Serotoninergic mechanisms of beta-endorphin-induced hypothermia in rats.
The effects of intraventricular administration of beta-endorphin on thermoregulatory responses of unanesthetized rats to different ambient temperatures (Ta) of 8, 22 and 30 degrees C were assessed. Administration of beta-endorphin produced a fall in rectal temperature at both Ta 8 and 22 degrees C. The hypothermia in response to beta-endorphin was brought about by both cutaneous vasodilation (as indicated by an increase in both the tail and the foot skin temperatures) and decreases in metabolic heat production. However, at Ta 30 degrees C, administration of beta-endorphin produced no change in rectal temperature or other thermoregulatory responses. Furthermore, the hypothermic effect induced by beta-endorphin was greatly attenuated by either the depletion of brain serotonin levels (with 5,6-dihydroxytryptamine and p-chlorophenylanine) or the blockade of opiate receptors (with naloxone). The data indicate that beta-endorphin leads to hypothermia in rats by increasing sensible heat loss and decreasing metabolic heat production, probably via the release of endogenous serotonin within brain.


Rupture of the radial collateral ligament of a metacarpophalangeal joint to one of the ulnar three fingers.
In six patients rupture of the radial collateral ligament of the metacarpophalangeal joint of one of the three ulnar fingers, surgical reconstruction was successful using local tissues in five and a tendon graft in one. Operative treatment of this injury is indicated only when significant instability is present.


Scientometric Analysis of Gastrointestinal Parasites Prevalence in Sheep and Goats of India.
In the present study, gastrointestinal parasites (GIP) prevalence in sheep and goats from India was estimated by scientometrics. The GIP prevalence studies (86) reported during 1998-2021 was obtained from online databases, and offline literatures, meta-analysis was undertaken by using "meta" package in R-Software. The pooled GIP prevalence in India was 65% (95% level CI 56-74%, PI 12-96%) in sheep, 74% (95% level CI 66-80%, PI 14-98%) in goats and 68% (95% level CI 62-73%, PI 15-96%) in sheep and goats. Period-wise analysis revealed a higher GIP prevalence during 1998-2010 than the recent periods. Among the zones, GIP prevalence was higher in the Central zone (79%) in sheep, North zone (82%) in goats, and Central zone (78%) in sheep and goats. Based on the state-wise analysis, a higher GIP prevalence was observed in Haryana for sheep, Himachal Pradesh for goats, and Uttarakhand for sheep and goats. In India, a higher prevalence was reported by nematodes than other parasite classes. Based on climatic regions, a higher GIP prevalence was observed in semi-arid Steppe type region (84%). The high prevalence zones, states, species, sample types, parasite classes, parasite species and climate regions of GIP will be useful in decision-making and resource use efficiency by policymakers and stake holders. There is an urgent need to prevent the occurrence of GIP infections in sheep and goats by adopting scientific management practices, effective therapeutic measures, and hygienic practices on farms to augment the economic benefits to sheep and goat farmers in India.


Systematic desensitization of erectile impotence: a controlled study.
Results of a study conducted to assess the therapeutic effectiveness of systematic desensitization of erectile impotence are described. Three groups of eight patients each were formed. They were treated with systematic desensitization or conventional medication and general advice, or put on a waiting list. Therapeutic effects were investigated on the behavioral, subjective, and physiological levels. There were no significant differences among the three groups except on the subjective level. On this level, after therapy the systematic desensitization group rated feelings in sexually arousing situations as associated with significantly less anxiety than the other two groups. Systematic desensitization used alone as a treatment for erectile impotence shows only limited therapeutic effect. The unimproved patients were later treated using a modification of the Masters and Johnson technique. Early results suggest that this technique may be superior to systematic desensitization alone.


The chemical constituents from Urtica fissa leaves.
A new ceramide urticamide (1), two new secolignans urticalactones I (2) and Ⅱ (3), and a new flavonoid glycoside urticaside (4), together with 15 known compounds (4-19), were isolated from the leaves of Urtica fissa, a folk medicine for rheumatism arthritis in China. The active evaluation results showed that 1, 2, 3, 8, and 13 possessed the potent anti-inflammatory. They could inhibit the release of NO and TNF-α in lipopolysaccharide (LPS) stimulated RAW 264.7 cells, with IC50 values less than 4.0 μM.


Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment: a prospective web-based multi-center study in multiple sclerosis patients with a relapse.
In a prospective multi-center observational study, we evaluated the frequency, severity, and impact on activities of daily living (ADL) of adverse effects (AEs) of high-dose intravenous methylprednisolone (IVMP) in relapsing remitting multiple sclerosis (MS) patients with a relapse. Online self-report questionnaires stating IVMP's most common AEs were completed at baseline, the 2nd day of treatment, and 1 day and 1 week after treatment. Eighty-five patients were included, 66 completed the baseline questionnaire, and 59 completed at least one post-baseline questionnaire. Patients reported on average 4 (median) AEs; two (3.4 %) reported no AE. Most frequent was change in taste (61 %), facial flushing (61 %), sick/stomach pain (53 %), sleep disturbance (44 %), appetite change (37 %), agitation (36 %), and behavioral changes (36 %). Of all AEs, 34.3 % were severe and 37.9 % impacted on ADL. A 3-day course resulted in 4 (median) AEs and a 5-day course in 7. All patients with high disease impact had two or more AEs, compared with 79 % of those with low impact (p < 0.01). Of patients with high disability, 45 % had severe AEs, compared with 16 % of those with low disability. Severe central nervous system (CNS)-related AEs occurred two times more frequently in patients with high disease impact, and two-and-a-half times more frequently in patients with high disability. Therefore, in virtually all patients, high-dose IVMP leads to AEs, with about one of three AEs being severe with impact on ADL. Patients with high disease impact or high disability may experience more (severe) AEs, due to a higher occurrence of severe CNS-related AEs.


Locomotive Syndrome is a Risk Factor for the Dropout of Continuous Positive Airway Pressure Treatment in Patients with Obstructive Sleep Apnea Syndrome.
Objective: The purpose of this study was to investigate the risk factors linked to patient dropout from continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea syndrome (OSAS). Methods: This study included 1191 patients with OSAS at baseline assessment, who were followed for 3 years. We evaluated clinical parameters, indicators related to OSAS treatment, exercise habits and the presence of locomotive syndrome (LS). LS was evaluated by a 'loco-check', as established by the Japanese Orthopedic Association. The OSAS patients were categorized at baseline as belonging to an 'LS group' or a 'non-LS group', and clinical parameters were compared. Results: Eighty-six patients (7.2%) dropped out of CPAP therapy during the 3 year follow-up period. The dropout rate of the LS group was significantly higher than that of the non-LS group. Using a Cox-proportional hazard model, the LS, old age and poor compliance were determined to be significant risk factors for dropping out of CPAP therapy. The hazard ratios (95% CI) of LS, elderly people and poor CPAP compliance were 2.11 (1.31-3.48), 1.80 (1.11-2.94) and 1.61 (1.04-2.47), respectively. Conclusion: LS may be the critical risk factor for dropping out of CPAP therapy among patients with OSAS.


Response of atmospheric deposition and surface water chemistry to the COVID-19 lockdown in an alpine area.
The effects of the COVID-19 lockdown on deposition and surface water chemistry were investigated in an area south of the Alps. Long-term data provided by the monitoring networks revealed that the deposition of sulfur and nitrogen compounds in this area has stabilized since around 2010; in 2020, however, both concentrations and deposition were significantly below the average values of the previous decade for SO4 and NO3. Less evident changes were observed for NH4 and base cation. The estimated decrease of deposition in 2020 with respect to the previous decade was on average - 54% and - 46% for SO4 and NO3, respectively. The lower deposition of SO4 and NO3 recorded in 2020 was caused by the sharp decrease of SO2 and particularly of NOx air concentrations mainly due to the mobility restrictions consequent to the COVID-19 lockdown. The limited effects on NH4 deposition can be explained by the fact that NH3 emission was not affected by the lockdown, being mainly related to agricultural activities. A widespread response to the decreased deposition of S and N compounds was observed in a group of pristine freshwater sites, with NO3 concentrations in 2020 clearly below the long-term average. The rapid chemical recovery observed at freshwater sites in response to the sharp decrease of deposition put in evidence the high resilience potential of freshwater ecosystems in pristine regions and demonstrated the great potential of emission reduction policy in producing further substantial ameliorations of the water quality at sensitive sites.


Closed Incision Negative Pressure Wound Therapy for Elective Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Persistent wound drainage after total joint arthroplasty (TJA) increases the risk of surgical site infections (SSIs). Closed incision negative pressure wound therapy (ciNPWT) decreases infections in traumatic wounds, but evidence for its use after elective TJA is limited. The purpose of this meta-analysis of level I studies is to determine the effect of ciNPWT on risk of SSI and wound complications following TJA. MEDLINE, EMBASE, CINAHL, and Cochrane Library were searched for randomized controlled trials comparing ciNPWT vs standard dressings after total hip (THA) and total knee arthroplasty (TKA). Studies exclusively involving THA for femoral neck fractures were excluded. Risk of SSI and noninfectious wound complications (blisters, seroma, hematoma, persistent drainage, dehiscence, and wound edge necrosis) following TJA were analyzed. SSI risk was lower with ciNPWT compared to standard dressings (3.4% vs 7%; relative risk [RR] 0.48, P = .007), specifically in revision THA and TKA (4.1% vs 10.5%; RR 0.41, P = .03). ciNPWT increased the noninfectious complication risk after primary TKA (RR 4.71, P < .0001), especially causing wound blistering (RR 12.66, P < .0001). ciNPWT decreased hospital length of stay by 0.73 days (P = .04) and reoperation rate (RR 0.28, P = .01). ciNPWT decreases SSI risk compared to standard dressings after revision TJA, but not primary TJA. ciNPWT is associated with >12-fold increased risk of wound blistering after primary TKA. ciNPWT plays a role in revision TJA management, but additional randomized controlled trials with uniform wound assessment methods must be performed to sufficiently power findings and draw conclusions on the use of ciNPWT after primary TJA.


