Stereospecific high-performance liquid chromatographic assay of lomefloxacin in human plasma.
This report describes an HPLC assay developed for the quantification of the enantiomers of lomefloxacin (LFLX), a quinolone antibiotic, in plasma. Following addition of racemic acebutolol (internal standard, IS), plasma samples were extracted at pH 7 with a mixture of chloroform-isopentyl alcohol-diethyl ether (71.25:3.75:25, v/v/v). The organic layer was evaporated, and LFLX and IS enantiomers in the resulting residue were derivatized with chloroform solutions of 1% triethylamine and 1% (S)-(+)-(1-naphthyl)ethyl isocyanate, followed by 2% ethyl chloroformate (ECF) 1 min later. Ethanolamine was added 30 s after the addition of ECF. The enantiomers were separated as diastereomers on an 8 x 100 mm Radial Pak normal phase column using a mobile phase of hexane-chloroform-methanol (64.5:33:2.5, v/v/v) pumped at 2.0 ml min-1. The IS was detected by fluorescence at 245 and 420 nm (excitation and emission, respectively) during the first 12 min, after which time the wavelengths were 280 and 470 nm for detection of LFLX. The method: (1) was sensitive and showed excellent linearity (10-1000 ng ml-1, r2 > 0.99) between added enantiomer concentrations and peak-area-ratio (LFLX/IS); and (2) separated LFLX and IS enantiomers within 25 min. The assay is suitable for the quantification of LFLX enantiomers in plasma samples.


Immunologically relevant aspects of the new COVID-19 vaccines-an ÖGAI (Austrian Society for Allergology and Immunology) and AeDA (German Society for Applied Allergology) position paper.
The vaccines against the coronavirus disease 2019 (COVID-19) approved in the European Union represent a decisive step in the fight against the pandemic. The application of these available vaccines to patients with pre-existing immunological conditions leads to a multitude of questions regarding efficacy, side effects and the necessary patient information. This review article provides insight into mechanisms of action of the currently available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and summarises the current state of science as well as expert recommendations regarding tolerability of the vaccines. In addition, the potential to develop protective immune responses is determined. A special focus is given on patients under immunosuppression or in treatment with immunomodulatory drugs. Special groups of the population such as children, pregnant women and the elderly are also considered. Despite the need for a patient-specific risk-benefit assessment, the consensus among experts is that patients with immunological diseases in particular benefit from the induced immune protection after COVID-19 vaccination and do not have an increased risk of side effects.


3D printed concentrated alginate/GelMA hollow-fibers-packed scaffolds with nano apatite coatings for bone tissue engineering.
Three-dimensional grafts/scaffolds with hierarchically biomimetic features from nano to macro scale and high porosity are required for bone tissue engineering. In this study, biomimetic organic/inorganic composite scaffolds with high porosity (78.7 ± 3.2%) and features from nano (nano apatite coatings) to macro (macro pores and hollow channels) scale were fabricated based on highly concentrated alginate/GelMA bioinks via co-axial 3D printing and in situ mineralization under mild conditions. Nano apatites were coated on both inner and outer surfaces of the hollow fiber scaffolds, homogeneously. Proteins were directly loaded in the bioinks achieving sustained release from the scaffolds over 28 days. The in vitro cell experiments showed that the scaffolds with good biocompatibility could support cells adhesion and proliferation. The nano apatite coatings presented remarkable osteogenic capability. The in vivo study indicated that the hollow fiber scaffolds with biomimetic nano apatite coatings showed the capability to enhance bone formation after 12 weeks of implantation. In conclusion, the prepared biomimetic organic/inorganic scaffolds with homogeneous nano apatite coatings and hollow channels structures might be potential candidates for bone tissue engineering.


Fetal type IV glycogen storage disease: clinical, enzymatic, and genetic data of a pure muscular form with variable and early antenatal manifestations in the same family.
We report on a family of three consecutive fetuses affected by type IV glycogen storage disease (GSD IV). In all cases, cervical cystic hygroma was observed on the 12-week-ultrasound examination. During the second trimester, fetal hydrops developed in the first pregnancy whereas fetal akinesia appeared in the second pregnancy. The diagnosis was suggested by microscopic examination of fetal tissues showing characteristic inclusions exclusively in striated fibers, then confirmed by enzymatic studies on frozen muscle. Antenatal diagnosis was performed on the third and fourth pregnancies: cervical cystic hygroma and low glycogen branching enzyme (GBE) activity on chorionic villi sample (CVS) were detected in the third pregnancy whereas ultrasound findings were normal and GBE activity within normal range on CVS in the fourth pregnancy. Molecular analysis showed that the mother was heterozygous for a c.1471G > C mutation in exon 12, leading to the replacement of an alanine by a tyrosine at codon 491 (p.A491T); the father was heterozygous for a c.895G > T mutation in exon 7, leading to the creation of a stop codon at position 299 (p.G299X). GSD IV has to be considered in a context of cervical cystic hygroma with normal karyotype, particularly when second trimester hydrops or akinesia develop. Enzymatic analysis of GBE must be performed on CVS or amniotic cells to confirm the diagnosis. Characteristic intracellular inclusions are specific to the disease and should be recognized, even in macerated tissues after fetal death. Genetic analysis of the GBE gene may help to shed some light on the puzzling diversity of GSD IV phenotypes.


