Weekday snacking prevalence, frequency, and energy contribution have increased while foods consumed during snacking have shifted among Australian children and adolescents: 1995, 2007 and 2011-12 National Nutrition Surveys.
There are limited data on the evolution of eating habits, including snacking, in Australia. This study aimed to understand snacking trends among Australian children over three previous National Nutrition Surveys. Data were analysed from a single weekday 24-h recall in the National Nutrition Surveys 1995, 2007, 2011-12 among children 2-16y (n = 8258). A snacking occasion was defined as an eating occasion that occurred between meals based on time of day. The percentage of children snacking increased over time (92.5 ± 0.5(SE) % in 1995, 98.1 ± 0.3% in 2007, and 95.8 ± 0.4% in 2011-12) (P < 0.001), particularly among those having four or more snacking occasions (7.1 ± 0.5% in 1995, 17.9 ± 0.6% in 2007, and 18.5 ± 0.8% in 2011-2) (P < 0.001). The mean number of snacking occasions increased from 2.0 ± 0.0 in 1995, to 2.5 ± 0.0 in 2007 and 2011-12 (P < 0.001). The energy contribution from snacking increased from 24.1 ± 0.3% in 1995 to 27.7 ± 0.3% in 2007 and 30.5 ± 0.4% in 2011-12 (P < 0.001), while the energy from discretionary food during snacking decreased from 56.5 ± 0.7% in 1995 to 47.3 ± 0.5% in 2007 and 47.9 ± 0.7% in 2011-12 (P < 0.001). There were differences in the top foods consumed during snacking: non-alcoholic beverages were prominent contributors in 1995 but not in 2007 or 2011, and pome fruit was the second top energy contributor during snacking in 2007 and 2011 but only fourth in 1995. Snacking is a prominent dietary pattern that has increased over time in frequency and energy contribution. Foods and beverages consumed during snacking occasions include a mix of core foods and discretionary foods, and while the contribution of discretionary foods has decreased, there is still an opportunity to encourage consumption of more nutrient dense foods during snacking.


Hamartomas of the spleen: a study of 20 biopsy cases.
Twenty hamartomas of the spleen were studied by histological, immuno- and enzyme-histochemical methods. In all cases nodules of varying size resembling proliferation of splenic red pulp structures were present that exhibited considerable morphological variation with regard to plasmacytosis, extramedullary haematopoiesis and phagocytic activity of macrophages. Splenic red pulp structures could be identified by immuno- and enzyme-histochemical markers reacting with sinus endothelium, including Factor VIII related antigen, proteinase inhibitors and non-specific esterases. In conjunction with the absence of organized lymphoid tissue and of dendritic reticulum cells these studies allow the differentiation of splenic hamartomas from haemangiomas that may possess a deceptively similar morphological appearance.


Histological and cytological studies on the fat body of the cockroach Nauphoeta cinerea during the first reproductive cycle.
The central fat body of the ovoviviparous cockroach Nauphoeta cinerea was studied during the first reproductive cycle of the female by means of light microscopy, autoradiography and electron microscopy. Comparative studies in larval stages were also undertaken. The fat body of Nauphoeta contains a large amount of lipid droplets and the remaining cytoplasm is very scarce. The cytological cyclicity of the fat body is consistent with the known biochemical rhythms of vitellogenin production. The proteosynthetic apparatus appears about 3 days after imaginal ecdysis, along with vitellogenin. The ribosomal endoplasmic reticulum (RER) shows a tremendous increase by the 7th day of the first cycle. The most active period of vitellogenin production lasts from day 7 to 12. The proteosynthetic apparatus then returns to an inactive stage and disappears. This inactive condition lasts to the end of the gestation period. The autoradiographic results are consistent with the cytological features.


Teaching ophthalmology residents about rehabilitation.
Ophthalmology is a medical specialty which deals with large numbers of patients who have irreversible impairments. A survey of all ophthalmology residency programs in the United States found that most programs require that residents receive training in low vision aids and devices, but they do not require training in seven other topics concerning the rehabilitation of visually impaired and blind patients. Those programs that do offer training in rehabilitation rely heavily on clinical training. Since practicing ophthalmologists themselves have an incomplete knowledge of the rehabilitation system, it is unlikely that the clinical model will provide residents with sufficient information about rehabilitation. Ophthalmologists need formal training about the rehabilitation process in order to ensure that their patients receive adequate referrals.


Surgical treatment of primary hyperparathyroidism during the third trimester.
Primary hyperparathyroidism is a rare diagnosis in the third trimester of pregnancy. A 58% fetal complication rate, including perinatal death and preterm labor, following late gestation parathyroidectomy has been reported. These statistics, however, are based on small sample sizes and were reported when our current technology was unavailable. A 30-year-old woman presented in the early third trimester with primary hyperparathyroidism. Despite conservative management, her ionized calcium level increased to 1.88 mmol/L (normal 1.17-1.33 mmol/L). At 3447 weeks, she had an uncomplicated parathyroidectomy. At 3837 weeks she delivered a 3182-g female infant. Neither the mother nor baby had complications. This supports the contention that pregnant women with hyperparathyroidism not controlled by conservative measures can be treated successfully with parathyroidectomy, regardless of gestational age.


Case-control study of the RFA therapeutic effect of newly developed 4D US and conventional 2D US.
For radiofrequency ablation (RFA) therapy of hepatocellular carcinoma (HCC), accurate positioning of the inserted needle in the index tumor seems to be an important factor affecting therapeutic effect. In a case-control study, we compared the therapeutic effect of RFA using 4D and 2D ultrasonography (US) to evaluate whether 4D US is more effective. Twenty subjects treated with percutaneous RFA using 4D US (4D group) and 20 subjects using conventional 2D US (2D group), who were matched for age, sex, and HCC diameter, were enrolled in this study. Aplio XG was used as the US system and PVT-375MV as the newly developed 4D US probe. The therapeutic effect of RFA was classified into four grades (A-D: "Grade A" is "absolutely curative"). In the 2D group, Grade A was achieved in 12 subjects (60 %). In contrast, Grade A was achieved in 19 subjects (95 %) in the 4D group. The proportion of cases in which Grade A was achieved was significantly higher in the 4D group (P < 0.01). By using a 4D US device for RFA, more accurate insertion could be achieved and more effective therapy could be performed.


MMP-7 (-181A>G) promoter polymorphisms and risk for cervical cancer.
Matrix metalloproteinase (MMP-7) is a secreted matrilysin, which contributes to tumor progression through breakdown of basement membranes and angiogenesis. Therefore, we aimed to investigate the association of MMP-7 -181A>G gene polymorphism with risk of cervical cancer. In the present case control study, we enrolled a total of 150 cervical cancer patients confirmed by histopathology and 162 unrelated healthy individuals. Polymorphism for MMP-7 gene (-181A>G) was genotyped by polymerase chain reaction and restriction enzyme length polymorphism. Frequency of MMP-7 -181GG genotype and -181G allele differed significantly between patients with cervical cancer (29.3%) and healthy individuals (19.4%) (P=0.041; OR(GG)=1.94 and P=0.048; OR(G)=1.94). Individuals with MMP-7 -181GG genotype were at higher risk of stage II of cervical cancer with borderline significance (P=0.05, OR=2.78; 95%CI: 0.89-8.69). However, interaction of MMP-7 -181AG and GG genotypes with tobacco usage did not modulate the cervical cancer risk significantly (OR 2.21, 95%CI=0.59-8.1 and OR 3.17, 95%CI=0.64-15.7). Individuals with MMP-7 -181GG genotype were at significantly higher risk of cervical cancer.


Prolactin modulation of the maternal-like behavior displayed by juvenile rats.
Reports of elevated prolactin (Prl) levels in juvenile rats of the same strain and approximate age, together with the established role of Prl in maternal behavior in adult female rats, prompted us to examine the possible involvement of Prl in the expression of maternal-like behavior in juvenile Sprague-Dawley males and females. Experiment 1 showed that at 25 days of age both sexes exhibited a rapid onset of full maternal behavior (FMB), with males (median = 2.0 days) responding significantly more quickly than females (median = 4.0 days). Moreover, blood sampled for Prl revealed that males had significantly higher levels of circulating Prl than females, (21.0 vs 10.4 ng/ml, respectively). In Experiment 2, CB-154 treatment significantly delayed the onset of FMB in males only, causing latencies to increase to 5.0 days vs 2.0 days for Controls. Female latencies were unaffected by CB-154, 7.0 and 7.5 days for CB-154 and Control groups, respectively. A second set of both male and female juveniles was treated with either CB-154 or vehicle. CB-154 reduced Prl levels in both sexes. In the Controls, the sex difference in Prl levels (males greater than females) was again evident. In Experiment 3 juvenile males were treated with either ovine Prl (0.5 mg) + CB-154, CB-154 + Vehicle, or Vehicle + Vehicle and tested for FMB. Males treated with Prl + CB-154 required 3.0 days to exhibit FMB, significantly faster than CB-154 + Vehicle males which responded in 8.0 days. The response of Vehicle + Vehicle males was intermediate, with a latency of 5.0 days. These results provide support for the idea that Prl is involved in the maternal-like responsiveness shown by 25 day old juvenile males, but that in females a maturational factor may have prevented both heightened responsiveness to pups by 25 days of age and sensitivity to the Prl releasing mechanism(s)/Prl feedback involved in the exhibition of maternal behavior.


Inpatient teaching with a clinical review game.
Shortened preclinical curricula, social distancing policies and the fast-paced nature of inpatient medicine make clinical education challenging. Crowdsourced learning and a review game derived from real-time patient cases can offer an engaging solution for inpatient teaching. We implemented a clinical review game with 67 participants (10 physician instructors, 40 residents and 17 medical students) rotating through the adult inpatient medicine service at an academic medical centre from July 2018 through July 2020. During 2-week rotations, participants identified shareable teaching points about their patients on rounds. Teaching points were compiled by an instructor into a 30-minute end-of-rotation review game formatted from a free gameshow-based PowerPoint template. After the review game was completed, learners were then asked to complete end-of-rotation evaluations. Learners were surveyed on their educational experience, and teaching point submissions were studied. After eight rotations, 39 participants (39/67 = 58.2% response rate) submitted a total of 268 teaching points, and nearly half of which were from learners (n = 131 [48.9%]). In the review game, 35 residents and 17 medical students participated and correctly answered 80% of questions. Learner evaluations highlighted the activity strengths including self-directed learning, peer teaching from primary literature and a warm, collaborative educational environment. Our crowdsourced clinical review game approach helped to highlight clinically relevant content for teaching rounds, build a collaborative culture across trainee levels and encourage self-study for trainees to stay informed with current evidence-based practice, even during pandemic restrictions.


