Effect of putative carcinoid mediators on gastric and small bowel transit in rats and the role of 5-HT receptors.
Whereas serotonin and substance P stimulate in-vivo and in-vitro myoelectric activity in the small intestine, their effects on transit are unclear. We used a validated in-vivo transit model in the chloral hydrate-anaesthetized rat to study the effects of serotonin, substance P and motilin, three putative mediators of carcinoid diarrhoea, on transit through the upper digestive tract. Intra-arterial serotonin accelerated gastric emptying of a radiolabelled liquid, while motilin accelerated overall upper gastrointestinal transit. Substance P slowed overall upper gastrointestinal transit without altering gastric emptying. The antagonists to serotonin receptor subtypes, R-zacopride (5-HT3) and ketanserin (5-HT2), also accelerated rat gastric emptying of liquids; in contrast, a 5-HT4 agonist, SC53116, resulted in a less pronounced effect on gastric emptying at the dose tested. We conclude that circulating substance P is unlikely to be an important accelerator of transit through the upper digestive tract; in contrast, hyperserotoninaemia significantly accelerates transit through the stomach, and 5-HT2 and 5-HT3 receptor subtypes may play a role in the motor effects of serotonin in the stomach.


Penetrating Keratoplasty Using the Femtosecond Laser: A Comparison of Postoperative Visual Acuity and Astigmatism by Suture Pattern.
To compare the effect of 3 common suturing techniques on eyes that received femtosecond laser-enabled penetrating keratoplasty (FLEK) with a zig-zag configuration at the Gavin Herbert Eye Institute, University of California- Irvine, California. This is a retrospective chart review of a series of 319 eyes of 286 patients who underwent FLEK with a zig-zag configuration. One hundred fifty-seven eyes had running sutures, 136 eyes had simple interrupted sutures, and 26 eyes had combined sutures (single running and simple interrupted). The main outcome measures were uncorrected distance visual acuity, best spectacle-corrected visual acuity (BSCVA), and topographic astigmatism (TCyl). These parameters were recorded for the first year of follow-up regardless of suture removal status and also after full suture removal. At 3 months, the BSCVA of the running, interrupted, and combined suture groups was 0.22 (±0.2), 0.41 (±0.3), and 0.29 (±0.1), respectively (P < 0.01). The mean TCyl of the running, interrupted, and combined groups at 3 months was 3.95 (±2.7), 6.41 (±4.4), and 5.44 (±3.3) D, respectively (P < 0.01) All sutures were removed in 190 of 319 eyes, and at the last recorded visit, the mean BSCVA was 0.18 (±0.2), 0.34 (±0.2), and 0.19 (±0.2) logarithm of the minimum angle of resolution in the running, interrupted, and combined groups, respectively (P < 0.01) and mean TCyl was 4.51 (±2.8), 5.62 (±3.7), and 4.57 (±2.9) D, respectively (P = 0.11). Better visual acuity after full suture removal was observed in the running suture group; however, the subgroups of patients with keratoconus were similar after all sutures were removed.


ProTstab - predictor for cellular protein stability.
Stability is one of the most fundamental intrinsic characteristics of proteins and can be determined with various methods. Characterization of protein properties does not keep pace with increase in new sequence data and therefore even basic properties are not known for far majority of identified proteins. There have been some attempts to develop predictors for protein stabilities; however, they have suffered from small numbers of known examples. We took benefit of results from a recently developed cellular stability method, which is based on limited proteolysis and mass spectrometry, and developed a machine learning method using gradient boosting of regression trees. ProTstab method has high performance and is well suited for large scale prediction of protein stabilities. The Pearson's correlation coefficient was 0.793 in 10-fold cross validation and 0.763 in independent blind test. The corresponding values for mean absolute error are 0.024 and 0.036, respectively. Comparison with a previously published method indicated ProTstab to have superior performance. We used the method to predict stabilities of all the remaining proteins in the entire human proteome and then correlated the predicted stabilities to protein chain lengths of isoforms and to localizations of proteins.


Malignant pleural mesothelioma in a female lion (Panthera leo).
An 18-year-old female lion (Panthera leo) was referred to the Department of Animal Pathology of the University of Turin (Italy). At necropsy, multiple nodular, 4-20-mm, confluent white firm nodules were scattered throughout the pleural surfaces of the thoracic wall and of the lungs. Histological lesions were represented by proliferations of papillary structures lined by cuboidal basophilic mesothelial cells with large, oval nuclei and abundant granular eosinophilic cytoplasm. Immunohistochemistry revealed immunoreactivity for pancytokeratin and vimentin. None of the cells expressed calretinin antigen. Asbestos fibers and asbestos bodies were not detected respectively by light microscopy and by Scanning Electron Microscope-Energy Dispersive Spectrometer investigations. On the contrary, chrysotile asbestos were identified in samples from shelter material. Histological and immunohistochemical findings were consistent with the diagnosis of an epithelial malignant mesothelioma. To our best knowledge, this is the first report of a pleural mesothelioma in a lion.


Inhibitory effect of PWM-stimulated OKT4+ subsets on erythro-, granulo- and megakaryocytopoiesis in vitro.
Normal human peripheral blood T cells and T-cell subsets defined by monoclonal antibodies of the OKT series were pretreated with pokeweed mitogen (PWM). Their effects on the haematopoietic precursors, erythroid (BFU-E, CFU-E), granulocyte-macrophage (CFU-GM) and megakaryocyte (CFU-M) colony forming cells were evaluated by coculture. While unstimulated T cells and T-cell subsets enhanced growth of autologous blood BFU-E, PWM-stimulated T and OKT4+ cells suppressed it, also inhibiting proliferation of both autologous and allogeneic bone marrow BFU-E, CFU-E, CFU-GM and CFU-M. PWM-stimulated OKT8+ cells had little effect on the growth of any of the precursors at the cell concentration at which growth was completely inhibited by PWM-stimulated OKT4+ cells. Irradiation of T or OKT4+ cells with 3000 rad before PWM stimulation completely abrogated the inhibition. These observations might be related to the mechanism of pancytopenia in some cases of immune-mediated aplastic anaemia.


Inpatient costs and paramilitary punishment beatings in northern Ireland.
Paramilitary punishment beatings are a common occurrence in Northern Ireland. Little is known about the costs such attacks impose on the health service. Data was collected retrospectively on victims treated by Northern Ireland's regional specialist orthopaedics unit. Data related to all victims treated in the unit between January 1999 and May 2000. Average inpatient care costs were 2010 Pounds ($2914). There was no significant difference in these between patients who were shot and those who were beaten. Punishment beatings present a small but significant cost burden to the health service. A fuller understanding of them from a health care perspective is warranted.


Mechanical behavior of infrapatellar fat pad of patients affected by osteoarthritis.
The infrapatellar fat pad (IFP) is an adipose tissue present in the knee that lies between the patella, femur, meniscus and tibia, filling the space between these structures. IFP facilitates the distribution of the synovial fluid and may act to absorb impulsive actions generated through the joint. IFP in osteoarthritis (OA) pathology undergoes structural changes characterized by inflammation, hypertrophy and fibrosis. The aim of the present study is to analyze the mechanical behavior of the IFP in patients affected by end-stage OA. A specific test fixture was designed and indentation tests were performed on IFP specimens harvested from OA patients who underwent total knee arthroplasty. Experiments allowed to assess the typical features of mechanical response, such as non-linear stress-strain behavior and time-dependent effects. Results from mechanical experimentations were implemented within the framework of a visco-hyperelastic constitutive theory, with the aim to provide data for computational modelling of OA IFP role in knee mechanics. Initial and final indentation stiffness were calculated for all subjects and statistical results reveled that OA IFP mechanics was not significantly influenced by gender, BMI and sample preparation. OA IFP mechanical behavior was also compared to that of other adipose tissues. OA IFP appeared to be a stiffer adipose tissue compared to subcutaneous, visceral adipose tissues and heel fat pads. It is reasonable that fibrosis induces a modification of the tissue destabilizing the normal distribution of forces in the joint during movement, causing a worsening of the disease.