Polymeric surfactants as ideal substitutes for sustainable corrosion protection: A perspective on colloidal and interface properties.
Surfactants are well known for their colloidal and corrosion inhibition potential (CIP) due to their strong propensity to interact with metallic surfaces. However, because of their small molecular size and the fact that they are only effective at relatively high concentrations, their application in aqueous phase corrosion inhibition is often restricted. Polymeric surfactants, a unique class of corrosion inhibitors, hold the potential to eradicate the challenges associated with using surfactants in corrosion inhibition. They strongly bond with the metallic surface and offer superior CIP because of their macromolecular polymeric structure and abundance of polar functional groups. In contrast to conventional polymeric corrosion inhibitors, the inclusion of polar functional groups also aids in their solubilization in the majority of popular industry-based electrolytes. Some of the major functional groups present in polymeric surfactants used in corrosion mitigation include O (ether), glycidyl (cyclic ether), -CONH2 (amide), -COOR (ester), -SO3H (sulfonic acid), -COOH (carboxyl), -NH2 (amino), - + NR3/- + NHR2/- + NH2R/- + NH3 (quaternary ammonium), -OH (hydroxyl), -CH2OH (hydroxymethyl), etc. The current viewpoint offers state-of-the-art information on polymer surfactants as newly developing ideal alternatives for conventional corrosion inhibitors. The industrial scale-up, colloidal, coordination, adsorption properties, and structural requirements of polymer surfactants have also been established based on the knowledge obtained from the literature. Finally, the challenges, drawbacks, and potential benefits of using polymer surfactants have also been discussed.


[Pulmonary diffusion capacity in patients with previous myocardial infarct (with respect to the influence of smoking and pulmonary congestion)].
Pulmonary diffusive capacity by the carbon monoxide method was evaluated in 43 patients two years after myocardial infarction, and without evidence of other types of heart disease. The patients did not have primary lung disease or clinic bronchitis. Special interest was given to the effects of cigarrette smoking and moderate pulmonary congestion. A significant decrease in diffusion capacity was observed in smokers and former smokers compared to none smokers. In moderate pulmonary congestive the oposite effects was registered. pO2 was decreased in half the patients with old myocardial infarction but there was no significant statistical correlations with D1co values. Mean values for pO2, pCO2, pH, EB did not show statistically valid differences among the subgroups under study. Different factors which may influence the evaluation of diffusion capacity are discussed.


The impact of the COVID-19 pandemic on the mental health of healthcare professionals.
Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the COVID-19 pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. To analyze the impact of the COVID-19 pandemic on the mental health of HPs. We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: a) COVID-19 exposure; b) epidemiological issues; c) material resources; d) human resources; and e) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs' distress. A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.


[Acrylic denture base materials in dentistry. The influence of immersion of bases on the palatal gap].
The method of experimental design, we used, is versatile enough to allow the study of immersion in water at 37 degrees C during 15 days after curing, as a new parameter able to influence the deformation of denture bases, without any additional experiment. According to the experimental conditions used to make up denture bases, this parameter can, in some cases, modify appreciably the deviation in the palate region.


Production and purification of melanoma gp100 antigen and polyclonal antibodies.
gp100 is a melanoma-associated antigen found to carry immunogenic epitopes that can induce a CTL response against tumor cells. Production and purification of large quantities of this polypeptide may be important in the context of diagnosis and vaccinating against melanoma. To overcome the hydrophobic nature of gp100, we cloned and expressed only a part of the protein, and obtained a hydrophilic recombinant polypeptide (HR-gp100) that contained most of the immunogenic peptides. High yield was achieved in an Escherichia coli expression system. The protein was purified by AKTA Prime using anionic-columns. Polyclonal antibodies developed in chicken against HR-gp100 were efficient at detecting gp100 in melanoma cells, as determined by Western blot analysis and by immunohistochemistry. HR-gp100 can be used to develop a vaccine against melanoma. Antibodies to HR-gp100 may be used to detect tumors of melanocytic origin or to determine the level of gp100 expression in tumors prior to immunotherapy with the protein or one of its peptides.


Molecular studies of CFTR interacting proteins.
Transport via the cystic fibrosis transmembrane conductance regulator (CFTR) is activated by its interactions with cytoplasmic cofactors, such as cAMP-activated protein kinases. CFTR activity is also known to couple to other ion channels and transporters. Although the genetic cause of human cystic fibrosis by CFTR mutations has been well established, little is known about the protein machinery that plays a role in linking the CFTR to other regulatory or ion-conducting proteins. Several regions of CFTR proteins are highly conserved among different species. The conserved motifs are thought to determine various aspects of channel and mediate interactions with other regulatory proteins. The C-termini, which are not required for functional expression of the CFTR chloride conductance, are also highly conserved. Several proteins that interact with the conserved C-terminus have now been identified. They contain several distinct protein interaction domains, which may be involved in the assembly of macromolecular CFTR channel complexes in vivo. Molecular understanding of these proteins may provide important insights into CFTR function in cystic fibrosis.


Relationship of Right Ventricular Size and Function with Respiratory Status in Duchenne Muscular Dystrophy.
The relationship between pulmonary function and right ventricle (RV) in Duchenne muscular dystrophy (DMD) has not been evaluated. Using cardiac magnetic resonance (CMR), we describe the relationship of RV size and function with spirometry in a DMD cohort. Fifty-seven boys undergoing CMR and pulmonary function testing within 1 month at a single center (2013-2015) were enrolled. Comparisons of RV ejection fraction (RVEF) and end-diastolic volume index (RVEDVI) were made across categories of percent forced vital capacity (FVC%), and relationships were assessed. Mean age was 15.5 ± 3.5 years. Spirometry and CMR were performed within 3.9 ± 4.1 days. Median FVC% was 92.0 % (67.5-116.5 %). Twenty-three (40 %) patients had abnormal FVC% (<80 %) of which 13 (57 %) had mild (FVC% 60-79 %), 6 (26 %) had moderate (FVC% 40-59 %), and 4 (17 %) had severe (FVC <40 %) reductions. Mean RVEF was 58.3 ± 3.7 %. Patients with abnormal FVC% were older and had lower RVEF and RVEDVI. Both RVEF and RVEDVI were significantly associated with FVC% (r = 0.31, p = 0.02 and r = 0.39, p = 0.003, respectively). In a large DMD cohort, RVEF and RVEDVI were related to FVC%. Worsening respiratory status may guide monitoring of cardiac function in these patients.


Conversion of carbohydrates into 5-hydroxymethylfurfural catalyzed by ZnCl2 in water.
The incompletely coordinated zinc ions in the concentrated aqueous ZnCl(2) solution catalyze the direct conversion of carbohydrates into 5-hydroxymethylfurfural, and a moderate HMF yield up to 50% can be achieved.


Endometrial cell-derived conditioned medium in combination with platelet-rich plasma promotes the development of mouse ovarian follicles.
Fertility preservation is one of the most important issues in assisted reproductive technology. Previous studies have shown that cytokines and growth factors can improve follicle growth. The endometrial stromal cells secrete various factors that are involved in maintaining the integrity of uterine and epithelial secretory function. The platelet-rich plasma contains a large assembly of platelets suspended in plasma that successfully improves the viability and growth of various cell lines. This work aimed to investigate the influences of conditioned medium (CM) and platelet-rich plasma (PRP) on the development of ovarian follicles in infertile mice due to cyclophosphamide (CYC) exposure. In this study, 65 healthy BALB/c female mice (∼28-30 g and 6-8 weeks old) in five groups were studied. Immunohistochemistry (IHC) was used to detect growth differentiation factor 9 (GDF9)-positive cells. The mRNA expression levels of SMAD1, SMAD2, and BMP15 was assessed using reverse transcription-polymerase chain reaction (RT-PCR) method. The expression levels of SMAD1, GDF9, BMP15, and SMAD2 in the CM+PRP group was significantly more than in the CM and PRP groups. In addition, live birth occurred in the CM+PRP group. Treatment with CM+PRP in infertile mice due to Cy exposure increased fertility and live-birth rate. In general, our study suggested that the CM and PRP combination could improve the growth of mice ovarian follicles in vivo.


Endothelial nitric oxide synthase (NOS) is upregulated in rapid progressive pulmonary hypertension of the newborn.
To provide evidence for the upregulation of endothelial nitric oxide synthase (eNOS) or inducible nitric oxide synthase (iNOS) in the assumed imbalance in the pathophysiology of rapid progressive pulmonary hypertension of the newborn (RPPHN), which is characterized by abnormal hypertrophy of the pulmonary arterioles and arteries leading to increased pulmonary vascular resistance. Furthermore, to determine the cellular source and topographic distribution of eNOS and iNOS. Lung biopsies were taken from two term neonates with clinical and echocardiographic evidence of RPPH and of three controls. Biopsies were obtained at an early stage of the disease as well as at post mortem and examined immunohistochemically for the presence of eNOS, iNOS and nitrotyrosine. The endothelial cells of pulmonary arterioles stained significantly for eNOS protein in RPPHN patients. This was not the case in the control infants. There were no differences for nitrotyrosine or iNOS between RPPHN patients and controls. Rapid progressive pulmonary hypertension of the newborn leads to compensatory induction of eNOS synthesis specifically in endothelial cells of the pulmonary arterioles. This mechanism of compensation can lead to delayed presentation of RPPHN during the late neonatal period. Exogenous inhaled nitric oxide therapy does not lead to suppression of the endogenous synthesis of nitric oxide.


Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies.
This study examined the association of diabetes with the onset of dementia (including Alzheimer's disease (AD), vascular dementia (VD) and any dementia) and mild cognitive impairment (MCI) by using a quantitative meta-analysis of longitudinal studies. EMBASE and MEDLINE were searched for articles published up to December 2010. All studies that examined the relationship between diabetes and the onset of dementia or MCI were included. Pooled relative risks were calculated using fixed and random effects models. Nineteen studies met our inclusion criteria for this meta-analysis, and 6184 subjects with diabetes and 38 530 subjects without diabetes were included respectively. All subjects were without dementia or MCI at baseline. The quantitative meta-analysis showed that subjects with diabetes had higher risk for AD (relative risk (RR):1.46, 95% confidence interval (CI): 1.20-1.77), VD (RR: 2.48, 95% CI: 2.08-2.96), any dementia (RR: 1.51, 95% CI: 1.31-1.74) and MCI (RR: 1.21, 95% CI: 1.02-1.45) than those without. The quantitative meta-analysis showed that diabetes was a risk factor for incident dementia (including AD, VD and any dementia) and MCI.


