A serological survey of brucellosis in wildlife in four major National Parks of Uganda.
Brucellosis is a contagious zoonotic disease of great public health and economic significance especially in developing countries. The disease affects humans and several species of livestock and wildlife. Studies on Brucellosis in wildlife in Uganda have been limited to single populations particularly in Queen Elizabeth National Park. This study aimed at estimating the percentage of positive samples of Brucella spp. in wildlife in four major national parks of Uganda. This was a retrospective survey which utilized archived samples collected from wildlife during the annual disease surveillance activities between 2013 and 2017. A total of 241 samples from seven species namely African buffalo (Syncerus caffer, n = 109), African elephant (Loxodonta africana, n = 22), giraffe (Giraffa camelopardalis rothschildi, n = 41), Uganda kob (Kobus kob thomasi, n = 36), lion (Panthera leo, n = 6), plain zebra (Equus quagga, n = 25), and bushbuck (Tragelaphus scriptus, n = 2), were tested for antibodies using the Rose Bengal Plate Test. The overall percentage of positive samples in the four national parks was 31.1% (75/241; 95% CI: 25.6-37.2). Kidepo Valley National Park had a significantly higher percentage of positive samples of 55.9% (19/34; 95% CI: 39.5-71.1) compared to other sampled national parks (p < 0.05). Lions had significantly higher percentage of positive samples at 66.7% (4/6) than African buffalo at 48.6% (53/109, p < 0.0001). There were no antibodies for Brucella spp. detected in African elephant and bushbuck. This study shows variations in percentage of positive samples with Brucella spp. between species and across national parks and notably a high percentage with Brucella spp. in wildlife in Uganda than that recorded elsewhere in sub-Saharan region of Africa. Potential for transmission to other wildlife and spill over to livestock is high especially in national parks with high livestock-wildlife interaction.


Registered trials report less beneficial treatment effects than unregistered ones: a meta-epidemiological study in orthodontics.
Clinical trial registration is widely recommended because it allows tracking of trials that helps ensure full and unbiased reporting of their results. The aim of the present overview was to provide empirical evidence on bias associated with trial registration via a meta-epidemiological approach. Six databases were searched in September 2017 for randomized clinical trials and systematic reviews thereof assessing the effects of orthodontic clinical interventions. After duplicate study selection and data extraction, statistical analysis included a two-step meta-epidemiological approach within- and across-included meta-analyses with a Paule-Mandel random-effects model to calculate differences in standardized mean differences (ΔSMD) between registered and unregistered trials and their 95% confidence intervals (CI), followed by subgroup and sensitivity analyses. A total of 16 meta-analyses with 83 trials and 4,988 patients collectively were finally included, which indicated that registered trials reported less beneficial treatment effects than unregistered trials (ΔSMD = -0.36; 95% CI = -0.60, -0.12). Although some small-study effects were identified, sensitivity analyses according to precision and risk of bias indicated robustness. Signs of bias from lack of trial protocol registration were found with nonregistered trials reporting more beneficial intervention effects than registered ones. Caution is warranted by the interpretation of nonregistered randomized trials or systematic reviews thereof.


Circulating Superoxide Dismutase Concentrations in Obstructive Sleep Apnoea (OSA): A Systematic Review and Meta-Analysis.
Obstructive Sleep Apnoea (OSA) is characterized by a pro-oxidant state that results from the recurrent hypoxia-reoxygenation cycles. Superoxide dismutase (SOD), a key antioxidant enzyme involved in the detoxification of superoxide radicals, could represent a reliable marker to monitor the antioxidant defences in OSA. In order to capture and critically appraise the available evidence, we performed a systematic review and meta-analysis of studies reporting SOD concentrations in OSA patients and non-OSA controls in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar. In total, 13 studies in 847 OSA patients and 438 non-OSA controls were included in the meta-analysis. Blood SOD concentrations were significantly lower in OSA patients (SMD = 0.87, p < 0.001). By contrast, serum/plasma SOD concentrations were not significantly different between the two groups. Although extreme between-study heterogeneity was observed, the SMD was not substantially modified when individual studies were sequentially removed. In conclusion, we observed that whole blood, but not serum/plasma, SOD concentrations were significantly lower in OSA patients compared with controls. Our meta-analysis suggests an impaired antioxidant defence in OSA that is more robustly assessed in the corpuscular biological matrix and provides useful background information for further studies investigating the association between SOD changes and clinical status in OSA.


Medical care of the deinstitutionalized mentally retarded.
Community-based group homes for the deinstitutionalized mentally retarded are becoming more common. Individuals in this setting have unique acute and chronic medical conditions. Long-term use of medications, exposure to hepatitis B, problems with sexuality and special contraception needs are commonly encountered. The physician who provides care for patients in this setting can serve as a central referral source and coordinator of medical services, as well as an educator to staff and family.


Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A).
X-linked sideroblastic anemia and ataxia (XLSA/A) is a recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia with hypochromia and microcytosis. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to Xq13, a region previously shown by linkage analysis to harbor the XLSA/A gene. This gene, ABC7, is an ortholog of the yeast ATM1 gene whose product localizes to the mitochondrial inner membrane and is involved in iron homeostasis. The full-length ABC7 cDNA was cloned and the entire coding region screened for mutations in a kindred in which five male members manifested XLSA/A. An I400M variant was identified in a predicted transmembrane segment of the ABC7 gene in patients with XLSA/A. The mutation was shown to segregate with the disease in the family and was not detected in at least 600 chromosomes of general population controls. Introduction of the corresponding mutation into the Saccharomyces cerevisiae ATM1 gene resulted in a partial loss of function of the yeast Atm1 protein. In addition, the human wild-type ABC7 protein was able to complement ATM1 deletion in yeast. These data indicate that ABC7 is the causal gene of XLSA/A and that XLSA/A is a mitochondrial disease caused by a mutation in the nuclear genome.


Characterisation of methicillin-resistant Staphylococcus aureus by biotyping, immunoblotting and restriction enzyme fragmentation patterns.
We have characterised 45 isolates of methicillin-resistant Staphylococcus aureus (MRSA) from Glasgow Royal Infirmary by means of simple biotyping, immunoblotting of exported proteins and restriction enzyme fragmentation patterns (REFP) of plasmid DNA. The strains were subdivided into four groups (A-D) on the basis of biotype. Immunoblotting and restriction enzyme fragmentation generated a number of unique patterns. Analysis of these patterns by means of Dice coefficients of similarity separated them into two major immunoblot groups (Blot1 and Blot2) and two major REFP groups (FP1 and FP2). There was strong positive correlation between Blot1 and FP1 groups and between Blot2 and FP2 groups. In addition, Blot1-FP1 isolates were almost exclusively of biotypes A or C, whereas Blot2-FP2 isolates were of biotypes B or D. The methods described here have provided comprehensive epidemiological information which has been valuable in studying the origin and spread of MRSA.


Two or four implants for maxillary overdentures in edentulous patients: 1-year results of a randomized controlled trial.
Maxillary implant overdenture therapy is a good treatment option for treating patients experiencing problems with their conventional maxillary denture. Retaining the overdenture with four implants and a bar attachment system serves as the current gold standard. However, there is a demand for less costly and less invasive treatment options. The aim of this randomized controlled trial was to compare marginal bone level change (MBLC), implant and overdenture survival, clinical, masticatory, and patient-related outcomes (PROMs) of maxillary implant overdentures with either two or four implants and a bar attachment system. Forty edentulous participants were randomly allocated to two groups (n = 20), to receive either two or four implants in the maxilla. After healing, all the participants received an implant overdenture retained by a bar attachment system. All the participants were evaluated 1 and 12 months after overdenture placement. The primary outcome was MBLC. Secondary outcomes were implant and overdenture survival, clinical, masticatory, and PROMs. The outcomes were analyzed using parametric and non-parametric tests. MBLC was -0.03 mm in the 2-implant group and -0.16 mm in the 4-implant group (p = 0.21). Implant survival was 83.3% in the 2-implant group and 94.4% in the 4-implant group (p = 0.03). The median pocket depth change and clinical outcomes were low, and masticatory performance along with PROMs improved in both groups and did not differ significantly between them. Maxillary 4-implant overdentures perform better than maxillary 2-implant overdentures with a bar attachment system in terms of implant and overdenture survival and therefore remains the gold standard. However, both overdentures perform similarly in terms of MBLC, clinical, masticatory, and PROMs.


The Relationship between the IC50 Values and the Apparent Inhibition Constant in the Study of Inhibitors of Tyrosinase Diphenolase Activity Helps Confirm the Mechanism of Inhibition.
Tyrosinase is the enzyme involved in melanization and is also responsible for the browning of fruits and vegetables. Control of its activity can be carried out using inhibitors, which is interesting in terms of quantitatively understanding the action of these regulators. In the study of the inhibition of the diphenolase activity of tyrosinase, it is intriguing to know the strength and type of inhibition. The strength is indicated by the value of the inhibition constant(s), and the type can be, in a first approximation: competitive, non-competitive, uncompetitive and mixed. In this work, it is proposed to calculate the degree of inhibition (iD), varying the concentration of inhibitor to a fixed concentration of substrate, L-dopa (D). The non-linear regression adjustment of iD with respect to the initial inhibitor concentration [I]0 allows for the calculation of the inhibitor concentration necessary to inhibit the activity by 50%, at a given substrate concentration (IC50), thus avoiding making interpolations between different values of iD. The analytical expression of the IC50, for the different types of inhibition, are related to the apparent inhibition constant (KIapp). Therefore, this parameter can be used: (a) To classify a series of inhibitors of an enzyme by their power. Determining these values at a fixed substrate concentration, the lower IC50, the more potent the inhibitor. (b) Checking an inhibitor for which the type and the inhibition constant have been determined (using the usual methods), must confirm the IC50 value according to the corresponding analytical expression. (c) The type and strength of an inhibitor can be analysed from the study of the variation in iD and IC50 with substrate concentration. The dependence of IC50 on the substrate concentration allows us to distinguish between non-competitive inhibition (iD does not depend on [D]0) and the rest. In the case of competitive inhibition, this dependence of iD on [D]0 leads to an ambiguity between competitive inhibition and type 1 mixed inhibition. This is solved by adjusting the data to the possible equations; in the case of a competitive inhibitor, the calculation of KI1app is carried out from the IC50 expression. The same occurs with uncompetitive inhibition and type 2 mixed inhibition. The representation of iD vs. n, with n=[D]0/KmD, allows us to distinguish between them. A hyperbolic iD vs. n representation that passes through the origin of coordinates is a characteristic of uncompetitive inhibition; the calculation of KI2app is immediate from the IC50 value. In the case of mixed inhibitors, the values of the apparent inhibition constant of meta-tyrosinase (Em) and oxy-tyrosinase (Eox), KI1app and the apparent inhibition constant of metatyrosinase/Dopa complexes (EmD) and oxytyrosinase/Dopa (EoxD), KI2app are obtained from the dependence of iD vs. n, and the results obtained must comply with the IC50 value.