Computational Models of Polymer Synthesis Driven by Dehydration/Rehydration Cycles: Repurination in Simulated Hydrothermal Fields.
Cycles of biologically relevant reactions are an alternative to an origin of life emerging from a steady state away from equilibrium. The cycles involve a rate at which polymers are synthesized and accumulate in microscopic compartments called protocells, and two rates in which monomers and polymers are chemically degraded by hydrolytic reactions. Recent experiments have demonstrated that polymers are synthesized from mononucleotides and accumulate during cycles of hydration and dehydration, which means that the rate of polymer synthesis during the dehydrated phase of the cycle is balanced (but not dominated) by the rate of polymer hydrolysis during the hydrated phase of the cycle. Furthermore, depurination must be balanced by the reverse process of repurination. Here we describe a computational model that was inspired by experimental results, can be generalized to accommodate other reaction parameters, and has qualitative predictive power.


The association between psychosocial care by physicians and patients' trust: a retrospective analysis of severely injured patients in surgical intensive care units.
Trust is an essential element in physician-patient interaction fostering in general adherence and improving patient- and physician-reported outcomes. Regarding severely injured patients, trust-building behaviour is important because of the severity of injuries and therefore potential associated physical and psychological consequences. The objective of this study was to identify significant and relevant determinants on trust of severely injured patients in their physicians in surgical intensive care units. Ninety-one severely injured patients completed a self-administered questionnaire after being transferred from surgical intensive care unit to surgical unit. All patients were treated in four hospitals of maximal care in North Rhine-Westphalia between 2001 and 2005. To assess different aspects of trust the "trust in physician" scale of the Cologne Patient Questionnaire (CPQ) was used. "Psychosocial care by physicians" is measured through: support, devotion, information and shared-decision making provided by physicians. Patient- and trauma related control variables are also included in a logistic regression model. Stepwise logistic regression identified "psychosocial care provided by physicians" as a significant contributor to severely injured patients' trust (Nagelkerke's R(2): 41%). "Trust in physicians" is correlated with all four dimensions of "psychosocial care by physicians": support (0.546), devotion (0.443), information (0.396), and shared-decision making behaviour (0.342) provided by physicians in surgical intensive care units. This finding confirms the importance of supportive communication style in physician-patient interaction concerning reported trust of severely injured patients on surgical intensive care units. Medical education should integrate sound knowledge about psychosocial aspects of interaction to provide effective emotional and informational support to build up and maintain patient trust.


Characterization of Mild and Moderate Dysarthria in Parkinson's Disease: Behavioral Measures and Neural Correlates.
Alterations in speech and voice are among the most common symptoms in Parkinson's disease (PD), often resulting in motor speech disorders such as hypokinetic dysarthria. We investigated dysarthria, verbal fluency, executive functions, and global cognitive function in relation to structural and resting-state brain changes in people with PD. Participants with mild-moderate PD (n = 83) were recruited within a randomized controlled trial and divided into groups with varying degrees of dysarthria: no dysarthria (noDPD), mild dysarthria (mildDPD), moderate dysarthria (modDPD), and also combined mildDPD and modDPD into one group (totDPD). Voice sound level and dysphonia, verbal fluency, motor symptoms, executive functions, disease severity, global cognition, and neuroimaging were compared between groups. Gray matter volume and intensity of spontaneous brain activity were analyzed. Additionally, regressions between behavioral and neuroimaging data were performed. The groups differed significantly in mean voice sound level, dysphonia, and motor symptom severity. Comparing different severity levels of dysarthria to noDPD, groups differed focally in resting-state activity, but not in brain structure. In totDPD, lower scores on semantic verbal fluency, a composite score of executive functions, and global cognition correlated with lower superior temporal gyrus volume. This study shows that severity of dysarthria may be related to underlying structural and resting-state brain alterations in PD as well as behavioral changes. Further, the superior temporal gyrus may play an important role in executive functions, language, and global cognition in people with PD and dysarthria.


Prevalence of neuropsychiatric adverse events and associated factors among adult patients on dolutegravir attending Mulago ISS clinic.
Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor that is recommended by the World Health Organization as the preferred first-line and second-line antiretroviral therapy (ART) in patients with HIV. In 2018, Uganda started using DTG-based regimens as the preferred first-line ART. However, concerns regarding the potential neurotoxicity of DTG have been increasing. Data on the occurrence of neuropsychiatric adverse events (NPAEs) and the associated factors among adult patients who are initiated on or switched to DTG-based first-line or second-line ART in Uganda are limited. This study aimed to determine the prevalence of NPAEs among adult patients on DTG and the factors associated with their occurrence. We conducted a cross-sectional study using questionnaires administered by a trained research assistant between 15 November 2021 and 15 December 2021. The study included patients aged ≥18 years with HIV who were either initiated on or switched to a DTG-based ART regimen between 1 January 2018 and 31 October 2021. Informed consent and data were collected from 892 participants attending Mulago ISS clinic, including data on age, sex, marital status, disclosure status, current regimen, duration on ART, concurrent illness, concurrent medications, year of switch to DTG, duration on DTG, whether the onset of NPAEs was immediate or delayed, history of alcohol use or smoking, level of education, report of NPAEs while on DTG, and history of NPAEs while on previous regimen. Data were entered into Epidata version 188.8.131.52 then exported to Stata version 14 for analysis. Of the 892 adults on DTG attending Mulago ISS clinic, 41.7% (95% confidence interval [CI] 38.5%-44.9%) experienced at least one NPAE. DTG duration in years (adjusted prevalence [aPR] = 1.21, p = 0.024), disclosure status (aPR = 1.40, p = 0.042), concurrent medications (aPR = 1.31, p = 0.026), year of switch to DTG, and concurrent illness were associated with an increased occurrence of NPAEs. The prevalence of NPAEs was higher than that reported by any clinical trial. About 9.1% of participants had experienced severe to life-threatening NPAEs that required intervention from a healthcare professional to improve tolerability. The high prevalence requires that clinicians screen for NPAEs at very visit and reassure patients to maximize the benefits of long-term ART.


Curcumin analogue inhibits lipid peroxidation in a freshwater teleost, Anabas testudineus (Bloch)--an in vitro and in vivo study.
The effect of a synthetic curcumin analogue (salicylcurcumin) on fish lipid peroxidation was investigated in both in vitro and in vivo conditions using a teleost model Anabas testudineus (Bloch). Curcumin analogue inhibited the formation of lipid peroxidation products and thiobarbituric acid reactive substances (TBARS) content at the three concentrations (10(-2) M, 10(-3) M and 10(-4) M) in vitro. TBARS content was reduced by 80% in the liver and 68% in brain by the higher concentration of salicylcurcumin. For in vivo study, salicylcurcumin (0.5%) was supplemented along with the basal feed for a period of 60 days. It produced a 60% reduction in liver TBARS content. The antioxidant enzyme superoxide dismutase (SOD) was stimulated, whereas catalase (CAT) and glutathione peroxidase (GPx) were inhibited. Glutathione (GSH) was reduced and glutathione reductase (GR) unchanged. Even though there was an increase in SOD activity, the CAT and GPx did not increase accordingly, maybe due to the direct scavenging of H(2)O(2) by salicylcurcumin. The protein content also increased in the curcumin-fed animals, indicating a positive growth-promoting effect. Therefore, it would be beneficial to supplement salicylcurcumin along with the aquaculture feed in order to help the fish to cope with adverse conditions in the environment. This would increase the survival rate, disease resistance and ultimately the growth rate.


A dataset on service crop phenotypic characteristics related to their ability to deliver a set of ecological functions.
The dataset presented in this article describe 33 species or varieties of service crops cultivated in population under non-limiting conditions. The description was made at flowering. 41 variables were measured on leaves, stems, roots and seeds. They related to plant phenology (1), morphology (13), physiology (1), biochemistry (18), size (6) and reproduction (2). This dataset is made available to enable comparisons between datasets, extended analysis and meta-analysis on cover crops. The data presented in this article were partly used in the research article entitled "A trait-based characterization of cover plants to assess their potential to provide a set of ecological services in banana cropping systems" (Damour et al., 2014).