Relationship Between Burnout, Professional Behaviors, and Cost-Conscious Attitudes Among US Physicians.
Despite the importance of professionalism, little is known about how burnout relates to professionalism among practicing physicians. To evaluate the relationship between burnout and professional behaviors and cost-conscious attitudes. Cross-sectional study in a national sample of physicians of whom a fourth received a sub-survey with items exploring professional behaviors and cost-conscious attitudes. Responders who were not in practice or in select specialties were excluded. Maslach Burnout Inventory and items on professional behaviors and cost-conscious attitudes. Among those who received the sub-survey 1008/1224 (82.3%) responded, and 801 were eligible for inclusion. Up to one third of participants reported engaging in unprofessional behaviors related to administrative aspects of patient care in the last year, such as documenting something they did not do to close an encounter in the medical record (243/759, 32.0%). Fewer physicians reported other dishonest behavior (e.g., claiming unearned continuing medical education credit; 40/815, 4.9%). Most physicians endorsed cost-conscious attitudes with over 75% (618/821) agreeing physicians have a responsibility to try to control health-care costs and 62.9% (512/814) agreeing that cost to society is important in their care decisions regarding use of an intervention. On multivariable analysis adjusting for personal and professional characteristics, burnout was independently associated with reporting 1 or more unprofessional behaviors (OR 2.01, 95%CI 1.47-2.73, p < 0.0001) and having less favorable cost-conscious attitudes (difference on 6-24 scale - 0.90, 95%CI - 1.44 to - 0.35, p = 0.001). Professional burnout is associated with self-reported unprofessional behaviors and less favorable cost-conscious attitudes among physicians.


Epistemic neural network based evaluation of online teaching status during epidemic period.
During the epidemic, online teaching became the mainstream. Online teaching evaluation aims to systematically test teachers' teaching process according to certain teaching objectives and standards, and evaluate its value, advantages and disadvantages, so as to improve the quality of teaching. It is not only an important part of the teaching process, but also the basis of all effective and successful teaching. In this paper, we propose an online teaching evaluation method based on Epistemic Neural Network (ENN), which is an evolutionary intelligence method. In terms of uncertainty modeling, ENN's design innovation provides the improvement effect of geometric progression in terms of statistical quality and calculation cost. Therefore, it is very suitable for teaching evaluation, which is an evaluation process guided by a variety of uncertain factors. Specifically, this paper considers the content and grade standards of online teaching evaluation from five aspects. (1) Teachers' syllabus, teaching progress, teaching plan, courseware and other teaching documents and teaching materials; (2) Abide by teaching discipline, the implementation of teaching plan and the completion of teaching tasks; (3) Teaching attitude, teaching investment, teaching and educating people, and the comprehensive quality of teachers; (4) Whether the concepts taught in the course are accurate, the expression is clear, whether the key points are prominent and whether the difficulties are clearly explained; (5) The depth, breadth and frontier of teaching content, and the amount of classroom information. According to the above five evaluation indexes which involves the big data analysis, we train ENN to get an evaluation score that can evaluate the teacher's online teaching process. In addition, we also test the average evaluation time to verify the effectiveness.


Multi-scale hyperspectral imaging of cervical neoplasia.
This preliminary study aimed at investigating the feasibility and effective of multi-scale hyperspectral imaging in detecting cervical neoplasia at both tissue and cellular levels. In this paper, we describe a noninvasive diagnosis method with a hyperspectral imager for detection and location of cervical intraepithelial neoplasia (CIN) at multiple scales. At the macroscopic level, the hyperspectral imager was applied to capture the reflectance images of the entire cervix in vivo at a series of wavelengths. At the microscopic level, the hyperspectral imager was coupled with a microscope to collect the transmittance images of the pathological slide. The collected image data were calibrated. A wide-gap second derivative analysis was applied to differentiate CIN from other types of tissue. At both macroscopic and microscopic levels, hyperspectral imaging analysis results were consistent with those of histopathological analysis, indicating the technical feasibility of multi-scale hyperspectral imaging for cervical neoplasia detection with accuracy and efficacy. We propose a multi-scale hyperspectral imaging method for noninvasive detection of cervical neoplasia. Comparison of the imaging results with those of gold standard histologic measurements demonstrates that the hyperspectral diagnostic imaging system can distinguish CIN at both tissue and cellular levels.


Unroofed coronary sinus and persistent left superior vena cava.
This report describes a case of unroofed coronary sinus and persistent left superior vena cava discovered during an echocardiographic investigation for dilated pulmonary artery. An unroofed coronary sinus is a rare interatrial shunt that is commonly associated with a persistent left superior vena cava. The latter is a usual cause of a dilated coronary sinus. The detection of a dilated coronary sinus should therefore prompt the search for abnormal coronary sinus drainage and other cardiac abnormalities. The treatment of unroofed coronary sinus and persistent left superior vena cava is undertaken only after assessing the pre- and post-treatment haemodynamics of all co-existing abnormalities.


Educational achievement and economic self-sufficiency in adults after childhood bacterial meningitis.
To our knowledge, no previous study has examined functioning in adult life among persons who had bacterial meningitis in childhood. To study educational achievement and economic self-sufficiency in adults diagnosed as having bacterial meningitis in childhood. Nationwide population-based cohort study using national registries of Danish-born children diagnosed as having meningococcal, pneumococcal, or Haemophilus influenzae meningitis in the period 1977-2007 (n=2784 patients). Comparison cohorts from the same population individually matched on age and sex were identified, as were siblings of all study participants. End of study period was 2010. Cumulative incidences of completed vocational education, high school education, higher education, time to first full year of economic self-sufficiency, and receipt of disability pension and differences in these outcomes at age 35 years among meningitis patients, comparison cohorts, and siblings. By age 35 years, among persons who had a history of childhood meningococcal (n=1338), pneumococcal (n=455), and H. influenzae (n=991) meningitis, an estimated 11.0% (41.5% vs 52.5%; 95% CI, 7.3%-14.7%), 10.2% (42.6% vs 52.8%; 95% CI, 3.8%-16.6%), and 5.5% (47.7% vs 53.2%; 95% CI, 1.9%-9.1%) fewer persons, respectively, had completed high school and 7.9% (29.3% vs 37.2%; 95% CI, 1.6%-14.2%), 8.9% (28.1% vs 37.0%; 95% CI, 0.6%-17.2%), and 6.5% (33.5% vs 40.0%; 95% CI, 1.4%-11.6%) fewer had attained a higher education compared with individuals from the comparison cohort. Siblings of meningococcal meningitis patients also had lower educational achievements, while educational achievements of siblings of pneumococcal and H. influenzae meningitis patients did not differ substantially from those in the general population. At end of follow-up, 3.8% (90.3% vs 94.1%; 95% CI, 1.1%-6.5%), 10.6% (84.0% vs 94.6%; 95% CI, 5.1%-16.1%), and 4.3% (90.6% vs 94.9%; 95% CI, 2.0%-6.6%) fewer meningococcal, pneumococcal, and H. influenzae meningitis patients were economically self-sufficient and 1.5% (3.7% vs 2.3%; 95% CI, -0.2% to 3.2%), 8.7% (10.0% vs 1.3%; 95% CI, 5.0%-12.4%), and 3.7% (6.2% vs 2.5%; 95% CI, 1.6%-5.8%) more received disability pension compared with individuals from the comparison cohort. In a Danish population, bacterial meningitis in childhood was associated with lower educational achievement and economic self-sufficiency in adult life. This association may apply particularly to pneumococcal and H. influenzae meningitis, whereas for meningococcal meningitis the lower educational achievement may be family-related.


Mutagenic activation of xenobiotics by plant enzymes.
Genetic evidence has indicated that plants can activate certain xenobiotics to mutagens, but biochemical evidence is as yet scarce. Nevertheless, plant microsomal enzymes and peroxidases have been shown to form reactive intermediates, the best studied examples being 2-aminofluorene, benzo[a]pyrene and pentachlorophenol. The latter two xenobiotics are converted to quinoid derivatives which are, in principle, able to redox cycle and generate active oxygen species. In analogy to results obtained in mammalian systems, covalent binding of reactive intermediates to DNA as well as fragmentation of DNA, are proposed as major mechanisms of action of mutagenic plant metabolites.


Proton magnetic resonance spectroscopy detects a relative decrease of N-acetylaspartate in the hippocampus of patients with dementia with Lewy bodies.
To characterize the cerebral metabolic changes in dementia with Lewy bodies patients. The metabolic ratios of NAA/Cr and Cho/Cr in bilateral hippocampus were determined by proton magnetic resonance spectroscopy in 8 patients and 8 age-matched healthy controls. Dementia with Lewy bodies patients showed significantly lower NAA/Cr ratios in bilateral hippocampus, while the Cho/Cr ratio did not differ from the control group. Our data show relatively decrease of N-acetylaspartate in the hippocampus of patients with early or intermediate stage DLB. Hence, damage of neurons seems to be an early alteration in DLB.


Patient-controlled epidural analgesia during labor using ropivacaine and fentanyl provides better maternal satisfaction with less local anesthetic requirement.
To test the hypothesis that patient-controlled epidural analgesia (PCEA) using ropivacaine and fentanyl provides better maternal satisfaction and less anesthetic requirement than conventional continuous epidural infusion (CEI) during labor, we studied 58 uncomplicated parturients (singleton, vertex presentation). After establishing effective epidural analgesia with 11 ml of 0.2% ropivacaine, all parturients were randomly divided into one of two groups: the PCEA group (n = 29) or the CEI group (n = 29). In the PCEA group, the pump was initiated to deliver a basal infusion at 6 ml x h(-1) and a demand dose of 5 ml; the lockout interval was 10 min, and there was a 31 ml x h(-1) limit. The drugs used were 0.1% ropivacaine + fentanyl 2 microg x ml(-1). In the CEI group, epidural analgesia was maintained with the same solution as the PCEA group at a constant rate of 10 ml x h(-1). If parturients requested additional analgesia in the CEI group, we added 8 ml of epidural 0.2% ropivacaine without fentanyl. Parturients' demographic data, such as duration of labor, mode of delivery, Apgar score, and umbilical arterial pH did not differ between the two groups. However, the hourly requirement of ropivacaine was significantly less in the PCEA group than in the CEI group (9.3 +/- 2.5 vs. 17.6 +/- 7.6 mg x h(-1); P < 0.05). Parturients' satisfaction assessed by the Visual Analogue Scale tended to be higher in the PCEA group than in the CEI group. Side effects such as nausea, hypotension, and itching were similar for the two groups. We found that PCEA was an effective means of providing optimal analgesia, with better satisfaction during labor and less local anesthetic requirement.