Perspectives on chronic musculoskeletal pain management among healthcare professionals in Bhutan: A qualitative study.
Musculoskeletal pain disorders continue to be one of the leading causes of disability worldwide. Best practice care recommends patient-centred biopsychosocial models of care. Little is known about the chronic musculoskeletal pain management in low- and middle-income countries. To explore the management of chronic musculoskeletal pain by healthcare professionals in Bhutan. This study employed a qualitative design involving 19 Bhutanese healthcare professionals managing chronic musculoskeletal pain in Bhutan. We collected data using a semi-structured interview guide. Thematic analysis was done manually. Healthcare professionals reported that patients rely on a combination of home remedies and seek help from local healers and hospitals for chronic musculoskeletal pain management. While healthcare professionals understand chronic musculoskeletal pain as multi-dimensional phenomenon, the primary focus was on identifying and treating structural anomalies. Time constraints, inadequate knowledge and skills, lack of confidence, facilities and expertise were reported as barriers to the effective management of chronic musculoskeletal pain. They proposed a need for clinical guidelines, relevant skills training and creating awareness of chronic musculoskeletal pain. The management of chronic musculoskeletal pain in Bhutan is focused on identifying and treating physical abnormalities. Healthcare professionals consider psychosocial dimensions important but lack any form of actionable interventions in this domain.


[The thyroid gland in emotional and pain stress].
The reaction of wild rodent thyroid gland on emotional and painful stress appearing as a result of animal's catching has been studied. The thyroid activity has been shown to raise considerably during the primary stage of stress reaction. Later on the function of the gland normalizes in animals without trauma and in traumatized animals it becomes weaker. The complete normalization of the thyroid function in traumatized animals coincides with osteal regeneration according to time.


E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans.
The discovery of RNA interference (RNAi) in C. elegans has had a major impact on scientific research, led to the rapid development of RNAi tools and has inspired RNA-based therapeutics. Astonishingly, nematodes, planaria and many insects take up double-stranded RNA (dsRNA) from their environment to elicit RNAi; the biological function of this mechanism is unclear. Recently, the E. coli OxyS non-coding RNA was shown to regulate gene expression in C. elegans when E. coli is offered as food. This was surprising given that C. elegans is unlikely to encounter E. coli in nature. To directly test the hypothesis that the E. coli OxyS non-coding RNA triggers the C. elegans RNAi pathway, we sequenced small RNAs from C. elegans after feeding with bacteria. We clearly demonstrate that the OxyS non-coding RNA does not trigger an RNAi response in C. elegans. We conclude that the biology of environmental RNAi remains to be discovered.


Association between quality of life and emotional overeating - a cross-sectional study in Danish children attending a multicomponent lifestyle camp.
Emotional eating seems to emerge during the transition from childhood to adulthood; however, limited research has explored the association between emotional overeating and quality of life (QoL) in children with overweight and obesity. Therefore, the aim of this study was to examine the association between QoL and emotional overeating in a Danish sample of children with overweight and obesity. The present cross-sectional study is based on baseline questionnaire data from a nonrandomized controlled trial. Children attending a 10-week multicomponent lifestyle camp from October 2020 to March 2022 was invited to participate. Multiple linear regressions were used to examine if QoL was associated with emotional overeating before starting camp. In total, 229 children were included, and 45 children were excluded due to missing data, leaving 184 children in this study. The children had a mean age of 11.8 years (SD ± 1.38), with 60.9% girls and 39.1% boys, and the majority (94.6%) had overweight or obesity defined by a Body Mass Index Standard Deviation Score (BMI-SDS) > 1 SD. On average, children with a high tendency of emotional overeating had a 13.7 (95% CI 18.9; 8.5, p < 0.01) lower QoL score compared to children with a low tendency of emotional overeating. Conclusions: This study shows that children with a high tendency of emotional overeating have lower quality of life, compared to children with a lower tendency of emotional overeating. Due to study limitations, the findings should be supported by further research. (Trial registration: clinicaltrials.gov with ID: NCT04522921). What is Known: • Emotional eating seems to emerge during the transition from childhood to adulthood. • Limited research has explored the association between quality of life and emotional overeating in children with overweight and obesity. What is New: • Children with a high tendency of emotional overeating had a lower quality of life compared to children with a lower tendency of emotional overeating. • Emotional overeating was negatively associated with quality of life in children with overweight and obesity.


Point-of-care screening for heart failure with reduced ejection fraction using artificial intelligence during ECG-enabled stethoscope examination in London, UK: a prospective, observational, multicentre study.
Most patients who have heart failure with a reduced ejection fraction, when left ventricular ejection fraction (LVEF) is 40% or lower, are diagnosed in hospital. This is despite previous presentations to primary care with symptoms. We aimed to test an artificial intelligence (AI) algorithm applied to a single-lead ECG, recorded during ECG-enabled stethoscope examination, to validate a potential point-of-care screening tool for LVEF of 40% or lower. We conducted an observational, prospective, multicentre study of a convolutional neural network (known as AI-ECG) that was previously validated for the detection of reduced LVEF using 12-lead ECG as input. We used AI-ECG retrained to interpret single-lead ECG input alone. Patients (aged ≥18 years) attending for transthoracic echocardiogram in London (UK) were recruited. All participants had 15 s of supine, single-lead ECG recorded at the four standard anatomical positions for cardiac auscultation, plus one handheld position, using an ECG-enabled stethoscope. Transthoracic echocardiogram-derived percentage LVEF was used as ground truth. The primary outcome was performance of AI-ECG at classifying reduced LVEF (LVEF ≤40%), measured using metrics including the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity, with two-sided 95% CIs. The primary outcome was reported for each position individually and with an optimal combination of AI-ECG outputs (interval range 0-1) from two positions using a rule-based approach and several classification models. This study is registered with ClinicalTrials.gov, NCT04601415. Between Feb 6 and May 27, 2021, we recruited 1050 patients (mean age 62 years [SD 17·4], 535 [51%] male, 432 [41%] non-White). 945 (90%) had an ejection fraction of at least 40%, and 105 (10%) had an ejection fraction of 40% or lower. Across all positions, ECGs were most frequently of adequate quality for AI-ECG interpretation at the pulmonary position (979 [93·3%] of 1050). Quality was lowest for the aortic position (846 [80·6%]). AI-ECG performed best at the pulmonary valve position (p=0·02), with an AUROC of 0·85 (95% CI 0·81-0·89), sensitivity of 84·8% (76·2-91·3), and specificity of 69·5% (66·4-72·6). Diagnostic odds ratios did not differ by age, sex, or non-White ethnicity. Taking the optimal combination of two positions (pulmonary and handheld positions), the rule-based approach resulted in an AUROC of 0·85 (0·81-0·89), sensitivity of 82·7% (72·7-90·2), and specificity of 79·9% (77·0-82·6). Using AI-ECG outputs from these two positions, a weighted logistic regression with l2 regularisation resulted in an AUROC of 0·91 (0·88-0·95), sensitivity of 91·9% (78·1-98·3), and specificity of 80·2% (75·5-84·3). A deep learning system applied to single-lead ECGs acquired during a routine examination with an ECG-enabled stethoscope can detect LVEF of 40% or lower. These findings highlight the potential for inexpensive, non-invasive, workflow-adapted, point-of-care screening, for earlier diagnosis and prognostically beneficial treatment. NHS Accelerated Access Collaborative, NHSX, and the National Institute for Health Research.


Effect of fish meal and expeller-processed soybean meal fed to dairy cows receiving bovine somatotropin (sometribove).
Forty-eight multiparous cows were blocked by calving date and milk production and assigned randomly to a TMR formulated to contain 68 or 55% of dietary CP as ruminally degradable CP. Diets contained corn silage, alfalfa haylage, and ground corn. Supplemental CP was soybean meal for the control diet or a combination of soybean meal, expeller-processed soybean meal, and fish meal for the low degradable protein diet. Two 10-wk phases began on d 31 +/- 3 (phase 1) and 110 +/- 7 postpartum [phase 2, all cows received subcutaneous implantations of pelleted (400 mg) bST (sometribove) every 14 d]. Dietary energy, CP, ruminally degradable CP, NDF, and ADF were similar between dietary treatments. Production of FCM increased in response to bST but was not affected by dietary treatment. Cows fed the expeller-processed soybean meal and fish meal TMR produced milk that contained less milk fat in phase 1 and less milk protein content in both phases. The DMI, BW, and body condition scores were not affected by diet. Hematocrit, plasma urea N, albumin, total protein, creatinine, glucose, and serum insulin were similar between dietary treatments. Replacing soybean meal with expeller processed soybean meal and fish meal did not affect ruminal degradation of protein or milk production but decreased milk fat and protein contents.


