Haptic object recognition based on shape relates to visual object recognition ability.
Visual object recognition depends in large part on a domain-general ability (Richler et al. Psychol Rev 126(2): 226-251, 2019). Given evidence pointing towards shared mechanisms for object perception across vision and touch, we ask whether individual differences in haptic and visual object recognition are related. We use existing validated visual tests to estimate visual object recognition ability and relate it to performance on two novel tests of haptic object recognition ability (n = 66). One test includes complex objects that participants chose to explore with a hand grasp. The other test uses a simpler stimulus set that participants chose to explore with just their fingertips. Only performance on the haptic test with complex stimuli correlated with visual object recognition ability, suggesting a shared source of variance across task structures, stimuli, and modalities. A follow-up study using a visual version of the haptic test with simple stimuli shows a correlation with the original visual tests, suggesting that the limited complexity of the stimuli did not limit correlation with visual object recognition ability. Instead, we propose that the manner of exploration may be a critical factor in whether a haptic test relates to visual object recognition ability. Our results suggest a perceptual ability that spans at least across vision and touch, however, it may not be recruited during just fingertip exploration.


Acute stress responses in Chinese soldiers performing various military tasks.
To examine Chinese soldiers' acute stress responses, we did this study. The soldiers completed the Acute Stress Response Scale (ASRS) when engaged in major tasks, such as earthquake rescue in Wenchuan, Sichuan, and maintaining social stability in Urumchi, Xinjiang. The ASRS has good reliability and validity. The study enrolled 1,832 male soldiers. The results showed significant differences among five dimensions and the overall response index when comparing four diverse military tasks. Further analysis found that reduced work efficiency and 24 symptom clusters were significantly positively correlated. The acute stress response of soldiers performing various tasks was influenced by many factors, including the task characteristics and external factors. In addition, the acute stress response affected their work efficiency.


Accessibility of information on patients' and family members' end-of-life wishes in advance care planning.
To describe healthcare professionals' accessibility and transfer of patients' and family members' end-of-life wishes in ACP to the palliative care unit. The study used a qualitative descriptive study design. Purposive sampling was used. The data (N = 33) were collected through interviews with physicians, registered nurses, practical nurses and social workers. The data were analysed by inductive content analysis. Two main categories emerged. Patients' and family members' end-of-life wishes documentation in relation to changing information needs was described in relation to patients' condition and care context. Transfer of patients' and family members' end-of-life wishes to palliative care unit included written and verbal communication. Results showed lack of implementation of ACP early, lack of implementation about the holistic interpretation of ACP into medical notes and lack of transferability of ACP into documenting systems impacting on accessibility and realization for the patient and family members at the end-of-life.


Dynamic characterization and substrate binding of cis-2,3-dihydrobiphenyl-2,3-diol dehydrogenase-an enzyme used in bioremediation.
In recent years, techniques involving the use of organisms to remove or neutralize pollutants from contaminated sites have attracted great attention. The aim of bioremediation is to use naturally occurring organisms to degrade dangerous substances to less toxic or non toxic molecules. The gram-negative bacterium Pandoraea pnomenusa strain B-356 (Pp) has been found to be able to transform a persistent class of organic pollutant compounds, namely the biphenyl and polychlorinated biphenyls (PCBs). A key enzyme in the PCB catabolic pathway is NAD-dependent cis-2,3-dihydrobiphenyl-2,3-diol dehydrogenase (BphB), for which the crystal structure from Pp has been crystallized in apo-, NAD-bound and biphenyldiol-/NAD-bound forms. The substrate binding loop structure has not been completely resolved to date in the former two bound states. Here we report the results of the first extensive molecular dynamics simulations on the three different states of PpBphB. This allowed an in depth characterization of the mechanism of ligand uptake and binding, including unraveling of the gating mechanism. Our simulations give a deep insight into several dynamic features of the enzyme that were not captured by crystal structures.


[Computerized prescription for medical devices: examples, interest and limits].
Related to the good practice contract implemented in hospitals, the prescription dedicated to medical devices, such as pharmaceuticals, could promote safety and good practice. We attempted to implement a computerized prescription for medical devices. In order to illustrate the method, two examples were selected: the Negative Pressure Wound Therapy (NPWT) and the Drug Eluting Stents (DES). In partnership with the medical teams was elaborated a computerized protocol which included all the needed items for the good use of NPWT. For DES, a pre-existing questionnaire was used. We updated it in order to integrate new items such as the prescriber's name, the patient's name, the characteristics of the wound, the DES references and the indications. Computerized prescriptions for high-risk and expensive medical devices seem to be an interesting approach to guarantee the patient care safety and to reduce the budget impacts. In order to monitor the indications funded as fee-for-service medical devices, a prescription will emerge as a gold standard in the future in France. Eventually, this study highlights a new activity of clinical pharmacy for hospital pharmacists dealing with medical devices.


Review of current evidence available for guiding optimal Enoxaparin prophylactic dosing strategies in obese patients-Actual Weight-based vs Fixed.
The current debate over the optimal Enoxaparin prophylactic dosing strategies in obese patients centre around whether it should be based on the actual weight of the patient (i.e. weight-based), or at an artificially fixed amount, as it is the case in Australia (40mg daily). The vast majority of the evidence available today is laboratory-based, measuring serum Antifactor-Xa activities as a marker for physiological response. The aim of the parent study is to compare the clinical outcomes for obese patients who received fixed doses of enoxaparin compared to those who received weight-based doses within the licensed dosage recommendations. This review was conducted to examine whether a gap in knowledge exists in relation to dosing obese patients with enoxaparin as VTE prophylaxis after hospital admission to aid in development of the parent study concept. Databases such as Medline, EBSCOhost, ProQuest were interrogated using combinations of words such as "enoxaparin", AND "dosing strategy", AND "obese/obesity" AND "prophylaxis". Only eleven out of 14 primary studies which were considered to be sufficiently similar in methodology and anticipated outcomes were reviewed and analysed. Pooled data from the eleven studies suggested that weight-based or higher-than-fixed dosing had a 36.2% higher success rate than fixed dosing, and was more likely to achieve the desired serum Anti-Xa activity levels (52.2% and 16% respectively). The rate of failure to achieve this is significantly lower in the weight-based groups (13.3%) than in fixed-dose groups (18.5%). These eleven studies reviewed included 601 patients in total. There is insufficient evidence to support or negate the current enoxaparin health outcomes in obese and very obese patients due to the lack of post-discharge follow-up from hospitals. Further research is required to compare long-term outcomes after fixed and weight-based dosing of enoxaparin. The optimal dose of enoxaparin per kilogram of body weight for prophylaxis remains to be determined.


[Localization of antigenes in the pig aorta by immunofluorescence with antisera against aortic fractions (author's transl)].
Immunization of rabbits with pig aorta homogenates and with aortic fractions (endothelial cells; media; "microsomal" and "soluble" fractions) yielded specific circulating anti-aortic tissue antibodies. Localization of these antibodies in frozen sections, by the indirect immunofluorescence technique, disclosed cross-reactions between endothelium and media, but no reaction was observed with elastic fibers.


Transcriptional adaptation of neuroblastoma cells to hypoxia.
Low oxygen pressure (hypoxia) is a physiological condition that has been linked to tumor progression and increased malignancy in several cancer forms. Cells of the childhood neoplasm neuroblastoma respond to hypoxia by attaining a lower grade of differentiation, which clinically is associated with poor prognosis. Furthermore, expression of the hypoxia inducible factor-2alpha correlates to poor outcome in neuroblastoma patients. In this report we have by microarray analysis studied transcriptional changes in seven neuroblastoma cell lines subjected to long term hypoxia. We find the gene regulatory response to be highly dependent on cell line background, however, a set of genes was coherently regulated by hypoxia and these genes are correlated to known hypoxia-induced transcriptional profiles.


Being cross pressured-parents' experiences of the transfer from paediatric to adult care services for their young people with long term conditions: A systematic review and qualitative research synthesis.
Family members of young people (13-24 years) with long-term conditions tend to experience multiple challenges when their children transfer from paediatric to adult care, as do the patients themselves. To identify, interpret and theoretically conceptualise the meaning of parents' experiences of the transfer from paediatric to adult care of their young people with long-term conditions. A qualitative research synthesis. We obtained articles from Medline, CINAHL, PsycINFO, EMBASE, Scopus, and Web of Science. Unpublished theses and dissertations were searched for using Google Scholar, Mednar, and ProQuest Dissertations and Theses. Based on a previously published protocol, we followed the guidelines from the Joanna Briggs Institute. Sandelowski and Barroso's qualitative research synthesis approach guided the metasynthesis. Articles published between 1999 and March 2019 were systematically searched for. Twenty-three reports from seven Western countries representing 454 parents including significant others such as aunts and grandparents of 462 young people with various diagnoses contributed to the review. 'Being cross-pressured' was the metasynthesis found to reflect parents' experiences of the transfer from paediatric to adult care of their young people with long-term conditions. The metasynthesis comprised four themes: 'Fluctuating between parental roles', 'Navigating contrasting healthcare contexts', 'Making decisions in the face of inner conflict', and 'Trusting their child's self-management ability'. Our metasynthesis finding of parents' experiences of being cross-pressured provides a new way of thinking about the study phenomena which is supported by transitions theory holding that multiple transitions can take place simultaneously involving myriads of concurrent and conflicting demands. The cross pressure may overwhelm parents. The clinical implications are to recognise parents' experiences and distress in healthcare planning to promote safe and predicable transfers of their young people. Provision of healthcare to parents during transfer needs to be tailored to a collaborative decision-making process between parents, their young people, and involved practitioners across paediatric and adult healthcare services. Tweetable abstract: Parents experienced being cross-pressured when their young people with long-term conditions were transferred from paediatric to adult care.