Conserved domains in the chicken homologue of BRCA2.
Germline mutation of the BRCA2 gene causes a high risk of developing breast and ovarian cancer. Although the BRCA2 protein has been implicated in homologous recombination (HR) of DNA and in transcription, it is still unclear how mutation leads to tumorigenesis. We have identified a non-mammalian homologue of BRCA2 from chicken, which encodes a protein with 3397 amino acids (aa) and shows only 40% identity to human BRCA2. However, comparison of the mammalian and chicken sequences revealed remarkably high homology in several segments. These include a N-terminal region (approximately 100 aa), which was previously shown to possess intrinsic transcriptional activity, and a C-terminal region (aa residue approximately 2480-approximately 3180 in human BRCA2), which has not been clearly assigned any function. In contrast, although the eight BRC repeats of mammalian BRCA2 are believed to play an important role in HR by interacting with Rad51, the BRC3, BRC5, and BRC6 repeats exhibit virtually no similarity to their mammalian counterparts. Among 311 missense mutations listed as unclassified variants in the NIH Breast Cancer Information Core database, only 83 of these sites are identical in chicken BRCA2. Thus, chicken BRCA2 may provide a means to identify domains and residues associated with cancer predisposition.


The relationships among anxiety, depression, and pain in a geriatric institutionalized sample.
This study sought to determine if depression and/or anxiety is uniquely related to pain after controlling for the strong association between anxiety and depression. Both depression and anxiety were assessed in an elderly institutionalized sample using: (1) research-based diagnoses based on Diagnostic and Statistical Manual-revised 3rd edition (DSM-IIIR) criteria, and (2) evaluations of one's recent affective states using the Profile of Moods States (POMS). Pain was assessed by pain intensity and number of pain complaints. A series of path models indicated that: (1) both research-based anxiety and depression share unique variance with pain, and (2) only POMS anxiety is uniquely related to pain. A path model using both measures of anxiety and depression indicated that only the anxiety measures are significantly related to pain. However, POMS anxiety sustained a significantly greater relationship with pain than did research-based anxiety.


Atypically distributed cutaneous lesions of Norwegian scabies in an HIV-positive man in South India: a case report.
Immune-compromised subjects, especially those with underlying HIV disease, are prone to be infected with Norwegian scabies, where the cutaneous lesions are classically distributed over the extremities. We report the case of an HIV-positive 16-year-old man with severe crusted Norwegian scabies initially misdiagnosed as a dermal fungal infection. The patient had extensive, generalized, thick, hyperkeratotic, crusting, yellowish papule lesions distributed on the entire body from his scalp to his toes.The patient was started with Ivermectin and topical Permethrin, which eventually resulted in complete resolution. Interestingly, despite quarantining efforts, one of the patient's acquaintances and a healthcare worker acquired the symptoms of itching. This atypical presentation of Norwegian scabies emphasizes the need to include scabies in the differential diagnosis when HIV-infected patients present with crusted, generalized cutaneous lesions.


Evidence against a synergistic effect of desmopressin with conditioning in the treatment of nocturnal enuresis.
To test the hypothesis that desmopressin facilitates acquisition of continence, we aimed to establish whether, in children with nocturnal enuresis who are desmopressin nonresponders, adjunct desmopressin increases the rate of sustained continence after treatment with a conditioning alarm. Study design Patients with nocturnal enuresis (n=358; age range, 6-16 years) completed a 4-week "run-in" course of intranasal desmopressin (20-40 microg). Of these, 207 defined as nonresponders (<50% reduction in wet nights) were randomly assigned to receive either desmopressin (n=101) or placebo (n=106) nasal spray, together with conditioning alarm therapy for 8 weeks. Principal outcome measures were remission (28 continuous dry nights) and relapse (>2 wet nights in 2 weeks after having achieved remission). Remission rates were similar in both groups (51.5% desmopressin, 48.1% placebo; 95% CI on difference, -10%, 17%; P=.63), and relapse rates were not significantly different (13.5% vs 5.9%; 95% CI on difference, -3.7%, 19%; P=.19). Although remission rates were similar, children treated with desmopressin had significantly more dry nights during treatment than those in the placebo group. Desmopressin did not act synergistically with alarm treatment to achieve remission. Therefore, we infer that in partial or nonresponders, desmopressin does not enhance learning.


Rare Helicobacter pylori Virulence Genotypes in Bhutan.
Both the prevalence of Helicobacter pylori infection and the incidence of gastric cancer are high in Bhutan. The high incidence of atrophic gastritis and gastric cancer suggest the phylogeographic origin of an infection with a more virulent strain of H. pylori. More than 90% of Bhutanese strains possessed the highly virulent East Asian-type CagA and all strains had the most virulent type of vacA (s1 type). More than half also had multiple repeats in East Asian-type CagA, which are rare in other countries and are reported characteristictly found in assciation with atrophic gastritis and gastric cancer consistent with Bhutanese strains having multiple H. pylori virulence factors associated with an increase in gastric cancer risk. Phylogeographic analyses showed that most Bhutanese strains belonged to the East Asian population type with some strains (17.5%) sharing East Asian and Amerindian components. Only 9.5% belonged to the European type consistant with H. pylori in Bhutan representing an intermediate evolutionary stage between H. pylori from European and East Asian countries.


Ischemic stroke and purpuric dermatitis as COVID-19-related complications in a peritoneal dialysis patient.
Patients on dialysis may have an elevated risk of severe coronavirus disease 2019 (COVID-19) and its complications due to their high prevalence of comorbidities. Here we describe the case of an 80-year-old male undergoing peritoneal dialysis with a moderate SARS-CoV-2 infection who developed a purpuric dermatitis and ischemic stroke after successful recovery from his bilateral pneumonia. Erythemato-papular lesions affecting trunk and lower limbs appeared 17 days after the onset of SARS-CoV-2 symptoms. These kind of lesions are an infrequent cutaneous manifestation of COVID-19. The pathology revealed a moderate purpuric dermatitis affecting superficial dermis and corticoesteroids were prescribed achieving complete resolution. Arterial thrombosis affecting cerebellar vermis emerged 30 days after the onset of COVID-19 symptoms. It occurred 5 days after withdrawal of antithrombotic prophylaxis that the patient received from his admission until 2 weeks after discharge. He completely recovered from his paresis and continued on his regular antiaggregation therapy. This is the first case report published of a patient with PD with such COVID-19-related complications. More experience is needed to determine the appropriate length of antithrombotic prophylaxis especially in high-risk individuals.


Stereotactic laser ablation of the splenium for intractable epilepsy.
Partial or complete corpus callosotomies have been applied, traditionally via open surgical or radiosurgical approaches, for the treatment of epilepsy in patients with multifocal tonic, atonic, or myoclonic seizures. Minimally invasive methods, such as MRI-guided laser interstitial thermal ablation (MTLA), are being employed to functionally remove or ablate seizure foci in the treatment of epilepsy. This therapy can achieve effectiveness similar to that of traditional resection, but with reduced morbidity compared with open surgery. Here, we present a patient with a history of prior partial corpus callosotomy who continued to suffer from medically refractory epilepsy with bisynchronous onset. We report on the utilization of laser ablation of the splenium in this patient to achieve full corpus callosotomy. Adequate ablation of the splenial remnant was confirmed by postoperative MRI imaging, and at four-month follow-up, the patient's seizure frequency had dropped more than 50%. This is the first reported instance of laser ablation of the splenium to achieve full corpus callosotomy following a previous unsuccessful anterior callosotomy in a patient with intractable generalized epilepsy.


Brain Region Size Differences Associated With Dystonia in People With Cerebral Palsy Born Premature.
Dystonia in cerebral palsy (CP) is classically associated with deep gray matter injury at term gestation, but the patterns of injury associated with dystonia following premature birth are unclear. We examined whether there were brain regional size differences associated with dystonia in people with CP born premature. In this retrospective cohort study, we identified subjects with CP born premature (<37 weeks gestational age) seen at a tertiary care CP center between February 1, 2017, to February 1, 2021, who had T1-weighted brain magnetic resonance imaging (MRI) done between ages one and five years available in the clinical record. We measured the following on these brain MRI images per the 2013 Kidokoro criteria: interhemispheric distance, biparietal width, lateral ventricle diameter, transcerebellar diameter, deep gray matter area, and corpus callosum thickness. We then compared the sizes of these structures between those with and without dystonia correcting for gestational age at birth and gross motor functional ability (univariate general linear models). Fifty-five subjects met the inclusion and exclusion criteria. Interhemispheric distance was significantly greater in those with dystonia, suggesting decreased cortical volume (P = 0.005). There was no significant difference in the other measured structures between those with and without dystonia, including deep gray matter area. Increased interhemispheric distance, not measures of deep gray matter size, correlate with the presence of dystonia in people with CP born premature.


Periodontal disease and risk of preeclampsia: a meta-analysis of observational studies.
Many epidemiological studies have found a positive association between periodontal disease (PD) and the risk of preeclampsia, but the magnitude of this association varies and independent studies have reported conflicting findings. We performed a meta-analysis to ascertain the relationship between PD and preeclampsia. The PubMed database was searched up to January 12, 2013, for relevant observational studies on an association between PD and the risk of preeclampsia. Data were extracted and analyzed independently by two authors. The meta-analysis was performed using comprehensive meta-analysis software. Thirteen observational case-control studies and two cohort studies, involving 1089 preeclampsia patients, were identified. Based on a random-effects meta-analysis, a significant association between PD and preeclampsia was identified (odds ratio = 2.79, 95% confidence interval CI, 2.01-3.01, P<0.0001). Although the causality remains unclear, the association between PD and preeclampsia may reflect the induction of PD by the preeclamptic state, or it may be part of an overall exaggerated inflammatory response to pregnancy. Larger randomized controlled trials with preeclampsia as the primary outcome and pathophysiological studies are required to explore causality and to dissect the biological mechanisms involved.