Generation and characterization of an induced pluripotent stem cell (iPSC) line from a patient with clozapine-resistant Schizophrenia.
Peripheral Blood Mononuclear Cells (PBMCs) were collected from a patient with clozapine-resistant (also known as "super-refractory") Schizophrenia. iPSCs were established with a non-integrating Sendai virus-based reprogramming system. A footprint-free hiPSC line was characterized to express the main endogenous pluripotency markers and to retain a normal karyotype. Cells showed pluripotency competency by giving rise to progeny of differentiated cells belonging to the three germ layers. This hiPSC line represents a valuable tool to obtain mature, pathology-relevant neuronal populations in vitro that are suitable to investigate the molecular background of the schizophrenic disorder and the resultant patients' response to treatments.


Amino acid, iodine, selenium, and coat color status among hyperthyroid, Siamese, and age-matched control cats.
Hyperthyroidism is common among older cats, but its pathogenesis remains poorly understood. Siamese and Himalayan cats have a reduced risk of hyperthyroidism compared with domestic short-hair cat breeds. A mechanism of risk reduction in pointed-coat breeds is unknown. To determine if tyrosine, phenylalanine, iodine, or selenium blood concentrations are altered in hyperthyroid cats and to describe the plasma amino acid profiles of client-owned cats with naturally occurring hyperthyroidism. Twenty-seven client-owned cats with (n = 12) and without (n = 15) hyperthyroidism were studied. Cross-sectional study. Hyperthyroid cats were prospectively recruited among cats presenting for radioiodine therapy. Control cats were recruited among pets of hospital personnel. Blood was collected for total thyroxine, plasma amino acid, selenium, and iodine determination. Coat color (8 white or pointed; 19 dark), breed, and diet history were recorded. Tyrosine, phenylalanine, iodine, and selenium levels were not significantly different among light or dark cats or cats with or without hyperthyroidism (P > .05). Plasma amino acid profiles of hyperthyroid cats and control cats were similar, and neither group was deficient in any of the amino acids. L-glutamine was significantly lower in cats with hyperthyroidism (mean ± SD: 648 ± 193) compared with control cats (816 ± 134; P < .05). Altered tyrosine, iodine, and selenium metabolism were not associated with coat color or hyperthyroidism in pointed or light coat-colored cats.


Associations between adverse childhood experiences and early adolescent problematic screen use in the United States.
Problematic screen use, defined as an inability to control use despite private, social, and professional life consequences, is increasingly common among adolescents and can have significant mental and physical health consequences. Adverse Childhood Experiences (ACEs) are important risk factors in the development of addictive behaviors and may play an important role in the development of problematic screen use. Prospective data from the Adolescent Brain Cognitive Development Study (Baseline and Year 2; 2018-2020; N = 9,673, participants who did not use screens were excluded) were analyzed in 2023. Generalized logistic mixed effects models were used to determine associations with ACEs and the presence of problematic use among adolescents who used screens based on cutoff scores. Secondary analyses used generalized linear mixed effects models to determine associations between ACEs and adolescent-reported problematic use scores of video games (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phones (Mobile Phone Involvement Questionnaire). Analyses were adjusted for potential confounders including age, sex, race/ethnicity, highest parent education, household income, adolescent anxiety, depression, and attention-deficit symptoms, study site, and participants who were twins. The 9,673 screen-using adolescents ages 11-12 years old (mean age 12.0) were racially and ethnically diverse (52.9% White, 17.4% Latino/Hispanic, 19.4% Black, 5.8% Asian, 3.7% Native American, 0.9% Other). Problematic screen use rates among adolescents were identified to be 7.0% (video game), 3.5% (social media), and 21.8% (mobile phone). ACEs were associated with higher problematic video game and mobile phone use in both unadjusted and adjusted models, though problematic social media use was associated with mobile screen use in the unadjusted model only. Adolescents exposed to 4 or more ACEs experienced 3.1 times higher odds of reported problematic video game use and 1.6 times higher odds of problematic mobile phone use compared to peers with no ACEs. Given the significant associations between adolescent ACE exposure and rates of problematic video and mobile phone screen use among adolescents who use screens, public health programming for trauma-exposed youth should explore video game, social media, and mobile phone use among this population and implement interventions focused on supporting healthy digital habits.


Dopamine Is Required for the Neural Representation and Control of Movement Vigor.
Progressive depletion of midbrain dopamine neurons (PDD) is associated with deficits in the initiation, speed, and fluidity of voluntary movement. Models of basal ganglia function focus on initiation deficits; however, it is unclear how they account for deficits in the speed or amplitude of movement (vigor). Using an effort-based operant conditioning task for head-fixed mice, we discovered distinct functional classes of neurons in the dorsal striatum that represent movement vigor. Mice with PDD exhibited a progressive reduction in vigor, along with a selective impairment of its neural representation in striatum. Restoration of dopaminergic tone with a synthetic precursor ameliorated deficits in movement vigor and its neural representation, while suppression of striatal activity during movement was sufficient to reduce vigor. Thus, dopaminergic input to the dorsal striatum is indispensable for the emergence of striatal activity that mediates adaptive changes in movement vigor. These results suggest refined intervention strategies for Parkinson's disease.


Continuous electroencephalogram monitoring in the critically ill.
The use of continuous electroencephalogram (cEEG) monitoring in the intensive care unit is becoming more widespread, with improvements in data storage capability and networking and the increasing awareness of nonconvulsive seizures. Current and potential uses for this technology include seizure detection, ischemia detection, and prognostication. Nonconvulsive seizures are common in the critically ill, particularly those with acute brain injury and those who are comatose. The implications of some of the electrographical patterns observed in critically ill patients are not yet clear. This article discusses findings with cEEG to date, pitfalls in performing and interpreting these studies, and where we should turn our attention with this underutilized brain monitoring technique.


Lineage-specific mechanism of drug and radiation resistance in melanoma mediated by tyrosinase-related protein 2.
A major obstacle in the clinical management of malignant melanoma is its intrinsic resistance to chemotherapy and radiation therapy. Consequently, most patients with melanoma often do not respond to conventional anticancer therapy in a clinically significant manner. Recent advances in cancer research have provided new insights into the mechanisms of intrinsic resistance in melanomas. We have recently reported that the over-expression of tyrosinase-related protein 2 (TYRP2), an enzyme that is well characterized for its function in melanin synthesis, is associated specifically with resistance to DNA damaging drugs and radiation treatment. This review will summarize our findings as well as discuss the possible mechanisms by which TYRP2 over-expression contributes to intrinsic resistance in human malignant melanoma.


[Detection of angiogenesis-dependent parameters by functional MRI: correlation with histomorphology and evaluation of clinical relevance as prognostic factor using cervix carcinoma as an example].
Purpose of this study is to compare functional MRI parameters with histomorphological markers of tumor microvessel density (MVD) and permeability (vascular endothelial growth factor) and to determine the ultimate value of both approaches by correlation with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the operative whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using logrank statistics. Significant (p < 0.05-0.01) associations were found between MVD and dynamic MRI parameters. No significant relationships were observed between VEGF expression and dynamic MRI parameters. Disease outcome was better assessed with dynamic MRI parameters than with the histomorphological approach. It is concluded that 1) the pathophysiological basis for the amplitude A in dynamic MRI is MVD but not VEGF expression; and 2) a functional, dynamic MRI approach may be more suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis.