Following Birth Hospitalization: Invasive Bacterial Infections in Preterm Infants Aged 7-90 Days.
To assess the incidence rate of invasive bacterial infections in preterm infants and compare invasive bacterial infection rates and pathogens between preterm and full-term infants at age 7-90 days. This is a retrospective cohort study of the incidence rate of invasive bacterial infections among all infants born at Kaiser Permanente Northern California (KPNC), with blood and cerebrospinal fluid cultures collected between 7 and 90 days of chronological age from outpatient clinics, from emergency departments, and in the first 24 hours of hospitalization presenting for care between January 1, 2005, and December 31, 2017. Incidence rates of invasive bacterial infection by chronological age and postmenstrual age (PMA) and pathogens were compared between preterm and full-term infants. Between January 1, 2005, and December 31, 2017, a total of 479 729 infants were born at KPNC, including 440 070 full-term infants and 39 659 preterm infants. There were 283 cases of bacteremia in 282 infants. The incidence rate of invasive bacterial infection was significantly higher for preterm infants compared with full-term infants. The highest incidence rates of invasive bacterial infection were in preterm infants at chronological age 7-28 days and/or 37-39 weeks PMA. There was a trend toward lower rates of invasive bacterial infection with increasing PMA in preterm infants aged 61-90 days. Preterm infants aged 29-60 days or at ≥40 weeks PMA and those aged 61-90 days or at ≥43 weeks PMA had a rate of invasive bacterial infection equivalent to the overall rate seen in full-term infants of the same chronological age group. The distribution of pathogens causing bacteremia and meningitis did not differ between preterm and full-term infants. PMA and chronological age together were more useful than either alone in informing the incidence rate of invasive bacterial infection in preterm infants during the first 90 days of life.


Menstrual status and menopausal age of middle-aged Swedish women. A population study of women in Göteborg 1968--69 and 1974--75.
A population study of women in Göteborg, Sweden, was carried out in 1968--69. Altogether 1 462 women participated (participation rate 90.1 per cent). Five age strata were studied: 38, 46, 50, 54 and 60 (women born in 1930, 1922, 1918, 1914 and 1908, respectively). The same women were re-studied in 1974--75. At this time 1 302 women participated, corresponding to 89.1 per cent of those studied in 1968--69 and 80.3 per cent of those initially sampled. The vast majority of the women had a natural menopause. The median age at the menopause was found to be about 50. The criteria for definition of menopause are discussed. No support was found for the theory of increased menopausal age with time. Estrogen therapy of postmenopausal women was found to be much more common in 1974--75 than in 1968--69.


A rare tumour in a rare location: desmoplastic fibroma in a toe.
We report a case of desmoplastic fibroma occurring in the 2nd toe. This lesion most frequently occurs in the long bones or the mandible. This is only the second reported case of desmoplastic fibroma in a toe in the English language. The importance and process of establishing a differential diagnosis in such lesions is highlighted. The similarity between the clinical and histological findings of this tumour and other tumours, both benign and malignant, makes familiarity with the character of desmoplastic fibroma essential for proper treatment.


Scrotal emergencies.
An acute scrotum is defined as an acute painful swelling of the scrotum or its contents, accompanied by local signs or general symptoms. Early identification and skillful management of testicular torsion is critical, as it may threaten testicular viability and future fertility if not managed expediently and appropriately. The cremasteric reflex and testicular sonography are frequently used, yet imperfect, diagnostic tools in assessing for testicular torsion. Other emergent conditions include incarcerated inguinal hernia, Fournier's gangrene, and any form of genitourinary trauma until proven otherwise. This article reviews the evaluation and management of the acute scrotum in the emergency department.


Advanced Modular Manikin and Surgical Team Experience During a Trauma Simulation: Results of a Single-Blinded Randomized Trial.
Our aim was assess whether an integrated Advanced Modular Manikin (AMM) provides improved participant experience compared with use of peripheral simulators alone during a standardized trauma team scenario. Simulation-based team training has been shown to improve team performance. To address limitations of existing manikin simulators, the AMM platform was created that enables interconnectedness, interoperability, and integration of multiple simulators ("peripherals") into an adaptable, comprehensive training system. A randomized single-blinded, crossover study with 2 conditions was used to assess learner experience differences when using the integrated AMM platform vs peripheral simulators. First responders, anesthesiologists, and surgeons rated their experience and workload with the conditions in a 3-scene standardized trauma scenario. Participant ratings were compared and focus groups conducted to obtain insight into participant experience. Fourteen teams (n = 42) participated. Team experience ratings were higher for the integrated AMM condition compared with peripherals (Cohen's d = .25, p = 0.016). Participant experience varied by background with surgeons and first responders rating their experience significantly higher compared with anesthesiologists (p < 0.001). Higher workload ratings were observed with the integrated AMM condition (Cohen's d = .35, p = 0.014) driven primarily by anesthesiologist ratings. Focus groups revealed that participants preferred the integrated AMM condition based on its increased realism, physiologic responsiveness, and feedback provided on their interventions. This first comprehensive evaluation suggests that integration with the AMM platform provides benefits over individual peripheral simulators and has the potential to expand simulation-based learning opportunities and enhance learner experience, especially for surgeons.


Epiploic appendagitis of the vermiform appendix--An unusual mimic of acute appendicitis.
Epiploic appendagitis is a condition resulting from ischemia or necrosis involving the appendage epiploica either due to torsion or spontaneous thrombosis of the venous outflow. It is one of the myriad causes of acute abdominal pain and can masquerade clinically as appendicitis, omental infarction, sclerosing mesenteritis and even diverticulitis. Epiploic appendagitis of the vermiform appendix is a rare entity, clinically indistinguishable from appendicitis. We present a 45-year-old male patient with 4-day duration of right iliac fossa pain and tenderness, with strong clinical suspicion of acute appendicitis. CT scan of the abdomen and pelvis demonstrated Epiploic appendagitis of the vermiform appendix, whilst the appendix remained uninflamed. The patient was thus discharged with conservative management without having to go undergo needless surgery, thereby avoiding the potential complications thereof.


Understanding Stakeholder Dissemination Preferences for an Agriculture, Forestry, and Fishing Injury Surveillance System.
Researchers and epidemiologists are working to improve the capture of agriculture, forestry, and fishing (AgFF) injuries in a variety of ways. A critical component of any surveillance system is the dissemination of information. The purpose of this paper is to report on a survey conducted with AgFF injury surveillance stakeholders to understand preferred dissemination strategies. The survey was distributed using REDCap via web link to organizational stakeholders, which included advisory board members, safety trainers, industry managers and workers, and research collaborators. In total, there were 75 respondents (21% response rate). Occupation and industry influenced preference in update methods. Regarding the length and breadth of updates, 63% of respondents prefer reports (one to five pages), followed by 57% desiring a summary (less than one page), while only 24% wanted a detailed analysis. Social media and news preferences were also different among stakeholders. Surveillance data were desired for 1) trend analysis, 2) tailoring activities and solutions for education, training, outreach and interventions and 3) for research purposes such as grant proposals and evaluation. The dissemination of injury surveillance data should be tailored to the intended audience. Greater attention needs to be paid to the ways in which we share our findings.


Different effects of calcium flux-blocking agents on light and potassium stimulated release of taurine from retina.
Conditions for the stimulation of taurine release by illumination or increased K+ concentrations were established. The effect of Mg2+, ruthenium red and verapamil on taurine release induced by both procedures was compared. All these agents antagonize Ca2+-dependent release of neurotransmitters. Illumination-induced release of taurine was not blocked by any of these agents while the K+-induced release was blocked by all of them. It is discussed whether illumination and potassium act through processes that increase Ca2+ influx through different mechanisms, or if illumination-induced release is a Ca2+-independent process.


Evaluation of adenosine deaminase and other purine salvage pathway enzymes in horses with combined immunodeficiency.
Foals with combined immunodeficiency had normal levels of purine salvage pathway enzymes, including adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase.


Low-dose versus standard-dose four-factor prothrombin complex concentrate for factor-Xa inhibitor reversal in spontaneous and traumatic intracranial hemorrhage.
Current neurocritical care guidelines recommend 50 IU/kg four-factor prothrombin complex concentrate (4PCC) for factor Xa inhibitor (FXaI) reversal in intracranial hemorrhage (ICH) based on few clinical studies conducted among non-ICH subjects. Two recent studies suggest that low-dose (25 IU/kg) 4PCC may be similar to 50 IU/kg in reversal of FXaI in ICH, and both 25 and 50 IU/kg doses are used in clinical practice for this indication. To our knowledge, no studies have directly compared 25 IU/kg versus 50 IU/kg 4PCC for FXaI reversal in ICH. The purpose of this study is to determine whether there is a difference in hemostatic efficacy between 25 IU/kg versus 50 IU/kg 4PCC for FXaI reversal in ICH. This multicenter, retrospective cohort study was performed in five hospitals in central Texas from November 2013 to December 2019. Patients were identified with a medication use report of 4PCC and were classified in the low- or standard-dose group based on whether the 25 IU/kg or 50 IU/kg dose was received, respectively. A total of 93 patients were included (25 IU/kg, n = 62; 50 IU/kg, n = 31). There was no difference in hemostatic efficacy between groups (82.3% low dose vs. 83.9% standard dose, p = 0.846). No differences were identified in-hospital mortality, length of stay, thrombotic events, or the need for surgery or additional blood products between groups. For the reversal of FXaI in ICH, a 25 IU/kg dose may be an effective alternative to 50 IU/kg 4PCC dosing.


Safety and effectiveness of standardized exercise training in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction (TRAIN-HFpEF-PH): study protocol for a randomized controlled multicenter trial.
Left heart failure (HF) is characterized by an elevation in left-sided filling pressures, causing symptoms of dyspnea, impairing exercise capacity, and leading to pulmonary venous congestion and secondary pulmonary hypertension (PH). There is an increased incidence of PH associated with left heart disease, particularly with heart failure with preserved ejection fraction (HFpEF-PH). Treatment possibilities in HFpEF-PH are non-specific and very limited, thus additional pharmacological and non-pharmacological therapeutic strategies are needed. Various types of exercise-based rehabilitation programs have been shown to improve exercise capacity and quality of life (QoL) of HF and PH patients. However, no study focused on exercise training in the population of HFpEF-PH. This study is designed to investigate whether a standardized low-intensity exercise and respiratory training program is safe and may improve exercise capacity, QoL, hemodynamics, diastolic function, and biomarkers in patients with HFpEF-PH. A total of 90 stable patients with HFpEF-PH (World Health Organization functional class II-IV) will be randomized (1:1) to receive a 15-week specialized low-intensity rehabilitation program, including exercise and respiratory therapy and mental gait training, with an in-hospital start, or standard care alone. The primary endpoint of the study is a change in 6-min walk test distance; secondary endpoints are changes in peak exercise oxygen uptake, QoL, echocardiographic parameters, prognostic biomarkers, and safety parameters. To date, no study has investigated the safety and efficacy of exercising specifically in the HFpEF-PH population. We believe that a randomized controlled multicenter trial, which protocol we are sharing in this article, will add important knowledge about the potential utility of a specialized low-intensity exercise and respiratory training program for HFpEF-PH and will be valuable in finding optimal treatment strategies for these patients. ClinicalTrials.gov NCT05464238. July 19, 2022.