Denitrifier Method for Nitrite Removal in Electrochemical Analysis of the Electron Accepting Capacity of Humic Substances.
Humic substances (HSs) are important electron acceptors and donors in soils and aquifers. The coupling of anoxic nitrogen (N) cycling to the function of HSs as a redox battery, however, remains poorly understood. Mediated electrochemical analysis is an emerging tool to determine the redox properties (i.e., electron donating capacity (EDC), electron accepting capacity (EAC), and redox state) of HS. However, the presence of nitrite (NO2-), a central intermediate of the N-cycle, interferes with the electrochemical determination of the EAC. To eliminate this interference, we developed a bioassay to remove nitrite in HS samples using the denitrifying bacterium Pseudomonas nitroreducens. Cell suspensions of P. nitroreducens completely removed NO2- at various concentrations (1, 2, and 5 mM) from humic acid samples (1 g HA/L) of different redox states. As P. nitroreducens is not able to exchange electrons with dissolved humic acids, the procedure allows an accurate and reliable determination of the EAC of humic acid samples. The proposed method thus opens new perspectives in biogeochemistry to study interactions between HSs and N cycling.


Metabolism of leukotriene D by porcine kidney.
An enzyme from porcine kidney converted leukotriene D4 into a less polar metabolite. The structure of this compound was 5-hydroxy-6-S-cysteinyl-7,9-trans-11,14-cis-eicosatetraenoic acid (leukotriene E4). Analogous products, viz. 5-hydroxy-6-S-cysteinyl-7,9,11-eicosatrienoic acid (leukotriene E3), 5-hydroxy-6-S-cysteinyl-7,9,11-trans-14-cis-eicosatetraenoic acid (11-trans-leukotriene E4), and 5-hydroxy-6-S-cysteinyl-7,9,11,14,17-eicosapentaenoic acid (leukotriene E5) were formed from leukotrienes D3, 11-trans-D4, and D5, respectively. Leukotriene E4 induced slow reacting substance-like contractions of guinea pig ileum but was less potent (8-12 times) than leukotriene C4. The biological potency of 11-trans-leukotriene E4 was similar to that of leukotriene E4.


Duodenal dislodgement of an ingested sharp foreign body by mucosal unfolding "Gilan maneuver"; A novel surgical approach.
Foreign body (FB) ingestion is a common challenge for pediatric health care providers globally. Although endoscopic approach for FB extraction is recommended, surgery remains life giving specifically in developing countries. We presented a novel surgical approach called 'Gilan maneuver' for removal of FB which lodged in duodenal loop. An eighteen months old male infant referred to emergency department while he lied on his mother's arm. Parents stated their son has ingested a sharp metallic pointy thick needle which applies for cattle injection. On examination mid epigastric tenderness was remarkable. Laboratory finding was normal. Plain thoracoabdominal radiologic study confirmed the diagnosis. Patient underwent explorative laparotomy and the needle was removed through 'Gilan maneuver' in which mucosal unfolding of duodenal loop facilitated dislodgement of the FB and it was extracted on the jujenal side. Duodenal lodge of sharp FB is rare and could be masked by gastric deposition diagnosis. Mucosal folding, narrow luminal diameter, retroperitoneal adherence, and hard surgical anatomy of the duodenal loop make both sharp and large FBs spontaneous dislodgement and favorable surgical outcome relatively unanticipated. Despite rarity of duodenal deposition of FB it is possible and could be harmful due to adjacent unforgiving organs. Although endoscopic extraction of FB is generally recommended in guidelines, surgical approach is safe and could be considered.


The Serum Level of CXCL9, CXCL10, and CXCL11 and the Expression of CXCR3 of Peripheral Blood Mononuclear Cells in Brucellosis Patients.
Brucella spp. can replicate in human endothelial cells, inducing an inflammatory response with increased expression of chemokines. Although Brucella infects humans, its ability to induce the production of chemokines by lung cells is unknown. Therefore, the current investigation was designed to examine the association between brucellosis and CXCL9, 10, and 11 chemokines. The patient group included 71 patients suffering from Brucella infection and the control group consisted of 50 healthy ranchers from the same geographical area. Serum levels of CXCL9, CXCL10, and CXCL11 were analyzed by ELISA. The fold changes of CXCR3 expression against β-actin were determined by real-time-PCR technique. Western blotting analysis was also applied for evaluating the expression of CXCR3 at protein level. The results of this study showed that the serum levels of CXCL9, CXCL10, and CXCL11 are significantly increased in acute brucellosis patients in comparison to control as indicated by ELISA test, mRNA levels of CXCR3 by Real-time PCR as well as protein levels of CXCR3 by Western blot analysis. According to findings, these chemokines have the potential to serve as markers for brucellosis patients. Taken together, cytokine/chemokine network was active in acute brucellosis patients, and it is suggested to evaluate other cytokines in future studies.


EPR spectroscopy of the iron-sulphur cluster and sirohaem in the dissimilatory sulphite reductase (desulphoviridin) from Desulphovibrio gigas.
Desulphoviridin in the oxidized state showed EPR signals around g = 6, consistent with the sirohaem being in the high-spin ferric state. This was unreactive with sulphite, sulphide or cyanide; but readily reduced by methyl viologen. When the enzyme was treated with Na2S2O4 the sirohaem was slowly reduced and a spectrum of a reduced iron-sulphur cluster at g = 2.07, 1.93, 1.91 appeared over the course of an hour. An intermediate in this reaction was indicated by a free radical signal which appeared within seconds and then gradually disappeared. On treatment with nitrite and reduced methyl viologen, the enzyme gave a spectrum of a nitroxide derivative similar to that seen with plant nitrite reductase. The midpoint reduction potential of the haem was estimated to be -310 mV or less. The iron-sulphur cluster has a very low potential, being only reduced in the presence of free Na2S2O4 around -560 mV. Desulphoviridin can be classed with sirohaem-containing iron-sulphur proteins.


Hearing thresholds in newborns with a cleft palate assessed by auditory brain stem response.
To objectively estimate the extent of hearing loss in infants with cleft palate and to measure the incidence of hearing loss. Retrospective consecutive case note review. Tertiary institutional regional referral center for cleft lip and palate. Consecutive cases of 90 infants with cleft palate who underwent auditory brain stem response (ABR) threshold estimation. ABR threshold estimation during natural sleep in infants with cleft palate under 2 months of age. Hearing level thresholds as estimated by auditory brain stem response and categorized as normal (< 25 < or = 35 dB nHL) , mild (> 35 < or = 45 dB nHL), moderate (> 45 < or = 65 dB nHL), severe (> 65 < or = 90 dB nHL), and profound (> 90 dB nHL) hearing loss. Hearing loss was present in 82% of the infants tested. Most of the hearing loss was conductive (89%), mild (86%), and bilateral (84%). Average age of ABR threshold estimation was 48.5 days. In 22% of infants there was an associated syndrome. The mean air conduction thresholds for the right and left ear were 40 and 39.7, respectively. The incidence of hearing loss in a cohort of cleft palate infants has been objectively estimated by auditory brain stem response thresholds and was found to be very high (82%).


Induced homotypic collateral sprouting of serotonergic fibers in the hippocampus of rat.
The organization of the raphe cells efferent to the dorsal hippocampus (DHipp) has been shown to consist of two homologous groups of cells in the median raphe nucleus (MRN). Their axons project by way of the cingulum bundle (CB) and the fornix-fimbria (FF)58. A group of neurons located in the interfascicular part of the dorsal raphe nucleus (IFN) was found to use the CB route exclusively. Quantitation of the HRP-labeled cells in the MRN neurons projecting to the DHipp decreased by 55% and 92% 3 days following CB and CB-FF 5,7-DHT injections respectively. There was a significant increase in HRP-labeled neurons in the MRN at 21 and 42 days compared to 3 days after CB injection (a 2% decrease at 21 days and 38% increase at 42 days compared to sham injected). No change in the number of labeled MRN cells was seen at these long-term time points after combined CB-FF 5,7-DHT microinjections. The labeled cells in the MRN increased in size in the long survival group of CB lesioned animals. The labeled cells localized in the IFN which were lost after CB 5,7-DHT injections did not reappear after long-term survival. These results indicate that CB 5-HT fibers do not regenerate into the DHipp, but FF 5-HT fibers increase their terminal territory by collateral sprouting in response to homotypic denervation.


Modulation of flash stimulation intensity and frequency: effects on visual evoked potentials and oscillatory potentials recorded in awake, freely moving mice.
Visual evoked potentials (VEP) responses to flash stimulation at nine intensities, from 0.611 to 945.6 cd/m(2)*s, and two frequencies (0.2 and 1 Hz) were recorded and oscillatory potentials (OPs) extracted after digital 50-Hz high pass filtering in unanaesthetized unrestrained mice. Both VEP and OPs morphology were replicable for all conditions and were similar to values reported in the literature. In particular OPs spectral analysis showed that the main frequency component remained stable at 66-77 Hz, for both stimulation frequencies, although it displayed an increase in amplitude, as a function of stimulus intensity. OPs amplitude at 1 Hz versus 0.2 Hz stimulus frequency was higher after taking into account the different noise contributions in the two conditions. Root mean square values calculated at selected time windows, revealed that, at 1 Hz, the main contribution to OPs occurs at the onset of the response (14-27 ms) while, at 0.2 Hz, the higher RMS was recorded later (42-56 ms). This difference accounts for the longer duration of the oscillatory event in the 0.2-Hz condition and suggests that oscillatory activity, modulated and carried along the visual pathway, is recorded at the cortical electrode after further elaboration at the cortical/subcortical level, depending on stimulus properties.


Escherichia coli isocitrate lyase: properties and comparisons.
The glyoxylate cycle was first discovered during studies on bacteria and fungi with the ability to grow on acetate or ethanol as the sole carbon source. Isocitrate lyase, the first enzyme unique to the glyoxylate cycle, has been studied in numerous prokaryotic and eukaryotic organisms. However, information on this enzyme from Escherichia coli is limited. We have recently reported the purification and in vitro phosphorylation of this enzyme. In the present study we have examined and characterized a variety of inhibitors, the divalent cation requirement and the amino acid composition of E. coli isocitrate lyase and compared these results to those obtained with other organisms.


Myohemerythrin from the sipunculid, Phascolopsis gouldii: purification, properties and amino acid sequence.
Two previously unknown isoforms, labelled iso I and iso II, of the oxygen-carrying protein, myohemerythrin, have been isolated from carcasses of the sipunculid worm, Phascolopsis gouldii. The two isoforms have non-identical N-terminal amino acid sequences and slightly different absorption spectra in the met form. Far-ultraviolet circular dichroism shows that iso I contains approximately 69% alpha-helix. The complete amino acid sequence for iso I was obtained. The molecular weight calculated from this amino acid sequence and including the active site Fe-O-Fe unit, is 13,829. All of the physical and chemical properties of iso I noted above, including the amino acid sequence, are very similar to those of T. zostericola myohemerythrin. Except for the amino acid sequence, these properties are also very similar to that of a subunit in hemerythrin, the octameric analog found in hemerythrocytes. Only 58 of the 113 residues in P. gouldii hemerythrin are conserved in iso I. Sequence comparisons were used to help identify residues responsible for maintaining the common tertiary and diiron site structures in hemerythrin and myohemerythrin. The seven iron ligand residues previously identified in crystal structures of hemerythrin and myohemerythrin are conserved in iso I. However, none of the ten residue pairs previously identified as engaging in direct salt-bridge or hydrogen bond interactions between subunits in the hemerythrin octamer are conserved in iso I.