[Masseter thickness measured by ultrasonography of 50 young healthy adults in relation to facial morphology].
To quantify the normal range of the ultrasonically measured thickness of the masseter which is related to the variation of the facial morphology in different young individuals. The masseter thickness of 50 young healthy adults (25 men and 25 women) was measured bilaterally under relaxed conditions and with maximal clenching by a real-time ultrasound imaging technique. The relation between masseter thickness and facial morphology was also observed. Under relaxed conditions, the mean thickness of the muscle in men was(11.83 +/- 1.19) mm, and under contracted conditions, (15.51 +/- 1.40) mm. In women, the respective measurements were(9.84 +/- 1.03) mm and (13.02 +/- 1.10) mm. In men the thickness of masseter had a negative linear correlation to the indices of FH/FWa (the ratio of the anterior facial height to the intergonial width) and FWz/FWa (the ratio of the bizygomatic facial width to the intergonial width). The mean thickness of the masseter in men was larger than that in women, and the thickness of the muscle was related to the male facial morphology.


[Balloon kyphoplasty for recent vertebral fractures in the elderly].
An increasing life expectancy is often accompanied by a possible increase of vertebral fractures. If operative therapy is necessary, open procedures might be problematic for elderly patients. In this case, balloon kyphoplasty might be an alternative. We present our prospective data of 30 patients with an average age of 72 years (range 65-82). The patients suffered from isolated thoracic and lumbar fractures (T6-L4) without neurological deficits and were operated on with balloon kyphoplasty. They were followed up an average of 13 months after surgery. Before surgery, the patients' average kyphotic angle was 12 degrees . After reduction with balloon kyphoplasty, this angle was significantly improved to 7 degrees , and at follow-up it was 8 degrees . Back pain, which was determined by a visual analogous scale, showed a significant reduction from 8.2 to 2.6 points at follow-up. No significant relationship between preoperative pain and improvement of the kyphotic angle could be found. Patients with a bad fracture reposition showed significantly more pain at follow-up. However, there was no difference between the reference group and the examined patients' quality of life regarding general health. Recent fractures of the thoracic or lumbar spine in elderly patients treated by balloon kyphoplasty showed good early results.


Effects of smoked marijuana on social interaction in small groups.
Twelve adult male research volunteers, in four groups of three subjects each, resided continuously in a residential laboratory for up to 18 days. Subject's behaviors, including social interaction, were continuously recorded. During the first part of the day (1000-1600), subjects remained in their private rooms doing work activities, and during the remainder of the day (1600-2345), they had the option to socialize with the other subjects. Four cigarettes containing active marijuana (1.84%, delta 9-tetrahydrocannabinol (delta 9 (THC)), w/w) or placebo were smoked daily: one each prior to the work and social access period, and two during the social access period. When the results were averaged across all groups and individuals, active marijuana significantly increased total daily social interaction time. However, drug effects were a function of the baseline amount of social interaction. The results of these experiments also showed that the pattern of increases in social interaction following smoked active marijuana varied within different groups of individuals.


Aphidicolin-resistant DNA polymerase of bacteriophage phi 29 APHr71 mutant is hypersensitive to phosphonoacetic acid and butylphenyldeoxyguanosine 5'-triphosphate.
Bacteriophage phi 29 DNA polymerase is sensitive to aphidicolin (APH). DNA polymerase of the APH-resistant mutant, APHr71, was more sensitive to phosphonoacetic acid and butylphenyldeoxyguanosine 5'triphosphate than the wild type. Nucleotide sequence analysis revealed a single transition of G at nucleotide 562 to A in the DNA polymerase gene of APHr71, indicating that APHr71 DNA polymerase (572 residues) had a single amino acid substitution from glycine at residue 188 to serine. The results suggest that the site and the neighboring conserved segment of phi 29 DNA polymerase constitute a structure interacting with deoxynucleotides, pyrophosphate, and APH.


Victor's justice: atrocities in postwar Nigeria.
The Nigerian Government's declaration of 'no victor, no vanquished' after the capitulation of Biafra on 12 January 1970, was applauded as the right step towards reconciliation and transition from war to peace. Despite this declaration and assurance of amnesty, the Nigerian Government and its soldiers still engaged in acts that amounted to retributive justice. They starved and killed innocent Biafran civilians, looted their property and raped their women. Surprisingly, these postwar atrocities committed against former Biafrans have been largely ignored in the historiography of the Nigeria-Biafra War. This paper seeks to fill the gap in the war literature by interrogating Nigerian Government's attitude towards the postwar humanitarian crisis and crimes against humanity in former Biafra. The paper argues that former Biafrans were not fully reintegrated into the Nigerian society and that the Nigerian Government deliberately neglected them to die in large numbers, thereby making it difficult for the war victims to recover from the hardships of the conflict.


Elevated C-Reactive Protein Is Associated with Cognitive Decline in Outpatients of a General Hospital: The Project in Sado for Total Health (PROST).
We aimed to determine whether the concentration of serum C-reactive protein (CRP) is associated with cognitive function in an adult Japanese population. Participants of this cross-sectional study were from a subgroup of the Project in Sado for Total Health (PROST; n = 454; mean age, 70.5 years). The cognitive state was evaluated using the Mini-Mental State Examination (MMSE), and those with an MMSE score <24 were considered 'cognitively declined'. Concentrations of serum high-sensitivity CRP were measured. Multiple logistic regression analysis was used to calculate odds ratios (ORs) for cognitive decline, adjusting for the covariates of age, sex, BMI, disease history, and APOE allele. Of the 454 participants, 94 (20.7%) were cognitively declined. Relative to the lowest (first) quartile of CRP concentration, adjusted ORs were 1.29 (95% CI 0.61-2.75) for the second, 1.78 (95% CI 0.82-3.86) for the third, and 3.05 (95% CI 1.45-6.42) for the highest (fourth) quartiles (p for trend = 0.018). When data were stratified by sex, the association between CRP concentration and cognitive decline was observed only in women. Our findings suggest an association between higher CRP concentration and lower cognitive function. Chronic inflammation may affect cognitive function in adults, in particular women.


Cellular immunosenescence in F344 rats: decreased natural killer (NK) cell activity involves changes in regulatory interactions between NK cells, interferon, prostaglandin and macrophages.
Natural killer (NK) activity of F344 rat spleen cells remained constant between 1 and 18 months of age under specific pathogen-free (SPF) conditions. Between 18 and 24 months of age, however, there was a dramatic decline in activity which remained at a low baseline throughout the normal lifespan. Removal of adherent cells on G-10 Sephadex columns revealed age-related changes in adherent cell regulation of NK activity. Young (4-6 week) NK activity was consistently decreased by adherent cell removal while old (24-30 month) NK activity was slightly but reproducibly increased. Moreover, splenic macrophages from old rats purified by adherence to microexudate-coated surfaces were highly suppressive to young nonadherent NK activity. A role for endogenous prostaglandin (PG) in suppressed old rat NK activity was suggested by the effectiveness of anti-PGE2 in vivo to boost old NK activity. Although old rat NK activity was boosted to a relatively greater extent by interferon (IFN) in vitro than was young NK activity, IFN-boosted NK activity of old rats was much more sensitive to PGE2 inhibition than was IFN-boosted young rat NK activity. IFN treatment in vitro or poly(I:C) treatment in vivo induced protection against PGE2 inhibition of NK activity in young rats, while no resistance to PGE2 inhibition was induced in old rat NK cells by similar treatments. In vivo, the same protocol of IFN administration which boosted young rat NK activity further suppressed old rat activity. These results support the hypothesis that immunosuppression related to aging, which supersedes the boosting effect of IFN, involves the combined effects of suppressor macrophages (via PGE2) and intrinsic changes in effector (NK) cells which render them more sensitive to PGE2 inhibition.


Change and continuity in patient theories of illness: the case of epilepsy.
Lay concepts of health and illness have attracted much interest in medical sociology. Empirical research has shown that lay theories present coherent views of health and illness which are often not compatible with medical concepts, but influenced by them. Nevertheless, knowledge on the nature of medical influence on individual patient theories over time is scare. This paper explores this issue by empirically analysing the illness theories of patients with epilepsy. In this qualitative study, the classification and description of illness theories is attempted through ideal types which describe theoretically significant properties of patient discourse. Data from a 4-year follow-up are compared with the original classification. While the continuities in patient theories seem to be primarily due to continuities in the illness careers, the changes in the direction of psychosomatic theories seen in some patients favour the view that patient theories have dynamic structures which are heavily influenced also on the individual level by historical developments in clinical practice.


Fused triazoles via tandem reactions of activated Cinchona alkaloids with azide ion. Second Cinchona rearrangement exemplified.
[reaction: see text] Intramolecular 1,3-dipolar cycloadditions of cinchona azides to the C10-C11 alkyne and C10-C11 olefin unit of the alkaloid have been designed via tandem strategy. A variety of fused triazoles and triazolines with a bis-azahomotwistane skeleton have been prepared. In trifluoroethanol, O-mesylcinchonidine 7-OMs and NaN(3) furnish triazole 8 as well as cage-expanded 1,5-diazatricyclo[188.8.131.52(3,8)]undecane derivative 10. Both fused triazoles 8 and 10 are formed with retention of configuration at C9 and C3, respectively. 1-Azabicyclo[3.2.2]cage expansion is shown to be reversible.


Comparison of PAM Systems for Acoustic Monitoring and Further Risk Mitigation Application.
We present results of the SIRENA 2011 research cruises conducted by the NATO Undersea Research Centre (NURC) and joined by the Research Department for Underwater Acoustics and Geophysics (FWG), Bundeswehr Technical Centre (WTD 71) and the Universities of Kiel and Pavia. The cruises were carried out in the Ligurian Sea. The main aim of the FWG was to test and evaluate the newly developed towed hydrophone array as a passive acoustic monitoring (PAM) tool for risk mitigation applications. The system was compared with the PAM equipment used by the other participating institutions. Recorded sounds were used to improve an automatic acoustic classifier for marine mammals, and validated acoustic detections by observers were compared with the results of the classifier.


Late onset chronic mucocutaneous candidiasis with lymphoma and specific serum inhibitory factor.
A patient with late onset chronic mucocutaneous candidiasis developed lymphocytic lymphoma. A specific inhibitor of in vitro lymphoproliferative responses to candidal antigen was detected in her serum which persisted following clinical remission of candidiasis after combined amphotericin-B and 5-Fluorocystosine therapy. It is unclear whether the combined therapy was exclusively anticandidal, nonspecific immunostimulant or cytotoxic affecting the underlying incipient lymphoma.


Angiotensin II augments advanced glycation end product-induced pericyte apoptosis through RAGE overexpression.
Advanced glycation end product (AGE)-their receptor (RAGE) and angiotensin II (AII) are implicated in diabetic retinopathy. However, a crosstalk between the two is not fully understood. In vivo, AGE injection stimulated RAGE expression in the eye of spontaneously hypertensive rats, which was blocked by an AII-type 1 receptor blocker, telmisartan. In vitro, AII-type 1 receptor-mediated reactive oxygen species generation elicited RAGE gene expression in pericytes through NF-kappaB activation. Further, AII augmented AGE-induced pericyte apoptosis, the earliest hallmark of diabetic retinopathy. Our present study may implicate a crosstalk between AGE-RAGE system and AII in diabetic retinopathy.