Physicians' understanding of the regulation of dietary supplements.
After passage of the Dietary Supplement Health and Education Act, herbs and other supplements were allowed to be sold to the public without Food and Drug Administration (FDA) approval or premarket evaluation. Data suggest that many people are unaware of this lack of governmental oversight and may rely on their physicians for education in this arena. This study was designed to evaluate physicians' level of understanding of dietary supplement regulation and the adverse event reporting process and to determine whether an interactive online curriculum could aid in improving knowledge. A multicenter online educational intervention was developed and administered to physicians at 15 internal medicine residency programs throughout the United States between March 1, 2006, and June 30, 2006. Pretest performance was used to measure baseline knowledge, while posttest performance compared with pretest performance measured the effectiveness of the educational intervention. A total of 335 physicians completed the module. Ninety percent of those completing the module were residents, while 10% were attending physicians. Baseline knowledge of dietary supplement regulatory issues was poor. The total average pretest score was only 59% (986/1675). The average score rose to 91% (1526/1675) after completion of the curriculum (P<.001). With regard to specific content areas, about one third of physicians were unaware that dietary supplements did not require FDA approval or submission of safety and efficacy data before being marketed. Similar percentages believed that there are regulations in place to ensure supplement quality. Most physicians were unaware that serious adverse events due to the use of supplements should be reported through the FDA MedWatch system. Physician knowledge of dietary supplement regulation and adverse event reporting is poor. An online didactic module may improve knowledge and potentially enhance patient-physician communication regarding the use of such products.


Informal faculty development in health professions education: Identifying opportunities in everyday practice.
Faculty development (FD) supports health professions educators to develop knowledge, skills, and expertise. Whilst formal FD is a focus in the health professions education (HPE) literature, little is known about how FD occurs informally. We sought to identify opportunities and constraints for informal FD amongst health professions educators in the academic (university) setting and understand how they engage with these opportunities. This exploratory study was conducted in one Australian university. Interviews and focus groups were conducted with undergraduate and postgraduate teachers and assessors (teachers) (n = 10); teaching team and program leaders (mid-level leaders) (n = 8); and senior (university-level) leaders (n = 2). We analysed data thematically and applied situated cognition theory. We identified three everyday educational practices that provide opportunities for informal FD in the academic setting: (1) applying evidence to; (2) evaluating; and (3) sharing, educational practice. Engaging with these opportunities was shaped by individuals' motivation and proactivity to engage in professional learning (effectivities) and organisational culture and structures (constraints). Applying evidence to, evaluating, and sharing educational practice provide valuable contexts for ongoing learning in the academic setting. Assisting educators and organisations to recognise and leverage these 'in situ' FD opportunities is vital in fostering a continuous learning culture.


Clinical follow-up of the first SF-1 insufficient female patient.
Steroidogenic factor 1 (SF-1/NR5A1) plays a crucial role in regulating adrenal development, gonad determination and differentiation, and in the hypothalamic-pituitary control of reproduction and metabolism. In men (46, XY), it is known that mutations in SF-1/NR5A1 gene cause a wide phenotypic spectrum with variable degrees of undervirilization. In recent years, the role of SF-1 in the ovarian function was increasingly discussed and alterations in the gene were related to primary ovarian insufficiency. We describe the follow-up of a 46, XX affected woman with a SF-1 mutation and by comparing our case with the known manifestations reported in the literature, we try to further elucidate the function of SF-1 in the ovary. During infancy, adrenal insufficiency was the only clinical sign of the loss-of-function as ovarian development and function seemed normal. To date, this young woman aged 16.5 years shows normal growth, normal BMI and psychomotor development, has a normal puberty and regular menstruation. This report shows one, to date uniquely described, phenotypic variant of SF-1 mutation in a 46, XX affected person with adrenocortical insufficiency but no ovarian dysfunction nor disturbance of pubertal development. To follow the natural history of SF-1 mutation in a 46, XX individual will further shed light on its role in the ovarian function and thus will help to counsel affected patients in future.


Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice.
The clinical onset of schizophrenia often coincides with cannabis use in adolescents and young adults. However, the neurobiological consequences of this co-morbidity are not well understood. In this study, we examined the effects of Δ9-THC exposure during early adulthood on schizophrenia-related behaviors using a developmental mouse model of schizophrenia. Phencyclidine (PCP) or saline was administered once in neonatal mice (at P7; 10mg/kg). In turn, Δ9-THC or saline was administered sub-acutely later in life to cohorts of animals who had received either PCP or saline (P55-80, 5mg/kg). Mice who were administered PCP alone displayed behavioral changes in the Morris water waze (MWM) and pre-pulse inhibition (PPI) task paradigm that were consistent with schizophrenia-related phenotypes, but not in the locomotor activity or novel object recognition (NOR) task paradigms. Mice who were administered PCP and then received Δ9-THC later in life displayed behavioral changes in the locomotor activity paradigm (p<0.001) that was consistent with a schizophrenia-related phenotype, as well as potentiated changes in the NOR (p<0.01) and MWM (p<0.05) paradigms as compared to mice that received PCP alone. Decreased cortical receptor expression of NMDA receptor 1 subunit (NR1) was observed in mice that received PCP and PCP+Δ9-THC, while mice that received Δ9-THC and PCP+Δ9-THC displayed decreases in CB1 receptor expression. These findings suggest that administration of Δ9-THC during the early adulthood can potentiate the development of schizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice.


Molecular Classification and Interpretation of Amyotrophic Lateral Sclerosis Using Deep Convolution Neural Networks and Shapley Values.
Amyotrophic lateral sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons to severely effect the functionality to control voluntary muscle movement. Most of the non-additive genetic aberrations responsible for ALS make its molecular classification very challenging along with limited sample size, curse of dimensionality, class imbalance and noise in the data. Deep learning methods have been successful in many other related areas but have low minority class accuracy and suffer from the lack of explainability when used directly with RNA expression features for ALS molecular classification. In this paper, we propose a deep-learning-based molecular ALS classification and interpretation framework. Our framework is based on training a convolution neural network (CNN) on images obtained from converting RNA expression values into pixels based on DeepInsight similarity technique. Then, we employed Shapley additive explanations (SHAP) to extract pixels with higher relevance to ALS classifications. These pixels were mapped back to the genes which made them up. This enabled us to classify ALS samples with high accuracy for a minority class along with identifying genes that might be playing an important role in ALS molecular classifications. Taken together with RNA expression images classified with CNN, our preliminary analysis of the genes identified by SHAP interpretation demonstrate the value of utilizing Machine Learning to perform molecular classification of ALS and uncover disease-associated genes.


Burn Injuries in Hospitalized Australian Children-An Epidemiological Profile.
Globally, First Nations children sustain burns at a higher rate than other children. Little is understood about how health inequities contribute, especially from an Indigenous viewpoint. We analyzed data from the Burns Registry of Australian and New Zealand (BRANZ) for acute burns in children (<16 years) admitted to hospital between October 2009 and July 2018. Descriptive statistics examined equity variables in patient and injury characteristics. Poisson regression was used to describe factors associated with bacterial infection. Indigenous research methods were used throughout. Aboriginal and Torres Strait Islander children represented 10.4% of the study population. Health inequities were present for Aboriginal and Torres Strait Islander children with longer hospital length of stay (9.5 vs 4.6 days), rural residency (61.3% vs 13.9%), lower socioeconomic status (72.2% vs 34.9%), and more flame burns (19.5% vs 10.6%) compared to other Australian children. Streptococcus sp. infection risk was four times greater in Aboriginal and Torres Strait Islander children compared to other Australian children. Flame burns and high percentage total body surface area burns were a risk for Staphylococcus sp. and Streptococcus sp. infection in all children. The epidemiological profile for burn injuries managed in Australian burns centers differs between Aboriginal and Torres Strait Islander children and other children, indicating persistent health inequities. These differences should be considered in the development of injury prevention strategies and the clinical management of burn injuries for Aboriginal and Torres Strait Islander children and their families.


Plasma Corticotropin-Releasing Factor Receptors and B7-2⁺ Extracellular Vesicles in Blood Correlate with Irritable Bowel Syndrome Disease Severity.
Extracellular vesicles (EVs) are composed of bilayer membranes that are released by different cell types and are present in bodily fluids, such as blood, urine, and bile. EVs are thought to play a key role in intracellular communication. Based on their size and density, EVs are classified into small, medium, or large EVs. Cargo composition in EVs reflects physiological changes in health and disease. Patients with irritable bowel syndrome (IBS) exhibit visceral hypersensitivity and mood disorders. Stressful episodes often precede disease symptoms in IBS patients. Stress-induced symptoms include, but are not limited to, abdominal pain and mood swings. Perceived stress responses are mediated by two known G protein-coupled receptors (GPCRs), corticotropin-releasing factor receptor 1 and 2 (CRFRs). CRFRs belong to the Class B secretin receptor family of GPCRs. Here, we show that CRFRs were present in human and murine plasma, and in EVs purified from mouse serum. CRFRs were present in plasma from IBS patients and healthy controls. EVs secreted from immune cells influence both adaptive and innate immune responses via exchange of EVs between different immune cell types. B7-2 (CD86), a plasma membrane antigen-presenting protein, is present on EVs secreted from dendritic, B-, and mast cells, whereas CD9 is present on EVs secreted from dendritic and intestinal epithelial cells. We found that plasma CRFR levels positively correlated with B7-2+ EVs (R = 0.8597, p < 0.0001), but no association was seen with CD9+ EVs. Plasma CRFRs expression negatively correlated with IBS severity scores. Our data suggests that plasma EVs from immune cells carry CRFRs as cargos and influence cell-cell communication in health and disease.


Effect of acupuncture on headache measured by reduction in number of attacks and use of drugs.
The experiment was performed in order to study the effect of acupuncture on headache by comparing the number of attacks during a 2-month period after acupuncture with the number of attacks during a similar period before treatment. Twenty-nine students (age: 19-24 years) all suffering from headache filled out questionnaires noting the days with attacks of headache and the amount and type of drugs used for 60 consecutive days. After acupuncture this observation procedure was repeated. One group of 10 students, however, received a placebo treatment instead of acupuncture but followed the identical questionnaire procedure. After 120 days acupuncture was given to this second group without revealing that the first treatment was a placebo. This treatment was again followed by a 60-day observation period. Comparison of the questionnaires before and after acupuncture showed a significant reduction in the number of days with headache. The placebo treatment resulted in a nonsignificant reduction in attacks of headache. A reduction in the amount of drugs used, especially the acetylsalicylate type, was noted following the acupuncture treatment. It is concluded that acupuncture is a relevant therapy for headache with a definite symptomatic effect.