Comparative in vitro activities of AC98-6446, a novel semisynthetic glycopeptide derivative of the natural product mannopeptimycin alpha, and other antimicrobial agents against gram-positive clinical isolates.
AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin alpha (AC98-1). In the present study the activity of AC98-6446 was evaluated against a variety of recent clinical gram-positive pathogens including multiply resistant strains. AC98-6446 demonstrated similar potent activities against methicillin-susceptible and methicillin-resistant staphylococci and glycopeptide-intermediate staphylococcal isolates (MICs at which 90% of isolates are inhibited [MIC(90)s], 0.03 to 0.06 microg/ml). AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC(90)s, 0.12 and 0.25 microg/ml, respectively) as well as against streptococcal strains (MIC(90)s, <or= 0.008 to 0.03 microg/ml). AC98-6446 demonstrated bactericidal activity in terms of the reduction in the viable counts (>3 log(10) CFU/ml) of staphylococcal and streptococcal isolates and a marked decrease in the viable counts of most enterococcal strains (from 0.2 to 2.5 log(10) CFU/ml). Unlike vancomycin, which demonstrates time-dependent killing, AC98-6446 demonstrated concentration-dependent killing. The potent activity, novel structure, and bactericidal activity demonstrated by AC98-6446 make it an attractive candidate for further development.


Release of norepinephrine from brain vesicular preparations: effects of an adenylate cyclase activator, forskolin, and a phosphodiesterase inhibitor.
1. The calcium-dependent K+-evoked release of [3H]norepinephrine from guinea pig cerebral cortical vesicular preparations is inhibited by norepinephrine, clonidine, and epinephrine. Isoproterenol has no effect and phentolamine prevents the inhibition by norepinephrine. The results indicate that an alpha-adrenergic receptor mediates an inhibitory input to the calcium-dependent release process. The inhibition by norepinephrine is prevented by high concentrations (3.0 mM) of calcium ions. 2. A cyclic AMP phosphodiesterase inhibitor, ZK 62771, slightly elevates [3H]cyclic AMP levels in the guinea pig cerebral cortical preparation and potentiates the marked elevation of [3H]cyclic AMP elicited by the adenylate cyclase activator, forskolin. 3. Neither ZK 62771 nor forskolin alone has significant effects on K+-evoked release of [3H]norepinephrine from the cerebral cortical vesicular preparation; however, a combination of ZK 62771 and forskolin inhibits K+-evoked release by as much as 60%. The inhibition is reversed by high concentrations (2.0 mM) of calcium ions. The results suggest that a marked accumulation of cyclic AMP elicited via both activation of adenylate cyclase and inhibition of phosphodiesterase can be inhibitory to neurotransmitter release from central synaptic terminals.


Clonidine intensifies memantine cutaneous analgesia in response to local skin noxious pinprick in the rat.
The purposes of this study were to evaluate the co-administration of clonidine with memantine and to determine whether it has a peripheral action in intensifying cutaneous analgesia. Cutaneous analgesia was examined through inhibition of the cutaneous trunci muscle reflex in response to the local noxious pinprick in rats. Effect of the added subcutaneous clonidine to memantine on infiltrative cutaneous analgesia was assessed and compared with the local anesthetic lidocaine. On the 50% effective dose (ED50) basis, the rank of drug potency was memantine [4.05 (3.95-4.18) μmol]>lidocaine [5.81 (5.70-5.98) μmol] (p<0.01). Clonidine at a dose of 0.12 μmol did not elicit cutaneous analgesia. Mixtures of clonidine (0.12 μmol) with drug (memantine or lidocaine) at ED50 or ED95 prolonged the duration of action and enhanced the potency as infiltrative cutaneous analgesia. Clonidine enhanced the lidocaine cutaneous analgesia in which had a better effect than added to memantine. Our resulting data showed that memantine displayed more potent cutaneous analgesia than lidocaine. Co-administration of memantine or lidocaine with clonidine increased the potency and duration of the cutaneous analgesia. Clonidine intensified the effects of lidocaine promoting cutaneous analgesia than added to memantine.


[Between research and genocide. The Nuremberg physician trials 1946/47: Raphael Lemkins point of view on human experimentation and genocide].
While the significance of the new concept of genocide, as introduced by the Polish émigré jurist Raphael Lemkin, has been recognised, its importance for the Nuremberg Medical Trial has been overlooked. Lemkin commented extensively on the Trial, and his views are presented here. These comments help illuminate a neglected facet of the Trial, that of eugenics and racial extermination, taken at the time as amounting to genocide. Far from neglecting eugenics as some have suggested, the eugenic component of the Trial was extensive.


Liver involvement in alpha1-antitrypsin-deficient phenotypes PiSZ and PiMZ.
The long-term outcome of 3 PiSZ and 57 PiMZ children affected by alpha1-antitrypsin deficiency-associated liver involvement during infancy was assessed. At 5 and 10 y of age all PiSZ and PiMZ children exhibited normal levels of liver enzymes. All families, except one, were deterred from smoking following counselling. Transient liver involvement observed during early infancy is likely to be a benign self-limiting process.


Therapeutic mild hypothermia improves early outcomes in rabbits subjected to traumatic uncontrolled hemorrhagic shock.
Survival benefits of mild hypothermia in animals suffering from uncontrolled hemorrhagic shock (HS) may be influenced by trauma severity. We hypothesized that mild hypothermia would improve early outcomes based on our rabbit model of severe traumatic HS. Fifty male New Zealand rabbits weighing between 1.6 and 2.2 kg were randomized into one of the five groups: group 1 (sham), group 2 (37°C/80 mm Hg), group 3 (37°C/40 mm Hg), group 4 (34°C/80 mm Hg), and group 5 (34°C/40 mm Hg). Under urethane anesthesia, animals that suffered fractures and uncontrolled HS received prehospital fluid resuscitation (aggressive or limited) with temperature controlled at normothermia or mild hypothermia, hemostasis, and hospital resuscitation followed by observation. Mild hypothermia significantly improved cardiac systolic function and decreased lung wet-to-dry weight ratios and total injury score compared with normothermia. Group 5 manifested the best results in lung injury. The decreased base excess and pH and increased lactate levels during HS and limited fluid resuscitation were not exacerbated by mild hypothermia. Electrolytes including potassium and calcium and blood glucose levels as well as coagulation were not significantly influenced after mild hypothermia treatment. Seven-hour survival in the hypothermic groups was higher than that in the normothermic groups, although there was no significant difference in survival between groups 5 and 3. Therapeutic mild hypothermia improves early outcomes through improving lung and cardiac performance without causing evident homeostasis disturbances in the rabbit model of traumatic uncontrolled HS. Animals may benefit most under the combination treatment with mild hypothermia and limited fluid resuscitation.


Technological advances shed light on left ventricular cardiac disturbances in cystic fibrosis.
Cystic fibrosis (CF), the most common autosomal recessive lethal disease in Caucasians, causes chronic pulmonary disease and can lead to cor pulmonale with right ventricular dysfunction. The presence of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiac myocardia has prompted debate regarding possible defective ion channel-induced cardiomyopathy. Clinical heart disease in CF is considered rare and is restricted to case reports. It has been unclear if this is due to the lack of physiological importance of CFTR in the heart, the relatively short lifespan of those with CF, or a technical inability to detect subclinical disease. Extensive echocardiographic investigations have yielded contradictory results, leading to the dogma that left ventricular defects in CF occur secondary to lung disease. In this review, we consider why studies examining heart function in CF have not provided clarity on this topic. We then focus on data from new echocardiographic and magnetic resonance imaging technology, which are providing greater insight into cardiac function in CF and demonstrating that, in addition to secondary effects from pulmonary disease, there may be an intrinsic primary defect in the CF heart. With advancing lifespans and activity levels, understanding the risk of cardiac disease is vital to minimizing morbidity in adults with CF.


Delocalization Transition for Critical Erdős-Rényi Graphs.
We analyse the eigenvectors of the adjacency matrix of a critical Erdős-Rényi graph G ( N , d / N ) , where d is of order log N . We show that its spectrum splits into two phases: a delocalized phase in the middle of the spectrum, where the eigenvectors are completely delocalized, and a semilocalized phase near the edges of the spectrum, where the eigenvectors are essentially localized on a small number of vertices. In the semilocalized phase the mass of an eigenvector is concentrated in a small number of disjoint balls centred around resonant vertices, in each of which it is a radial exponentially decaying function. The transition between the phases is sharp and is manifested in a discontinuity in the localization exponent γ ( w ) of an eigenvector w , defined through ‖ w ‖ ∞ / ‖ w ‖ 2 = N - γ ( w ) . Our results remain valid throughout the optimal regime log N ≪ d ⩽ O ( log N ) .


Outcomes of cardiac resynchronization therapy in patients with intermittent atrial fibrillation or atrial flutter in the COMPANION trial.
Controlled clinical trial data are lacking for cardiac resynchronization therapy (CRT) outcomes in patients with advanced heart failure (HF) from reduced left ventricular ejection fraction (HFrEF) and intermittent atrial fibrillation or flutter (IAF/AFL). The purpose of this study was to describe CRT outcomes in patients with IAF/AFL and advanced HF. HF outcomes in patients in the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial with New York Heart Association class III or IV HFrEF, left ventricular ejection fraction ≤0.35, sinus rhythm at randomization, and no history of baseline arrhythmia were compared with those with a history of IAF/AFL. In those with no history of baseline arrhythmia (n = 887), compared with optimal pharmacological therapy (OPT) with no CRT, the CRT + OPT arms exhibited a significant reduction in the end points of death or any hospitalization (hazard ratio [HR] 0.73 [95% Confidence Interval (CI): 0.60 to 0.89]; P = .002) and death or HF hospitalization (HR 0.53 [95% CI: 0.41 to 0.68]; P < .001). In contrast, in the IAF/AFL subgroup (n = 293), CRT did not result in improved outcomes compared with OPT (death or any hospitalization: HR 1.16 [95% CI: 0.83 to 1.63]; P = .38; death or HF hospitalization: HR 0.97 [95% CI: 0.64 to 1.46]; P = .88). The interaction between history of AF/AFL and CRT was statistically significant for both outcomes (P < .05). In the COMPANION trial, patients with moderate to severe HFrEF and a history of IAF/AFL had no benefit from CRT.