Recent Advances and Clinical Applications of PET Cardiac Autonomic Nervous System Imaging.
The purpose of this review was to summarize current advances in positron emission tomography (PET) cardiac autonomic nervous system (ANS) imaging, with a specific focus on clinical applications of novel and established tracers. [11C]-Meta-hydroxyephedrine (HED) has provided useful information in evaluation of normal and pathological cardiovascular function. Recently, [11C]-HED PET imaging was able to predict lethal arrhythmias, sudden cardiac death (SCD), and all-cause mortality in heart failure patients with reduced ejection fraction (HFrEF). In addition, initial [11C]-HED PET imaging studies have shown the potential of this agent in elucidating the relationship between impaired cardiac sympathetic nervous system (SNS) innervation and the severity of diastolic dysfunction in HF patients with preserved ejection fraction (HFpEF) and in predicting the response to cardiac resynchronization therapy (CRT) in HFrEF patients. Longer half-life 18F-labeled presynaptic SNS tracers (e.g., [18F]-LMI1195) have been developed to facilitate clinical imaging, although no PET radiotracers that target the ANS have gained wide clinical use in the cardiovascular system. Although the use of parasympathetic nervous system radiotracers in cardiac imaging is limited, the novel tracer, [11C]-donepezil, has shown potential utility in initial studies. Many ANS radioligands have been synthesized for PET cardiac imaging, but to date, the most clinically relevant PET tracer has been [11C]-HED. Recent studies have shown the utility of [11C]-HED in relevant clinical issues, such as in the elusive clinical syndrome of HFpEF. Conversely, tracers that target cardiac PNS innervation have been used less clinically, but novel tracers show potential utility for future work. The future application of [11C]-HED and newly designed 18F-labeled tracers for targeting the ANS hold promise for the evaluation and management of a wide range of cardiovascular diseases, including the prognostication of patients with HFpEF.


Retinal neurochemical changes following application of glutamate as a metablolic substrate.
Retinal neural and glial cells share an intricate relationship that includes uptake and recycling of the amino acid neurotransmitters, glutamate and gamma-amino butyric acid (GABA), as well as metabolic links. The aim of this work was to determine the neurochemical and morphological changes induced by the removal of glucose but with the provision of exogenous glutamate in the isolated retinal preparation incubated under aerobic conditions. The carbon skeleton of glutamate can enter the tricarboxylic acid cycle as alpha-ketogluterate, providing an alternative metabolic substrate in cases of glucose deprivation. Isolated rat retinas were incubated in physiological media with and without glucose, using a range of glutamate concentrations to provide an alternative source of metabolic substrate. We conducted post-embedding immunocytochemistry and quantified the change in glutamate and GABA immunoreactivity within Müller cells under these different incubation conditions. The provision of glutamate with normal (6 mM) glucose levels resulted in a gradual accumulation of glutamate and GABA in Müller cells, with Müller loading when exogenous glutamate concentrations were above 0.1 mM. However, when these varying levels of glutamate were applied in the absence of glucose, glutamate accumulation in Müller cells was decreased compared to the 6 mM glucose condition and GABA accumulation in Müller cells was at a minimum at moderate (0.5 and 1 mM) glutamate levels. Under hypoglycaemic conditions, exogenous glutamate (0.5 to 1 mM) is rapidly metabolised by Müller cells to the extent that no glial loading is evident, despite the high concentrations. Normal neurochemical function appears to be maintained secondary to exogenous glutamate provision of 0.5 to 1 mM when glucose is not in the incubation medium, implying that glutamate can be used as an alternative metabolic substrate. We also show that Müller cells possess more rapid glutamate metabolic capabilities compared to the metabolism of GABA.


Hildegard of Bingen (c. 1098-1179) on sleep and dreams in her Causae et curae and Physica: a historical perspective.
Saint Hildegard of Bingen (c. 1098-1179) was a 12th century Benedictine abbess, a visionary, a composer, a poet, a healer, and one of few medieval women who produced treatises on medicine. In her medical writings, Causae et curae and Physica, the abbess described, among other topics, physical functions and mechanisms of sleep, dreams and waking, emphasizing the importance of sleep for the human body. She regarded sleep as both a passive and an active process. Hildegard warned her readers about sleeping too little or too much, evaluated possible causes of insomnia and nightmares, and discussed potential treatments for these sleep disorders. In this paper, we analyze Hildegard's writings in the context of Greco-Roman physiological theories, which were held to the end of the Middle Ages and later. We also discuss questions concerning the abbess's putative education, the originality of her works, and the significance of her writings in the context of current knowledge on sleep medicine.


A model for mylohyoid muscle mechanics.
The purpose of the present study was to develop a mathematical model of the mylohyoid muscle allowing to analyze the complex mechanics of the muscle during jaw movement. The model was based on muscle morphology and physiological properties. Bending of fibers was incorporated into the model by pulleys located along the upper lateral border of the anterior belly of the digastric muscle. The dynamical properties of the muscle portions, i.e. force length and force velocity relationships, were related to sarcomere length changes. In addition, the effective force component produced by each portion in the sagittal plane was calculated. The model provided information on the geometrical changes of the muscle portions and the concomitant effect on sarcomere length, dynamical properties and effective force component as a function of jaw opening angle. Muscle configuration changed drastically and non-uniformly during jaw opening. However, sarcomere length changes were relatively small and differed but slightly between the muscle portions. The muscle portions all operated near optimum length regarding to their force-length relationship. In all muscle portions effective muscle force was the smallest (10-20% of maximum isometric force) in the beginning of the opening movement. With an increase of jaw angle effective muscle force gradually increased to 60-70% of maximum isometric force in the posteriormost muscle portion and to 20% in the anteriormost portion. Muscle fiber bending appeared to increase the sagittal plane component of the muscle force substantially.


Ultrasound-Guided Attenuation Parameter (UGAP) for the quantification of liver steatosis using the Controlled Attenuation Parameter (CAP) as the reference method.
Nonalcoholic Fatty Liver Disease (NAFLD) is increasing in frequency in daily practice and evaluation of liver steatosis, fibrosis and inflammation severity are essential for prognosis assessment. The aim was to evaluate the usefulnessof a new liver steatosis quantification system - Ultrasound-Guided Attenuation Parameter (UGAP) from General Electric Healthcare, using Controlled Attenuation Parameter (CAP) as the reference method. 179 consecutive subjects, in whom liver steatosis was assessed in the same session using UGAP, implemented on LOGIQ E10 system (GE Healthcare), and CAP (FibroScan, EchoSens). To discriminate between steatosis stages by CAP, we used the cut-offs recommended by the manufacturer: S1 (mild) - 230 dB/m, S2 (moderate) - 275 dB/m, S3 (severe) - 300 dB/m. We classified our cohort by means of CAP into the following groups: S0 (no steatosis): 48/176 (27.2%), S1 (mild): 56/176 (31.6%), S2 (moderate): 14/176 (7.3%) and S3 (severe): 59/176 (33.9%). The mean UGAP values increased with the steatosis grade and for each group were the following: S0: 198.3±25.7 dB/m, S1: 216.86±26.3 dB/m, S2: 237.79±26.3 dB/m, and S3: 270.8±31.62 dB/m respectively (p<0.001). A very good positive correlation was found between UGAP and CAP values (r=0.73, p<0.0001). The best cut-off values for predicting different grades of liver steatosis using CAP as the reference were: S1 - 192.5 dB/m (AUC 0.83); S2 - 231 dB/m (AUC 0.90) and S3 - 248 dB/m (AUC 0.91). UGAP seems to be a good method for liver steatosis quantification and correlates strongly with CAP values.


Decreased serum selenium and magnesium levels in drunkenness arrestees.
Serum levels of selenium magnesium, copper, zinc and iron were studied in chronic drunkenness arrestees and a healthy control group. The mean serum concentrations of selenium and magnesium were both significantly lower (P less than 0.01) in drunkenness arrestees than in the control subjects. The mean alcohol intake was 190 g of absolute alcohol daily in drunkenness arrestees and 14 g in controls. The erythrocyte glutathione peroxidase concentrations of the study groups did not support poor selenium intake as a principal cause of low selenium concentration in the serum.


Bicuspid pulmonary valve with atrial septal defect leading to pulmonary aneurysm.
Pulmonary artery aneurysms are rare. We describe 2 adult patients with pulmonary artery aneurysm with normal pulmonary pressure associated with bicuspid pulmonary valve and atrial septal defect. One patient presented with moderate pulmonary valve stenosis and was treated with open surgery; the other patient had a small atrial septal defect and mild pulmonary valve insufficiency and is periodically still being evaluated. Hemodynamic alterations associated with a pulmonary artery aneurysm are described; the influence of additional volume overload and intrinsic wall abnormalities in pulmonary valvular lesions as potential triggers for the development of these aneurysms are analyzed and therapeutic strategies are discussed.


The cost burden of metastatic prostate cancer in the US populations covered by employer-sponsored health insurance.
Recent advancements in the clinical management of metastatic prostate cancer include several costly therapies and diagnostic tests. The objective of this study was to provide updated information on the cost to payers attributable to metastatic prostate cancer among men aged 18 to 64 years with employer-sponsored health plans and men aged 18 years or older covered by employer-sponsored Medicare supplement insurance. By using Merative MarketScan commercial and Medicare supplemental data for 2009-2019, the authors calculated differences in spending between men with metastatic prostate cancer and their matched, prostate cancer-free controls, adjusting for age, enrollment length, comorbidities, and inflation to 2019 US dollars. The authors compared 9011 patients who had metastatic prostate cancer and were covered by commercial insurance plans with a group of 44,934 matched controls and also compared 17,899 patients who had metastatic prostate cancer and were covered by employer-sponsored Medicare supplement plans with a group of 87,884 matched controls. The mean age of patients with metastatic prostate cancer was 58.5 years in the commercial samples and 77.8 years in the Medicare supplement samples. Annual spending attributable to metastatic prostate cancer was $55,949 per person-year (95% confidence interval [CI], $54,074-$57,825 per person-year) in the commercial population and $43,682 per person-year (95% CI, $42,022-$45,342 per person-year) in the population covered by Medicare supplement plans, both in 2019 US dollars. The cost burden attributable to metastatic prostate cancer exceeds $55,000 per person-year among men with employer-sponsored health insurance and $43,000 among those covered by employer-sponsored Medicare supplement plans. These estimates can improve the precision of value assessments of clinical and policy approaches to the prevention, screening, and treatment of prostate cancer in the United States.