From animal cage to aircraft cabin: an overview of evidence translation in jet lag research.
Recent laboratory experiments on rodents have increased our understanding of circadian rhythm mechanisms. Typically, circadian biologists attempt to translate their laboratory-based findings to treatment of jet lag symptoms in humans. We aimed to scrutinise the strength of the various links in the translational pathway from animal model to human traveller. First, we argue that the translation of findings from pre-clinical studies to effective jet lag treatments and knowledge regarding longer-term population health is not robust, e.g. the association between circadian disruption and cancer found in animal models does not translate well to cabin crew and pilots, who have a lower risk of most cancers. Jet lag symptoms are heterogeneous, making the true prevalence and the effects of any intervention difficult to quantify precisely. The mechanistic chain between in vitro and in vivo treatment effects has weak links, especially between circadian rhythm disruption in animals and the improvement of jet lag symptoms in humans. While the number of animal studies has increased exponentially between 1990 and 2014, only 1-2 randomised controlled trials on jet lag treatments are published every year. There is one relevant Cochrane review, in which only 2-4 studies on melatonin, without baseline measures, were meta-analysed. Study effect sizes reduced substantially between 1987, when the first paper on melatonin was published, and 2000. We suggest that knowledge derived from a greater number of human randomised controlled trials would provide a firmer platform for circadian biologists to cite jet lag treatment as an important application of their findings.


A slip connecting the peroneus longus and tibialis posterior tendons at the forefoot: MRI, anatomic, and histologic findings in a cadaver.
The anatomy of the peroneus longus and tibialis posterior tendons is well described in literature from both anatomy and radiology. Though a slip connecting these two structures is described in the anatomic literature, its existence has not been confirmed with magnetic resonance imaging (MRI). In this study in a cadaver, such a connection is documented using high-resolution MRI with anatomic and histologic correlation. This connection can provide support to the Lisfranc joint complex and further stabilize the region of the first and second metatarsal bases.


Contrast Agents of Magnetic Resonance Imaging and Future Perspective.
In recent times, magnetic resonance imaging (MRI) has emerged as a highly promising modality for diagnosing severe diseases. Its exceptional spatiotemporal resolution and ease of use have established it as an indispensable clinical diagnostic tool. Nevertheless, there are instances where MRI encounters challenges related to low contrast, necessitating the use of contrast agents (CAs). Significant efforts have been made by scientists to enhance the precision of observing diseased body parts by leveraging the synergistic potential of MRI in conjunction with other imaging techniques and thereby modifying the CAs. In this work, our focus is on elucidating the rational designing approach of CAs and optimizing their compatibility for multimodal imaging and other intelligent applications. Additionally, we emphasize the importance of incorporating various artificial intelligence tools, such as machine learning and deep learning, to explore the future prospects of disease diagnosis using MRI. We also address the limitations associated with these techniques and propose reasonable remedies, with the aim of advancing MRI as a cutting-edge diagnostic tool for the future.


[Thymus implant in a case of DiGeorge syndrome (author's transl)].
A boy with III-IV pharingeal pouch malformative syndrome, hypocalcemia and recurrent infections is presented. The immunological work-up disclosed deficiency in the specific cellular immunity with normal serum immunoglobulin levels. An adult thymus in Millipore diffusion chambers was implanted in the rectus adominalis muscle. One week later clinical and analytical data suggesting immunological reconstitution was recorded. Two years later the patient remains in good health, T and B lymphocyte percentages are normal, being the only immunological abnormality a low serum level of IgG.


External Stenting (Exostenting) to Correct Vascular Torsion and Angulation.
Organ transplantation can be associated with vascular torsions and angulations of both recipient and donor vessels. Such kinks and/or torsions of vessels can compromise the vascular integrity, obstruct inflow and/or outflow, and result in loss of the organ and/or body parts. On many occasions, mild angulations and torsions can be successfully addressed by repositioning the organ. In cases where the abnormal findings persist, maneuvers such as placing a fat pad to create a smoother curve, or even opening the peritoneum (in the case of kidney transplants) to allow for a better positioning of the organ, are associated with successful outcomes. When such torsions/angulations persist despite these approaches, further innovative tactics are required. In the current report, we propose a technique that involves longitudinally opening of a synthetic graft that is rigid enough to maintain its shape, such as a ringed polytetrafluoroethylene graft, and placing it as an external stent around the angulated/torsioned vessel. This maneuver will correct the underlying vascular compromise without having to perform any further invasive interventions, such as reimplanting the organ or resecting part of the involved vessel. Although primarily illustrated for application by describing an instance in which exostenting was applied during kidney transplantation, our approach could be applied to any vessel under many circumstances where angulations/twists are encountered. In this report, we describe the use of an external stent, also called exostenting, to correct a severe torsion/angulation of the external iliac artery in a kidney transplant recipient where all other measures were unsuccessful.


The return of two-class medicine--ill effects of Medi-Cal reform.
California's drastic Medi-Cal reforms have created great difficulties in health care for the poor. Patients' clinical problems seldom are apparent in descriptions of changes in public insurance programs. Rapidly escalating costs of Medi-Cal led to irresistible pressures for reform, especially from the business community. The new Medi-Cal regulations provide for prospective contracts with hospitals for inpatient services, the transfer of "Medically Indigent Adults" to the responsibility of county governments and various other straightforward funding cutbacks. Confusion, disruption of services and adverse health outcomes have accompanied the Medi-Cal reforms.


Association between sleep duration and mortality is mediated by markers of inflammation and health in older adults: the Health, Aging and Body Composition Study.
Inflammation may represent a common physiological pathway linking both short and long sleep duration to mortality. We evaluated inflammatory markers as mediators of the relationship between sleep duration and mortality in community-dwelling older adults. Prospective cohort with longitudinal follow-up for mortality outcomes. Pittsburgh, Pennsylvania, and Memphis, Tennessee. Participants in the Health, Aging and Body Composition (Health ABC) Study (mean age 73.6 ± 2.9 years at baseline) were sampled and recruited from Medicare listings. Baseline measures of subjective sleep duration, markers of inflammation (serum interleukin-6, tumor necrosis factor-α, and C-reactive protein) and health status were evaluated as predictors of all-cause mortality (average follow-up = 8.2 ± 2.3 years). Sleep duration was related to mortality, and age-, sex-, and race-adjusted hazard ratios (HR) were highest for those with the shortest (< 6 h HR: 1.30, CI: 1.05-1.61) and longest (> 8 h HR: 1.49, CI: 1.15-1.93) sleep durations. Adjustment for inflammatory markers and health status attenuated the HR for short (< 6 h) sleepers (HR = 1.06, 95% CI = 0.83-1.34). Age-, sex-, and race-adjusted HRs for the > 8-h sleeper group were less strongly attenuated by adjustment for inflammatory markers than by other health factors associated with poor sleep with adjusted HR = 1.23, 95% CI = 0.93-1.63. Inflammatory markers remained significantly associated with mortality. Inflammatory markers, lifestyle, and health status explained mortality risk associated with short sleep, while the mortality risk associated with long sleep was explained predominantly by lifestyle and health status.


Synthesis and secretion of active lipoprotein lipase in Chinese-hamster ovary (CHO) cells.
Cultured Chinese-hamster ovary cells (CHO cells) were found to produce and secrete a lipase, which was identified as a lipoprotein lipase by the following criteria. Its activity was stimulated by serum and apolipoprotein CII, and was inhibited by high salt concentration. The lipase bound to heparin-agarose and co-eluted with 125I-labelled bovine lipoprotein lipase in a salt gradient. A chicken antiserum to bovine lipoprotein lipase inhibited the activity and precipitated a labelled protein of the same apparent size as bovine lipoprotein lipase from media of CHO cells labelled with [35S]methionine. The lipase activity and secretion were similar in growing cells and in cells that had reached confluency. Hence, lipoprotein lipase appears to be expressed constitutively in CHO cells and is not linked to certain growth conditions, as in pre-adipocyte and macrophage cell lines. At 37 degrees C, but not at 4 degrees C, heparin increased the release of lipase to the medium 2-4-fold. This increased release occurred without depletion of cell-associated lipase activity, suggesting that heparin enhanced release of newly synthesized lipase.


Conjunctival Stromal Tumor: Report of 2 New Cases and Review of the Literature.
Conjunctival stromal tumor (COST) is an emerging entity with only a limited number of cases reported in the literature. In this report, we describe 2 additional cases, review the accumulative clinical and histopathological features and expand on the immunophenotypic property of this entity. COST appears to have a sporadic presentation, affecting both sexes and patients of variable ethnicity and age group and predominantly occurring on the bulbar conjunctiva as a slow-growing asymptomatic or slightly tender mass-like lesion. Histopathologically, COST is characterized by singly dispersed spindle to round cells, often with some degree of degenerative nuclear atypia, within a myxomatous to collagenous stroma. Lesional cells are characteristically positive for CD34 and vimentin, negative for S100, SOX10 and STAT6 and show a normal pattern of staining with RB1 by immunohistochemistry. The reported cases to date have shown an indolent biological behavior, reliably treated by a complete surgical excision.


Binary choice health state valuation and mode of administration: head-to-head comparison of online and CAPI.
Health state valuation exercises can be conducted online, but the quality of data generated is unclear. To investigate whether responses to binary choice health state valuation questions differ by administration mode: online versus face to face. Identical surveys including demographic, self-reported health status, and seven types of binary choice valuation questions were administered in online and computer-assisted personal interview (CAPI) settings. Samples were recruited following procedures employed in typical online or CAPI studies. Analysis included descriptive comparisons of the distribution of responses across the binary options and probit regression to explain the propensity to choose one option across modes of administration, controlling for background characteristics. Overall, 422 (221 online; 201 CAPI) respondents completed a survey. There were no overall age or sex differences. Online respondents were educated to a higher level than were the CAPI sample and general population, and employment status differed. CAPI respondents reported significantly better general health and health/life satisfaction. CAPI took significantly longer to complete. There was no effect of the mode of administration on responses to the valuation questions, and this was replicated when demographic differences were controlled. The findings suggest that both modes may be equally valid for health state valuation studies using binary choice methods (e.g., discrete choice experiments). There are some differences between the observable characteristics of the samples, and the groups may differ further in terms of unobservable characteristics. When designing health state valuation studies, the advantages and disadvantages of both approaches must be considered.