The morphogenesis of the exstrophy-epispadias complex: a new concept based on observations made in early embryonic cases of cloacal exstrophy.
The term exstrophy-epispadias complex (EEC) has been coined for a group of congenital malformations that includes epispadias, bladder exstrophy and cloacal exstrophy. It is usually thought that these malformations develop against a similar embryological background. This background, however, is still obscure. This is mainly due to the lack of availability of abnormal human or non-human embryos showing the crucial developmental steps in the morphogenesis of EEC malformations. In this paper, we present chick embryos that show cloacal exstrophy at early developmental stages. To the best of our knowledge, this is the first documentation of this rare malformation in young embryos. Embryos with cloacal exstrophy (n=4) were found among embryos from two experimental series (n=50) that were primarily performed to document the early morphogenesis of facial and cardiovascular malformations. The malformations were induced by the administration of suramin according to established protocols. Suramin can induce a spectrum of malformations including facial clefts, heart defects, and cloacal exstrophy. Besides the presence of an abnormal opening into the cloaca, all embryos were characterised by an abnormal broadening of the caudal trunk at the level of the leg buds, which, in the youngest embryos, was associated with the abnormal presence of large aneurysmatic swellings of the dorsal aortae at this side. We postulate that these aneurysmatic swellings might be the primary defects leading to the development of EEC malformations. These space-occupying anomalies seem to cause abnormal distensions of the developing pelvis and of the infra-umbilical portion of the developing body wall. In consequence, the mid-portion of the developing ventral body wall between the origin of the umbilical cord and the cloacal plate becomes stretched and thinned out. Tension and thinning of the ventral body wall might ultimately lead to its rupture with exposure of the lumen of the embryonic cloaca and allantois. This new concept on the morphogenesis of the EEC is the first not to be inferred from the conditions seen in fetal or postnatal human cases but is based entirely on data from malformed embryos.


C/N-Dependent Element Bioconversion Efficiency and Antimicrobial Protein Expression in Food Waste Treatment by Black Soldier Fly Larvae.
The black soldier fly (BSF), Hermetia illucens, has emerged as a promising species for waste bioconversion and source of antimicrobial proteins (AMPs). However, there is a scarcity of research on the element transformation efficiency and molecular characterization of AMPs derived from waste management. Here, food waste treatment was performed using BSF larvae (BSFL) in a C/N ratio of 21:1−10:1, with a focus on the C/N-dependent element bioconversion, AMP antimicrobial activity, and transcriptome profiling. The C-larvae transformation rates were found to be similar among C/Ns (27.0−35.5%, p = 0.109), while the N-larvae rates were different (p = 0.001), with C/N 21:1−16:1 (63.5−75.0%) being higher than C/N 14:1−10:1 (35.0−45.7%). The C/N ratio did not alter the antimicrobial spectrum of AMPs, but did affect the activities, with C/N 21:1 being significantly lower than C/N 18:1−10:1. The lysozyme genes were found to be significantly more highly expressed than the cecropin, defensin, and attacin genes in the AMP gene family. Out of 51 lysozyme genes, C/N 18:1 and C/N 16:1 up-regulated (p < 0.05) 14 and 12 genes compared with C/N 21:1, respectively, corresponding to the higher activity of AMPs. Overall, the element bioconversion efficiency and AMP expression can be enhanced through C/N ratio manipulation, and the C/N-dependent transcriptome regulation is the driving force of the AMP difference.


Clinical predictors of posttraumatic stress disorder after closed head injury in children.
To describe injury, demographic, and neuropsychiatric characteristics of children who develop posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) after closed head injury (CHI). Ninety-five children with severe CHI and amnesia for the event were prospectively followed for 1 year. Structured interviews were administered twice to the parents: shortly after injury to cover the child's premorbid status, and 1 year after injury. The child was also interviewed twice: shortly after injury to cover current status, and 1 year after injury. Outcome measures were diagnostic status (PTSD by parent or child) and symptom severity (PTSS by parent or child). Twelve children developed PTSD by 1 year after injury, 5 according to parent report, 5 according to child report, and 2 according to both parent and child report. Predictors of PTSD at 1 year post-CHI included female gender and early post-CHI anxiety symptoms. Predictors of PTSS at 1 year post-CHI were (1) premorbid psychosocial adversity, premorbid anxiety symptoms, and injury severity; and (2) early post-CHI depression symptoms and nonanxiety psychiatric diagnoses. PTSD developed in 13% of children with severe CHI accompanied by traumatic amnesia. Predictors of PTSD and PTSS after CHI, according to parent and child report, are consistent with predictors of PTSD and PTSS that develop after non-head injury trauma.


Whole-genome analysis of monozygotic Brazilian twins discordant for type 1 narcolepsy: a case report.
Narcolepsy type 1 (NT1) is a rare and chronic neurological disease characterized by sudden sleep attacks, overwhelming daytime drowsiness, and cataplexy. When associated with a sudden loss of muscle tone (cataplexy) narcolepsy is classified as type 1, while the absence of cataplexy indicates type 2. Genetic, degenerative, and immunological hypotheses to explain the pathophysiology of NT1 are still a matter of debate. To contribute to the understanding of NT1 genetic basis, here we describe, for the first time, a whole genome analysis of a monozygotic twin pair discordant for NT1. We present the case of a pair of 17-year-old male, monozygotic twins discordant for NT1. The affected twin had Epworth Sleepiness Scale (ESS) of 20 (can range from 0 to 24), cataplexy, hypnagogic hallucinations, polysomnography without abnormalities, multiple sleep latency tests (MSLT) positive for narcolepsy, a mean sleep latency of 3 min, sleep-onset REM periods SOREMPs of 5, presence of allele HLA-DQB1*06:02, and Hypocretin-1 level of zero pg/mL (normal values are > 200 pg/mL). The other twin had no narcolepsy symptoms (ESS of 4), normal polysomnography, MSLT without abnormalities, presence of allele HLA-DQB1*06:02, and Hypocretin-1 level of 396,74 pg/mL. To describe the genetic background for the NT1 discordant manifestations in this case, we present the whole-genome analysis of this monozygotic twin pair. The whole-genome comparison revealed that both twins have identical NT1 pathogenic mutations in known genes, such as HLA-DQB1*06:02:01, HLA-DRB1*11:01:02/*15:03:01. The affected twin has the expected clinical manifestation while the unaffected twin has an unexpected phenotype. The unaffected twin has significantly more frameshift mutations as compared to the affected twin (108 versus 75) and mutations that affect stop codons (61 versus 5 in stop gain, 26 versus 2 in start lost). The differences observed in frameshift and stop codon mutations in the unaffected twin are consistent with loss-of-function effects and protective alleles, that are almost always associated with loss-of-function rare alleles. Also, overrepresentation analysis of genes containing variants with potential clinical relevance in the unaffected twin shows that most mutations are in genes related to immune regulation function, Golgi apparatus, MHC, and olfactory receptor. These observations support the hypothesis that NT1 has an immunological basis although protective mutations in non-HLA alleles might interfere with the expression of the NT1 phenotype and consequently, with the clinical manifestation of the disease.


Predictive role of vitamin A serum concentration in psoriatic patients treated with IL-17 inhibitors to prevent skin and systemic fungal infections.
The use of biological drugs in psoriasis is replacing traditional therapies due to their specific mechanism and limited side effects. However, the use of Interleukin 17 inhibitors and the modification of its cytokine pathway could favor the risk of fungal infections. All-trans retinoic acid is an active metabolite of vitamin A with anti-inflammatory and immunoregulatory properties through its capacity to stimulate both innate and adaptive immunity and to its effects on proliferation, differentiation and apoptosis in a variety of immune cells. Furthermore, it has been recently discovered that All-trans retinoic acid has a direct fungistatic effect against Candida and Aspergillus Fumigatus. On the basis of these new insights, in the current review, we suggest that the evaluation of serum level of All-trans retinoic acid or vitamin A should be considered as a predictive marker for the development of fungal infections among psoriatic patients treated with Interleukin 17 inhibitors. In clinical practice, vitamin A test could be added in the routine hospital diagnostic management for a better selection of psoriatic patients eligible to Interleukin 17 inhibitors.


Molecular identification of non-tuberculous mycobacterial species isolated from extrapulmonary samples using real-time PCR and rpoB sequence analysis.
Tuberculosis (TB) is one of the leading causes of mortality among infectious diseases and accounts for a serious health hazard wordwide. Apart from TB, the members of non-tuberculous mycobacteria (NTM), which includes around 170 species, may also cause different diseases in humans. Therefore this study aimed to investigate the distribution of NTM strains isolated from extrapulmonary (EP) samples by Real-Time PCR and PCR-sequencing methods in Southwest Iran. Three hundred and twenty-five suspected EP samples were collected from patients referred to the referral hospitals in Ahvaz, Iran. The isolates were initially screened by acid fast staining and identified by phenotypic culture and biochemical tests. The Real-Time PCR and rpoB- based PCR methods were performed followed by sequence analysis of rpoB gene. From 124 samples, 77 (62%) were positive for NTM by culture and rpoB sequence analysis. M. fortuitum was the most commonly isolated NTM in present study. In Real-Time PCR, only 69 (55.64%) isolates showed more homology with standard NTM isolates. In general, the growing trend of EPNTM infections in Iran needs specific programs and resources to get a better diagnosis. PCR sequencing is a reliable method, it can be used for definitive identification of positive cultures for identification of NTM species.


Differential expression of single-cell RNA-seq data using Tweedie models.
The performance of computational methods and software to identify differentially expressed features in single-cell RNA-sequencing (scRNA-seq) has been shown to be influenced by several factors, including the choice of the normalization method used and the choice of the experimental platform (or library preparation protocol) to profile gene expression in individual cells. Currently, it is up to the practitioner to choose the most appropriate differential expression (DE) method out of over 100 DE tools available to date, each relying on their own assumptions to model scRNA-seq expression features. To model the technological variability in cross-platform scRNA-seq data, here we propose to use Tweedie generalized linear models that can flexibly capture a large dynamic range of observed scRNA-seq expression profiles across experimental platforms induced by platform- and gene-specific statistical properties such as heavy tails, sparsity, and gene expression distributions. We also propose a zero-inflated Tweedie model that allows zero probability mass to exceed a traditional Tweedie distribution to model zero-inflated scRNA-seq data with excessive zero counts. Using both synthetic and published plate- and droplet-based scRNA-seq datasets, we perform a systematic benchmark evaluation of more than 10 representative DE methods and demonstrate that our method (Tweedieverse) outperforms the state-of-the-art DE approaches across experimental platforms in terms of statistical power and false discovery rate control. Our open-source software (R/Bioconductor package) is available at https://github.com/himelmallick/Tweedieverse.


SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY FINDINGS OF COMMOTIO RETINAE WITH ASSOCIATED SEROUS RETINAL DETACHMENT.
To describe the appearance of a serous retinal detachment associated with commotio retinae on spectral domain optical coherence tomography. Case report. This case demonstrates the rare presentation of subretinal fluid in commotio retinae. Characteristic outer retinal changes associated with commotio retinae were also seen. Treatment was deferred and the subretinal fluid resolved within 1 week. Commotio retinae is rarely associated with a serous retinal detachment. This presentation is important to identify as it can avoid unnecessary workup and treatment.


Appendiceal inflammation affects the length of stay following appendicectomy amongst children: a myth or reality?
The effect of the severity of appendiceal inflammation on post-operative stay in children following appendicectomy has shown conflicting results. This study was conducted to determine the association between the severity of appendiceal inflammation and post-operative stay amongst children undergoing open appendicectomy. A retrospective cohort study was conducted at a District General Hospital for two years. A total of 204 patients were included in the study with an age range between 3 and 16 years. Females were 54.9% while the rest were male. Mean age was 12.5 ± 3 years. The association of the severity of appendiceal inflammation and post-operative stay was assessed by multivariable Cox Proportional hazards model. Mean post-operative stay was 2.32 days (95% CI 2.14-2.51). Macroscopically perforated appendix, histological inflammation and post-operative complications were significantly associated with post-operative stay on univariable analysis (P < 0.05). Whereas, the multivariable analysis showed that the post-operative stay was significantly prolonged only in case of either perforated appendix or post-operative complications while it remained unaffected by the histological inflammation.


Induction of meibocyte differentiation by three-dimensional, matrigel culture of immortalized human meibomian gland epithelial cells to form acinar organoids.
Recent studies have shown that two-dimensional (2D) culture of primary rabbit and immortalized human meibomian gland epithelial cells (iHMGEC) do not recapitulate normal meibocyte differentiation and fail to express critical enzymes necessary for synthesis of meibum lipids. The purpose of this study was to test the hypothesis that 3D-spheroid culture of iHMGEC can facilitate meibocyte differentiation and induce the expression of acyl-CoA wax-alcohol acyltransferase 2 (AWAT2), shown to be required for synthesis of meibum wax esters. iHMGEC were suspended in matrigel/basement membrane matrix and grown in proliferation media to form distinct cell clusters or spheroids. Cells were then treated with serum-free, differentiation media (advanced DMEM/F12) with and without FGF10 and synthetic agonists for the nuclear lipid receptor, peroxisome proliferator activator receptor gamma (PPARγ). Cells were then evaluated for differentiation markers using western blotting, immunocytochemistry (ICC) and real-time PCR. Control cells were grown in standard 2D culture systems. Under proliferative conditions, 3D culture induced the formation of KRT5+ spheroids that contained a Ki67+/P63+ undifferentiated, basal cell population. When spheroids were switched to differentiation media containing PPARγ agonists, two different organoid populations were detected, a KRT6low population that was AWAT2+/PPARγ+ and a KRT6high population that was AWAT2-/PPARγ-, suggesting that iHMGEC exhibit a dual differentiation potential toward either a ductal or meibocyte organoid phenotype. The 3D culturing of iHMGEC can induce the formation of both meibocyte and ductal organoids and may thus serve as a better in vitro model system for studying the regulatory mechanisms controlling meibomian gland function.


Retinal OCT speckle as a biomarker for glaucoma diagnosis and staging.
This paper presents a novel image analysis strategy that increases the potential of macular Optical Coherence Tomography (OCT) by using speckle features as biomarkers in different stages of glaucoma. A large pool of features (480) were computed for a subset of macular OCT volumes of the Leuven eye study cohort. The dataset contained 258 subjects that were divided into four groups based on their glaucoma severity: Healthy (56), Mild (94), Moderate (48), and Severe (60). The OCT speckle features were categorized as statistical properties, statistical distributions, contrast, spatial gray-level dependence matrices, and frequency domain features. The averaged thicknesses of ten retinal layers were also collected. Kruskal-Wallis H test and multivariable regression models were used to infer the most significant features related to glaucoma severity classification and to the correlation with visual field mean deviation. Four features were selected as being the most relevant: the ganglion cell layer (GCL) and the inner plexiform layer (IPL) thicknesses, and two OCT speckle features, the data skewness computed on the retinal nerve fiber layer (RNFL) and the scale parameter (a) of the generalized gamma distribution fitted to the GCL data. Based on a significance level of 0.05, the regression models revealed that RNFL skewness exhibited the highest significance among the features considered for glaucoma severity staging (p-values of 8.6×10-6 for the logistic model and 2.8×10-7 for the linear model). Furthermore, it demonstrated a strong negative correlation with the visual field mean deviation (ρ=-0.64). The post hoc analysis revealed that, when distinguishing healthy controls from glaucoma subjects, GCL thickness is the most relevant feature (p-value of 8.7×10-5). Conversely, when comparing the Mild versus Moderate stages of glaucoma, RNFL skewness emerged as the only feature exhibiting statistical significance (p-value = 0.001). This work shows that macular OCT speckle contains information that is currently not used in clinical practice, and not only complements structural measurements (thickness) but also has a potential for glaucoma staging.


Inhibition of influenza A virus replication by antagonism of a PI3K-AKT-mTOR pathway member identified by gene-trap insertional mutagenesis.
Host genes serving potential roles in virus replication may be exploited as novel antiviral targets. Small interfering RNA (siRNA)-mediated knockdown of host gene expression was used to validate candidate genes in screens against six unrelated viruses, most importantly influenza. A mouse model of influenza A virus infection was used to evaluate the efficacy of a candidate FDA-approved drug identified in the screening effort. Several genes in the PI3K-AKT-mTOR pathway were found to support broad-spectrum viral replication in vitro by RNA interference. This led to the discovery that everolimus, an mTOR inhibitor, showed in vitro antiviral activity against cowpox, dengue type 2, influenza A, rhino- and respiratory syncytial viruses. In a lethal mouse infection model of influenza A (H1N1 and H5N1) virus infection, everolimus treatment (1 mg/kg/day) significantly delayed death but could not prevent mortality. Fourteen days of treatment was more beneficial in delaying the time to death than treatment for seven days. Pathological findings in everolimus-treated mice showed reduced lung haemorrhage and lung weights in response to infection. These results provide proof of concept that cellular targets can be identified by gene knockout methods, and highlight the importance of the PI3K-AKT-mTOR pathway in supporting viral infections.


[In vitro study of the effects of pioglitazone on endothelial cell functions of human umbilical vein and the mechanisms involved].
To determine whether pioglitazone (PIO) has effects on human umbilical vein endothelial cells (HUVECs) in vitro and to clarify the possible mechanisms therein involved. The HUVECs were selected to be a model, which was cultured with 5.5 mmol/L glucose (control group), 30 mmol/L glucose (high glucose group), and 30 mmol/L glucose+PIO at 10(-9), 10(-7), 10(-5) mol/L respectively (PIO+high glucose groups). The effects of the drugs on the endothelial dysfunction induced by high glucose were studied. The role of protein kinase C (PKC) alpha and delta in the endothelial dysfunction induced by high glucose and the effects of PIO were assessed. The translocation of PKCdelta or PKCalpha in a single HUVEC was observed by Laser-Scanning Confocal Microscope, and the expression analysis was conducted quantificationally by Western blotting. High glucose could induce HUVECs apoptosis; the concentration of NO reduced and the level of sICAM-1 increased in high glucose group. PIO could inhibit the increasing apoptosis peaks induced by high glucose and could reverse the concentration of NO and sICAM-1 to normal level. PIO could inhibit the translocation of PKCa from plasm to nucleus in HUVECs induced by high glucose; it also could inhibit the translocation of PKCdelta from nucleus to plasm and membrane in HUVECs. PIO could inhibit the increasing expression of PKCdelta in HUVECs induced by high glucose. The expression level of PKCalpha in the high glucose group was not significantly different from that in the control. PIO could correct the endothelial cell dysfunction induced by high glucose, and this drug action of PIO may be effected via the inhibition of PKCalpha and PKCdelta.


Investigation of diabetic patient's fingernail quality to monitor type 2 diabetes induced tissue damage.
Long-term Type 2 Diabetes (T2D) affects the normal functioning of heart, kidneys, nerves, arteries, bones, and joints. The T2D gradually alters the intrinsic material properties, and structural integrity of the tissues and prolonged hyperglycemia causes chronic damages to these tissues quality. Clinically no such technique is available which can assess the altered tissues quality associated with T2D. In the present study, the microstructural characterization (surface morphology, surface roughness and density and calcium content), material characterization (modulus, hardness), and macromolecular characterization (disulfide bond content, protein content and its secondary structure) are investigated among healthy, diabetic controlled (DC) and uncontrolled diabetic (UC) group of fingernail plate. It is found that T2D has an adverse effect on the human fingernail plate quality. The parameters of nail plate quality are changing in a pattern among all the three groups. The properties mentioned above are degrading in DC group, but the degradation is even worst in the case of severity of T2D (UC group) as compared to the healthy group (Healthy<DC<UC). This study suggests that the fingernail plate quality has a potential to become a new avenue to assess the secondary diabetic complications, i.e. to assess the bone quality.


The Effective Management of Fever in Pediatrics and Insights on Remote Management: Experts' Consensus Using a Delphi Approach.
Even after the publication of the 2017 update of Italian guidelines on treatment of fever in pediatrics, some fundamental questions are still open and new ones emerged during the COVID-19 pandemic. To assess the level of consensus among Italian pediatricians on different topics related to treatment of fever in children by using the Delphi technique. A Delphi study was undertaken between June and September 2021, when two questionnaires were consecutively sent to a panel of experts to be answered anonymously. An invitation to participate was sent to 500 pediatricians distributed over the whole national territory and 80 (16%) of them accepted to participate on a voluntary basis. The questionnaires were structured into three specific topics: "therapeutic appropriateness and management of the febrile child," "management of the febrile child in the presence of other diseases," and "future perspectives in remote management." Each topic had six statements. A first-round questionnaire was sent to 80 accepting pediatricians from different Italian regions. Of the 72 respondents (23% working in hospitals and 72% outside), 33% were from northern, 12% central, and 55% southern Italy or islands. A second-round questionnaire was sent to the same 80 pediatricians and 69 of them responded, without significant differences for workplaces or geographical distribution as compared with the first questionnaire. Overall, 75 participants answered at least one of the two questionnaires. All the statements on the topics of "therapeutic appropriateness and management of the febrile child" and "future perspectives in remote management" reached the predefined cut off for consensus (75% or more). Only one statement on "management of the febrile child in the presence of other diseases" did not achieve the consensus even after the second round. Italian pediatricians agree on several aspects of treatment of febrile children and their expert opinions could support everyday decision process complementary to recommendations by regulatory agencies and guidelines.