A cross-cultural examination of use of corporal punishment on children: a focus on Sweden and the United States.
It appears that Sweden and the United States may be a study in contrasts regarding the sanction and use of corporal punishment on children. A 1979 study of American parents noted that 81% of them employed corporal punishment with children. A different study done in Sweden in 1978 noted that only 26% of parents used corporal punishment with children. What points to the differences in these parenting patterns within the two countries? In addition, a 1977 U.S. Supreme Court case entitled Ingraham vs. Wright ruled that "schools are empowered to carry out corporal punishment." This court case involved two high school boys in Florida who had been repeatedly struck with wooden paddles. In contrast, Sweden had statutes which prohibited corporal punishment of children in their secondary schools as early as the 1920s. In 1957, the country passed a law which defined corporal punishment as unacceptable for small children in the schools. Then, in 1979, the Swedish government passed a statute prohibiting corporal punishment by parents. Are there differences in the way the two countries view law and its uses? Or, do the cultures sanction violence in general or just violence against children in different ways? This article examines some of the similarities and differences found in American and Swedish treatment of children and proposes what appear to be extreme differences in the way the countries and their people approach corporal punishment.


Enhanced T-lineage acute lymphoblastic leukaemia cell survival on bone marrow stroma requires involvement of LFA-1 and ICAM-1.
The bone marrow (BM) microenvironment supports leukaemia cell survival and proliferation. The roles played by adhesive receptor interactions in the survival of T-lineage acute lymphoblastic leukaemia (T-ALL) cells on BM stromal cells are not well understood. Recently, we have developed an assay that partially recapitulates the BM microenvironment using HS-5 BM stromal cells. In this assay, the magnitude of ex vivo T-ALL lymphoblast survival predicts patient outcome. We examined the molecular basis for cell-cell adhesive events leading to T-ALL lymphoblast survival on HS-5 and on donor-derived BM stroma. Lympho cyte function-associated antigen-1 (LFA-1) on T-ALL cell lines bound intercellular adhesion molecule-1 (ICAM-1) on HS-5 monolayers, and survival was inhibited 85-98% with monoclonal antibodies directed against LFA-1 or ICAM-1. We compared these results with patient-derived T-ALL lymphoblasts co-cultured on either HS-5 BM or normal BM monolayers and found that LFA-1 and ICAM-1 were required, but not alone sufficient for ex vivo leukaemic cell survival. On normal BM stroma, but not HS-5 monolayers, two additional adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, were highly expressed and contributed to T-ALL cell survival. This is the first report to demonstrate the importance of LFA-1/ICAM-1-mediated adhesion as a critical event in a cascade of cell surface receptor-ligand interactions that regulate T-ALL survival in the BM microenvironment.


[Differences in Area Specific Life Satisfaction Between East and West Germans in the Years 1991, 2006 and 2020].
Question How did the general and area specific life satisfaction evolve between East and West Germany between 1991 and 2020? Based on three representative surveys in the years 1991, 2006 and 2020 life satisfaction between East and West Germany was examined using mean comparison with tests of significance. The influence of relevant sociodemographic variables was calculated using Univariate Variance Analyses. 1991 large differences in the general life satisfaction as well as with satisfaction in the areas of living, spare time, health, finances and occupational did occur, with people in East Germany reporting to be less satisfied. These differences align during the observation time. The discrepancy in the general and area specific life satisfaction between East and West Germans did align during the last 30 years. A reason might be the improved economical living conditions in East Germany.


The MSH2 c.793-1G>A variant disrupts normal splicing and is associated with Lynch syndrome.
Lynch syndrome (LS) is the most common inherited cancer predisposition disorder of colorectal cancer (CRC) which is associated with pathogenic variants in 4 mismatch repair (MMR) genes. Here, we reported a multi-generation Chinese family clinically diagnosed with LS. To identify the underlying pathogenic gene variants, 30 whole blood samples and 4 colorectal cancer tissue samples and their clinical data were obtained from this four-generation family. Microsatellite instability-high (MSI) testing, immunohistochemistry (IHC), and Whole-Exome Sequencing (WES) were performed to identify the MMR/MSI and the underlying gene variants. The minigene splicing assay and in vitro splicing assay were used to explore the function of this variant. MSI-H and dMMR was revealed by the MSI testing and IHC, Whole-Exome Sequencing (WES) in 3 patients successfully identified a splicing variant (c.793-1G>A) in intron 4 of MSH2. Sanger sequencing validated the WES results, and all the "healthy" individuals carrying the variant have been identified in the family by PCR. Bioinformatics analysis and in vitro minigene assay showed that the pathogenic variant affected the splicing process of MSH2 gene to generate 2 kinds defective transcription products, and consequently reduced the expression of MSH2 protein. The mutation carriers were later recommended for colonoscopy and other important cancer diagnostic inspections every 1-2 years because they both have a higher risk of LS. We found a pathogenic splicing variant (rs863225397, c.793-1G>A) of MSH2 gene, and furtherly confirmed that this mutation plays an important role in LS patients of this pedigree based on the vitro study. Our study indicates that one splicing mutation in the MSH2 gene (c.793-1G>A) causes LS and highlights the importance of LS gene testing.


Percutaneous Transcatheter Mitral Valve Replacement: Patient-specific Three-dimensional Computer-based Heart Model and Prototyping.
Mitral regurgitation is the most prevalent valvular heart disease worldwide. Despite the widespread availability of curative surgical intervention, a considerable proportion of patients with severe mitral regurgitation are not referred for treatment, largely due to the presence of left ventricular dysfunction, advanced age, and comorbid illnesses. Transcatheter mitral valve replacement is a promising therapeutic alternative to traditional surgical valve replacement. The complex anatomical and pathophysiological nature of the mitral valvular complex, however, presents significant challenges to the successful design and implementation of novel transcatheter mitral replacement devices. Patient-specific 3-dimensional computer-based models enable accurate assessment of the mitral valve anatomy and preprocedural simulations for transcatheter therapies. Such information may help refine the design features of novel transcatheter mitral devices and enhance procedural planning. Herein, we describe a novel medical image-based processing tool that facilitates accurate, noninvasive assessment of the mitral valvular complex, by creating precise three-dimensional heart models. The 3-dimensional computer reconstructions are then converted to a physical model using 3-dimensional printing technology, thereby enabling patient-specific assessment of the interaction between device and patient. It may provide new opportunities for a better understanding of the mitral anatomy-pathophysiology-device interaction, which is of critical importance for the advancement of transcatheter mitral valve replacement.


An oxidative metabolic pathway of 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEHU) from alginate in an alginate-assimilating bacterium.
Alginate-assimilating bacteria degrade alginate into an unsaturated monosaccharide, which is converted into 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEHU). DEHU is reduced to 2-keto-3-deoxy-D-gluconate by a DEHU-specific reductase using NAD(P)H. This is followed by pyruvate production via the Entner-Doudoroff pathway. Previously, we identified FlRed as a DEHU reductase in an alginate-assimilating bacterium, Flavobacterium sp. strain UMI-01. Here, we showed that FlRed can also catalyze the oxidation of DEHU with NAD+, producing 2-keto-3-deoxy-D-glucarate (KDGR). FlRed showed a predilection for NADH and NAD+ over NADPH and NADP+, respectively, and the Km value for NADH was approximately 2.6-fold less than that for NAD+. Furthermore, we identified two key enzymes, FlDet and FlDeg, for KDGR catabolism. FlDet was identified as an enzyme of the ribonuclease activity regulator A family, which converts KDGR to α-ketoglutaric semialdehyde (α-KGSA). FlDeg, a type II α-KGSA dehydrogenase, generated α-ketoglutaric acid by oxidizing the aldehyde group of α-KGSA using NAD(P)+. Consequently, unlike the conventional DEHU reduction pathway, DEHU can be directly converted to α-ketoglutaric acid without consuming NAD(P)H. Alginate upregulated the expression of not only FlRed and two enzymes of the DEHU-reduction pathway, but also FlDet and FlDeg. These results revealed dual pathways of DEHU metabolism involving reduction or oxidation by FlRed.


Postexercise electrocardiographic and clinical changes in patients with sick sinus syndrome.
Forty patients with sick sinus syndrome, 15 women and 25 men with a mean age of 53.83 +/- 13.34 years, were studied using a maximal graded bicycle stress test. None of the patients were using a pacemaker or being treated with drugs that would interfere with the sinus node function; one patient had family myocardiopathy and eight suffered from essential hypertension. All patients, including those suffering from very marked bradycardia (less than 40 beats/min) responded to the increased effort with increased heart rate. The exercise test was stopped in 22 patients (55%) after the appearance of clinical signs and in 4 (10%) after ST-segment depression greater than 1 mm. Eight (20%) finished the stress test after reaching the maximal heart rate according to age, due to an increase in sinus rate. The exercise produced or increased extrasystoles in five patients (12.5%), but only one was forced to suspend the test. The Q-T interval, corrected for heart rate according to Bazett's formula (QTc), was measured on the resting ECG before the start of the test and on the ECG recorded immediately following the end of the exercise in all patients, except one with atrial fibrillation. In 24 patients (60%), a QTc mean increase of 0.040 +/- 0.022 sec was observed at the end of the stress test. Fourteen (35%) had the usual shortening due to the increase in heart rate. One patient showed no variation of the QTc. A lengthening of the QTc at the end of the exercise in more than half of the patients was the most intriguing electrocardiographic change.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of nuclear scanning in the evaluation of arterial injuries.
Nuclear scanning appears to be a useful test to screen patients with penetrating injuries to the extremities who have proximity as the only finding suggestive of vascular injury. Patients with abnormal scans should be further studied with standard angiography. Interpretation of the scan is dependent on the reader's experience.


Preparation of microencapsulated liposomes, II. Systems containing nylon-gelatin and nylon-gelatin-acacia walling material.
Liposome suspension was encapsulated and isolated in nylon-gelatin and nylon-gelatin-acacia walled microcapsules. The resulting liposomal microcapsules could be stored in the dry state as a free-flowing powder. Liposomes remained intact after the microencapsulation, and encapsulation efficiency was greater than 90 per cent. The release of drug from microcapsules was retarded in the presence of drug-loaded liposomes.