Comparative efficacy of inhalers in mild-to-moderate asthma: systematic review and network meta-analysis.
The comparative effectiveness of different inhaler therapies in mild-to-moderate asthma remains unclear. To assess this, we performed a systematic review and network meta-analysis of randomized controlled trials on the use of inhalers for mild-to-moderate asthma by searching PubMed, Cochrane, and Embase. A total of 29 trials including 43,515 patients and 12 types of inhaler therapies were included. For the prevention of severe and moderate-to-severe exacerbations, inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) as maintenance and reliever (SMART) showed the highest rank for effectiveness. As-needed ICS/LABA or short-acting β2-agonist (SABA) was similar to low-dose ICS and superior to as-needed SABA or LABA for the prevention of severe and moderate-severe exacerbations. As for lung function (FEV1), low-dose ICS/LABA had the highest rank; as-needed ICS/LABA was inferior to regular low-dose ICS but superior to placebo. Higher-dose ICS had a superior effect on the Asthma Control Questionnaire (ACQ) scores, and as-needed ICS/LABA and as-needed SABA or LABA had lower ranks in p-rankogram than did the regular use of low-dose ICS. As-needed ICS with LABA or SABA was more effective than a similar dose of regular ICS for preventing exacerbation in mild-to-moderate asthma. As-needed ICS showed some weakness in improving lung function and controlling asthma symptoms.


Effector properties and glycosylation patterns of recombinant human anti-D-IgG1 antibodies produced by human PER.C6(®) cells.
Creation of effective monoclonal anti-D immunoglobulin for prevention of hemolytic disease of the newborn remains an unsolved problem because there is still no producer cell strain providing stable production and adequate glycosylation of antibodies. Recombinant anti-D have been obtained on the basis of human PER.C6(®) cells and characterized. Anti-D antibodies expressed in PER.C6(®) exhibited lower hemolytic activity in antibody-dependent cytotoxicity (ADCC) reaction mediated by low-affinity Fcγ receptors in comparison with identical antibodies of lymphoblastoid origin. Monoclonal antibodies produced by PER.C6(®) are completely fucosylated and desialylated, i.e. are characterized by abnormal glycosylation. Addition of kifunensine (α-mannosidase I inhibitor) to the medium led to production of antibodies with high hemolytic activity. Reduced activity of monoclonal antibodies in PER.C6(®) cells and the effect of kifunensine (causing synthesis of defucosylated glycans) suggest that the absence of fucose is the key factor responsible for Fc affinity for low-affinity receptors.


Shared biology of GVHD and GVT effects: potential methods of separation.
The difficult separation of clinical graft-versus-tumor (GVT) effects from graft-versus-host disease (GVHD) reflects their shared biology. Experimental approaches to mediate GVT effects while limiting GVHD include: (1) allograft T cell depletion followed by immune enhancement; (2) modulation of T cell dose or T cell subset composition; (3) donor lymphocyte infusion; (4) reduced-intensity host preparation; (5) modulation of Th1/Th2 and Tc1/Tc2 cell balance; (6) cytokine therapy or neutralization; (7) T regulatory cell therapy; (8) co-stimulatory pathway modulation; (9) chemokine pathway modulation; (10) induction of antigen-specific T cells; (11) alloreactive NK cell therapy; and (12) targeted pharmaceutical inhibition of proteosome, mammalian target of rapamycin, and histone deacetylase pathways. Clearly, a multitude of approaches exist that hold promise for separating GVT effects from GVHD. Future success in this endeavor will require a strong commitment towards translational research and continued advances in cell, vaccine, cytokine, monoclonal antibody, and targeted molecular therapy.


Psychological impact on healthcare workers, general population and affected individuals of SARS and COVID-19: A systematic review and meta-analysis.
Any infectious disease outbreak may lead to a negative detrimental psychological impact on individuals and the community at large, however; there was no systematic review nor meta-analysis that examined the relationship between the psychological/mental health impact of SARS and COVID-19 outbreak in Asia. A systematic search was conducted using PubMed, EMBASE, Medline, PsycINFO, and CINAHL databases from 1/1/2000 to 1/6/2020. In this systematic review and meta-analysis, we analyzed the psychological impact on confirmed/suspected cases, healthcare workers and the general public during the Severe Acute Respiratory Syndrome (SARS) outbreak and Coronavirus disease (COVID-19) epidemics. Primary outcomes included prevalence of depression, anxiety, stress, post-traumatic stress disorder, aggression, sleeping problems and psychological symptoms. Twenty-three eligible studies (N = 27,325) were included. Random effect model was used to analyze the data using STATA. Of these studies, 11 were related to the SARS outbreak and 12 related to COVID-19 outbreaks. The overall prevalence rate of anxiety during SARS and COVID-19 was 37.8% (95% CI: 21.1-54.5, P < 0.001, I2 = 96.9%) and 34.8% (95% CI: 29.1-40.4), respectively. For depression, the overall prevalence rate during SARS and COVID-19 was 30.9% (95% CI: 18.6-43.1, P < 0.001, I2 = 97.3%) and 32.4% (95% CI: 19.8-45.0, P < 0.001, I2 = 99.8%), respectively. The overall prevalence rate of stress was 9.4% (95% CI: -0.4 -19.2, P = 0.015, I2 = 83.3%) and 54.1% (95% CI: 35.7-72.6, P < 0.001, I2 = 98.8%) during SARS and COVID-19, respectively. The overall prevalence of PTSD was 15.1% (95% CI: 8.2-22.0, P < 0.001) during SARS epidemic, calculated by random-effects model (P < 0.05), with significant between-study heterogeneity (I2 = 93.5%). The SARS and COVID-19 epidemics have brought about high levels of psychological distress to individuals. Psychological interventions and contingent digital mental health platform should be promptly established nationwide for continuous surveillance of the increasing prevalence of negative psychological symptoms. Health policymakers and mental health experts should jointly collaborate to provide timely, contingent mental health treatment and psychological support to those in need to reduce the global disease burden. CRD42020182787, identifier PROSPER.


Reversible single-crystal-to-single-crystal guest exchange in a 3-D coordination network based on a zinc porphyrin.
A self-complementary tecton based on a zinc porphyrin core bearing two pyridines at the opposite meso positions leads to the formation of a 3-D coordination network in the crystalline phase which offers channels which are filled with solvent molecules; reversible exchange of the guest molecules has been proven to take place in a single-crystal-to-single-crystal type transformation demonstrating the robustness of the coordination framework.


[Studies on the analysis of nifedipine considering in particular transformation products formed by light exposition (author's transl)].
Under the influence of light (VIS and UV) on thin-layer plates and in liquid solutions, 1,4-dihydro-2,6-dimethyl-4-(0-nitro-phenyl)-pyridine-3,5-carboxylic acid dimethylester (nifedipine, Adalat) is converted to the nitroso compound 4-(2-'nitrosophenyl)-2,6-dimethyl-3,5-dicarbomethoxy-pyridine. The article also describes TLC-, GLC-, UV-, IR- and MS-data of nifedipine, the nitroso and the nitro derivative.


Countershading by physiological colour change in the fish louse Anilocra physodes L. (Crustacea: Isopoda).
Specimens of the fish louse Anilocra physodes L. from the Mediterranean Sea exhibited a striking colour asymmetry in their dorsal pigmentation: one longitudinal half of their back was dark, the opposite half was lightcoloured. The dark side corresponded with the physiological upper side when the fish louse was attached to the flank of a host fish.The colour pattern derives from the different shape (stellate/punctate) of chromatophores, which lie immediately beneath the epidermis. The appearance and distribution of the chromatophore stages indicate the possibility of physiological colour change in Anilocra. In this way the fish louse probably achieves adaptive countershading and thus additional protection from predators, advantageous for both parasite and host.