Loosening of DNA/polycation complexes by synthetic polyampholyte to improve the transcription efficiency: effect of charge balance in the polyampholyte.
High mobililty group proteins are amphoteric nuclear proteins that are known to unfold chromatin to stimulate transcription. To mimic their structures, we synthesized the novel polyethylene glycol (PEG) derivatives, PEG-ACs, consisting of both amino- and carboxyl-pendants in various ratios, and their loosening and transcription-improving activity on the DNA complex was examined. Fluorescence anisotropy measurement revealed that anionic PEG-ACs with more carboxyls than amines could efficiently loosen the DNA/polyethyleneimine complex. Those anionic PEG-ACs showing a loosening effect on the DNA complex evidently increased the transcription rate to >20 times higher than that of the original complex, probably owing to the facilitated approach of transcriptional factors to the DNA segments in the loosened complexes. The complexes with anionic PEG-ACs also showed improved transgene expression level on the cultured cells, indicating the effectiveness of improving transcriptional activity to attain a high extragene expression by the plasmid complex. The loosening mechanism of DNA/polycation complexes was investigated with a simplified model via Monte Carlo simulation to discern the difference in the presence of cationic polyampholytes, anionic polyampholytes, and polyanions.


Substrate-dependent kinetics in tyrosinase-based biosensing: amperometry vs. spectrophotometry.
Despite the broad use of enzymes in electroanalytical biosensors, the influence of enzyme kinetics on the function of prototype sensors is often overlooked or neglected. In the present study, we employ amperometry as an alternative or complementary method to study the kinetics of tyrosinase, whose catalytic activity results in o-quinone products. We further compare our results for four monophenolic substrates with those obtained from ultraviolet-visible spectrophotometry and show that the results from both assays are in good agreement. We also observe large variations in the enzyme kinetics for different monophenolic substrates depending on the R-group at the para position. To further study this effect, we investigate the stability of quinone products in the enzymatic assay. This information can in principle be utilized to discriminate between different phenolic species by monitoring the reaction rate.


Inherited Predisposition to Gastric Cancer.
Approximately 10% of patients with gastric cancer show familial aggregation and up to 3% are related to an inherited cancer syndrome. There are multiple germline pathogenic variants and cancer syndromes associated with an increased risk of gastric cancer. Appropriate assessment of familial and genetic risk may allow a personalized approach to gastric cancer prevention through screening and risk-reducing surgeries. The ability to better identify carriers with pathogenic genetic variants associated with gastric cancer before a diagnosis of cancer requires effective genetic risk assessment and testing, followed by optimal screening and surveillance recommendations to further reduce the morbidity and mortality.


Ileostomy in ulcerative colitis. A questionnaire study of 1,803 patients.
A questionnaire regarding details of their illness, social, educational and religious background and various aspects of rehabilitation since surgery was completed by 1,803 persons who underwent ileostomy for ulcerative colitis between 1930 and 1970. The majority of participants were operated on since 1960, reported an above-average education, lived in metropolitan areas, had surgery performed as a single stage proctocolectomy, and were chronically ill for an average of almost 7 years from the onset of disease to ileostomy. An unexplained high incidence of Jewish patients was noted; in addition, Jewish patients comprised almost half of those who had a family history of inflammatory bowel disease. Although some participants reported major postoperative problems including unfavorable alterations in stomal structure and function, bowel obstruction, delayed perineal healing and nephrolithiasis, most patients were satisfied with life with an ileostomy, presently maintaining their health, employment, marriage and sexuality.


An adverse outcome pathway for immune-mediated and allergic hepatitis: a case study with the NSAID diclofenac.
Many drugs have the potential to cause drug-induced liver injury (DILI); however, underlying mechanisms are diverse. The concept of adverse outcome pathways (AOPs) has become instrumental for risk assessment of drug class effects. We report AOPs specific for immune-mediated and drug hypersensitivity/allergic hepatitis by considering genomic, histo- and clinical pathology data of mice and dogs treated with diclofenac. The findings are relevant for other NSAIDs and drugs undergoing iminoquinone and quinone reactive metabolite formation. We define reactive metabolites catalyzed by CYP monooxygenase and myeloperoxidases of neutrophils and Kupffer cells as well as acyl glucuronides produced by uridine diphosphoglucuronosyl transferase as molecular initiating events (MIE). The reactive metabolites bind to proteins and act as neo-antigen and involve antigen-presenting cells to elicit B- and T-cell responses. Given the diverse immune systems between mice and dogs, six different key events (KEs) at the cellular and up to four KEs at the organ level are defined with mechanistic plausibility for the onset and progression of liver inflammation. With mice, cellular stress response, interferon gamma-, adipocytokine- and chemokine signaling provided a rationale for the AOP of immune-mediated hepatitis. With dogs, an erroneous programming of the innate and adaptive immune response resulted in mast cell activation; their infiltration into liver parenchyma and the shift to M2-polarized Kupffer cells signify allergic hepatitis and the occurrence of granulomas of the liver. Taken together, diclofenac induces divergent immune responses among two important preclinical animal species, and the injury pattern seen among clinical cases confirms the relevance of the developed AOP for immune-mediated hepatitis.


Kidney transplantation from brain-dead donors in Nepal: Report of first six cases.
and importance: Kidney transplantation is one of the best treatment options for patients with end-stage renal disease. More than 90% of patients awaiting renal transplantation die without getting the kidney for transplantation. Brain dead donor kidney transplantation can bridge this gap proficiently. We aim to report details of the first six patients who had undergone brain-dead donor kidney transplantation in the history of transplantation in Nepal. We conducted a descriptive analysis of clinical data of six adult recipients with kidney transplantation from three brain-dead donors. We described postoperative complications, length of stay, graft function which was documented with serum creatinine, acute rejection episode, delayed graft function, and patient/graft survival of recipient. Recipients were between 15 and 56 years old. Three patients experienced delayed graft function. Urinary tract infection was observed in two patients, both of whom were treated with antibiotics. One patient had acute graft rejection. None of our patients required reoperation. Length of hospital stay ranged from 9 to 32 days. The postoperative graft function was 100% in all patients. There was no graft loss, and no death was observed during follow-up. Following the initiation of the brain-dead donor transplantation program, a lot of work needs to be done to make it a regular practice. Thus, this program needs support from all sections of society and government. This can be the only solution to decrease the huge gap between the supply and demand of organs in Nepal. This case reports indeed revealed impressive success in initiating a brain-dead donor kidney transplantation program in a developing country that in terms of quality, meets comprehensive standard with acceptable graft function and patient/graft survival in under limited resources healthcare setting.


Morphological changes in continuously stretched skeletal muscles in sheep.
The effects of continuous elongation of skeletal muscles were studied on six sheep who underwent a lengthening osteotomy of the right tibia. Open muscle biopsies were taken from the biceps femoris muscle preoperatively (Group A), after 5 weeks of bone distraction (Group B) and after another 5 weeks without further distraction (Group C). The size and distribution of type 1 (slow-twitch) and type 2 (fast-twitch) muscle fibres were determined from sections stained for myofibrillar ATPase activity. All sections were also evaluated by light microscopy, especially with regard to myopathic changes. The type 2 fibres showed a significant decrease in size from group A to B and from group B to C. The reduction in fibre size from group A to C was 44.2%. The type 1 fibres, on the other hand, showed no significant differences in mean fibre size between the groups. However, there were considerable individual variations in type 1 fibre size between the groups. The distribution of both fibre types was similar in groups A and B (appr. 17% type 1 fibres) whereas the relative number of type 1 fibres was reduced to 12.4% in group C (P less than 0.01). Myopathic changes, i.e. muscle fibre necroses, were not seen in any of the groups. It is concluded that the type 2 fibre atrophy is mainly caused by muscular inactivity during the postoperative period, but an additional effect of continuous stretching of the muscle cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)


Traumatic cervical spinal cord injury: relation between somatosensory evoked potentials, neurological deficit, and hand function.
Median and ulnar somatosensory evoked potentials (SEP) in the assessment of cervical spinal cord injury (SCI) in relation to the outcome of hand function. Cohort analytical study. Spinal cord injury center, university hospital. Consecutively sampled, 23 acute and 46 chronic tetraplegics. (1) Median and ulnar SEP recordings graded in 5 categories, from normal to absent; (2) clinical examination of algesia/aesthesia in dermatomes C5/6 and C8/Th1 graded in categories of normal, impaired, and loss of sensation; (3) clinical examination of hand function graded in 4 categories, from active to inactive hand function. Pathological median and ulnar SEP were found in 46% and 76% of patients, respectively. A differentiation between upper (C3-C6) and lower (C6/C7-Th1) cervical SCI was possible by comparing the SEP N20 latencies (but not amplitudes) of both nerves (Mann-Whitney U test, p < .01). In follow-up examinations over 6 months the N20 amplitude increased significantly (ANCOVA, p < .001), while the N20 latency did not change. By both ulnar SEP recordings and assessment of the sensory deficit in dermatome C8/Th1 the outcome of hand function, i.e., the development of active or inactive hand function, could be predicted (Mann-Whitney U test, p < .01). Median and ulnar SEP are valuable to indicate the level of injury, the degree of sensory impairment and to predict the outcome of hand function even in unconscious patients. They can improve the diagnostic assessment of cervical SCI.