Guidelines for the use of clozapine in individuals with developmental disabilities.
Clozapine is the most effective antipsychotic medication currently in use, but there has been a paucity of well-controlled research on its efficacy with people with developmental disabilities. We present a set of guidelines to ensure proper utilization of clozapine in individuals with developmental disabilities, because it can offer them therapeutic advantages similar to those observed in people with schizophrenia. We provide recommendations regarding the use of clozapine that are based on three main sources: literature and published professional practice guidelines regarding the use of clozapine in individuals who do not have developmental disabilities, the limited literature on the use of clozapine in individuals who have developmental disabilities, and our own clinical experience. The first part of the guidelines contains an overview of necessary practical knowledge regarding side effects, dose and blood level considerations, and interactions with other medications, diet and tobacco smoking. In the second part, we offer procedures for selecting individuals for clozapine therapy based on proper indications and contraindications for treatment. We also include requirements regarding informed consent, dosage and special laboratory and clinical monitoring.


Factors associated with choice of high lethality methods in suicide attempters: a cross-sectional study.
Most attempted suicides have a low lethality, but hanging, drowning, and jumping from a great height have a high risk of completed suicide. The aim of this study was to assess the sociodemographic profiles of patients who attempted suicide using high lethality methods relative to all other methods of attempted suicide. We retrospectively investigated all attempted suicides treated at a tertiary university hospital in Seoul between January 2008 and February 2012. The following variables were considered: the patients' attempted suicide methods, age, sex, history of attempted suicides, previous psychiatric history, occupation, and living conditions. The suicide methods were categorized into two groups: high lethality (e.g., hanging, falling, and drowning) and low lethality methods (e.g., self-poisoning and cutting). We investigated risk factors related to the choice of high lethality methods. A total of 560 patients were enrolled in this study. Deliberate self-poisoning was the most common method of attempted suicide (61.6%), followed by cutting (22.5%), hanging (10.4%), falling (4.1%), and drowning (1.4%). In logistic regression analyses, odds ratios for the choice of high lethality methods were 1.02 (95% CI = 1.01 to 1.03, p < .01), 7.22 (95% CI = 3.06 to 17.04, P < .01), and 0.59 (95% CI = 0.35 to 0.99, p = .04) for age, previous attempted suicide with a high lethality method, and alcohol co-ingestion, respectively. Our findings indicated that age and past attempted suicide using a high lethality method are associated with the use of high lethality methods for attempting suicide.


A study by immunofluorescence microscopy of the NC1 domain of collagen type IV in glomerular basement membranes of two patients with hereditary nephritis.
The NC1 domain of the collagen type IV molecule, the major component of glomerular basement membranes (GBM), consists of dimers and 24 kilodalton (K), 26 K and 28 K monomers in man, and contains the Goodpasture antigen. Serum obtained from patients with Goodpasture's syndrome has been reported not to stain GBM of most male and some female patients with hereditary nephritis (HN) by immunofluorescence (IF) microscopy. In the present study, GBM seen on the renal biopsies of 2 patients (one male and one female) with HN were examined by IF to ascertain whether NC1 monomers were detectable. Three reagents were used: a plasmapheresis fluid (PPF) obtained from a patient who was treated for anti-GBM nephritis (human anti-GBM PPF); a commercial rabbit antibody against human NC1; and a rabbit antibody raised by us against dog NC1, which cross-reacted with human NC1. All 3 reagents detected NC1 determinants in GBM of normal human kidney by IF and reacted with human NC1 by a plate-binding radioimmunoassay (RIA). The human anti-GBM PPF bound to 28 K and 26 K monomer components of NC1 by Western blotting, the rabbit anti-human NC1 antibody bound to 26 K and 24 K monomers, while the rabbit anti-dog NC1 antibody bound only to the 26 K monomer. By IF, the human anti-GBM PPF did not stain GBM of the male patient with HN, but produced segmental staining of GBM (i.e., some GBM stained, while others did not) of the female patient. In contrast, the rabbit anti-NC1 antibodies produced global staining by IF of GBM of both patients. The absence of staining (i.e., global or segmental) seen with the human anti-GBM PPF implied that the 26 K and 28 K monomers of NC1 were either absent from GBM, or were present but altered structurally, leading to a diminution in their immunological reactivity. However, the positive staining observed with the rabbit anti-NC1 antibodies implied that the 26 K monomer was actually present in GBM. Hence, we postulate that the 26 K monomer of NC1 in GBM was structurally altered, and that the 28 K monomer was either absent, or present but altered. These findings suggest that there is an abnormality of more than one monomer of NC1 in GBM of patients with HN.


Genome-wide analysis of long noncoding RNA and mRNA profiles in PRRSV-infected porcine alveolar macrophages.
Porcine reproductive and respiratory syndrome (PRRS), which is caused by PRRS virus (PRRSV), is one of the most globally devastating swine diseases. It is essential to develop new strategy to control PRRS via an understanding of mechanisms that PRRSV utilizes to interfere with the host's innate immunity. In this study, we deeply sequenced and analyzed long noncoding RNA (lncRNA) and mRNA expression profiles of the porcine alveolar macrophages (PAMs) after PRRSV infection. 126 lncRNAs and 753 mRNAs were differentially expressed between PRRSV-infected and control PAMs. The co-expressed genes of down-regulated lncRNAs were significantly enriched within NF-kappa B and toll-like receptor signaling pathways. Co-expression network analysis indicated that part of the dysregulated lncRNAs associated with the interferon-induced genes. These dysregulated lncRNAs may play an important role in the host's innate immune responses to PRRSV infection. However, further research is required to characterize the function of these lncRNAs.


Discovery and characterization of a stable lipase with preference toward long-chain fatty acids.
To identify novel lipases with stability and long-chain fatty acids preference by phylogenetic evolution analysis methods from database. Thermo-stable Candida antarctica Lipase-A (CALA) was set as a template for gene mining by PSI-BLAST. Based on phylogenetic analysis, three candidate lipases exhibiting 97%, 55%, and 35% identities with CALA, respectively, were selected for overexpression and characterization. Lipase, PhLip from Pseudozyma hubeiensis SY62 showed highest activity towards long-chain fatty acids, and showed maximum activity at pH 9.0 and 60 °C, and stability between 40 and 50 °C for 4 h and at pH 7-10 for 12 h. Enzymatic hydrolysis of Mucor circinelloides WJ11 oils by PhLip was about twofold higher than that by CALA, with respect to hydrolysis of long-chain fatty acids. Besides, fatty acids with 18 carbons, including oleic acid, linoleic acid, and linolenic acid, were preferred as substrates. The current investigation discovered a stable lipase PhLip with long-chain fatty acids preference. PhLip may be a potential candidate for producing polyunsaturated fatty acids from natural oils.


Gastric inhibitory polypeptide mechanisms of augmenting insulin secretion.
The cellular mechanisms whereby gastric inhibitory polypeptide (GIP) augments glucose-dependent insulin secretion remains poorly defined. Since glucose-dependent insulin secretion is modulated by membrane associated phospholipase A2 (PLA2) and intracellular lipoxygenase (LPX) and cyclooxygenase (CO) we hypothesize that GIP's augmentation of insulin secretion involves these enzyme systems. Neonatal rat pancreatic islet cell cultures were preincubated with 5.6mM glucose for 60 minutes. The cultures were then stimulated for 60 minutes with 16mM glucose alone or with GIP with or without the addition of PLA2, LPX, and CO inhibitors. Insulin secretion significantly increased (P less than 0.05) when the glucose concentration was raised from 5.6 to 16mM glucose and this was further augmented by the addition of GIP (P less than 0.05). PLA2 inhibitors significantly (P less than 0.025) decreased 16mM glucose insulin secretion but this was restored by the simultaneous addition of GIP. LPX inhibitors significantly (P less than 0.01) decreased glucose-dependent insulin secretion and this decrease persisted despite the addition of GIP. Simultaneous treatment of islet cell cultures with GIP and CO inhibitors yielded insulin responses that were indistinguishable from CO inhibition alone. These studies suggest that GIP exerts its influence in part by modulating membrane associated PLA2 activity. Furthermore, the formation of intracellular LPX products appears to be a pivotal step in the insulinotrophic action of GIP.


Contingent conversations build more than language: How communicative interactions in toddlerhood relate to preschool executive function skills.
High-quality communicative interactions between caregivers and children provide a foundation for children's social and cognitive skills. Although most studies examining these types of interactions focus on child language outcomes, this paper takes another tack. It examines whether communicative, dyadic interactions might also relate to child executive function (EF) skills and whether child language might mediate this relation. Using a subset of data from the NICHD Study of Early Child Care and Youth Development, dyadic interactions between 2-year-olds and their mothers were coded for three behaviors: symbol-infused joint engagement, routines and rituals, and fluency and connectedness. Child language was assessed at age 3 and three facets of EF (self-regulation, sustained attention, and verbal working memory) were assessed at age 4.5. Structural equation modeling showed that dyadic interaction related to later child sustained attention and verbal working memory, indirectly through child language and directly related with child self-regulation. This suggests that communicative interactions with caregivers that include both verbal and non-verbal elements relate to child EF, in part through child language. Our findings have implications for the role of caregiver interactions in the development of language and cognitive skills more broadly. RESEARCH HIGHLIGHTS: Using structural equation modeling, we examined how communicative interactions between caregivers and toddlers relate to preschool executive function skills Communicative interactions relate to later language which in turn relates to sustained attention and verbal working memory in preschool Communicative interactions relate directly to self-regulation in preschool Associations between communicative interactions, language, and executive function vary across facets of executive function and may not be unidirectional.


Application of integrated GIS and multimedia modeling on NPS pollution evaluation.
In Taiwan, nonpoint source (NPS) pollution is one of the major causes of the impairment of surface waters. I-Liao Creek, located in southern Taiwan, flows approximately 90 km and drains toward the Kaoping River. Field investigation results indicate that NPS pollution from agricultural activities is one of the main water pollution sources in the I-Liao Creek Basin. Assessing the potential of NPS pollution to assist in the planning of best management practice (BMP) is significant for improving pollution prevention and control in the I-Liao Creek Basin. In this study, land use identification in the I-Liao Creek Basin was performed by properly integrating the skills of geographic information system (GIS) and global positioning system (GPS). In this analysis, 35 types of land use patterns in the watershed area of the basin are classified with the aid of Erdas Imagine process system and ArcView GIS system. Results indicate that betel palm farms, orchard farms, and tea gardens dominate the farmland areas in the basin, and are scattered around on both sides of the river corridor. An integrated watershed management model (IWMM) was applied for simulating the water quality and evaluating NPS pollutant loads to the I-Liao Creek. The model was calibrated and verified with collected water quality and soil data, and was used to investigate potential NPS pollution management plans. Simulated results indicate that NPS pollution has significant contributions to the nutrient loads to the I-Liao Creek during the wet season. Results also reveal that NPS pollution plays an important role in the deterioration of downstream water quality and caused significant increase in nutrient loads into the basin's water bodies. Simulated results show that source control, land use management, and grassy buffer strip are applicable and feasible BMPs for NPS nutrient loads reduction. GIS system is an important method for land use identification and waste load estimation in the basin. Linking the information of land utilization with the NPS pollution simulation model may further provide essential information of potential NPS pollution for all subregions in the river basin. Results and experience obtained from this study will be helpful in designing the watershed management and NPS pollution control strategies for other similar river basins.