The "resistant hypertension team": focus on a multidisciplinary approach to hypertension.
Renal denervation (RDN) as a catheter-based procedure was introduced in 2009. As a reinvention of an old concept this approach in treating resistant hypertension has been gathering an unprecedented momentum in the world of hypertension. The incredible success in introducing this technique, followed by its quick and wide distribution, introduced new challenges and requirements for hypertension centres in offering optimal patient care. The challenges of these new parameters and requirements have to be met not only by a multidisciplinary team of doctors who can provide excellent evaluation, treatment and follow-up of these patients, but also by the hypertension centres themselves, who wish to provide this treatment option to their patients.


Effects of group metacognitive training (MCT) on mental capacity and functioning in patients with psychosis in a secure forensic psychiatric hospital: a prospective-cohort waiting list controlled study.
Metacognitive Training (MCT) is a manualised cognitive intervention for psychosis aimed at transferring knowledge of cognitive biases and providing corrective experiences. The aim of MCT is to facilitate symptom reduction and protect against relapse. In a naturalistic audit of clinical effectiveness we examined what effect group MCT has on mental capacity, symptoms of psychosis and global function in patients with a psychotic illness, when compared with a waiting list comparison group. Of 93 patients detained in a forensic mental health hospital under both forensic and civil mental health legislation, 19 were assessed as suitable for MCT and 11 commenced. These were compared with 8 waiting list patients also deemed suitable for group MCT who did not receive it in the study timeframe. The PANSS, GAF, MacArthur Competence Assessment Tool- Treatment (MacCAT-T) and MacArthur Competence Assessment Tool-Fitness to Plead (MacCAT-FP) were recorded at baseline and repeated after group MCT or following treatment as usual in the waiting list group. When baseline functioning was accounted for, patients that attended MCT improved in capacity to consent to treatment as assessed by the MacCAT-T (p = 0.019). The more sessions attended, the greater the improvements in capacity to consent to treatment, mainly due to improvement in MacCAT-T understanding (p = 0.014) and reasoning . The GAF score improved in patients who attended the MCT group when compared to the waiting list group (p = 0.038) but there were no changes in PANSS scores. Measures of functional mental capacity and global function can be used as outcome measures for MCT. MCT can be used successfully even in psychotic patients detained in a forensic setting. The restoration of elements of decision making capacity such as understanding and reasoning may be a hither-to unrecognised advantage of such treatment. Because pharmacotherapy can be optimised and there is likely to be enough time to complete the course, there are clear opportunities to benefit from such treatment programmes in forensic settings.


A Multi-Year Rancidity Analysis of 72 Marine and Microalgal Oil Omega-3 Supplements.
There exists significant heterogeneity in the 'freshness' of consumer marine- and plant-derived omega-3 (Ω3) supplements. Fears of rancidity, or the oxidation of consumer Ω3 supplements, has been debated in the literature with several prior authors reporting contradictory findings. We report the peroxide value (PV), para-anisidine value (p-AV) and total oxidation values (TOTOX) associated with 72 consumer Ω3 supplements sold in the United States sampled from 2014-2020. The effect of flavoring on the oxidation of the supplements was examined in an adjusted fixed effects model controlling for type of delivery system (enteric, liquid, animal- and vegetable-derived gelatin softgel, spray), source (algae, calamari, fish, krill, mussels), and certifications assigned by third-party organizations (e.g. USP). Overall, our results revealed that 68% (23/34) of flavored and 13% (5/38) unflavored consumer Ω3 supplements exceeded the TOTOX upper limit set by the Global Organization for EPA and DHA (GOED) voluntary monograph standard of ≤ 26, with 65% (22/34) flavored supplements and 32% (12/38) unflavored supplements failing the PV upper limit of ≤ 5 and 62% (21/34) flavored supplements exceeding the p-AV upper limit of ≤ 20. To our knowledge, no prior authors have modeled the impact of flavoring on oxidative status in 72 marine- and plant-derived Ω3 products sold in the U.S. We present our findings in this context and discuss the clinical implications related to the consumption of oxidized consumer fish oils and their effects on human health.


Dual regulation of PTH-stimulated adenylate cyclase activity by GTP.
Guanyl nucleotide regulation of parathyroid hormone (PTH)-activated adenylate cyclase was studied in membrane preparations of cultured opossum kidney cells. Guanosine triphosphate (GTP) (100 microM) decreased PTH-stimulated activity by 70%. Pertussis toxin enhanced PTH stimulation in intact cells and membranes, completely blocked the inhibitory effect of GTP, and catalyzed the [32P]ADP-ribosylation of a 38,000-dalton protein migrating in the position of the alpha-subunit of the inhibitory GTP-regulatory protein Ni. Cholera toxin was used to identify the alpha-subunit of the stimulatory GTP-binding protein Ns, a 42,000-dalton protein. We tested the idea that Ni may be involved in mediating the reduced response of opossum kidney cells to PTH after pretreatment with the hormone (desensitization). GTP inhibited PTH-stimulated activity to approximately the same degree in membranes from PTH-pretreated cells and control cells whether or not the cells had also received pertussis toxin. We conclude that GTP inhibits PTH action in opossum kidney cells through Ni but that PTH-induced desensitization is not mediated by Ni.


Dual Role of p21 in the Progression of Cancer and Its Treatment.
Cancer develops due to an imbalance between cell proliferation and cell death. Various mechanisms of carcinogenesis as well as of novel anticancer agents that could be targeted for the treatment of cancer have been proposed by different studies. Among these, p21 is recognized as a potent cyclin-dependent kinase inhibitor that facilitates cell-cycle arrest by interacting with different stimuli such as p53, DNA repair process, CDK, E2F1, MYC, PCNA, STAT3 AP4, proteasomes, K1F, CDX2, and ER-α. p21 acts both as a tumor-suppressor gene and an inhibitor of apoptosis by interacting with various molecules and transition factors. In this review, we discuss the complex role of p21 in the development of cancer and as a target in its treatment. We conclude that, in the future, the tumor-suppressor activity of p21 should be the focus of a novel treatment strategies, which may lead to the devolvement of new and selective anti-cancer agents for the targeted therapy of cancers.


Neuroanatomical changes in people with high schizotypy: relationship to glutamate levels.
Cortical glutamatergic dysfunction is thought to be fundamental for psychosis development, and may lead to structural degeneration through excitotoxicity. Glutamate levels have been related to gray matter volume (GMV) alterations in people at ultra-high risk of psychosis, and we previously reported GMV changes in individuals with high schizotypy (HS), which refers to the expression of schizophrenia-like characteristics in healthy people. This study sought to examine whether GMV changes in HS subjects are related to glutamate levels. We selected 22 healthy subjects with HS and 23 healthy subjects with low schizotypy (LS) based on their rating on a self-report questionnaire for psychotic-like experiences. Glutamate levels were measured in the bilateral anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, and GMV was assessed using voxel-based morphometry. Subjects with HS showed GMV decreases in the rolandic operculum/superior temporal gyrus (pFWE = 0.045). Significant increases in GMV were also detected in HS, in the precuneus (pFWE = 0.043), thereby replicating our previous finding in a separate cohort, as well as in the ACC (pFWE = 0.041). While the HS and LS groups did not differ in ACC glutamate levels, in HS subjects ACC glutamate was negatively correlated with ACC GMV (pFWE = 0.026). Such association was absent in LS. Our study shows that GMV findings in schizotypy are related to glutamate levels, supporting the hypothesis that glutamatergic function may lead to structural changes associated with the expression of psychotic-like experiences.


Do false predictions of seizures depend on the state of vigilance? A report from two seizure-prediction methods and proposed remedies.
Available seizure-prediction algorithms are accompanied by high numbers of false predictions to achieve high sensitivity. Little is known about the extent to which changes in EEG dynamics contribute to false predictions. This study addresses potential causes and the circadian distribution of false predictions as well as their relation to the sleep-wake cycle. In 21 patients, each with 24 h of interictal invasive EEG recordings, two methods, the dynamic similarity index and the mean phase coherence, were assessed with respect to time points of false predictions. Visual inspection of the invasive EEG data and additional scalp electroencephalogram data was performed at times of false predictions to identify possible correlates of changes in the EEG dynamics. A dependency of false predictions on the time of day is shown. Renormalized to the duration of the period patients are asleep and awake, 86% of all false predictions occurred during sleep for the dynamic similarity index and 68% for the mean phase coherence, respectively. Combining two reference intervals, one during sleep and one in an awake state, the dynamic similarity index increases its performance by reducing the number of false predictions by almost 50% without major changes in sensitivity. No obvious dependence of false predictions was noted on visible epileptic activity, such as spikes, sharp waves, or subclinical ictal patterns. Changes in the EEG dynamics related to the sleep-wake cycle contribute to limits of specificity of both seizure-prediction methods investigated. This may provide a clue for improving prediction methods in general. The combination of reference states yields promising results and may offer opportunities to increase further the performance of prediction methods.


The effect of air exposure on leucocyte and cytokine activation in an in-vitro model of cardiotomy suction.
Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory and immune response. An in-vitro model of cardiotomy suction was designed to quantify the effects of incrementally increased air-blood exposure on leucocyte marker CD11b and cytokine activation in two common anticoagulants, heparin and citrate. Fresh human blood was exposed to increasing amounts of air flow for ten minutes. Leucocyte and cytokine levels were measured prior to and after ten minutes of air flow. Cytokine levels were also measured after air exposure when incubated for 24 hours at 37oC. Leucocyte activation, measured by CD11b, was elevated between baseline and air flow rates up to 50 mL/min. After 10 minutes of air exposure, no measured cytokine levels were elevated. After 24 hours of incubation, cytokine levels of TNFα, IL-10, IL-6, and IL-8 were elevated. However, only IL-8 was significantly elevated in citrated blood, but not in heparinized blood, when compared to baseline samples that were also incubated for 24 hours. This study investigates CD11b levels in response to an air stimulus in blood that was anticoagulated with citrate or heparin. Exposure to an air stimulus activates leucocytes. Activation of CD11b was less when using heparin as an anticoagulant compared to citrate. Cytokine activation occurs with air stimulation, but levels do not immediately rise, indicating that time is required to generate free cytokines.