Cumulative Sun Exposure and Melanoma in a Population-Based Case-Control Study: Does Sun Sensitivity Matter?
Cutaneous melanoma (CM) has consistently been associated with intermittent sun exposure, while the association with chronic sun exposure is debated. The goal of this research was to examine the complex relationship between CM, sun sensitivity and sun exposure based on theoretical concepts of how these factors may be associated. Detailed sun exposure histories across life periods and various measures of sun sensitivity were collected in a population-based case-control study of melanoma in Iowa, USA. Participants were asked about their hours of sun exposure per day between March and October each year over periods or decades of life to estimate cumulative lifetime hours of sun exposure. Increased odds ratios (ORs) for CM were seen for most standard measures of sun sensitivity except for the tendency to sunburn. Minimal associations were seen with total hours of sun exposure early in life. However, an interaction was seen between fair skin color and lifetime hours of sun exposure, where the strongest associations with CM were seen among medium-skinned and dark-skinned participants. This suggests that cumulative sun exposure at high levels may increase CM among non-sun-sensitive individuals typically at lower risk of CM. Such a finding has implications for the prevention effort for melanoma regarding time in the sun among darker-skinned individuals.


ANOX: A robust computational model for predicting the antioxidant proteins based on multiple features.
As an indispensable component of various living organisms, the antioxidant proteins have been studied for anti-aging and prevention of various diseases, such as altitude sickness, coronary heart disease, and even cancer. However, the traditional experimental methods for identifying the antioxidant proteins are very expensive and time-consuming. Thus, to address the challenge, a new predictor, named ANOX, was developed in this study. Multiple features, such as frequency matrix features (FRE), amino acid and dipeptide composition (AADP), evolutionary difference formula features (EEDP), k-separated bigrams (KSB), and PSI-PRED secondary structure (PRED), were extracted to generate the original feature space. To find the optimized feature subset, the Max-Relevance-Max-Distance (MRMD) algorithm was implemented for feature ranking and our model received the best performance with the top 1170 features. Rigorous tests were performed to evaluate the performance of ANOX, and the results showed that ANOX achieved a major improvement in the prediction accuracy of the antioxidant proteins (AUC:0.930 and 0.935 using 5-fold cross-validation or the jackknife test) compared to the state-of-the-art predictor AOPs-SVM (AUC:0.869 and 0.885). The dataset used in this study and the source code of ANOX are all available at https://github.com/NWAFU-LiuLab/ANOX.


Exercise and physical activity in individuals at risk of fracture.
This is a review of evidence and practical tips on exercise for individuals with osteoporosis, including individuals with hip and vertebral fractures. Balance and functional training, with or without strength training, can prevent falls. Several types of exercise can improve outcomes that are important to patients, such as physical functioning or quality of life. Individuals with osteoporosis should prioritize balance, functional and resistance training ≥ twice weekly, where exercises, volume, intensity, and progression are aligned with the patient's goals and abilities. Patients who want to participate in other activities (e.g., walking, impact exercise, yoga, Pilates) can do them in addition to, but not instead of, balance and functional or strength training, if they can be done safely or modified. Avoid generic advice like "Don't bend or twist", which is difficult or impossible to operationalize, and may create fear and activity avoidance. Instead, be specific about the types of activities to avoid or modify, and provide tips on how to make daily activities safer, or signpost to resources from national osteoporosis societies. For example, not all bending or twisting is bad; it is activities that involve rapid, repetitive, sustained, weighted, or end range of motion twisting or flexion of the spine that may need to be modified, especially in individuals at high risk of fracture.


Prevalence of extra-hepatic incidental findings on ultrasound screening for hepatocellular carcinoma.
Abdominal ultrasound is a cost-effective method for screening for hepatocellular carcinoma (HCC) in high-risk individuals. Currently, at many institutions the protocol for obtaining HCC screening ultrasounds includes a traditional examination of the right upper quadrant, including the pancreas and right kidney. There is no consensus on the role of imaging of extra-hepatic structures and there are limited data describing the frequency and clinical significance of incidental findings discovered during HCC screening. The purpose of this retrospective study is to assess the prevalence and significance of extra-hepatic incidental findings during HCC screening ultrasounds. A single-center retrospective review of all right upper quadrant HCC screening ultrasounds identified 432 HCC screening ultrasounds performed on 294 adults over a 2.5-year period. Findings in all organs evaluated were recorded. Any incidental finding was classified as minor, moderate, or major clinical significance. At least one extra-hepatic finding was documented in 57.4% of examinations. The most common extra-hepatic findings occurred in the gallbladder (40.3%), most commonly gallstones (25.4%). Four moderate clinically significant incidental findings were recorded (0.9%). Only one of these incidental findings required specific imaging follow up (0.2%). No major clinical significance incidental findings were identified. Potentially clinically significant incidental findings during ultrasound HCC screenings are rare. Incidental findings identified on HCC screening did not result in significant additional follow-up imaging or interventions.


Electronic cigarettes: the road ahead.
Electronic cigarettes (e-cig) are proliferating in the world's lucrative nicotine delivery market at an alarmingly fast pace. E-cig are aggressively marketed as an alternative to conventional tobacco cigarettes, although very little is known about the health consequences of e-cig use. Chemical analysis of e-cig vapor/liquid has shown that many toxicants and carcinogens present in cigarette smoke are also found, albeit generally in lower concentrations, in a wide range of e-cig products. Notwithstanding the presence of toxicants and carcinogens in e-cig products, the biological effects of exposure to these contaminants have not been determined in e-cig users. The ongoing research and future investigations on e-cig initiation, use, perceptions, dependence, and toxicity are expected to provide empirical evidence that can be used to inform the general public, scientific community, and regulatory authorities of the health risks/benefits associated with e-cig use. This information will help stimulate scientists in the field of tobacco research, as well as assist the regulatory agencies in making scientifically based decisions on the development and evaluation of regulations on tobacco products to protect the public's health. Finding the scientific underpinnings for the health risks/benefits of e-cig use can impact millions of people who are increasingly turning to e-cig as a replacement for or complement to conventional tobacco cigarettes.


Reliability of home-based remote and self-assessment of transfers using the Transfer Assessment Instrument among wheelchair users with spinal cord injury.
Cross-sectional study. To evaluate the reliability of home-based remote and self-assessment of transfer quality using the Transfer Assessment Instrument (TAI) among wheelchair users with spinal cord injury (SCI). Participant's home environment. Eighteen wheelchair users with SCI transferred from their wheelchair to a surface of their choice (bed, sofa, or bench) in their homes. During a live video conference, the transfer was recorded and evaluated live using the TAI (rater 1). Participants completed a self-assessment of their transfer using the TAI- questionnaire (TAI-Q). Two additional raters (raters 2 & 3) completed asynchronous assessments by watching recorded videos. Interrater reliability was assessed using Intraclass Coefficient Correlations (ICC) to compare rater 1 with the average of raters 2 & 3 and TAI-Q. Intrarater reliability was assessed by rater 1 completing another TAI by watching the recorded videos after a 4-week delay. Assessments were compared using paired sample t-tests and level of agreement between TAI scores was evaluated using Bland-Altman plots. Moderate to good interrater and good intrarater reliability were found for the total TAI score with ICCs: 0.57-0.90 and 0.90, respectively. Moderate to good intrarater and interrater reliability were found for all TAI subscores (ICC: 0.60-0.94) except for interrater reliability of flight/landing which was poor (ICC: 0.20). Bland-Altman plots indicate no systematic bias related to the measurement of error. The TAI is a reliable outcome measure for assessing the wheelchair and body setup phases of home-based transfers remotely and through self-assessment among individuals with SCI.


Coagulometer international sensitivity index (ISI) derivation, a rapid method using the prothrombin time/international normalized ratio (PT/INR) Line: a multicenter study.
The original WHO procedure for prothrombin time (PT) standardization has been almost entirely abandoned because of the universal use of PT coagulometers. These often give different international normalized ratio (INR) results from the manual method, between individual makes of instruments and with instruments from the same manufacture. A simple procedure is required to derive local INR with coagulometers. The PT/INR Line method has recently been developed using five European Concerted Action on Anticoagulation (ECAA) certified plasmas to derive local INR. This procedure has been modified to derive a coagulometer PT/INR Line providing International Sensitivity Index (ISI) and mean normal PT (MNPT) for coagulometers and give local INR. Results have been compared with conventional ISI calibrations at the same laboratories. With human thromboplastins, mean ISI by local calibration was 0.93 (range: 0.77-1.16). With the PT/INR Line, mean coagulometer ISI was higher, for example 0.99 (0.84-1.23) but using the PT/INR Line derived MNPT there was no difference in local INR. Between-centre INR variation of a certified validation plasma was reduced with human and bovine reagents after correction with local ISI calibrations and the PT/INR Line. The PT/INR Line-ISI with its derived MNPT is shown to provide reliable local INR with the 13 different reagent/coagulometer combinations at the 28 centres in this international study.


Sequence and evolution of rhesus monkey alphoid DNA.
Analysis of rhesus monkey alphoid DNA suggests that it arose by tandem duplication of an ancestral monomer unit followed by independent variation within two adjacent monomers (one becoming more divergent than the other) before their amplification as a dimer unit to produce tandem arrays. The rhesus monkey alphoid DNA is a tandemly repeated, 343-bp dimer; the consensus dimer is over 98% homologous to the alphoid dimers reported for baboon and bonnet monkey, 81% homologous to the African green monkey alpha monomer, and less than 70% homologous to the more divergent human alphoid DNAs. The consensus dimer consists of two wings (I and II, 172 and 171 bp, respectively) that are only 70% homologous to each other, but share seven regions of exact homology. These same regions are highly conserved among the consensus sequences of the other cercopithecid alphoid DNAs. The three alpha-protein binding sites reported for African green monkey alpha DNA by F. Strauss and A. Varshavsky (Cell 37: 889-901, 1984) occur in wings I and II, but with one site altered in wing I. Two cloned dimer segments are 98% homologous to the consensus, each containing 8 single-base-pair differences within the 343-bp segment. Surprisingly, 37% of these differences occur in regions that are evolutionarily conserved in the alphoid consensus sequences, including the alpha-protein binding sites. Sequence variation in this highly repetitive DNA family may produce unique nucleosomal architectures for different members of an alphoid array. These unique architectures may modulate the evolution of these repetitive DNAs and may produce unique centromeric characteristics in primate chromosomes.