High-dose intravenous immunoglobulin in the treatment of Guillain-Barré syndrome: a preliminary open study.
We report the effects of intravenous gamma-globulin (IVGG) in severe Guillain-Barré syndrome (GBS) in a small open study. Seven patients were given IVGG (0.4 g/kg/day) for 5 consecutive days. At the start of treatment all had progressing limb weakness and none could stand unaided. Within 24 h all but one patient started to improve, without the expected plateau phase, and progress was maintained with a mean time to independent walking of 14 days. One patient started treatment 9 h prior to ventilation for 15 days but was walking independently 31 days after admission. This study provides further evidence that IVGG is a promising therapeutic alternative to plasmapheresis in GBS. The rapidity of the response to IVGG raises the possibility that a single dose regimen might be equally or more effective.


Elastin stabilization in cardiovascular implants: improved resistance to enzymatic degradation by treatment with tannic acid.
The long-term performance of tissue-derived, glutaraldehyde (Glut)-treated cardiovascular implants such as prosthetic heart valves and vascular grafts is limited by the bio-degeneration of tissue components. While collagen is satisfactorily preserved by Glut, elastin is not stabilized and is highly vulnerable to degradation. The aim of our studies was to develop methods for efficient stabilization of elastin and subsequently reduce its vulnerability towards enzymatic degradation. More specifically, we investigated the use of tannic acid (TA)1 as a novel agent that specifically targets elastin stabilization. Basic investigations on in vitro interactions between Glut, TA and pure aortic elastin provided clear evidence that Glut treatment does not protect elastin from enzymatic degradation. TA bound to elastin in a time-dependent pattern and this binding increased the resistance of elastin to enzymatic degradation. In addition, when TA was used in mixture with Glut, the kinetic of TA binding to elastin was enhanced and this was translated into improved elastin stabilization. Our results clearly documented the superiority of TA as an elastin-stabilizing agent by comparison with the commonly utilized Glut-based tissue crosslinking techniques.


Impact of smoking on the eradication of Helicobacter pylori.
Although the association between the eradication of Helicobacter pylori (H. pylori) and smoking has been confirmed through a meta-analysis, many new studies have reported inconsistent conclusions. An up-to-date meta-analysis based on published relevant studies was conducted in this study to address this issue. Eligible studies up to January 2021 were screened and retrieved using PubMed and Web of Science as well as by performing a manual review of references. We calculated the pooled odd ratios (OR) with the 95% confidence interval (CI). Subgroup and sensitivity analyses were also performed. Begg's test was used to determine the publication bias. In total, 39 studies were included in the meta-analysis. The results showed that smoking increases the failure rate of H. pylori eradication treatment (OR = 1.70, 95%CI, 1.49-1.93). The risk of failure also increases with an increase in the smoking dose (>5 cigarettes per day) (OR = 2.59, 95%CI, 1.28-5.24) and the current smoking status (continued to smoke during treatment) (OR = 2.49, 95%CI, 1.52-4.06). Studies with a large proportion of patients with peptic ulcer (OR = 2.14, 95%CI, 1.51-3.02) revealed a higher failure rate among smokers than those with a low proportion of patients with peptic ulcer (OR = 1.57, 95%CI, 1.36-1.81). When vonoprazan (VPZ) was used to treat H. pylori infection, smoking did not affect the eradication rate (OR = 0.94, 95%CI, 0.51-1.75). Smoking increases the failure rate of H. pylori eradication treatment. The risk of H. pylori eradication failure in smokers increases with a current smoking status and a high smoking dose. However, when VPZ is used to treat the H. pylori infection, smoking has no effect on the eradication rate.


TGF-β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro.
Nickel oxide nanoparticles (Nano NiO) bears hepatotoxicity, while whether it leads to liver fibrosis remains unclear. The aim of this study was to establish the Nano NiO-induced hepatic fibrosis model in vivo and investigate the roles of transforming growth factor β1 (TGF-β1) in Smad pathway activation, epithelial-mesenchymal transition (EMT) occurrence, and extracellular matrix (ECM) deposition in vitro. Male Wistar rats were exposed to 0.015, 0.06, and 0.24 mg/kg Nano NiO by intratracheal instilling twice a week for 9 weeks. HepG2 cells were treated with 100 μg/mL Nano NiO and TGF-β1 inhibitor (SB431542) to explore the mechanism of collagen formation. Results of Masson staining as well as the elevated levels of type I collagen (Col-I) and Col-III suggested that Nano NiO resulted in hepatic fibrosis in rats. Furthermore, Nano NiO increased the protein expression of TGF-β1, p-Smad2, p-Smad3, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase9 (MMP9), and tissue inhibitors of metalloproteinase1 (TIMP1), while decreased the protein content of E-cadherin and Smad7 in rat liver and HepG2 cells. Most importantly, Nano NiO-triggered the abnormal expression of the abovementioned proteins were all alleviated by co-treatment with SB431542, implying that TGF-β1-mediated Smad pathway, EMT and MMP9/TIMP1 imbalance were involved in overproduction of collagen in HepG2 cells. In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF-β1-mediated Smad pathway activation, EMT occurrence, and ECM deposition.


Liver transplantation for biliary atresia: a systematic review.
Biliary atresia (BA) is an idiopathic neonatal cholangiopathy characterized by progressive inflammatory obliteration of the intrahepatic or extrahepatic bile ducts. Although the Kasai operation has dramatically improved the outcomes in children with BA, most patients with BA eventually require liver transplantation (LT) even after undergoing a successful Kasai procedure. The Japanese LT Society (JLTS) was established in 1980 to characterize and follow trends in patient characteristics and the graft survival among all liver transplant patients in Japan. The 1-, 5-, 10-, 15- and 20-year survival rates for the patients and grafts undergoing living donor LT were 91.6, 91.5, 87.1, 85.4 and 84.2 and 90.5, 90.4, 84.6, 82.0 and 79.9%, respectively. LDLT was able to be performed even in patients weighing less than 5 kg with early liver failure following a Kasai operation using a reduced left lateral segments. As LT has been revealed to increase the donor pool and decrease the waiting list mortality with an excellent long-term graft survival, early referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history, especially in adolescents.


TLR2 modulates gut colonization and dissemination of Candida albicans in a murine model.
Invasive candidiasis often arises from translocation of endogenous yeasts from the gastrointestinal tract to the bloodstream. Here we describe that both wild type and TLR2-/- mice strains, orally administered with Candida albicans yeasts, display similar sustained high level of gut colonization when oral antibacterial treatment is present, while removal of antibiotic treatment causes a progressive clearance of yeasts in control but not in TLR2-/- mice. Fungal invasion of internal organs, following immunosuppression of colonized mice, was increased in TLR2-/- mice. These results point out to a role of TLR2 in gut protection against colonization and endogenous invasion by C. albicans.


Neuropsychologic aspects of multiple sclerosis.
The psychological well being of the patient and the patient's entire family is critically important to successful rehabilitation of individuals with multiple sclerosis (MS). This article deals with the psychotherapeutic management and problems faced by the person with MS, including fatigue, chronic pain, stressful life events, and cognitive defects.


Cerebellar aminergic neuromodulation: towards a functional understanding.
Although a number of neuromodulators influence the cerebellar circuitry, their functions remain largely unknown. By reviewing and combining results from data-driven and theory-driven studies, we attempt to provide an integrated systems view of cerebellar neuromodulation. First, we review the short- and long-term effects of neuromodulators on the cerebellar circuitry. Second, we review recent theories of the cerebellum and show that a number of modulatory signals are needed for powerful cerebellar learning and control. Finally, we attempt to match each theoretically derived modulatory signal with a specific neuromodulator. In particular, we propose that serotonin controls the 'responsibility' of each cerebellar unit (or microcomplex) in cerebellar learning and control; norepinephrine gates unsupervised learning in the cerebellar cortex; dopamine enhances goal-oriented cerebellar learning; and, finally, acetylcholine controls the speed of supervised learning in Purkinje cells.


Membrane estrogen signaling enhances tumorigenesis and metastatic potential of breast cancer cells via estrogen receptor-α36 (ERα36).
Protein kinase C (PKC) signaling can be activated rapidly by 17β-estradiol (E(2)) via nontraditional signaling in ERα-positive MCF7 and ERα-negative HCC38 breast cancer cells and is associated with tumorigenicity. Additionally, E(2) has been shown to elicit anti-apoptotic effects in cancer cells counteracting pro-apoptotic effects of chemotherapeutics. Supporting evidence suggests the existence of a membrane-associated ER that differs from the traditional receptors, ERα and ERβ. Our aim was to identify the ER responsible for rapid PKC activation and to evaluate downstream effects, such as proliferation, apoptosis, and metastasis. RT-PCR, Western blot, and immunofluorescence were used to determine the presence of ER splice variants in multiple cell lines. E(2) effects on PKC activity were measured with and without ER-blocking antibodies. Cell proliferation was determined by [(3)H]thymidine incorporation, and cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, (MTT) whereas apoptosis was determined by DNA fragmentation and TUNEL. Quantitative RT-PCR and sandwich ELISA were used to determine the effects on metastatic factors. The role of membrane-dependent signaling in cancer cell invasiveness was examined using an in vitro assay. The results indicate the presence of an ERα splice variant, ERα36, in ERα-positive MCF7 and ERα-negative HCC38 breast cancer cells, which localized to plasma membranes and rapidly activated PKC in response to E(2), leading to deleterious effects such as enhancement of proliferation, protection against apoptosis, and enhancement of metastatic factors. These findings propose ERα36 as a novel target for the development of therapies that can prevent progression of breast cancer in the primary tumor as well as during metastasis.