Distinguishing Energy- and Charge-Transfer Processes in Layered Perovskite Quantum Wells with Two-Dimensional Action Spectroscopies.
Interest in photovoltaic devices based on layered perovskites is motivated by their tunable optoelectronic properties and stabilities in humid conditions. In these systems, quantum wells with different sizes are organized to direct energy and charge transport between electrodes; however, these relaxation mechanisms are difficult to distinguish based on conventional transient absorption techniques. Here, two-dimensional "action spectroscopies" are employed to separately target processes that lead to the production of photocurrent and energy loss due to fluorescence emission. These measurements show that energy transfer between quantum wells dominates the subnanosecond time scale, whereas electron transfer occurs at later times. Overall, this study suggests that while the intense exciton transitions promote light harvesting, much of the absorbed energy is lost by way of spontaneous emission. This limitation may be overcome with alternate layered perovskite systems that combine smaller exciton binding energies with large absorbance cross sections in the visible spectral range.


Isolation of a planar 1,2-dilithio-disilene and its conversion to a Si-B hybrid 2π-electron system and a planar tetraboryldisilene.
Lithium reagents have long played important roles in synthetic chemistry. However, unsaturated organosilicon lithium reagents are few in number. Herein, we describe the first isolation of a 1,2-dilithiodisilene: [(boryl)SiLi]2 (2) was prepared in 73% yield by the reduction of (boryl)tribromosilane (1, boryl = (HCArN)2B, Ar = 2,6-iPr2C6H3) with lithium in Et2O. The salt elimination reaction of 2 with dihaloboranes RBX2 afforded disilaborirenes [(boryl)Si]2BR (3a-c), whereas the reaction with two equivalents of B-bromocatecholborane ((cat)BBr) yielded the first tetraboryldisilene [(boryl)(cat)BSi]2 (4). X-ray diffraction analysis and density functional theory calculations indicated that the disilene 2 and tetraboryldisilene 4 feature an almost planar geometry and disilaborirenes 3a-c are aromatic with a silicon-boron hybrid 2π-electron delocalized structure. The results indicate that 1,2-dilithiodisilene 2 is a powerful synthetic reagent for the construction of novel silicon multiply bonded species with unique electronic structures and that the boryl substituents have significant electronic effects on the structure of silicon multiple bonding.


The incidence of oral candidiasis with use of inhaled corticosteroids.
The incidence of thrush occurring among patients receiving inhaled corticosteroids as reported by various investigators is presented. The data were standardized according to diagnostic criteria, duration of treatment and size of patient population. Although proper assessment of the relative risk of thrush incurred with the use of aerosolized corticosteroids must await large-scale randomized, blind, comparative trials, these results of past studies give a general indication of what may be expected.


Procedural training in family practice residencies: current status and impact on resident recruitment.
Although procedural training in family practice has recently received greater emphasis, the current status of this training in residency programs has not been reported. Considerable variation in procedural training among family practice residencies is allowed by the American Board of Family Practice and accreditation requirements. This study was performed to report the current status of procedural training in family practice residencies and to determine whether a correlation exists between the number of procedures taught in family practice residencies and successful resident recruitment. A one-page questionnaire was developed to determine availability of teaching and type of instructor for 24 selected procedures. This questionnaire was mailed to all 398 family practice residency directors in the United States. Data from the survey were compared with the published residency match results in 1993 and 1994. Questionnaires were received from 363 programs, for a response rate of 91 percent. The current status of training in these procedures, presented by program type and geographic region, reflects considerable regional variation. Training in colposcopy and in cardiac stress testing was reported to be available in a greater percentage of programs than in previous studies. A significant positive correlation was found between the number of procedures taught by family physicians and residency match results. The 91 percent response rate lends credibility to this status report and indicates that family practice program directors recognize procedural training as an important issue. The trend toward greater availability of procedural training in family practice residencies is confirmed for selected procedures. Emphasis on procedural training by family physicians has a positive correlation with successful resident recruiting. The impact on medical student interest in family practice deserves further study.


Risk factors for infection of tibial plateau fractures.
Tibial plateau fractures are injuries prone to postoperative infection, with its reported incidence being higher than that of other fractures, between 5% and 12%. The primary objectives of this study were to quantify the postoperative infection rate of internal fixation of tibial plateau fractures (TPF) and to identify the risk factors for this. Retrospective cohort study including patients who underwent TPF osteosynthesis between 2015 and 2020, in the same center. The study population was divided into two groups, according to the presence or absence of postoperative infection. Demographic variables related to the fracture, surgical parameters, as well as the need for reoperation were collected. Finally, in the case of debridement, the number of positive cultures and the pathogen responsible for the infection were collected, as well as the treatment applied. One hundred and twenty-four patients were included, with a total of 14 infections (global infection rate of 11.3%). Risk factors for developing infection were open fractures (P=.002), Schatzker V and VI type fractures (P=.002) and the use of external fixation (P<.001). Regarding the surgical variables, only the longest ischemia time (P=.032) was identified as a risk factor. S. aureus was the most frequently identified microorganism (43%), followed by E. cloacae (35.7%). The overall infection rate after osteosynthesis of tibial plateau fractures was 11.3%. Different factors are associated with a higher risk of infection, including diabetes mellitus, open fractures, the use of external fixation, a higher grade in the Schatzker classification or a longer intraoperative ischemia time.


Emission of Dioxin-like Compounds and Flame Retardants from Commercial Facilities Handling Deca-BDE and Their Downstream Sewage Treatment Plants.
Commercial mixtures of decabromodiphenyl ether (deca-BDE), a brominated flame retardant, contain not only polybrominated diphenyl ethers (PBDEs, mainly BDE-209) as the main component but also dioxin-like compounds (DLCs) such as polybrominated dibenzofurans (PBDFs). Deca-BDE handling facilities (DHFs) and sewage treatment plants receiving effluent from DHFs are point sources of DLC and flame retardant (FR) pollution. Here, we examined their emission in Japan. For DHF effluents, DLCs detected by the dioxin-responsive chemically activated luciferase expression (DR-CALUX) assay were 1.3-890 pg TCDD-EQ/L (median 46 pg TCDD-EQ/L), while PBDEs and other FRs were <2.0-110,000 ng/L (610 ng/L) and 150-4,800,000 ng/L (41,000 ng/L). Risk quotients based on predicted no-effect concentrations suggested that DLCs, decabromodiphenyl ethane (DBDPE), tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), and bisphenol A bis(diphenyl phosphate) (BPA-BDPP) present significant risks for aquatic organisms. The concentrations of PBDFs, which are impurities in deca-BDE, were expected to decrease with the inclusion of deca-BDE in the Stockholm Convention list of persistent organic pollutants (May 2017). However, DLCs other than PBDFs and alternative FRs such as DBDPE, TDBP-TAZTO, and BPA-BDPP are likely still discharged. Additional findings indicate that strong (e.g., DLCs, DBDPE, and BPA-BDPP), but not weak (e.g., TDBP-TAZTO), hydrophobic compounds are sufficiently removed by current wastewater treatment processes in Japan.


[Medical management of HIV infected and AIDS patients in the Hannover metropolitan area as an interdisciplinary construct].
Two wards for consultation of AIDS have opened in Hannover in 1987, one in the Public Health Department for the city of Hannover, the other in the Public Health Department for the surroundings. It was a big step towards prevention of AIDS. At the same time a centre, especially for AIDS, was opened at the Medical college of Hannover, consisting of an ambulance and beds in a ward. An official laboratory tests the medical analyses. Today the doctor in the Public Health Department plays an important part: he is the first partner with whom the infected patient can talk. He must also maintain contact with all institutions including the family doctor for optimum patient care.


Characterization of bacteria from a Swine manure digester.
One-hundred thirty bacteria isolated from a swine manure digester were predominately gram-positive anaerobes which were tentatively classified into the following genera: Peptostreptococcus, Eubacterium, Bacteroides, Lactobacillus, Peptococcus, Clostridium, and Streptococcus plus two unidentified groups. The major fermentation products formed by these organisms included acetate, propionate, succinate, lactate, and ethanol, singly or in various combinations. Acetate was the sole end product of several groups. Few of the isolates (14%) reduced the pH below 6.0. The predominate bacteria appear to differ from the predominate organisms isolated from other anaerobic ecosystems.


Efficacy and safety of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC): a systematic literature review.
Therapeutic strategies with immune checkpoint inhibitors (ICIs) counteract the immunosuppressive effects of programmed cell death protein-1 (PD-1) and ligand-1 (PD-L1). ICI treatment has emerged in first- and second-line therapy of non-small cell lung cancer (NSCLC). As immunotherapeutic treatment with ICIs is a dynamic field where new drugs and combinations are constantly evaluated, we conducted an up-to-date systematic review on comparative efficacy and safety in patients with advanced NSCLC. We searched PubMed up to February 2020 and Embase, CENTRAL, and clinical trial registries up to August 2018. Additionally, we checked reference lists. We dually screened titles, abstracts and, subsequently, full-texts for eligibility. Two reviewers assessed the risk of bias and graded the certainty of evidence following GRADE (Grading of Recommendations Assessment, Development and Evaluation). For second-line therapy, we performed random-effects meta-analyses. Due to considerable clinical heterogeneity, we reported first-line results narratively. Of 1497 references, we identified 22 relevant publications of 16 studies. For first-line therapy, a combination of an ICI with chemotherapy improved progression-free survival and overall survival compared to chemotherapy but increased the risk of serious adverse events. Single-agent pembrolizumab increased overall and progression-free survival in patients with PD-L1 expression of ≥50% and resulted in less TRAE than chemotherapy. Compared to placebo, maintenance therapy with durvalumab increased overall and progression-free survival at the downside of higher risk of TRAE. For second-line therapy, a random-effects meta-analysis yielded a statistically significantly improved overall survival (OS) and progression-free survival (PFS) for ICIs compared to docetaxel (HR 0.69; 95% CI: 0.63-0.75 for OS; HR 0.85; 95% CI: 0.77 - 0.93 for PFS; 6 studies, 3478 patients; median OS benefit in months: 2.4 to 4.2). In meta-analysis, risk of any treatment-related adverse events of any grade was lower for ICI than docetaxel as second-line therapy (RR 0.76, 95% CI: 0.73-0.79; 6 studies, 3763 patients). In first-line therapy of patients with advanced NSCLC, ICI is effective when combined with chemotherapy not depending on PD-L1 expression, or as monotherapy in high PD-L1 expressing tumors. For second-line therapy, single-agent ICI improves efficacy and safety compared to docetaxel.


Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds.
Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal-habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities.


Photoreflectance/scattering measurements of spider silks informed by standard optics.
The silks of certain orb weaving spiders are emerging as high-quality optical materials. This motivates study of the optical properties of such silk and particularly the comparative optical properties of the silks of different species. Any differences in optical properties may impart biological advantage for a spider species and make the silks interesting for biomimetic prospecting as optical materials. A prior study of the reflectance of spider silks from 18 species reported results for three species of modern orb weaving spiders (Nephila clavipes, Argiope argentata and Micrathena Schreibersi) as having reduced reflectance in the UV range. (Modern in the context used here means more recently derived.) The reduced UV reflectance was interpreted as an adaptive advantage in making the silks less visible to insects. Herein, a standard, experimental technique for measuring the reflectance spectrum of diffuse surfaces, using commercially available equipment, has been applied to samples of the silks of four modern species of orb weaving spiders: Phonognatha graeffei, Eriophora transmarina, Nephila plumipes and Argiope keyserlingi. This is a different technique than used in the previous study. Three of the four silks measured have a reduced signal in the UV. By taking the form of the silks as optical elements into account, it is shown that this is attributable to a combination of wavelength-dependent absorption and scattering by the silks rather than differences in reflectance for the different silks. Phonognatha graeffei dragline silk emerges as a very interesting spider silk with a flat 'reflectance'/scattering spectrum which may indicate it is a low UV absorbing dielectric micro-fibre. Overall the measurement emerges as having the potential to compare the large numbers of silks from different species to prospect for those which have desirable optical properties.


Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and poly(ethylene glycol) groups.
Poly(amidoamine) (PAMAM) dendrimer derivatives have been investigated for their biological applications, especially for delivery of drugs, including antimicrobial drugs to eukaryotic cells, but their effects on bacterial cells are largely unexplored. Herein we report that amino-terminated PAMAM dendrimers are highly toxic to the common Gram-negative pathogen Pseudomonas aeruginosa. The concentration that kills 50% of the bacteria (EC50) was in the range of approximately 0.9-1.5 microg/mL for the generation 5, amino-terminated dendrimers with or without partial (43%) coating of poly(ethylene glycol) (PEG). These EC50 values were lower than that ( approximately 1.9-2.8 microg/mL) for LL-37, a potent antimicrobial peptide expressed in a variety of epithelia. On the contrary, the dendrimers were far less toxic (EC50 > 21 microg/mL) to the Gram-positive pathogen Staphylococcus aureus than LL-37 (EC50 = approximately 1.9 microg/mL). In agreement with the previous studies on other cell types, the dendrimers were not cytotoxic to human corneal epithelial cells at the concentrations that were toxic to P. aeruginosa. Our findings indicate that amino-terminated PAMAM dendrimers and their partially PEG-coated derivatives possess attractive antimicrobial properties, particularly against Gram-negative bacteria, thus expanding the potential biological application of the dendrimers.


General medication adherence scale in patients with chronic illnesses: Persian translation and psychometric evaluation.
This study was conducted with the aim of determining the validity and reliability of the Persian version of "General Medication Adherence Scale (GMAS)" in chronic patients in Iran. The study was conducted among patients with chronic diseases in five hospitals of Iran. In this study, after cultural validation, using the steps of Content, Response Reaction, and Internal structure evaluations, the research sample was increased to 150 individuals for exploratory factor analysis (EFA) and 313 chronic patients for confirmatory factor analysis (CFA) to confirm the construct validity. Cronbach's alpha coefficient was used to assess internal consistency, and test-retest method was used to evaluate the reliability of the tool. The results of EFA and CFA confirmed the tool with three factors and 11 items. The R2 index in the above model was estimated at 0.99, indicating that 99% of the variation in medication adherence scores in research units was explained by GMAS with 11 items. The main indices of the model in factor analysis were all above 0.9, indicating a good fit for the model. Overall, the study results showed that the Persian version of GMAS has acceptable and practical characteristics for evaluating medication adherence, and it can be used as a valid tool in various related fields.


Patient-risk due to negligence by Locum General Practitioners outside of office hours.
In Holland, first tier medical care outside of office hours is provided by regular GP's acting as Locum GP's. On several occasions concerns have been expressed about Locum GP's not visiting the patient when necessary. The number of complaints against Locum GP's submitted to the Medical Boards has been increasing over time and relate in particular to refusals of Locum GP's to visit the patient. In many of these cases the patient died. The paper develops a quantitative estimate of the risk for the patient due to negligence of Locum GP's. The measure of the risk is taken as the number of patients who died unnecessarily due to negligence of Locum GP's as determined by the Medical Boards. The paper estimates that in Holland in the year 2000 about 1500 patients would probably not have died had the Locum GP's working out-of-hours not been negligent by contravening professional standards. In more than half of these cases the Locum GP's did not visit the patient, or did not visit the patient in time, when necessary. This level of patient risk must be regarded as socially unacceptable. One important explanation for these accidents could be that doctors are largely unfamiliar with the professional standards developed by the Medical Boards. Because of the assumptions made and the uncertainty regarding the data used, the actual numbers of these accidents may be higher or lower than estimated here. Although more reliable data will allow the results to be determined more reliably, this is unlikely to change the acceptability of the risk.


Confocal backscattering spectroscopy for leukemic and normal blood cell discrimination.
Leukemia is the most common pediatric cancer and leading cause of cancer related deaths in children. Improvements in the assessment of leukemic cells have the potential to influence not only the diagnosis of leukemia, but also the risk assessment of patients during the course of the treatment, both of which are important for improving the cure rate for this disease. In this study, we report on the design and performance of a confocal laser based system built to collect backscattered light over a range of 26° at 405, 488, and 633 nm to discriminate leukemic cells from normal red blood cells (RBC) and white blood cells (WBC). The design of the system is based on the spectral differences observed from spectroscopy measurements with a similar system designed with a white light source. Significant differences are observed in the intensity and wavelength dependence of leukemic cells from normal RBC and WBC. Specifically, the distinct light scattering of RBC is due to hemoglobin absorption, allowing for its discrimination from leukemic cells, mononuclear, and polymorphonuclear WBC particularly at certain wavelengths. Meanwhile, the high scattering intensities of polymorphonuclear WBC reflect the intracellular complexity of these cells in comparison to the leukemic or normal lymphocytes. Additionally, the detected light scattering spectra for leukemic cells are consistently steeper in comparison to normal WBC, which we attributed to differences in the fractal organization of intracellular scatterers. Based on our findings, the system has potential applications in the detection and quantification of leukemic cells in blood either in vivo or in vitro, using microfluidic-based systems, for disease monitoring.


[Effect of leu-enkephalin in striatum on modulating cellular immune during electropuncture].
Zusanli points of rat were used to study the effect of acupuncture on the synthesis and release of endogenous leu-enkephalin (LEK) in modulating immune function as assayed by T lymphocyte proliferative response, i.e. the lymphocyte transformation test (LTT). The results are as follows: (1) LEK level in striatum was increased as LTT was enhanced by puncture. The latter effect could be inhibited by microinjection of naloxone into striatum. (2) Injection of LEK into striatum caused a significant enhancement of LTT, an effect being more powerful than did by electropuncture. (3) Following injection of LEK antiserum into striatum, electropuncture enhanced LTT was inhibited. The above results demonstrate that the LEK plays an important role in modulating cellular immune function during electropuncture, through its action in striatum either as a neurotransmitter or as a neuromodulator.


Organ exclusion simulation with multi-finger haptic interaction for open surgery simulator.
Exclusion is a surgical manipulation of pushing aside organ in open surgery. Recently, training opportunity of surgeon is decreasing due to animal protection and patient's rights. In this study, we propose an organ exclusion training simulator with multi-finger haptic device and stress visualization. The method was applied to a medical application of exclusion which is an important manipulation to make a hidden tissue visible or to enlarge workspace. The system equips FEM-based soft tissue deformation and multi-finger haptic device. Real-time simulation was achieved with a prototype system. Experimental results of training trial suggested the effectiveness of the system and stress visualization for exclusion training. Results of subjective evaluation by surgeons were highly positive as to realism of manipulation and usefulness of the simulator.


Effectiveness of Dunaliella salina Extracts against Bacillus subtilis and Bacterial Plant Pathogens.
Several bacteria pathogens are responsible for plant diseases causing significant economic losses. The antibacterial activity of Dunaliella salina microalgae extracts were investigated in vitro and in vivo. First, biomass composition was chemically characterized and subjected to extraction using polar/non-polar solvents. The highest extraction yield was obtained using chloroform:methanol (1:1 v/v) equal to 170 mg g-1 followed by ethanol (88 mg g-1) and hexane (61 mg g-1). In vitro examination of hexane extracts of Dunaliella salina demonstrated antibacterial activity against all tested bacteria. The hexane extract showed the highest amount of β-carotene with respect to the others, so it was selected for subsequent analyses. In vivo studies were also carried out using hexane extracts of D. salina against Pseudomonas syringae pv. tomato and Pectobacterium carotovorum subsp. carotovorum on young tomato plants and fruits of tomato and zucchini, respectively. The treated young tomato plants exhibited a reduction of 65.7% incidence and 77.0% severity of bacterial speck spot disease. Similarly, a reduction of soft rot symptoms was observed in treated tomato and zucchini fruits with a disease incidence of 5.3% and 12.6% with respect to 90.6% and 100%, respectively, for the positive control.