The effects of local cold application on fibromyalgia pain.
This study was conducted to evaluate the effects of local cold application on pain when applied to the trapezius muscles of patients with fibromyalgia. A one-group, pre-test/post-test, pre-experimental model was applied in this study, which was conducted with 55 fibromyalgia patients who presented to a rheumatology outpatient clinic. A 10-min cold application was administered to one trapezius muscle of each patient. The participants' pain was evaluated, in total, four times (before the cold application and 10 min, 1.5 h and 24 h after the cold application). The visual analogue scale (VAS) for pain was used to collect data for the study, and Friedman and Wilcoxon tests were used to assess the data. The patients' pain mean score before (6.45, SD:1.27) the cold applications was found to be significantly higher than the scores noted 10 min (2.75, SD:1.73), 1.5 h (2.45, SD:1.29), and 24 h (3.36, SD:1.30) after the application (P < 0.001). The study found that local cold applications performed on the trapezius muscles of patients with fibromyalgia significantly decreased their pain. With its discovery of a new method of pain control in fibromyalgia patients, this study will significantly contribute to science and will serve as a guide for pain management, especially in nursing practice. Further studies to evaluate the maximum effect duration and effect mechanisms of local cold applications to the trapezius muscles of FM patients are indicated.


Ischaemic myelopathy secondary to disseminated intravascular coagulation in AIDS.
A 39-year-old patient with AIDS presented with a rapidly progressive myelopathy with a partial Brown-Séquard syndrome. He died, 9 weeks after onset of the first neurological signs, from diffuse encephalopathy. Neuropathological examination revealed multiple, usually small, frequently haemorrhagic, infarcts or various ages and numerous fibrin thrombi in medium and small penetrating vessels and capillaries of the brain and spinal cord, characteristic of disseminated intravascular coagulation. There were no inflammatory changes. Immunohistochemical studies for human immunodeficiency virus, cytomegalovirus, varicella zoster virus, herpes simplex virus type 1 and type 2 were negative. Ischaemic spinal cord lesions due to disseminated intravascular coagulation may represent an unusual cause of focal, non-inflammatory, non-tumoral, myelopathic syndrome in AIDS.


Postoperative biliary anastomotic strictures after pancreaticoduodenectomy.
Biliary anastomotic stricture (BAS) is an uncommon complication of pancreaticoduodenectomy (PD). As PDs are performed more frequently, BAS may become a more common pathologic entity requiring clinical engagement. The aim of this study was to report the incidence of BAS in the modern era of pancreatic surgery and identify risk factors associated with it. Patients undergoing PD at the Johns Hopkins Hospital between 2007 and 2016 were identified using an institutional registry and clinicopathological features were analyzed to identify risk factors associated with BAS. Of 2125 patients identified, 103 (4.9%) developed BAS. Factors independently associated with BAS included laparoscopic approach (HR:2.83,95%CI:1.35-5.92, p = 0.006), postoperative pancreatic fistula (HR:2.45,95%CI:1.56-4.16,p < 0.001), postoperative bile leak (BL) (HR:5.26,95%CI:2.45-11.28,p < 0.001), and administration of adjuvant radiation therapy (HR:6.01,95%CI:3.19-11.34,p < 0.001). Malignant pathology was associated with lower rates of BAS (HR:0.52,95%CI:0.30-0.92, p = 0.025). BL was associated with higher rates of early-BAS (HR:16.49,95%CI:3.28-82.94, p = 0.001) while use of Vicryl suture for biliary enteric anastomosis was associated with lower rates of early-BAS (HR:0.20,95%CI:0.05-0.93, p = 0.041). Approximately 5% of patients undergoing PD experience BAS. Multiple factors are associated with the development and timing of BAS.


Utility of the Revised Version of the Ability for Basic Movement Scale in Predicting Ambulation during Rehabilitation in Poststroke Patients.
This study aims to test the hypothesis that the Revised Version of the Ability for Basic Movement Scale (ABMSII) can predict ambulation during rehabilitation in poststroke patients. The study included first-ever stroke patients who were admitted to the rehabilitation ward and were dependent in walking. ABMSII scores were assessed by physical therapists on admission to the hospital. Functional ambulation category (FAC) was assessed every 2 weeks during hospitalization. The primary outcome was independent ambulation, defined as 4 points or higher on the FAC. After setting the inclusion criteria, data of 374 stroke patients (mean age: 70 years, 153 women) were eligible for the analysis. Of these, 193 patients achieved independent ambulation during hospitalization. The ABMSII score was significantly higher in the patients who regained independent walking ability than in those who required assistance in walking. Based on receiver operating characteristic curve analysis, an ABMSII score of 16 points or higher had a sensitivity of 93% and a specificity of 71%. Kaplan-Meier curve analysis after log-rank test demonstrated a significantly higher event rate in patients with an ABMSII score of 16 or higher compared to those with an ABMSII score lower than 16. Univariate and multivariate Cox regression analyses identified the ABMSII score as a significant and independent predictor of ambulation during rehabilitation. Our results suggest that the ABMSII score is a potentially useful tool to predict ambulation during rehabilitation in poststroke patients.


QUARTERplus: Accurate disorder predictions integrated with interpretable residue-level quality assessment scores.
A recent advance in the disorder prediction field is the development of the quality assessment (QA) scores. QA scores complement the propensities produced by the disorder predictors by identifying regions where these predictions are more likely to be correct. We develop, empirically test and release a new QA tool, QUARTERplus, that addresses several key drawbacks of the current QA method, QUARTER. QUARTERplus is the first solution that utilizes QA scores and the associated input disorder predictions to produce very accurate disorder predictions with the help of a modern deep learning meta-model. The deep neural network utilizes the QA scores to identify and fix the regions where the original/input disorder predictions are poor. More importantly, the accurate QUATERplus's predictions are accompanied by easy to interpret residue-level QA scores that reliably quantify their residue-level predictive quality. We provide these interpretable QA scores for QUARTERplus and 10 other popular disorder predictors. Empirical tests on a large and independent (low similarity) test dataset show that QUARTERplus predictions secure AUC = 0.93 and are statistically more accurate than the results of twelve state-of-the-art disorder predictors. We also demonstrate that the new QA scores produced by QUARTERplus are highly correlated with the actual predictive quality and that they can be effectively used to identify regions of correct disorder predictions. This feature empowers the users to easily identify which parts of the predictions generated by the modern disorder predictors are more trustworthy. QUARTERplus is available as a convenient webserver at http://biomine.cs.vcu.edu/servers/QUARTERplus/.


Periodontal disease may be associated with oral and gastrointestinal cancer.
The association between periodontal disease and cancer:a review of the literature. Fitzpatrick SG, Katz J.J Dent 2010;38(2):83-95. Epub 2009 Nov 4. Zoann Nugent, Ph. D. To assess the published research to date on the relationship between periodontal disease and cancer. Information not available. Comprehensive literature review. Level 3: Other evidence. Grade C: Consensus, disease-oriented evidence, expert opinion.


Age differences in Copulatory behavior and serum 17 beta-estradiol in female rhesus monkeys.
Young, sexually mature female rhesus monkeys housed in outdoor groups have been found to exhibit significantly longer mating periods associated with first conception compared with the duration of the annual period exhibited by older, multiparous females. An analysis of the sexual behavior and corresponding serum concentration of 17 beta-estradiol (E2) a progesterone, (P) in two age groups of rhesus females revealed that young females copulated on significantly more days prior to the E2, ovulatory peak than did older females. Serum concentrations of E2 were significantly higher from -30 to Day- 10 prior to the E2 peak (Day 0) in young females. Estradiol concentrations were similar for both age groups during the remaining follicular and periovulatory period. No age differences in serum P were observed between the two groups. Serum E2 levels associated with the onset of mating were similar in the two age groups with levels rising from 73.5 +/- 4.0 pg/ml prior to mating to 97.2 +/- 4.6 pg/ml. Thus the hormonal profile associated with the onset of mating is similar for both age groups, and the earlier occurrence of mating behavior prior to ovulation in young females is accounted for by an earlier rise in serum E2.


Psychiatric comorbidities in Asperger syndrome are related with polygenic overlap and differ from other Autism subtypes.
There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The study of the common genetic variation in ASD has suggested a greater contribution of other psychiatric conditions in Asperger syndrome (AS) than in the rest of the DSM-IV ASD subtypes (Non_AS). Here, using available genetic data from previously performed genome-wide association studies (GWAS), we aimed to study the genetic overlap between five of the most related disorders (schizophrenia (SCZ), major depression disorder (MDD), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorders (OCD) and anxiety (ANX)), and AS, comparing it with the overlap in Non_AS subtypes. A Spanish cohort of autism trios (N = 371) was exome sequenced as part of the Autism Sequencing Consortium (ASC) and 241 trios were extensively characterized to be diagnosed with AS following DSM-IV and Gillberg's criteria (N = 39) or not (N = 202). Following exome imputation, polygenic risk scores (PRS) were calculated for ASD, SCZ, ADHD, MDD, ANX, and OCD (from available summary data from Psychiatric Genomic Consortium (PGC) repository) in the Spanish trios' cohort. By using polygenic transmission disequilibrium test (pTDT), we reported that risk for SCZ (Pscz = 0.008, corrected-PSCZ = 0.0409), ADHD (PADHD = 0.021, corrected-PADHD = 0.0301), and MDD (PMDD = 0.039, corrected-PMDD = 0.0501) is over-transmitted to children with AS but not to Non_AS. Indeed, agnostic clustering procedure with deviation values from pTDT tests suggested two differentiated clusters of subjects, one of which is significantly enriched in AS (P = 0.025). Subsequent analysis with S-Predixcan, a recently developed software to predict gene expression from genotype data, revealed a clear pattern of correlation between cortical gene expression in ADHD and AS (P < 0.001) and a similar strong correlation pattern between MDD and AS, but also extendable to another non-brain tissue such as lung (P < 0.001). Altogether, these results support the idea of AS being qualitatively distinct from Non_AS autism and consistently evidence the genetic overlap between AS and ADHD, MDD, or SCZ.