Signatures of bosonic Landau levels in a finite-momentum superconductor.
Charged particles subjected to magnetic fields form Landau levels (LLs). Originally studied in the context of electrons in metals1, fermionic LLs continue to attract interest as hosts of exotic electronic phenomena2,3. Bosonic LLs are also expected to realize novel quantum phenomena4,5, but, apart from recent advances in synthetic systems6,7, they remain relatively unexplored. Cooper pairs in superconductors-composite bosons formed by electrons-represent a potential condensed-matter platform for bosonic LLs. Under certain conditions, an applied magnetic field is expected to stabilize an unusual superconductor with finite-momentum Cooper pairs8,9 and exert control over bosonic LLs10-13. Here we report thermodynamic signatures, observed by torque magnetometry, of bosonic LL transitions in the layered superconductor Ba6Nb11S28. By applying an in-plane magnetic field, we observe an abrupt, partial suppression of diamagnetism below the upper critical magnetic field, which is suggestive of an emergent phase within the superconducting state. With increasing out-of-plane magnetic field, we observe a series of sharp modulations in the upper critical magnetic field that are indicative of distinct vortex states and with a structure that agrees with predictions for Cooper pair LL transitions in a finite-momentum superconductor10-14. By applying Onsager's quantization rule15, we extract the momentum. Furthermore, study of the fermionic LLs shows evidence for a non-zero Berry phase. This suggests opportunities to study bosonic LLs, topological superconductivity, and their interplay via transport16, scattering17, scanning probe18 and exfoliation techniques19.


[Evaluation of the mutagenic activity of chemical substances in an in vitro human peripheral blood lymphocyte culture after their activation in the body of mammals].
To evaluate mutagenic activity of human metabolites a method is suggested for treating the culture of human lymphocytes with whole mammalian blood after their exposure to a chemical. This method was used to study the cytogenic activity of cyclophosphamide metabolites available in blood of CBA female mice after intraperitoneal injection of different doses of the chemical.


Feasibility of carotid artery stenting with double cerebral embolic protection in high-risk patients.
Previous trials comparing carotid artery stenting (CAS) with carotid endarterectomy have shown that the former can increase the stroke rate. However, in the last years, because of the improvements either of the technique or the improvement of the stents and embolic protection devices (EPD), CAS has become a very competitive procedure. In this study, we tried to assess the feasibility and the safety of using double EPD (proximal and distal) in high-risk patients. We collected data about all consecutive patients with carotid artery stenosis who underwent CAS and compared clinical and procedural characteristics as well as immediate and 30-day outcomes between the use of double vs. single EPD. Between November 2007 and August 2014, 294 patients underwent CAS. In 35 of them (11.9%) double EPD was used. In comparison with the patients treated with single EPD, those with double EPD presented more with acute carotid syndrome (recurrent TIAs < 48 hr, minor stroke < 14 days) and with complex plaque (79.4 vs. 33.6%, P < 0.0001). There was no difference between the 2 groups in primary success (100 vs. 99.6%, P = 0.16) and in 30-days major complications: death (0 vs. 0.8%, P = 0.6), major stroke (0 vs. 0.8%, P = 0.42), and minor stroke (0 vs 1.1%, P = 0.66). In our experience, in high-risk patients with high-risk lesions, the use of double EPD (proximal and distal) is safe and effective in minimizing the risk of cerebral embolization, but, to validate such a technique in wide range of patients, further studies are warranted.


Author Correction: The challenge of mapping the human connectome based on diffusion tractography.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


It's not just the animals that are STRANGE.
A "STRANGE" framework has been proposed to mitigate the effects of sampling biases in animal experiments (Webster & Rutz, Nature, 582, 337-340, 2020). While sampling biases are likely a major cause of poor replicability and generalizability in animal behavior research, a more comprehensive and cautious approach is needed to effectively guide decision-making in animal research.


Unexpectedly fast transfer of positron-emittable artificial substrate into N-terminus of peptide/protein mediated by wild-type L/F-tRNA-protein transferase.
This article demonstrates the fastest enzymatic introduction of a positron emission tomography (PET) probe into acceptor peptides/proteins. It is site-specifically introduced at the basic N-terminus of the acceptors by using L/F-transferase in combination with aminoacyl-tRNA synthetase, namely the NEXT-A/PET reaction. Estimated from kinetic analysis, the transfer efficiency of O-(2-fluoromethyl)-L-tyrosine as an artificial amino acid PET probe mediated by the wild-type transferase is almost as good as that of the natural substrate, phenylalanine.


Trends and comparison of female first authorship in high impact medical journals: observational study (1994-2014).
To examine changes in representation of women among first authors of original research published in high impact general medical journals from 1994 to 2014 and investigate differences between journals. Observational study. All original research articles published in Annals of Internal Medicine, Archives of Internal Medicine, The BMJ, JAMA, The Lancet, and the New England Journal of Medicine (NEJM) for one issue every alternate month from February 1994 to June 2014. Time and journal of publication. Prevalence of female first authorship and its adjusted association with time of publication and journal, assessed using a multivariable logistic regression model that accounted for number of authors, study type and specialty/topic, continent where the study was conducted, and the interactions between journal and time of publication, study type, and continent. Estimates from this model were used to calculate adjusted odds ratios against the mean across the six journals, with 95% confidence intervals and P values to describe the associations of interest. The gender of the first author was determined for 3758 of the 3860 articles considered; 1273 (34%) were women. After adjustment, female first authorship increased significantly from 27% in 1994 to 37% in 2014 (P<0.001). The NEJM seemed to follow a different pattern, with female first authorship decreasing; it also seemed to decline in recent years in The BMJ but started substantially higher (approximately 40%), and The BMJ had the highest total proportion of female first authors. Compared with the mean across all six journals, first authors were significantly less likely to be female in the NEJM (adjusted odds ratio 0.68, 95% confidence interval 0.53 to 0.89) and significantly more likely to be female in The BMJ (1.30, 1.01 to 1.66) over the study period. The representation of women among first authors of original research in high impact general medical journals was significantly higher in 2014 than 20 years ago, but it has plateaued in recent years and has declined in some journals. These results, along with the significant differences seen between journals, suggest that underrepresentation of research by women in high impact journals is still an important concern. The underlying causes need to be investigated to help to identify practices and strategies to increase women's influence on and contributions to the evidence that will determine future healthcare policies and standards of clinical practice.


Bilateral Blindness Following Chemoradiation for Locally Advanced Oropharyngeal Carcinoma.
Wernicke's encephalopathy is a life-threatening neurologic complication of thiamine deficiency. Though the presentation of symptoms can vary widely, the classical triad is founded on ophthalmoplegia, alteration of mental status, and gait disturbance. We describe a case of Wernicke's encephalopathy in an oncology patient shortly after concurrent 5-fluorouracil, carboplatin, and radiotherapy for locally advanced oropharyngeal cancer, presenting as complete bilateral blindness, ataxia, nystagmus, and confusion. Thiamine was given based on clinical suspicion and rapid improvement of clinical findings occurred. An MRI performed later supported the diagnosis of Wernicke's encephalopathy. A multifactorial etiology of thiamine deficiency from nutritional deficits and neurotoxic effects of chemotherapy are hypothesized.


First evidence for the existence of pennate diatom viruses.
Diatoms are considered the most successful and widespread group of photosynthetic eukaryotes. Their contribution to primary production is remarkably significant to the earth's ecosystems. Diatoms are composed of two orders: Centrales and Pennales. Thus far, viruses infecting centric diatom species have been isolated and characterized; however, viruses infecting pennates have not been reported. Here, we describe the first isolations and preliminary characterizations of two distinct pennate diatom viruses, AglaRNAV (31 nm in diameter, accumulates in the host cytoplasm) and TnitDNAV (35 nm in diameter, accumulates in the host nuclei) infecting Asterionellopsis glacialis and Thalassionema nitzschioides, respectively. Their genomes contain a single-stranded RNA of approximately 9.5 kb, and a closed, circular single-stranded DNA of approximately 5.5 kb harboring a partially double-stranded region, respectively. Further analysis of these viruses may elucidate many aspects of diatom host-virus relationships.


Resveratrol attenuates neuropathic pain through balancing pro-inflammatory and anti-inflammatory cytokines release in mice.
Anti-inflammatory activity of resveratrol has been widely studied, while its beneficial effect on the management of neuropathic pain, a refractory chronic syndrome with pro-inflammation implicated in, is very little investigated. In the present study, the effects of different doses and various time window of administration of resveratrol were explored in a neuropathic mouse model of chronic constriction injury (CCI) of the sciatic nerve. It was demonstrated that pretreatment of resveratrol (5, 10, 20 and 40 mg/kg) for 7 consecutive days before CCI did not alleviate neuropathic pain, while it clearly relieved the pain when administrated after CCI and such pain relief effect was more pronounced when administrated right after the peak of pain symptom at day 7 after CCI, as evidenced by the alleviation of thermal hyperalgesia and mechanical allodynia. Such a beneficial effect of resveratrol was in a dose-dependent manner. Mechanistic study showed that resveratrol repressed the expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, and promoted the expression of anti-inflammatory cytokine IL-10 at the same time, which was further confirmed in a cell model of microglia. It was also shown that neuropathic pain inversely correlated with pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, but not with anti-inflammatory cytokine IL-10 in all experimental mice from Spearman correlation coefficient. Our study reveals that resveratrol displays a significant neuropathic pain relief effect and paved a way for novel treatment of chronic pain.


Development of a polymerase chain reaction-restriction fragment length polymorphism assay for Leishmania major/Leishmania killicki/Leishmania infantum discrimination from clinical samples, application in a Tunisian focus.
Topoisomerase II gene of Leishmania genus was used to develop a molecular tool for detection and species differentiation of Leishmania from clinical samples. Identification was achieved by a polymerase chain reaction followed by digestion with 2 restriction endonucleases BstU1 and Taq1. Despite the relatively low sensitivity, it is able to differentiate between 3 complexes responsible for cutaneous leishmaniasis.