Separate Effects of Intensity and Amount of Exercise on Interindividual Cardiorespiratory Fitness Response.
To determine the separate effects of exercise intensity and amount on interindividual cardiorespiratory fitness (CRF) response. Participants were 121 (75 females, 62%) sedentary, middle-aged (mean [SD] age, 53.2 [7.5] years), abdominally obese adults who completed at least 90% of 5 weekly exercise sessions prescribed over a 24-week intervention. Participants were randomly assigned to (1) low-amount, low-intensity exercise (LALI) (180 and 300 kcal per session for women and men, respectively, at 50% of CRF [VO 2peak]; n=39), (2) high-amount, low-intensity exercise (HALI) (360 and 600 kcal per session for women and men, respectively, at 50% of CRF; n=51), or high-amount, high-intensity exercise (HAHI) (360 and 600 kcal per session for women and men, respectively, at 75% of CRF; n=31). Cardiorespiratory fitness was measured using a treadmill test at 4, 8, 16, and 24 weeks. The study duration was September 1, 2009, through May 31, 2013. Cardiorespiratory fitness increased within all 3 groups at 24 weeks (P<.001). At 24 weeks, 38.5% (15 of 39), 17.6% (9 of 51), and 0% (0 of 31) of the participants within the LALI, HALI, and HAHI groups, respectively, were CRF nonresponders. At a fixed exercise intensity, increasing exercise amount reduced the rate of nonresponse by 50% (P=.02). At a fixed amount of exercise, increasing the exercise intensity eliminated nonresponse (P=.001). Exposure to exercise decreased the number of CRF nonresponders between 4 and 8 weeks for LALI and by 16 weeks for HALI but plateaued thereafter. For HAHI, the number of CRF nonresponders decreased continually over the 24 weeks. For a fixed amount of exercise, increasing exercise intensity consistent with consensus recommendations eliminated CRF nonresponse. Low-intensity exercise may not be sufficient to improve CRF for a substantial proportion of sedentary obese adults.


Fate of tetracycline, sulfonamide and fluoroquinolone resistance genes and the changes in bacterial diversity during composting of swine manure.
This study monitored the abundance of antibiotic resistant genes (ARGs) and the bacterial diversity during composting of swine manure spiked with chlortetracycline, sulfadiazine and ciprofloxacin at two different levels and a control without antibiotics. Resistance genes of tetracycline (tetQ, tetW, tetC, tetG, tetZ and tetY), sulfonamide (sul1, sul2, dfrA1 and dfrA7) and fluoroquinolone (gyrA and parC) represented 0.02-1.91%, 0.67-10.28% and 0.00005-0.0002%, respectively, of the total 16S rDNA copies in the initial composting mass. After 28-42 days of composting, these ARGs, except parC, were undetectable in the composting mass indicating that composting is a potential method of manure management. Polymerase chain reaction-denaturing gradient gel electrophoresis analysis of bacterial 16S rDNA of the composting mass indicated that the addition of antibiotics up to 100, 20 and 20mg/kg of chlortetracycline, sulfadiazine and ciprofloxacin, respectively, elicited only a transient perturbation and the bacterial diversity was restored in due course of composting.


Genome-scale metabolic reconstructions and theoretical investigation of methane conversion in Methylomicrobium buryatense strain 5G(B1).
Methane-utilizing bacteria (methanotrophs) are capable of growth on methane and are attractive systems for bio-catalysis. However, the application of natural methanotrophic strains to large-scale production of value-added chemicals/biofuels requires a number of physiological and genetic alterations. An accurate metabolic model coupled with flux balance analysis can provide a solid interpretative framework for experimental data analyses and integration. A stoichiometric flux balance model of Methylomicrobium buryatense strain 5G(B1) was constructed and used for evaluating metabolic engineering strategies for biofuels and chemical production with a methanotrophic bacterium as the catalytic platform. The initial metabolic reconstruction was based on whole-genome predictions. Each metabolic step was manually verified, gapfilled, and modified in accordance with genome-wide expression data. The final model incorporates a total of 841 reactions (in 167 metabolic pathways). Of these, up to 400 reactions were recruited to produce 118 intracellular metabolites. The flux balance simulations suggest that only the transfer of electrons from methanol oxidation to methane oxidation steps can support measured growth and methane/oxygen consumption parameters, while the scenario employing NADH as a possible source of electrons for particulate methane monooxygenase cannot. Direct coupling between methane oxidation and methanol oxidation accounts for most of the membrane-associated methane monooxygenase activity. However the best fit to experimental results is achieved only after assuming that the efficiency of direct coupling depends on growth conditions and additional NADH input (about 0.1-0.2 mol of incremental NADH per one mol of methane oxidized). The additional input is proposed to cover loss of electrons through inefficiency and to sustain methane oxidation at perturbations or support uphill electron transfer. Finally, the model was used for testing the carbon conversion efficiency of different pathways for C1-utilization, including different variants of the ribulose monophosphate pathway and the serine cycle. We demonstrate that the metabolic model can provide an effective tool for predicting metabolic parameters for different nutrients and genetic perturbations, and as such, should be valuable for metabolic engineering of the central metabolism of M. buryatense strains.


In this case report, a woman with no risk factors was admitted with bilateral tubal ectopic pregnancy. Bilateral ectopic pregnancy is a rare clinical condition with clinical findings which in their symptoms do not differ from those of unilateral ectopic pregnancy. The condition can therefore easily be missed. The risk of rupture and haemorrhagic shock might be increased because of the increased danger of both tubes presenting with complications. Thus, it is important to examine both adnexa by transvaginal ultrasound. Even if unilateral ectopic pregnancy is considered before operation, the inspection of the abdomen, especially of the other fallopian tube, must always be done during surgery.


Neurologic aspects of the 9p- syndrome.
The 9p- syndrome is a chromosomal disorder which is easily recognized by its characteristic craniofacial features. Neurologic abnormalities are evident in all reported cases, the most common of which is severe mental retardation. We add another case with unusual features including glaucoma, seizures, and polydactyly, and review the somatic and neurologic features from 41 previously reported cases.


Progress Toward the Asymmetric de Novo Synthesis of Lanostanes: A Counter Biomimetic Cucurbitane-to-Lanostane Type Transformation.
An oxidative rearrangement has been established that enables a cucurbitane-to-lanostane type rearrangement that is counter to known biomimetic transformations that proceed in an opposite direction by way of a lanostane-to-cucurbitane transformation. Here, an oxidative dearomatization/Wagner-Meerwein rearrangement with a substrate bearing the characteristic cucurbitane triad of quaternary centers at C9, C13 and C14, and possessing an alkene at C11-C12, proceeds in a manner that selectively shifts the methyl group at C9 to C10 in concert with the establishment of a sterically hindered allylic cation. The major product isolated from this transformation is formed by trapping of the allylic cation by addition of acetate to C12, rather than termination of the cascade by loss of a proton at C8. While proceeding by way of a unique sequence of bond-forming reactions that begins by oxidative dearomatization, this process achieves what we believe is an unprecedented cucurbitane-to-lanostane transformation, generating a product that contains the characteristic lantostane triad of quaternary centers at C10, C13 and C14 while also delivering a functionalized C-ring.


Delta opiate receptors mediate tail-shock induced antinociception at supraspinal levels.
Previous work has demonstrated that 3 pharmacologically and neuroanatomically distinct analgesia systems can be sequentially activated by increasing numbers of transcutaneous tail-shock. To date, the categorization of the early (after 2 tail-shocks) and late (after 80-100 tail-shocks) analgesias as opiate-mediated has been based on the ability of systemic naltrexone and morphine tolerance to block these effects. In contrast, the analgesia observed after 5-40 tail-shocks is unaffected by these manipulations, leading to its categorization as non-opiate. The preceding companion paper and the present work were aimed at identifying the neuroanatomical loci at which opiates exert their analgesic effects in this tail-shock paradigm and, further, to identify which opiate receptor subtypes are involved. The 8 experiments included in the present paper examined the effect of microinjecting either naltrexone (a relatively non-selective opiate receptor antagonist), binaltorphimine (kappa receptor antagonist), Cys2-Tyr3-Orn5-Pen7-amide (CTOP) (mu receptor antagonist), or naltrindole (delta receptor antagonist) either into the third ventricle or over the frontal cortex. Taken together, these experiments demonstrate that the late (80-100 shock) opiate analgesia is mediated by delta opiate receptors located within subcortical structures rostral to the 4th ventricle. No evidence for supraspinal opiate involvement in the early (2 shock) opiate analgesia was found.