Effect of exophthalmometer design on its accuracy.
To investigate the effect of the design of different exophthalmometers on their measurement accuracy. Eight different exophthalmometers were tested with a specially developed calibrator by experienced orbital surgeons. Exophthalmometers with one mirror and a straight footplate were found to be more accurate than others. One-mirror exophthalmometers were less accurate when assessing low (< or =12 mm) and high (> or =23 mm) exophthalmometric values. The design of an exophthalmometer affects its accuracy.


Causal associations of Insomnia and postpartum depression: a two-sample mendelian randomization study.
Postpartum depression (PPD), a prevalent social-mental condition, impacts the mother and the newborn and several facets of their lives. It has been suggested that insomnia is related to both the occurrence and progression of PPD. However, because of lingering confounding and bias, it is impossible to determine the cause of this connection using observational analysis. In this study, we evaluate the causal importance of insomnia on postpartum depression using Mendelian randomization (MR). Utilizing summary data from genome-wide association studies (GWAS), a two-sample MR study was conducted. A GWAS dataset of IEU study of the United Kingdom Biobank phenotypes comprising 462,341 people of European heritage yielded 38 single-nucleotide polymorphisms (SNPs) for insomnia. The PPD data were provided by the FinnGen project and comprised 7604 cases and 59,601 controls. Inverse variance weighting (IVW) was utilized for the primary MR analysis, with weighted median and MR-Egger as sensitivity analyses. As a result, we found that genetically predicted insomnia was positively associated with postpartum depression. The odds ratios (OR) of PPD were 1.849 (95% (confidence interval) CI 1.011-3.381; p = 0.046). For the first time, the causative role of sleeplessness for postpartum depression has been extensively evaluated in the current two-sample MR investigation. Our findings show that insomnia and PPD are related causally.


Exposure-based treatments for childhood abuse-related post-traumatic stress disorder in adults: a health-economic evaluation.
Background: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based treatments in patients with childhood abuse-related PTSD.Method: A net-benefit analysis was conducted alongside a pragmatic randomized controlled trial with participants (N = 149) randomized to three conditions: PE (n = 48), intensified PE (i-PE, n = 51), and phase-based PE [Skills Training in Affective and Interpersonal Regulation (STAIR) + PE, n = 50]. Assessments took place at baseline (T0), post-treatment (T3), 6 month follow-up (T4), and 12 month follow-up (T5). Costs stemming from healthcare utilization and productivity losses were estimated using the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness. Quality-adjusted life-years (QALYs) were based on the 5-level EuroQoL 5 Dimensions (EQ-5D-5L) using the Dutch tariff. Missing values of costs and utilities were multiply imputed. To compare i-PE to PE and STAIR + PE to PE, pair-wise unequal-variance t-tests were conducted. Net-benefit analysis was used to relate costs to QALYs and to draw acceptability curves.Results: Intervention costs did not differ across the three treatment conditions. Total medical costs, productivity losses, total societal costs, and EQ-5D-5L-based QALYs did not differ between treatment conditions either (all p > .10). At the relevant €50,000/QALY threshold, the probability of one treatment being more cost-effective than another was 32%, 28%, and 40% for PE, i-PE, and STAIR-PE, respectively.Conclusion: Three equally effective treatments were compared and no differences in cost-effectiveness between treatments were found. Therefore, we advocate the implementation and adoption of any of the treatments and endorse shared decision making.


Molecular characterization and antibiotic resistance of Vibrio parahaemolyticus from Indian oyster and their probable implication in food chain.
Vibrio parahaemolyticus is one of the leading causes of diarrhoea and gastroenteritis in human on consumption of raw or insufficiently cooked seafood. This study was aimed at isolating and characterizing the pathogenic and pandemic V. parahaemolyticus from oysters (n = 90) in coastal parts of West Bengal, India; their antibiotic resistance and potential for involvement in the food chain. During bacteriological culture, typical V. parahaemolyticus colony was recovered in 88.9% samples followed by presumptive identification in 71 (78.9%) samples by characteristic biochemical (K/A) test. All the presumptive isolates (n = 71) were confirmed by species specific Vp-toxR PCR assay. Of these, 10 (14.08%) were tdh+ and none for the trh. Further, 5 (50%) of these tdh+ isolates were found to carry the pandemic potential gene in PGS-PCR assay; however, none in GS-PCR. Majority (80%) of these pathogenic (tdh+) isolates belonged to pandemic serovars (OUT: KUT; OUT: K24; O1: KUT; O1:K25; O10: KUT) and only 20% to non-pandemic serovars (OUT: K15; O9:K17). All the isolates (100%) exhibited resistance to cefpodoxime followed by ampicillin and cefotaxime (90%), ceftizoxime (60%), tetracycline (50%), ceftriaxone (40%), ciprofloxacin and nalidixic acid (10% each). Overall, the study findings suggested that 11.1% (10/90) of commonly marketed oysters in this area were harbouring pathogenic V. parahaemolyticus. Moreover, 5.5% (5/90) of the oyster population were harbouring pandemic strains of this pathogen. Besides, the pathogenic isolates from oysters were exhibiting a considerable genetic relatedness (53 to 70%) to human clinical isolates in PFGE analysis that relates to a substantial public health risk. Further, their multidrug resistance added gravity to the antimicrobial resistance (AMR), a globally growing public health threat and this is a critical area of concern especially during the treatment of foodborne gastroenteritis.


cis-Diamminedichloroplatinum (II) modified chromatin and nucleosomal core particle probed with DNase I.
Chromatin and nucleosomal core particles were modified with cis-diamminedichloroplatinum (II) and the nucleoprotein complexes then digested with DNase I. Limited digestion of the modified chromatin containing cis-Pt(NH3)2Cl2 mediated cross-links involving the non-histone chromosomal proteins (Scovell et al. (1987) Biochem. Biophys. Res. Commun. 142, 826-835) does not release the low mobility proteins and excises only about 20% of the high mobility proteins 1, 2, and E. This supports previous findings that the low mobility proteins are involved primarily in protein-protein cross-links. In addition, the covalent cross-links between DNA and the high mobility proteins 1, 2, and E are relatively inaccessible to DNase I, in marked contrast to their accessibility to micrococcal nuclease. Furthermore, gels of the denatured DNA fragments obtained from digestion of both modified chromatin and nucleosomal core particle reveal virtually no difference in the 10n base repeat pattern, indicating no detectable change in the DNA-protein interactions upon DNA modification. This suggests that the predominant modification produced on core particle DNA, whether contained within higher order chromatin structure or in the core particle itself, is one which does not significantly alter the helical twist of the DNA within these nucleoprotein assemblies.


The amino acid sequence of the major parvalbumin of the whiting (Gadus merlangus).
1. The amino acid sequence of the major parvalbumin of the Whiting has been determined; the polypeptide chain is made of 108 residues, the terminal amino acid group is acetylated, there is no disulfide bridges, the structure of the two calcium binding sites is preserved and the distribution along the polypeptide chain of the hydrophobic residues implicated in the compact hydrophobic core of the protein is also maintained. 2. The comparison of this amino acid sequence with other parvalbumins indicates that it belongs to the beta type and that within the Gadidae family two types of parvalbumins also occur.


Monoaminergic influences on temporal patterning of sexual behavior in male rats.
We evaluated the effects of the serotonin (5-HT) presynaptic uptake blocker fluoxetine (FLX) and the dopamine (DA)/noradrenaline (NE) releaser amantadine (AMA), separately and in combination, on the temporal patterning of male rat sexual behavior. FLX alone increased intermount-bout intervals, time-outs, grooming time, ejaculation latency, number of mounts per mount bout, and number of mount bouts per ejaculation. AMA alone had the opposite effect on these measures. Additionally, AMA, when given in combination with FLX, completely reversed the FLX-induced deficits in copulatory behavior. We interpret our results as suggesting an interaction between 5-HT and catecholamines in the temporal patterning of male rat copulatory behavior.


Assessment of red blood cell distribution width and mean platelet volume in children with epistaxis.
This study aimed to investigate whether there is a relationship between red blood cell distribution width, mean platelet volume and epistaxis in children. Between January 2015 and July 2016, 105 children who were referred to our clinic with epistaxis and 100 sex- and age-matched controls were retrospectively analyzed. Red blood cell distribution width (RDW) and mean platelet volume (MPV) values were determined in both groups. RDW values were found significantly (P < 0.05) lower in the group with epistaxis than in the control group (11.95 ± 1.31 vs. 12.74 ± 1.21). MPV was 7.49 ± 1.33 in the group with epistaxis and 7.23 ± 1.06 in the control group, and there was no significant difference between the groups (p > 0.05). We found no difference between MPV values of both groups and significantly lower RDW values in children with epistaxis. Decreased RDW values were considered as an accompanying marker rather than a result of epistaxis. In addition, it may be thought that low RDW values may increase the bleeding tendency by disrupting the thrombotic activities. Further studies are needed to validate the relation of these parameters with epistaxis and its mechanisms.


The effectiveness of remote delivered intervention for loneliness reduction in older adults: A systematic review and meta-analysis.
Remotely delivered intervention is widely applied to loneliness treatment in older adults, but the effect is controversial. This study aimed to evaluate the effects of remotely delivered intervention on loneliness using a systematic review and meta-analysis. The PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL (EBSCO), PsycINFO (EBSCO) databases were searched for studies, the search ended on 7 July 2021. Thirteen randomized controlled trials of remotely delivered intervention compared with usual care, brief contact, or no intervention for loneliness were included. A random-effects model measured estimation of loneliness reduction. Furthermore, standardized mean differences (SMDs), 95% confidence intervals (CIs), publication bias, and heterogeneity were calculated. Subgroup analysis was used to explore the factors that might affect the treatment effects. The evidence of remotely delivered intervention on loneliness reduction was certain (SMD = -0.41 [95% CI, -0.70 to -0.13]). Media subgroup analysis supported the effectiveness of intervention delivered by video call (SMD = -0.54 [95% CI, -0.83 to -0.25]); treatment strategy subgroup analysis found evidence to support the effectiveness of increasing social support and maladaptive social cognition treatment strategy (SMD = -0.47 [95% CI, -0.77 to -0.18] and SMD = -1.04 [95% CI, -1.98 to -0.10], respectively); participants subgroup analysis shown the effectiveness of intervention for older adults living in LTC and social isolation (SMD = -1.40 [95% CI, -2.43 to -0.36] and SMD = -0.55 [95% CI, -0.74 to -0.36], respectively); group format subgroup analysis testified the effectiveness of intervention carried out in individual format (SMD = -0.39 [95% CI, -0.71 to -0.07]); measurement time points subgroup analysis found the positive effect of intervention at 3 months and 3 to 6 months stage (SMD = -0.33 [95% CI, -0.52 to -0.14] and SMD = -0.32 [95% CI, -0.57 to -0.07], respectively). Significant publication bias was detected (p < 0.05), and the heterogeneity of the studies was substantial. This systematic review and meta-analysis demonstrate that remotely delivered intervention can reduce loneliness in older adults, and it appears to be affected by media type, treatment strategy, participants characteristics, group format, and measurement time points.