Foiled carbenes revisited: When sigma-stabilization surpasses pi-stabilization.
The bicyclic alkenylidenes 9 (bicyclo[3.2.1]oct-2-en-8-ylidene) and 17 (bicyclo[3.3.1]non-2-en-9-ylidene) were claimed to be stabilized foiled carbenes. Our B3LYP and MP2 computations confirm previous experimental data. Moreover, they show that these carbenes are very reactive and rearrange rapidly, mainly through a 1,2-vinyl shift by overcoming a low barrier (1.2 to 5.4 kcal/mol). This is in contrast to the high barriers (up to 30 kcal/mol) predicted for the same type of rearrangements in norborn-2-en-7-ylidene derivatives. In 17 and bicyclo[4.1.1]oct-2-en-7-ylidene (23), the divalent carbon atom is even bent away from the double bond!


Desloratadine inhibits heterotopic ossification by suppression of BMP2-Smad1/5/8 signaling.
Heterotopic ossification (HO) is a pathological condition in which ectopic bone forms within soft tissues such as skeletal muscle. Human platelet-derived growth factor receptor α positive (PDGFRα+) cells, which were proved to be the original cells of HO were incubated in osteogenic differentiation medium with Food and Drug Administration-approved compounds. Alkaline phosphatase activity was measured as a screening to inhibit osteogenic differentiation. For the compounds which inhibited osteogenic differentiation of PDGFRα+ cells, we examined dose dependency of its effect using alizarin red S staining and its cell toxicity using WST-8. In addition, regulation of bone morphogenetic proteins (BMP)-Smad signaling which is the major signal of osteogenic differentiation was investigated by Western blotting to elucidate the mechanism of osteogenesis inhibitory effect by the compound. In vivo experiment, complete transverse incision of Achilles tendons in mice was made and mice were fed the compound by mixing with drinking water after operation. Ten weeks after operation, we assessed and quantified HO by micro-computed tomography scan. Intriguingly, we discovered desloratadine inhibited osteogenic differentiation of PDGFRα+ cells using the drug repositioning method. Desloratadine inhibited osteogenic differentiation of the cells dose dependently without cell toxicity. Desloratadine suppressed phosphorylation of Smad1/5/8 induced by BMP2 in PDGFRα+ cells. In Achilles tenotomy mice model, desloratadine treatment significantly inhibited ectopic bone formation compared with control. In conclusion, we discovered desloratadine inhibited osteogenic differentiation using human PDGFRα+ cells and proved its efficacy using Achilles tenotomy ectopic bone formation model in vivo. Our study paved the way to inhibit HO in early clinical use because of its guaranteed safety.


Spatio-temporal structure of single neuron subthalamic activity identifies DBS target for anesthetized Tourette syndrome patients.
Deep brain stimulation (DBS) of basal ganglia effectively tackles motor symptoms of movement disorders such as Tourette syndrome (TS). The precise location of target stimulation site determines the range of clinical outcome in DBS patients, and the occurrence of side-effects of DBS. DBS implant procedures currently localize stimulation target relying on a combination of pre-surgical imaging, standardized brain atlases and on-the-spot clinical tests. Here we show that temporal structure of single unit activity in subthalamic nucleus (STN) of patients affected by pure TS can contribute to identify the optimal target location of DBS. Neural activity was recorded at different depths within STN with microelectrodes during DBS implant surgery. Depth specific neural features were extracted and correlated with the optimal depth for tic control. We describe for the first time temporal spike patterns of single neurons from sensorimotor STN of anesthetized TS patients. A large fraction of units (31.2%) displayed intense bursting in the delta band (<4 Hz). The highest firing irregularity and hence the higher density of bursting units (42%) were found at the optimal spot for tic control. Discharge patterns irregularity and dominant oscillations frequency (but not firing rate) carried significant information on optimal target. We found single unit activity features in the STN of TS patients reliably associated to optimal DBS target site for tic control. In future works measures of firing irregularity could be integrated with current target localization methods leading to a more effective and safer DBS for TS patients.


Vaccine-relevant human papillomavirus (HPV) infections and future acquisition of high-risk HPV types in men.
Little is known about type-specific associations between prevalent human papillomavirus (HPV) infections and risk of acquiring other HPV types in men. Data on natural clustering of HPV types are needed as a prevaccine distribution to which postvaccine data can be compared. Using data from a randomized controlled trial of male circumcision in Kisumu, Kenya, adjusted mean survival ratios were estimated for acquisition of any-HPV, high-risk (HR) HPV, and individual HR-HPV types among men uninfected as compared to those infected with vaccine-relevant HPV types 16, 18, 31, 45, 6, or 11 at baseline. Among 1097 human immunodeficiency virus-negative, uncircumcised men, 2303 incident HPV infections were detected over 2534 person-years of follow-up. Although acquisition of individual HR-HPV types varied by baseline HPV type, there was no clear evidence of shorter times to acquisition among men without vaccine-relevant HPV-16, -18, -31, -45, -6, or -11 infections at baseline, as compared to men who did have these infections at baseline. These prospective data on combinations of HPV infections over time do not suggest the potential for postvaccination HPV type replacement. Future surveillance studies are needed to definitely determine whether elimination of HPV types by vaccination will alter the HPV type distribution in the population.


Acid-base formalism in dispersion-stabilized S-H···Y (Y═O, S) hydrogen-bonding interactions.
The role of sulfhydryl (S-H) group as hydrogen bond donor is not as well studied as that of hydroxyl (O-H). In this work we report on the hydrogen-bonding properties of S-H donor in 1:1 complexes of H2S with diethyl ether (Et2O), dibutyl ether (Bu2O), and 1,4-dioxane (DO). The complexes were prepared in supersonic jet and investigated using infrared predissociation spectroscopy based on VUV photoionization detection. The IR spectra of all the complexes showed the presence of a broad, intensity-enhanced, and red-shifted hydrogen-bonded S-H stretching transition. The S-H stretching frequency was red-shifted by 46, 63, and 49 cm(-1) in H2S-Et2O, H2S-Bu2O, and H2S-DO complexes, respectively, suggesting that all the complexes are S-H···O bound. Computationally, two different S-H···O bound structures, namely, "coplanar" and "perpendicular", were obtained as the minimum energy structures for these complexes at the MP2/6-311++G** level, with the former being the global minimum. However, with Dunning-type basis sets (aug-cc-pVDZ and aug-cc-pVTZ) only the perpendicular structures were found to be stable at the MP2 level. The large widths of the bound S-H stretch observed in the experimental spectra (fwhm of 35 to 80 cm(-1)) were attributed to inhomogeneous broadening due to multiple conformations of the alkyl chains in the coplanar and perpendicular structures populated in the jet. The frequency shifts in the hydrogen-bonded S-H stretching mode as well as the bond dissociation energies of all S-H···Y (Y═O,S) complexes of H2S, which includes the H2S dimer and H2S-methanol (H2S-MeOH) complexes reported in our previous work (ChemPhysChem 2013, 14, 905-914), were found to scale linearly with the proton affinity of the acceptor molecule. In this regard the S-H group, like O-H, is found to conform to the widely accepted acid-base nature of hydrogen-bonding interactions.


Design and Analysis of In-Pipe Hydro-Turbine for an Optimized Nearly Zero Energy Building.
Pakistan receives Direct Normal Irradiation (DNI) exceeding 2000 kWh/m²/annum on approximately 83% of its land, which is very suitable for photovoltaic production. This energy can be easily utilized in conjunction with other renewable energy resources to meet the energy demands and reduce the carbon footprint of the country. In this research, a hybrid renewable energy solution based on a nearly Zero Energy Building (nZEB) model is proposed for a university facility. The building in consideration has a continuous flow of water through its water delivery vertical pipelines. A horizontal-axis spherical helical turbine is designed in SolidWorks and is analyzed through a computational fluid dynamics (CFD) analysis in ANSYS Fluent 18.1 based on the K-epsilon turbulent model. Results obtained from ANSYS Fluent have shown that a 24 feet vertical channel with a water flow of 0.2309 m3/s and velocity of 12.66 m/s can run the designed hydroelectric turbine, delivering 168 W of mechanical power at 250 r.p.m. Based on the turbine, a hybrid renewable energy system (HRES) comprising photovoltaic and hydroelectric power is modelled and analyzed in HOMER Pro software. Among different architectures, it was found that architecture with hydroelectric and photovoltaic energy provided the best COE of $0.09418.


Sphinganine potentiation of cellular differentiation induced by various anti-leukemia drugs in human leukemia cell line HL-60.
A slight induction of cellular differentiation (myelocytes and granulocytes) of HL-60 cells occurred after treatment with anti-tumor agents etoposide (VP-16), mitoxantrone (MXT), mitomycin C (MMC), actinomycin D (Act-D) or novobiocin (NOVO). Addition of sphinganine (SP), an inhibitor of protein kinase C (PKC) enhanced (2-3 fold) the VP-16, MXT, MMC or Act-D-induced differentiation but not the NOVO-induced differentiation. No induction of differentiation was observed with 5-fluorouracil (5-FU) in the absence or presence of SP. The addition of SP in the fresh medium after the removal of VP-16, MXT, or MMC (0.5 h treatment) enhanced the induction of differentiation. In contrast, SP post-treatment did not have any effect on enhancing the differentiation which was induced by Act-D short exposure (0.5 h). In an attempt to characterize the biochemical requirements for potentiation of VP-16-induced differentiation, we examined the effects of calcium depletion using calcium chelator ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) or calcium channel blocker verapamil. Potentiation of VP-16-induced differentiation by SP was not observed in EGTA- or verapamil-treated cells. Calcium supplementation to the cells during the treatment with EGTA restored the SP-potentiation of VP-16-induced differentiation. Our results also showed that the induction of differentiation was accompanied by a decrease in PKC activity (70% of the control). PKC activity decreased to a greater extent (50% of control) in SP potentiation of differentiation induction. Our results suggested that calcium-dependent biological action of antitumor agents and the inhibition of PKC activity are required for SP-potentiation of differentiation induction.