Specific detection of foot-and-mouth disease serotype Asia 1 virus by carboxyl-magnetic beads conjugated with single-domain antibody.
Immunomagnetic nanobead (IMNB) labeled with specific antibody, has been demonstrated to be useful for the capturing and detection of viruses. In this study, we developed an imunomagnetic bead based on carboxyl-magnetic beads (MNB) labeled with a single-domain antibody (sdAb) for capturing foot-and-mouth disease (FMD) Asia 1 virus. After magnetic separation, complexes of MNB-sdAb-virus were detected with either a sandwich ELISA or QDs-C5 probe under a fluorescence microscope, and the complexes were used as templates for extraction of total RNA for amplification of the VP1 or 3D gene fragments using RT-PCR and real-time RT-PCR. The Asia 1 VLPs were efficiently captured through IMNB with a high binding rate of 5.09 μg of antigen/μl of bead suspension. Moreover, this method has been successfully used to capture Asia 1 antigen in synthetic samples. Ultimately, a specific and highly sensitive capture FMDV Asia 1 tool has been established that has the potential to enhance the sensitivity and reliability when diagnosing FMDV Asia 1.


Molecular phylogenetic analysis of Fasciola flukes from eastern India.
Fasciola flukes from eastern India were characterized on the basis of spermatogenesis status and nuclear ITS1. Both Fasciola gigantica and aspermic Fasciola flukes were detected in Imphal, Kohima, and Gantoku districts. The sequences of mitochondrial nad1 were analyzed to infer their phylogenetical relationship with neighboring countries. The haplotypes of aspermic Fasciola flukes were identical or showed a single nucleotide substitution compared to those from populations in the neighboring countries, corroborating the previous reports that categorized them in the same lineage. However, the prevalence of aspermic Fasciola flukes in eastern India was lower than those in the neighboring countries, suggesting that they have not dispersed throughout eastern India. In contrast, F. gigantica was predominant and well diversified, and the species was thought to be distributed in the area for a longer time than the aspermic Fasciola flukes. Fasciola gigantica populations from eastern India were categorized into two distinct haplogroups A and B. The level of their genetic diversity suggests that populations belonging to haplogroup A have dispersed from the west side of the Indian subcontinent to eastern India with the artificial movement of domestic cattle, Bos indicus, whereas populations belonging to haplogroup B might have spread from Myanmar to eastern India with domestic buffaloes, Bubalus bubalis.


Aspergillus spondylodiscitis in an immunocompetent paraplegic patient.
A case of an immunocompetent 60 year old patient is reported, who suffered extensive thoracic spinal injury and paraplegia after polytrauma. In the course of rehabilitation he developed aspergillus spondylodiscitis in a part of the thoraco-lumbar spine which was primarily uninjured. The diagnostic assessment and therapeutic approach of this rare disorder is elucidated and discussed in the context of paraplegia and polytrauma. Possible mechanisms of inoculation and spreading of the moulds as well as predisposing factors of the disease are discussed in this paper and a review of the recent literature is provided.


Salmonella Typhimurium U32 peptidase, YdcP, promotes bacterial survival by conferring protection against in vitro and in vivo oxidative stress.
YdcP, a U32 peptidase, is characterized as a putative collagenase with a role in several bacterial infections. However, its role in the pathogenesis of Salmonella Typhimurium remains elusive. Here, we investigated the role of U32 peptidase, YdcP, in the intracellular survival of S. Typhimurium (STM). Our study revealed a novel function of YdcP in protecting wild-type Salmonella from in vitro and in vivo oxidative stress. The ydcP knockout strain showed attenuated intracellular proliferation within the murine and human macrophages. Incubation of wild-type Salmonella with H2O2 induced the transcript level expression of ydcP. Moreover, deleting ydcP increased the susceptibility of the bacteria to in vitro oxidative stress. STM ΔydcP showed increased colocalization with the gp91phox subunit of the NADPH phagocytic oxidase in RAW264.7 cells. Further, we observed a reduction in the expression of bacterial anti-oxidant genes in STM ΔydcP growing within the RAW264.7 cells. The delay in the death of BALB/c mice infected with STM ΔydcP proved the association of ydcP with the in vivo pathogenesis of Salmonella. Finally, the attenuated growth of the ydcP mutant in wild-type C57BL/6 mice and the recovery of their growth inhibition in gp91phox-/- C57BL/6 mice endorsed the role of ydcP in protecting Salmonella from in vivo oxidative stress. Together, our study depicts a novel role of Salmonella Typhimurium YdcP, a putative U32 peptidase in rendering protection against oxidative stress.


Specular microscopic study of X-ray-irradiated rabbit cornea.
To investigate the influence of ionizing radiation on the corneal epithelium and endothelium of rabbit eyes. Five healthy mature albino rabbits were unilaterally irradiated with 20 Gy of X-rays (250 kV, 12 mA). Slit-lamp biomicroscopic observation and specular microscopic examination of the corneal epithelium and endothelium were carried out before and 1, 4, 8, 12, 16, 20, 24, and 36 weeks after irradiation. We evaluated mean area of the superficial corneal epithelial cells, mean area and the percentage of hexagonal cells of the corneal endothelial cells, and corneal thickness. The statistical difference between the irradiated and control eyes was assessed using paired t-test. All animals developed cataract within 24 weeks. Slit-lamp biomicroscopy showed no apparent corneal abnormalities over the 36-week follow-up period. Specular microscopy revealed a significant enlargement of the superficial corneal epithelial cells from 4 to 12 weeks after irradiation (P<0.01), which disappeared at 16 weeks post-irradiation. Specular microscopy of the corneal endothelium showed enlargement and morphological alterations of the cells beginning 8 weeks after irradiation (P<0.05). These changes persisted throughout the study period. There were no statistically significant changes in corneal thickness. After X-ray radiation of 20 Gy, transient damage occurred in the corneal epithelium, while delayed and irreversible changes were seen in the endothelium.


New method for preparing more stable microcapsules for the entrapment of genetically engineered cells.
In this paper, we studied a new preparation method of microcapsules for entrapment of genetically engineered cells. Polyvinyl alcohol microcapsules having well defined shape, high mechanical strength, good biochemical and permeability properties were prepared by using low temperature physical cross-linking method. Comparing with currently used alginate-polylysine-alginate microcapsules, polyvinyl alcohol microcapsules have much higher mechanical strength. The low temperature physical crosslinking procedure of polyvinyl alcohol is nontoxic to the genetically engineered E. coli DH5alpha cell, which attained high activity in decomposing and metabolizing urea in vitro studies.


[Supra trochlear femoral erosions. Their relations with gonarthrosis and chondrocalcinosis (author's transl)].
Studying one hundred cases of simple gonarthrosis we found only one supra trochlear femoral erosion (STFE). Such a lesion was discovered in 14 cases among 150 chondrocalcinosis with arthrosic lesions. The cases involving STFE trend to a commun marked chondro-osteolytic evolution. The caracteristic patella sizes show clearly that STFE is not in relation with en anomaly of patella (patella alta...). The upper osteophyte of the patella presents only a minor importance in the formation of STFE. This STFE formation begins probably with a progressive chondro-osteolysis of patella and trochlea. Then, appears a progressive nipping between the upper point of patella and the supra trochlear femoral bone.


Serum bicarbonate concentration and the risk of death in type 2 diabetes: the Fremantle Diabetes Study Phase II.
To examine whether all-cause mortality is independently associated with serum bicarbonate concentration below the laboratory reference interval in a representative, well-characterised community-based cohort of people with type 2 diabetes. 1478 FDS2 participants with type 2 diabetes (mean age 65.8 years, 51.6% males, median diabetes duration 9.0 years) from the longitudinal, observational Fremantle Diabetes Study Phase II (FDS2) were followed from study entry to death or end-2016. Independent associates of a low baseline serum bicarbonate (< 22 mmol/L) were determined using multiple logistic regression. The role of important covariates in influencing the association between bicarbonate and mortality was assessed by a stepwise Cox regression approach. A low serum bicarbonate was associated with increased all-cause mortality in unadjusted analysis (hazard ratio (HR) 1.90 (95% confidence limits (CL) 1.39, 2.60 per mmol/L). Mortality remained significantly associated with low serum bicarbonate (HR 1.40 (95% CL 1.01, 1.94) per mmol/L) in a Cox regression model with adjustment for factors associated with mortality but not low serum bicarbonate, but inclusion of estimated glomerular filtration rate categories rendered the association non-significant (HR 1.16 (95% CL 0.83, 1.63) per mmol/L). A low serum bicarbonate is not an independent prognostic marker in people with type 2 diabetes but it may be a manifestation of the pathway between the development of impaired renal function and death.