Correlations between histopathological and biological findings in nasopharyngeal carcinoma and its prognostic significance.
Forty-five consecutive cases of nasopharyngeal carcinoma were morphologically and immunocytochemically studied using monoclonal (anti-B and anti-T cell) and polyclonal (anti-S100 protein and antilysozyme) antibodies with the peroxidase-anti-peroxidase method to identify infiltrating lymphocytes (T and B cell) and histiocytes (monocytic/macrophagic and dendritic cells) in nasopharyngeal carcinoma. A variable density of dendritic cells was found within the tumor nests in 22 (49%) of 45 nasopharyngeal carcinomas examined; infiltrating macrophages were demonstrated in 15 (33%) specimens and around the tumor in almost all cases. Cases with moderate or marked density of dendritic cells (S100+) survived longer than those without such infiltration (mean 5-year survival rates of 31%, 55%, or 64% in patients with absent, moderate, or marked densities, respectively; P less than 0.05). A significant relationship between monocytic/macrophagic cells (lysozyme+) within the tumor and survival was also found (mean 5-year survival rate of 27% or 61% in patients with absent, moderate, or marked densities, respectively). However, lymphocytic infiltration was not statistically related to a better survival. Analyzing lymphocytic infiltration, we found a large prevalence of T cells in the neoplastic tissue without any prognostic significance. These data were correlated to different histological subtypes according to the principal histological classifications of nasopharyngeal carcinomas (Micheau, et al.; World Health Organization; Cologne University) to individualize the scheme which correlates best with prognosis and biological features of nasopharyngeal carcinomas. Our data suggest that, considering dendritic cells and macrophages within cancer nests, nasopharyngeal carcinoma histiotypes can be correlated to patient prognosis.


The ventromedial hypothalamic nucleus in the zebra finch (Taeniopygia guttata): Afferent and efferent projections in relation to the control of reproductive behavior.
Sex-specific mating behaviors occur in a variety of mammals, with the medial preoptic nucleus (POM) and the ventromedial hypothalamic nucleus (VMH) mediating control of male and female sexual behavior, respectively. In birds, likewise, POM is predominantly involved in the control of male reproductive behavior, but the degree to which VMH is involved in female reproductive behavior is unclear. Here, in male and female zebra finches, a combination of aromatase immunohistochemistry and conventional tract tracing facilitated the definition of two separate but adjacent nuclei in the basal hypothalamus: an oblique band of aromatase-positive (AR+) neurons, and ventromedial to this, an ovoid, aromatase-negative (AR-) nucleus. The AR- nucleus, but not the AR+ nucleus, was here shown to receive a projection from rostral parts of the thalamic auditory nucleus ovoidalis and from the nucleus of the tractus ovoidalis. The AR- nucleus also receives an overlapping, major projection from previously uncharted regions of the medial arcopallium and a minor projection from the caudomedial nidopallium. Both the AR- and the AR+ nuclei project to the intercollicular nucleus of the midbrain. No obvious sex differences in either the pattern of AR immunoreactivity or of the afferent projections to the AR- nucleus were observed. The significance of these results in terms of the acoustic control of avian reproductive behavior is discussed, and a comparison with the organization of VMH afferents in lizards suggests a homologous similarity of the caudal telencephalon in sauropsids.


Alginate extraction from Sargassum seaweed in the Caribbean region: Optimization using response surface methodology.
Sargassum valorization has become increasingly important as the Caribbean region continues to struggle with the massive growth of the seaweed and its damaging effects. Sodium alginate extraction is one method where the seaweed biomass can be utilized to produce a useful biopolymer. However, current processing generally giving low yields of inferior quality, making it unattractive for commercialization. This article seeks to optimize the extraction process using a Box-Behnken Response Surface Design combined with multistage extraction to obtain higher product yield and purity, as well as giving insights, for the first time, into the physiochemical properties of the extracted alginate from Sargassum biomass. Optimum conditions were found and confirmed through validation, with a crude yield as high as 28 % after 2 stages and a purity of 92 % for purified alginate samples. Characterization of the bleached alginate through NMR studies validated with FTIR, gave an M/G ratio of 0.45 with a molecular weight of 3.14 × 105 g mol-1 and viscosity of 14.10 cP aligned to high gelling capabilities.


Realizing high-performance and low-cost lithium-ion capacitor by regulating kinetic matching between ternary nickel cobalt phosphate microspheres anode with ultralong-life and super-rate performance and watermelon peel biomass-derived carbon cathode.
Lithium-ion capacitors (LICs) are emerging as one of the most advanced energy storage devices by combining the virtues of both supercapacitors (SCs) and lithium-ion batteries (LIBs). However, the kinetic and capacity mismatch between anode and cathode is the main obstacle to wide applications of LICs. Therefore, the effective strategy of constructing a high-performance LIC is to improve the rate and cycle performance of the anode and the specific capacity of the cathode. Herein, the nickel cobalt phosphate (NiCoP) microspheres anode is demonstrated with robust structural integrity, high electrical conductivity, and fast kinetic feature. Simultaneously, the watermelon-peel biomass-derived carbon (WPBC) cathode is demonstrated a sustainable synthesis strategy with high specific capacity. As expected, the NiCoP exhibits high specific capacities (567 mAh g-1 at 0.1 A g-1), superior rate performance (300 mAh g-1 at 1A g-1), and excellent cycle stability (58 mAh g-1 at 5 A g-1 after 15,000 cycles). The WPBC possesses a high specific surface area (SSA) of 3303.6 m2 g-1 and a high specific capacity of 226 mAh g-1 at 0.1 A g-1. Encouragingly, the NiCoP//WPBC-6 LIC device can deliver high energy density (ED) of 127.4 ± 3.3 and 67 ± 3.8Wh kg-1 at power density (PD) of 190 and 18240 W kg-1 (76.4% capacity retention after 7000 cycles), respectively.


Association of the V122I Transthyretin Amyloidosis Genetic Variant With Cardiac Structure and Function in Middle-aged Black Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study.
The variant V122I is commonly enriched in the transthyretin (TTR) gene in individuals of African ancestry and associated with greater risk of heart failure (HF) in older adulthood, after age 65 years. Prevention of HF may be most effective earlier in life, but whether screening with echocardiography can identify subclinical cardiac abnormalities during middle age to risk-stratify individuals appears to be unknown. To examine the association between the V122I TTR variant and cardiac structure and function during middle age in those without prevalent HF. This serial cross-sectional study of 875 Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort was conducted at 4 urban sites across the US. Recruiting was completed in 1985-1986, and follow-up examinations occurred 25 and 30 years later. A subset of Black adults from the CARDIA cohort who underwent TTR genotyping was included. Data analysis was completed from January 2020 to October 2020. The V122I TTR genotype. Echocardiographic left ventricular (LV) circumferential and longitudinal systolic strain and LV structure, measured at years 25 and 30 of follow-up. The analyses were adjusted for age, sex, echocardiography quality, genetic ancestry, and field center. Among the 875 Black adults (mean [SD] age, 49.4 [3.8] years at year 25; 543 women [62.1%]), there were 31 individuals who were heterozygous and 1 who was homozygous for the V122I TTR variant. Of the adults who had an echocardiogram at year 25, rates of hypertension (312 [46%]), diabetes (102 [15%]), and current smoking (128 [19%]) were not significantly different between those who did and did not carry V122I TTR. At year 25, there was no difference in LV circumferential strain, longitudinal strain, or LV structure between those who did vs did not carry V122I TTR. At year 30, those who carried V122I TTR had significantly lower absolute LV circumferential strain (mean [SD], 12.4 [4.2] percentage units) compared with those who did not carry the variant (mean [SD], 14.5 [3.7] percentage units). Those who carried V122I TTR also had significantly higher LV mass index values (mean [SD], 97.5 [34.1] g/m2) compared with those who did not (mean [SD], 83.7 [22.6] g/m2) at year 30. Carrier status for the V122I TTR variant is associated with subclinical cardiac abnormalities in middle age (worse LV systolic function and higher LV mass) that have been associated with increased risk of incident HF. Midlife screening of individuals who carry V122I TTR with echocardiography may prognosticate risk of symptomatic HF and inform prevention strategies.


3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease.
Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the gene encoding Huntingtin. The mechanisms underlying the preferential degeneration of the striatum, the most striking neuropathological change in HD, are unknown. Of those probably involved, mitochondrial defects might play an important role. The behavioural and anatomical similarities found between HD and models using the mitochondrial toxin 3-nitropropionic acid (3NP) in rats and primates support this hypothesis. Here, we discuss the recently identified mechanisms of 3NP-induced striatal degeneration. Two types of important factor have been identified. The first are the 'executioner' components that have direct roles in cell death, such as c-Jun N-terminal kinase and Ca2+-activated protease calpains. The second are 'environmental' factors, such as glutamate, dopamine and adenosine, which modulate the striatal degeneration induced by 3NP. Interestingly, these recent studies support the hypothesis that 3NP and mutated Huntingtin have certain mechanisms of toxicity in common, suggesting that the use of 3NP might give new insights into the pathogenesis of HD. Research on 3NP provides additional proof that the neurochemical environment of a given neurone can determine its preferential vulnerability in neurodegenerative diseases.