[Empowerment and Stigma as Mediator Variables Between Illness Severity and Quality of Life of Patients with Affective Disorders].
The investigation of mediating effects of empowerment and stigmatization on the association between depressive symptoms and subjective quality of life in patients with affective disorders. Depressive Symptoms (BDI-II), internalized and perceived stigmatization (ISMI; PDDQ), empowerment (EPAS) and subjective quality of life (WHOQOL-BREF) were assessed in 37 patients with affective disorders (F31 - F33; ICD-10), age 18+ in inpatient, day hospital or outpatient psychiatric treatment. Data analyses were conducted by means of path-analysis. Empowerment and in low proportion internalized and perceived stigma turned out to be mediating variables between the severity of depression and subjective quality of life. 57 % of the variance of the subjective quality of life could be explained by the path model. Empowerment has meaningful influence mediating between depression and subjective quality of life. In order to improve the quality of life of patients with an affective disorder, strategies for increasing empowerment are to be integrated into treatment.


Phylogenetic analysis, molecular characterization and virulence profiling based on toxoflavin gene of an Indian BG1 strain of Burkholderia glumae causing panicle blight of rice.
Bacterial panicle blight (BPB) caused by Burkholderia glumae (BG) has become significantly more prevalent in the rice-growing regions of North India. Based on virulence screening and in vitro quantification of toxoflavin, the BG strains were classified as hyper- (BG1 and BG3), moderate- (BG2, BG4, BG6, BG8, and BG9), and hypo- (BG5, BG7, and BG10) virulent. Plant inoculation assays with cell-free culture filtrate revealed strains with higher toxoflavin-producing ability had higher virulence. Based on 16S rRNA sequence, 6 isolates from Uttar Pradesh were grouped in clad C1; whereas, clad C2 exhibited 4 isolates, two each from Delhi and Uttar Pradesh. Strain BG1 being the most virulent Indian strain from Uttar Pradesh was further profiled for 11 tox genes. We found all the 11 tox genes present in strain BG1. In toxRABCDE cluster, all tox genes showed high similarity to B. glumae BGR1 except toxB, whereas in toxFGHIJ cluster toxF, toxG, toxH and toxI shared maximum similarity to B. glumae 336gr-1. tox genes of BG1 exhibited homology as well as divergence with B. gladioli. The domain prediction and protein association network analysis indicated the possible involvement of tox genes in the toxoflavin biosynthesis. As per our knowledge, this is the first report in India on characterization of tox genes cluster in B. glumae. Altogether, our study unravels a reliable method for identifying and characterizing B. glumae using tox genes and its relationship with disease production. The online version contains supplementary material available at 10.1007/s13205-023-03660-6.


Surgical safety checklists and understanding of Never Events, in UK and Irish dental hospitals.
Aim To identify the procedures in dental hospitals where a surgical safety checklist is used and in addition, in England, to identify the understanding of hospitals regarding patient safety incidents requiring reporting as Never Events to NHS England.Method A self-completed questionnaire survey asking about the use of checklists was distributed to 16 dental hospitals associated with undergraduate dental schools in the UK and Ireland in the summer of 2015. For hospitals in England (10), additional questions regarding their understanding of incidents to be reported as Never Events were asked.Results Thirteen hospitals replied (8 in England). All use a surgical safety checklist in an operating theatre setting. Ten use a surgical safety checklist in an outpatient setting for the extraction of teeth. There is variable use of checklists for other procedures. The majority of English hospitals thought that the reporting of a 'Never Event' was required following wrong tooth extraction in whatever setting it occurred, including general dental practice.Conclusion Surgical safety checklists are increasingly used in dental hospitals, especially for oral surgery procedures. Beyond 'wrong tooth extraction', English dental hospitals have different understandings of what other oral and dental procedures require reporting as Never Events to NHS England.


Strengthening flash light effect with a pond-tubular hybrid photobioreactor to improve microalgal biomass yield.
Poor light utilization efficiency and large occupied area of traditional raceway pond photobioreactors result in low areal microalgal biomass yield in industrial applications. In this study, a pond-tubular hybrid photobioreactor (PTH-PBR) comprising raceway ponds and horizontal tubes was developed to strengthen flash light effect and improve areal microalgal biomass yield. The highest flash cycle frequency (0.63 Hz) of microalgae cells along flow pathway was obtained in the raceway pond of PTH-PBR when shaded area percentage was 20% and ratio of adjacent tube interval to tube diameter was 1, which enhanced microalgal biomass yield by 31.2% than traditional raceway pond. Meanwhile, intracellular chlorophyll content increased by 33.6% and PSII maximum quantum yield (Fv/Fm) increased by 8.1% due to decreased photoinhibition stress. The areal microalgal biomass yield of PTH-PBR was 54.7% higher than that of traditional raceway pond without horizontal tubes.


Microbial diversity in paddy rhizospheric soils around a large industrial thallium-containing sulfide utilization zone.
Thallium (Tl) is a rare and extremely toxic metal whose toxicity is significantly higher than cadmium (Cd), lead (Pb) and antimony (Sb). The extensive utilization of Tl-bearing minerals, such as mining activities, has led to severe Tl pollution in a variety of natural settings, while little is known to date about its effect on the microbial diversity in paddy soils. Also, the geochemical behavior of Tl in the periodical alterations between dry and wet conditions of paddy soils remains largely unknown. Herein, the sequential extraction method and 16S rRNA gene sequence analysis were adopted to analyze Tl's migration and transformation behavior and the microbial diversity in the paddy soils with different pollution levels. The results indicated that Tl was mainly concentrated in reducible fraction, which is different from other types of soils, and may be closely attributed to the abundance of Fe-Mn (hydr)oxides in the paddy rhizospheric soils. Further analysis revealed that pH, total S, Pb, Sb, Tl and Cd were the dominant environmental factors, and the enrichment level of these potentially toxic metal(loid)s (PTMs) exerted obvious impacts on the diversity and abundance of microorganism in the rhizospheric soils, and regulating microbial community. The geochemical fractionation of Tl was closely correlated to soil microorganisms such as Fe reducing bacteria (Geothrix) and sulfate reducing bacteria (Anaerolinea), playing a critical role in Tl geochemical cycle through redox reaction. Hence, further study on microorganisms of paddy rhizospheric soils is of great significance to the countermeasures for remediating Tl-polluted paddy fields and protect the health of residents.


Changes in the lesion surface suggesting transformation of oral potentially malignant disorders to malignancy - a report of eight cases.
In the case of oral potentially malignant disorders (OPMD), the possibility of malignant transformation of the lesion necessitates a decision on the need for an additional biopsy at each visit. Among many clinical characteristics, change on the lesion surface is one of the important factors that determine the need for additional biopsy at each visit. The purpose of the study was to provide information on the characteristics of lesions related to malignant transformation during the follow-up period of OPMD. Eight patients (four men and four women) with OPMD that transformed into malignancy during long-term follow-up were included and their mean age was 65.8 ± 12.4 years. Clinical information and histopathological diagnosis were investigated at the initial visit and during the long-term follow-up period. The focus was on information on changes on the lesion surface at the time the lesion was confirmed to be malignant. The period from initial diagnosis to dysplasia and from dysplasia to malignancy was also investigated. The OPMD diagnoses were oral lichen planus or oral lichenoid lesions (n = 2), oral leukoplakia (n = 5), and hyperplastic candidiasis (n = 1). During the follow-up period of the lesions, when dysplasia was obtained by additional biopsy, changes in the lesions consisted of an increase in the size of the white or red area. The lesion surface of the OPMD showed verrucous, papillary, exophytic, corrugated, and ulcerative changes at the time of malignancy diagnosis. The period for the initial lesion to become dysplasia, from dysplasia to malignancy, and from the initial lesion to malignancy was very variable. Attention should be paid to verrucous, papillary, exophytic, corrugated, and ulcerative changes on the lesion surface of OPMD. Considering that the period for OPMD to become malignant is highly variable, a longer follow-up of the lesion is necessary.


Prevalence and risk factors of long COVID 6-12 months after infection with the Omicron variant among nonhospitalized patients in Hong Kong.
Long COVID has been reported among patients with COVID-19, but little is known about the prevalence and risk factors associated with long COVID 6-12 months after infection with the Omicron variant. This is a large-scale retrospective study. A total of 6242 out of 12 950 nonhospitalized subjects of all ages with SARS-CoV-2 infection (confirmed by polymerase chain reaction/rapid antigen test) during the Omicron dominant outbreak (December 31, 2021-May 6, 2022) in Hong Kong were included. Prevalence of long COVID, frequencies of symptoms, and risk factors were analyzed. Three thousand four hundred and thirty (55.0%) subjects reported at least one long COVID symptom. The most reported symptom was fatigue (1241, 36.2%). Female gender, middle age, obesity, comorbidities, vaccination after infection, having more symptoms, and presenting fatigue/chest tightness/headache/diarrhea in the acute stage of illness were identified as associated risk factors for long COVID. Patients who had received three or more doses of vaccine were not associated with a lower risk of long COVID (adjusted odds ratio 1.105, 95% confidence interval 0.985-1.239, p = 0.088). Among patients with at least three doses of vaccine, there was no significant difference in the risk of long COVID between the CoronaVac vaccine and BNT162b2 vaccine (p > 0.05). Omicron infection can lead to long COVID in a significant proportion of nonhospitalized patients 6-12 months after infection. Further investigation is needed to uncover the mechanisms underlying the development of long COVID and determine the impact of various risk factors such as vaccines.


Cytokine expression in murine cytomegalovirus-induced myocarditis: modulation with interferon-alpha therapy.
Cytomegalovirus-induced myocarditis is largely immune-mediated. BALB/c mice produced higher levels of IL-4 in the heart indicative of a Th2-like response. Although IL-6, IL-10, IL-18, and TNF-alpha were produced in the heart during acute infection, BALB/c mice lacked a substantial IL-2 and IFN-gamma response. Conversely, C57BL/6 mice produced significant levels of IFN-gamma in the heart with no significant levels of IL-4 or IL-6, suggestive of a dominant Th1-like response to virus infection. IFN-alpha/beta immunotherapy is known to suppress the development of MCMV-myocarditis. Cytokine secretion in IFN-stimulated MCMV-infected BALB/c myocytes was found to be IFN subtype-dependent with elevation of IL-6 and IL-18 levels. During the chronic phase of disease, IFNA6 DNA treatment in vivo increased IL-18 production in the heart. These results suggest that IFN subtype therapy may have immunomodulating effects in reducing disease severity in BALB/c mice via regulation of cytokine production in the heart.