Acute intra-cavity 4D flow cardiovascular magnetic resonance predicts long-term adverse remodelling following ST-elevation myocardial infarction.
Despite advancements in percutaneous coronary intervention, a significant proportion of ST-elevation myocardial infarction (STEMI) survivors develop long-term adverse left ventricular (LV) remodelling, which is associated with poor prognosis. Adverse remodelling is difficult to predict, however four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) can measure various aspects of LV intra-cavity flow beyond LV ejection fraction and is well equipped for exploring the underlying mechanical processes driving remodelling. The aim for this study was to compare acute 4D flow CMR parameters between patients who develop adverse remodelling with patients who do not. Fifty prospective 'first-event' STEMI patients underwent CMR 5 days post-reperfusion, which included cine-imaging, and 4D flow for assessing in-plane kinetic energy (KE), residual volume, peak-E and peak-A wave KE (indexed for LV end-diastolic volume [LVEDV]). All subjects underwent follow-up cine CMR imaging at 12 months to identify adverse remodelling (defined as 20% increase in LVEDV from baseline). Quantitative variables were compared using unpaired student's t-test. Tests were deemed statistically significant when p < 0.05. Patients who developed adverse LV remodelling by 12 months had significantly higher in-plane KE (54 ± 12 vs 42 ± 10%, p = 0.02), decreased proportion of direct flow (27 ± 9% vs 11 ± 4%, p < 0.01), increased proportion of delayed ejection flow (22 ± 9% vs 12 ± 2, p < 0.01) and increased proportion of residual volume after 2 consecutive cardiac cycles (64 ± 14 vs 34 ± 14%, p < 0.01), in their acute scan. Following STEMI, increased in-plane KE, reduced direct flow and increased residual volume in the acute scan were all associated with adverse LV remodelling at 12 months. Our results highlight the clinical utility of acute 4D flow in prognostic stratification in patients following myocardial infarction.


Three-dimensional voltammetry assisted by parametric signal fitting: a new perspective for the electrochemical evaluation of metal binding in the presence of electrodic adsorption.
A new perspective of three-dimensional voltammetry is given for the study of metal complexation in the presence of adsorption phenomena and, eventually, when the electrochemical reversibility of the processes decreases. For this purpose, 3D-voltammograms are obtained as usual, i.e., by combination of chronoamperograms measured at different potential steps, but they are analysed by the new methodology of parametric signal fitting (PSF), which uses the full data matrix to fit a five-parameter equation to every component. The parametric signals can be time-dependent peaks or waves and the optimised parameters inform about the concentrations in both dissolved and adsorbed phases. The analysis can be carried out on both individual and augmented matrices. The preliminary tests on the well-known Cd(II)-glutathione system yield promising results and encourage the combination of 3D-voltammetry and PSF as a complementary tool for the study of metal complexation in complicated systems.


The β-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice.
The membrane protein seizure 6-like (SEZ6L) is a neuronal substrate of the Alzheimer's disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases.


Patterns of neoplastic foci and lymph node micrometastasis within the mesorectum.
Local recurrence after rectal cancer surgery is conceived to result from microscopically incomplete resection. We aimed to investigate the patterns of mesorectal neoplastic foci, and examined the involvement and micrometastasis of lymph nodes. Observation of large tissue slice and analysis of tissue microarray were integrated in the pathological study of 31 total mesorectal excision (TME) specimens. Altogether, 349 mesorectal neoplastic foci were examined from 18 specimens. Almost 33% of them were in the outer layer of mesorectum. Concerning position of primary tumor, ipsilateral neoplastic foci were significantly more than contralateral neoplastic foci. Distal mesorectal spread was found in four patients with the distance ranging from 1 to 3.5 cm. Four specimens were diagnosed to have circumferential margin involved. Nine hundred seventy-two lymph nodes were harvested with 128 involved by tumor. No significant difference in occurrence of micrometastasis was observed among tumors of different stage. Combination of large tissue slice and tissue microarray provided a more detailed method in studying the metastasis of rectal cancer. Complete excision of the mesorectum with fascia propria circumferentially intact is essential. Circumferential margin involvement and micrometastasis suggested that tumor spread may go beyond the scope of a single TME procedure.


A new approach to enhance reproductive performance in sheep using royal jelly in comparison with equine chorionic gonadotropin.
The objective was to compare the effects of royal jelly (RJ) and eCG treatments on reproductive performance of ewes synchronized using intravaginal progesterone-releasing devices. Forty-two cycling Awassi ewes were treated intramuscularly (i.m.) with 15 mg PGF2alpha. On the following day, all ewes were administered with CIDR-G for 12 days and were randomly allocated to three (RJ, eCG and control) groups of 14 ewes each. Ewes in the RJ-treated group received daily i.m. treatments of 400mg RJ during the period of CIDR-treatment. Each ewe in the eCG-treated group received an i.m. treatment of 500 IU eCG at the time of CIDR-G removal (day 0) and no further treatment was given to ewes in the control group. Ewes were exposed to four fertile rams for 72 h, from the time of CIDR-G removal, and checked for breeding marks at 6-h intervals. Blood samples were collected from day -13 until day 0 and thereafter until day 19 for progesterone analysis. Royal jelly treatment resulted in a greater rate of decline and lower (P<0.02) progesterone concentrations between days -10 and 0 than eCG-treated and control ewes. Expression of estrus was similar among the three groups and intervals to onset of estrus were shorter (P<0.01) in RJ-treated (31.3h) and eCG-treated (29.8h) than control (41.3h) ewes. First-cycle pregnancy and lambing rates were greater (P<0.05) in RJ-treated (71.4 and 71.4%) and eCG-treated (85.7 and 78.6%) than in control (42.9 and 35.7%) ewes, respectively. Results demonstrate that the treatments of RJ and eCG in conjunction with CIDR-G were similarly effective in induction of estrus and improvement of pregnancy and lambing rates.


A single factor dominates the behavior of rhythmic genes in mouse organs.
Circadian rhythm, regulated by both internal and external environment of the body, is a multi-scale biological oscillator of great complexity. On the molecular level, thousands of genes exhibit rhythmic transcription, which is both organ- and species-specific, but it remains a mystery whether some common factors could potentially explain their rhythmicity in different organs. In this study we address this question by analyzing the transcriptome data in 12 mouse organs to determine such major impacting factors. We found a strong positive correlation between the transcriptional level and rhythmic amplitude of circadian rhythmic genes in mouse organs. Further, transcriptional level could explain over 70% of the variation in amplitude. In addition, the functionality and tissue specificity were not strong predictors of amplitude, and the expression level of rhythmic genes was linked to the energy consumption associated with transcription. Expression level is a single major factor impacts the behavior of rhythmic genes in mouse organs. This single determinant implicates the importance of rhythmic expression itself on the design of the transcriptional system. So, rhythmic regulation of highly expressed genes can effectively reduce the energetic cost of transcription, facilitating the long-term adaptive evolution of the entire genetic system.