Changes in T-lymphocytes and response to high-dose gamma-globulin therapy in idiopathic thrombocytopenic purpura.
Peripheral blood lymphocytes were studied using OKT3, OKT4 and OKT8 monoclonal antibodies in patients with idiopathic thrombocytopenic purpura ITP) before and after high dose gammaglobulin therapy. Total lymphocyte counts increased in 8 of 10 patients studied within 16 weeks of presentation (acute ITP) but decreased in all 6 with chronic (6 months-14 years) thrombocytopenia (P = 0.003). A relative increase in the proportion of inducer-helper (OKT4) cells was seen in 5 of 6 patients with sustained responses whereas there was no clear cut change or a relative increase in suppressor-cytotoxic (OKT8) cells in 7 or 9 with transient responses. The data suggest that short term gammaglobulin therapy may induce sustained responses by immunoregulation of T-lymphocyte subsets.


XLF regulates filament architecture of the XRCC4·ligase IV complex.
DNA ligase IV (LigIV) is critical for nonhomologous end joining (NHEJ), the major DNA double-strand break (DSB) repair pathway in human cells, and LigIV activity is regulated by XRCC4 and XLF (XRCC4-like factor) interactions. Here, we employ small angle X-ray scattering (SAXS) data to characterize three-dimensional arrangements in solution for full-length XRCC4, XRCC4 in complex with LigIV tandem BRCT domains and XLF, plus the XRCC4·XLF·BRCT2 complex. XRCC4 forms tetramers mediated through a head-to-head interface, and the XRCC4 C-terminal coiled-coil region folds back on itself to support this interaction. The interaction between XLF and XRCC4 is also mediated via head-to-head interactions. In the XLF·XRCC4·BRCT complex, alternating repeating units of XLF and XRCC4·BRCT place the BRCT domain on one side of the filament. Collective results identify XRCC4 and XLF filaments suitable to align DNA molecules and function to facilitate LigIV end joining required for DSB repair in vivo.


Electrochemically reduced phytic acid-doped TiO2 nanotubes for the efficient electrochemical degradation of toxic pollutants.
Element-doped TiO2 nanotube arrays (TNAs) with optimized active sites provide an effective approach for significantly improving electrocatalytic performance. The challenges in such construction mainly include selection of green dopant and control of active sites. Herein, we present phytic acid as a phosphorus source for P-doped TNAs. An oxygen vacancy (Ov) and P co-doped TNAs (P-TiO2-y) was prepared as an electrochemical oxidation anode. P-TiO2-y exhibits excellent degradation activity due to the formation of Ti-O-P bonds and generation of Ov. P-doping was beneficial in improving the oxygen evolution potential of the electrode, which would be benefit for electrocatalytic degradation of pollutants. Using the P-TiO2-y anode with a current density of 10 mA/cm2 for tetracycline degradation, after a 3 h treatment, the removal rate, chemical oxygen demand and total organic carbon removal rates were 100%, 90.32% and 76.60%, respectively. The P-TiO2-y also has excellent degradation performance for phenol, hydroquinone, p-nitrophenol and metronidazole.


Bacopaside-I Alleviates the Detrimental Effects of Acute Paraquat Intoxication in the Adult Zebrafish Brain.
Paraquat (PQ), an environmental neurotoxicant, causes acute fatal poisoning upon accidental or intentional ingestion (suicidal cases) worldwide. To date, an effective remedy for PQ toxicity is not available. In this study, we have evaluated the therapeutic efficacy of Bacopaside-I (BS-I), an active compound found in the plant extract of Bacopa monnieri (Brahmi), against acute PQ intoxication using zebrafish as a model organism. Adult zebrafish were injected with a dose of either 30 mg/kg or 50 mg/kg PQ. PQ-intoxicated zebrafish showed an increased rate of mortality and oxidative imbalance in their brain. Also, the proliferation of neural cells in the adult zebrafish brain was inhibited. However, when BS-I pretreated zebrafish were intoxicated with PQ, the toxic effects of PQ were ameliorated. PQ treatment also affected the expression of particular genes concerned with the apoptosis and dopamine signaling, which was not altered by BS-I administration. Our results highlight the efficiency of BS-I as a novel therapeutic agent for PQ intoxication. It further compels us to search and evaluate the molecular mechanisms targeted by BS-I to develop a potent therapy for acute PQ intoxication.


Quantifying the small-area spatio-temporal dynamics of the Covid-19 pandemic in Scotland during a period with limited testing capacity.
Modelling the small-area spatio-temporal dynamics of the Covid-19 pandemic is of major public health importance, because it allows health agencies to better understand how and why the virus spreads. However, in Scotland during the first wave of the pandemic testing capacity was severely limited, meaning that large numbers of infected people were not formally diagnosed as having the virus. As a result, data on confirmed cases are unlikely to represent the true infection rates, and due to the small numbers of positive tests these data are not available at the small-area level for confidentiality reasons. Therefore to estimate the small-area dynamics in Covid-19 incidence this paper analyses the spatio-temporal trends in telehealth data relating to Covid-19, because during the first wave of the pandemic the public were advised to call the national telehealth provider NHS 24 if they experienced symptoms of the virus. Specifically, we propose a multivariate spatio-temporal correlation model for modelling the proportions of calls classified as either relating to Covid-19 directly or having related symptoms, and provide software for fitting the model in a Bayesian setting using Markov chain Monte Carlo simulation. The model was developed in partnership with the national health agency Public Health Scotland, and here we use it to analyse the spatio-temporal dynamics of the first wave of the Covid-19 pandemic in Scotland between March and July 2020, specifically focusing on the spatial variation in the peak and the end of the first wave.


A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.
Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.


Marinobacter profundi sp. nov., a slightly halophilic bacterium isolated from a deep-sea sediment sample of the New Britain Trench.
A piezotolerant, cold-adapted, slightly halophilic bacterium, designated strain PWS21T, was isolated from a deep-sea sediment sample collected from the New Britain Trench. Cells were observed to be Gram-stain negative, rod-shaped, oxidase- and catalase-positive. Growth of the strain was observed at 4-45 °C (optimum 37 °C), at pH 5.0-9.0 (optimum 7.0) and in 0.5-20% (w/v) NaCl (optimum 3-4%). The optimum pressure for growth was 0.1 MPa (megapascal) with tolerance up to 70 MPa. 16S rRNA gene sequence analysis showed that strain PWS21T is closely related to Marinobacter guineae M3BT (98.4%) and Marinobacter lipolyticus SM19T (98.2%). Multilocus sequence analysis (MLSA) based on sequences of housekeeping genes gyrB, recA, atpD, rpoB and rpoD indicates that strain PWS21T represents a distinct evolutionary lineage within the genus Marinobacter. Furthermore, strain PWS21T showed low ANI and diDDH values to the closely related species. The principal fatty acids were identified as C12:0, C12:0 3-OH, C16:1ω9c, C16:0 and C18:1ω9c. Ubiquinone-9 was identified as the major respiratory quinone. The polar lipids were identified as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), aminophospholipid (APL), two unidentified lipids and an unidentified phospholipid (PL). The G + C content of the genomic DNA was determined to be 60.3 mol%. On the basis of phenotypic, chemotaxonomic and molecular data, we conclude that strain PWS21T represents a novel species of the genus Marinobacter, for which the name Marinobacter profundi sp. nov. is proposed (type strain PWS21T = KCTC 52990T = MCCC 1K03345T).


Low frequency stimulation of the nucleus tegmenti pedunculopontini increases cortical metabolism in parkinsonian patients.
To evaluate the effects of 25-Hz deep brain stimulation of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity. Six patients with Parkinson's disease (PD) who had bilateral stereotactic implantation of PPTg at least 12 months prior to evaluation were included in our study. All underwent, in separate sessions, 18-FDG-PET in core assessment programme for intra-cerebral transplantation as well as motor evaluation [Unified Parkinson's disease rating scale (UPDRS)--Section III] and a battery of cognitive testing. PPTg-ON (low bipolar contacts, 25 Hz) promoted a significant increase of glucose utilization in bilateral prefrontal areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito-frontal cortex (BA47), anterior cingulate (BA 25-32), superior frontal gyrus (BA 10) and supramarginal gyrus (BA40); a significant increase of uptake and consumption of FDG also occurred in the left ventral striatum, left subgyral (BA 46), right insula (BA 13) and right superior temporal gyrus (BA 22). PPTg-ON was associated with a significant decrease of glucose utilization in the left cerebellar anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same patients, PPTg-ON improved delayed recall (P < 0.05) and executive functions whilst the UPDRS revealed a modest (-21%) and variable treatment effect. Low frequency stimulation of PPTg, a sub-region of the pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar profile of cognitive improvement associated with a significant increase in FDG consumption in both prefrontal areas and mono-lateral ventral striatum. These data are consistent with multiple limbic and/or associative domains modulated by PPTg stimulation in our patients with PD.


New Advances in the Biosynthesis of Glycopeptide Antibiotics of the Vancomycin Type from Amycolatopsis mediterranei.
Linear biosynthesis products from balhimycin, a tricyclic glycopeptide antibiotic of the vancomycin type, were isolated from mutants of Amycolatopsis mediterranei. The structures of these intermediates, determined by NMR spectroscopy, give new impulses for the understanding of the vancomycin biosynthesis.


Science communication in the media and human mobility during the COVID-19 pandemic: a time series and content analysis.
The relationship between human mobility and nature of science (NOS) salience in the UK news media was examined. This is a mixed-method study. A time series NOS salience data set was established from the content analysis of 1520 news articles related to non-pharmaceutical interventions of COVID-19. Data were taken from articles published between November 2021 and February 2022, which correlates with period of the change from pandemic to endemic status. Vector autoregressive model fitting with human mobility took place. The findings suggest that it was not the number of COVID-19 news articles nor the actual number of cases/deaths, but the specific NOS content that was associated with mobility change during the pandemic. Data indicate a Granger causal negative direction (P < 0.1) for the effect of the NOS salience represented in the news media on mobility in parks, as well as the effect of scientific practice, scientific knowledge and professional activities communicated in news media on recreational activities and grocery shopping. NOS salience was not associated with the mobility for transit, work or residential locations (P > 0.1). The findings of the study suggest that the ways in which the news media discuss epidemics can influence changes in human mobility. It is therefore essential that public health communicators emphasise the basis of scientific evidence to eliminate potential media bias in health and science communication for the promotion of public health policy. The present study approach, which combines time series and content analysis and uses an interdisciplinary lens from science communication, could also be adopted to other interdisciplinary health-related topics.