The effects of ozone therapy on caspase pathways, TNF-α, and HIF-1α in diabetic nephropathy.
Accelerated apoptosis plays a vital role in the development of diabetic vascular complications. Ozone may attenuate diabetic nephropathy by means of decreased apoptosis-related genes. The aim of our study was to investigate the effect of ozone therapy on streptozotocin-induced diabetic nephropathy in rats. Also the histopathological changes in diabetic kidney tissue with ozone treatment were evaluated. The rats were randomly divided into six groups (n = 7): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). D, DI, and DOI groups were induced by a single intraperitoneal injection of streptozotocin. Ozone was given to the O, DO, and DOI groups. Group DI and DOI received subcutaneous (SC) insulin (3 IU). All animals received daily treatment for 6 weeks. Expressions of caspase-1-3-9, HIF-1α, and TNF-α genes were significantly higher in D group compared to C group (p < 0.05 for all). Ozone treatment resulted in significant decrease in the expressions of these genes in diabetic kidney tissue compared to both C and D group (p < 0.05 for all). Caspase-1-3-9, HIF-1α, and TNF-α gene expressions were found to be lower in DOI group compared to C group (p < 0.05 for all). Also adding ozone treatment to insulin therapy resulted in more significantly decrease in the expressions of these genes in diabetic tissue compared to only insulin-treated diabetic group (p < 0.05 for all). Regarding histological changes, ozone treatment resulted in decrease in the renal corpuscular inflammation and normal kidney morphology was observed. Both insulin and ozone therapies apparently improved kidney histological findings with less degenerated tubules and less inflammation of renal corpuscle compared to D, DO, and DI groups. Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes.


FastFung: A novel medium for the culture and isolation of fastidious fungal species from clinical samples.
We developed a novel culture medium, referred to FastFung medium as suitable for the culture of clinical fungi, including fastidious ones, for both research and diagnostic studies. It is based on Schædler agar supplemented with many essential components for the growth of fastidious fungi. It also contains selective antibacterial agents for the inhibition of contaminant bacteria growth. In this preliminary study, the FastFung medium was compared to the gold standard Sabouraud medium for 98 fungal and 20 bacterial strains. The fungal strain positive culture rate was 100% vs. 95% and the bacterial strain inhibition was 100% vs. 20%, for the FastFung and Sabouraud media, respectively. When compared to the Sabouraud medium on 120 clinical samples, the FastFung medium displayed both a higher fungal colonies count, and a lower culture contamination rate. Storage at 4 °C for 4 weeks did not alter the FastFung culture medium performances for the six isolates of Candida, Cryptococcus, and Penicillium tested. These encouraging results suggest future development of using the FastFung medium in clinical mycology and in mycobiome characterization. Further prospective evaluation aiming at assessing whether implementing the FastFung medium in the routine workflow simplifies and strengthen fungal isolation capacities in the clinical laboratory is warranted.


LIPUS-SCs-Exo promotes peripheral nerve regeneration in cavernous nerve crush injury-induced ED rats via PI3K/Akt/FoxO signaling pathway.
Clinical treatment of erectile dysfunction (ED) caused by cavernous nerve (CN) injury during pelvic surgery is difficult. Low-intensity pulsed ultrasound (LIPUS) can be a potential strategy for neurogenic ED (NED). However, whether Schwann cells (SCs) can respond to LIPUS stimulation signals is unclear. This study aims to elucidate the signal transmission between SCs paracrine exosome (Exo) and neurons stimulated by LIPUS, as well as to analyze the role and potential mechanisms of exosomes in CN repair after injury. The major pelvic ganglion (MPG) neurons and MPG/CN explants were stimulated with LIPUS of different energy intensities to explore the appropriate LIPUS energy intensity. The exosomes were isolated and purified from LIPUS-stimulated SCs (LIPUS-SCs-Exo) and non-stimulated SCs (SCs-Exo). The effects of LIPUS-SCs-Exo on neurite outgrowth, erectile function, and cavernous penis histology were identified in bilateral cavernous nerve crush injury (BCNI)-induced ED rats. LIPUS-SCs-Exo group can enhance the axon elongation of MPG/CN and MPG neurons compared to SCs-Exo group in vitro. Then, the LIPUS-SCs-Exo group showed a stronger ability to promote the injured CN regeneration and SCs proliferation compared to the SCs-Exo group in vivo. Furthermore, the LIPUS-SCs-Exo group increased the Max intracavernous pressure (ICP)/mean arterial pressure (MAP), lumen to parenchyma and smooth muscle to collagen ratios compared to the SCs-Exo group in vivo. Additionally, high-throughput sequencing combined with bioinformatics analysis revealed the differential expression of 1689 miRNAs between the SCs-Exo group and the LIPUS-SCs-Exo group. After LIPUS-SCs-Exo treatment, the phosphorylated levels of Phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and forkhead box O (FoxO) in MPG neurons increased significantly compared to negative control (NC) and SCs-Exo groups. Our study revealed that LIPUS stimulation could regulate the gene of MPG neurons by changing miRNAs derived from SCs-Exo, then activating the PI3K-Akt-FoxO signal pathway to enhance nerve regeneration and restore erectile function. This study had important theoretical and practical significance for improving the NED treatment.


NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population.
Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. Serum NT-ProBNP levels were measured in 5502 people aged 45-79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100-300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12-2.32, p = 0.012 and HR 2.96, 95% CI 1.75-5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17-2.10, p = 0.011 and HR 2.08, 95% CI 1.47-2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex. Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.


Ultrasound detection of fetal anomalies in conjunction with first-trimester nuchal translucency screening: a feasibility study.
The purpose of this study was to determine the effectiveness of a fetal anatomy survey in conjunction with first-trimester nuchal translucency (NT) screening ultrasound in an unselected pregnant population performed by sonographers. This was a prospective observational study of women presenting for NT screening for chromosomal defects. An anatomic survey was performed after a standardized protocol with a maximum scan time of 30 minutes. Three hundred twenty-five singleton fetuses (11+0 to 13+6 weeks) were examined and pregnancy outcome was available for 300 (92.3%) of cases. In 89 (24.6%) cases, transvaginal ultrasound was performed. The following fetal structures were seen in 95% of cases: cranium and intracranial anatomy, face, cord insertion, stomach, and all 4 limbs. The bladder was visualized in 89.5% of cases, the cardiac 4 chamber view in 84%, and the spine in only 45% of cases. Complete anatomy was seen in 109 (33%). Crown rump length greater than 55 mm and sonographer experience were important factors contributing to anatomic visibility. Of a total of 6 congenital defects in this cohort, 1 was detected in the first trimester (neural tube defect), 4 at the 18- to 20-week anatomic scan, and 1 postnatally. A complete anatomy survey was successful in 33% of first-trimester fetuses in a time-limited sonographer based screening program. Since some anomalies are not evident in the first trimester, the 18- to 20-week scan remains the gold standard.


Diurnal changes in photochemical efficiency, the reduction state of Q, radiationless energy dissipation, and non-photochemical fluorescence quenching in cacti exposed to natural sunlight in northern Venezuela.
Diurnal measurements of chlorophyll a fluorescence from cacti (Nopalea cochenillifera, Opuntia ficus-indica, and Opuntia wentiana) growing in northern Venezuela were used to determine photochemical fluorescence quenching related to the reduction state of the primary electron acceptor of PS II as well as non-photochemical fluorescence quenching which reflects the fraction of energy going primarily into radiationless deexcitation. The cladodes used in this study were oriented such that one surface received direct sunlight in the morning and the other one during the afternoon. Both surfaces exhibited large increases in radiationless energy dissipation from the photochemical system accompanied by decreases in PS II photochemical efficiency during direct exposure to natural sunlight. During exposure to sunlight in the morning, dissipation of absorbed light energy through photosynthesis and radiationless energy dissipation was sufficient to maintain Q, the primary electron acceptor for PS II, in a low reduction state. During exposure to sunlight in the afternoon, however, the reduction state of Q rose to levels greater than 50%, presumably due to a decrease in photosynthetic electron transport as the decarboxylation of the nocturnally accumulated malic acid was completed. Exposure to direct sunlight in the afternoon also led to more sustained increases in radiationless energy dissipation. Furthermore, the increases in radiationless energy dissipation during exposure of a water-stressed cladode of O. wentiana to direct sunlight were much greater than those from other well-watered cacti, presumably due to sustained stomatal closure and decreased rates of photosynthetic electron transport. These results indicate that the radiationless dissipation of absorbed light is an important process in these CAM plants under natural conditions, and may reflect a protective mechanism against the potentially damaging effects of the accumulation of excessive energy, particularly under conditions where CO2 availability is restricted.