Successful hemostasis in refractory alveolar hemorrhage using low-dose recombinant activated factor VII.
Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring prompt recognition. Conventional therapy, even when initiated early, may not have an immediate effect, and in severe cases, bleeding can persist despite treatment. We report the case of a previously healthy 33-year-old male who developed DAH secondary to granulomatosis with polyangiitis, resulting in respiratory failure and the need for mechanical ventilation. High-dose corticosteroids, plasma exchange, and remission induction with cyclophosphamide failed to control bleeding, leading to severely impaired gas exchange. 20 mcg/kg of systemic recombinant activated Factor VII (rFVIIa), a dose lower than previously reported for management of DAH, resulted in hemostasis and improved oxygenation after only three doses. No complications were observed, and our patient was liberated from ventilatory support eight days later. In the setting of DAH with refractory bleeding, hemostasis may be achievable with a lower dose of rFVIIa than commonly used, potentially mitigating the risk of dose-dependent side effects.


Arsenic Resistance Mechanisms in Pseudomonas mendocina SMSKVR-3 Strain Isolated from Khetri Copper Mines, Rajasthan, India.
An arsenic resistant bacteria SMSKVR-3 has been isolated from the rhizospheric soil of the metal-contaminated site of khetri copper mines situated in the Jhunjhunu district of Rajasthan, India. The strain showed homology with Pseudomonas mendocina strain ATCC 25411. This gram-negative isolate exhibited optimal growth in M9 minimal media with temperature and salt concentration as 30 °C and 0.25% (w/v), respectively, at pH 7.0. The similar growth pattern and SEM analysis of this strain exposed to M9 minimal media alone, M9 media supplemented with 300 mM arsenate [As(V)] or M9 media supplemented with 1.34 mM arsenite [As(III)] indicate the existence of the strong arsenic resistance mechanism. The isolate was able to produce siderophores and was able to reduce As(V) to As(III). A decrease in polyP concentration from 354.8 µg/1010 CFU mL-1 at 0 h to 0.043 µg/1010 CFU mL-1 at 8 h incubation with As(V) was in correlation with the change in intracellular As(V) concentration (116.98 mg L-1/1010 cells at 0 h to 88.65 mg L-1/1010 at 8 h) with time. This shows the possible role of polyP bodies in the regulation of As(V) concentration inside the cell. The presence of arsC gene in P.mendocina SMSKVR-3 was confirmed by the PCR amplification of arsC gene. The BLAST analysis of the sequenced gene represented 98.59% identity with the P. mendocina S5.2 arsenate reductase. These results indicate that the observed arsenic resistance in SMSKVR-3 is due to a combination of siderophore production, the transformation of As(V) to As(III) by arsenate reductase, multi-drug efflux pump, and polyP bodies mediated metal resistance mechanism.


Cost-effectiveness analysis of ankle-brachial index screening in patients with coronary artery disease to optimize medical management.
Screening for peripheral artery disease (PAD) with the ankle-brachial index (ABI) test is currently not recommended in the general population; however, previous studies advocate screening in high-risk populations. Although providers may be hesitant to prescribe low-dose rivaroxaban to patients with coronary artery disease (CAD) alone, given the reduction in cardiovascular events and death associated with rivaroxaban, screening for PAD with the ABI test and accordingly prescribing rivaroxaban may provide additional benefits. We sought to describe the cost-effectiveness of screening for PAD in patients with CAD to optimize this high-risk populations' medical management. We used a Markov model to evaluate the ABI test in patients with CAD. We assumed that all patients screened would be candidates for low-dose rivaroxaban. We assessed the cost of ABI screening at $100 per patient and added additional charges for physician visits ($100) and rivaroxaban cost ($470 per month). We used a 30-day cycle and performed analysis over 35 years. We evaluated quality-adjusted life years (QALYs) from previous studies and determined the incremental cost-effectiveness ratio (ICER) according to our model. We performed a deterministic and probabilistic sensitivity analyses of variables with uncertainty and reported them in a Tornado diagram showing the variables with the greatest effect on the ICER. Our model estimates decision costs to screen or not screen at $94,953 and $82,553, respectively. The QALYs gained from screening was 0.060, generating an ICER of $207,491 per QALY. Factors most influential on the ICER were the reduction in all-cause mortality associated with rivaroxaban and the prohibitively high cost of rivaroxaban. If rivaroxaban cost less than $95 per month, this would make screening cost-effective based on a willingness to pay threshold of $50,000 per QALY. According to our model, screening patients with CAD for PAD to start low-dose rivaroxaban is not currently cost-effective due to insufficient reduction in all-cause mortality and high medication costs. Nevertheless, vascular surgeons have a unique opportunity to prescribe or advocate for low-dose rivaroxaban in patients with PAD to improve cardiovascular outcomes.


Palliative shoulder and elbow surgery in obstetrical brachial plexus birth palsy.
Palliative surgery in a child with incomplete recovery following obstetric brachial plexus birth palsy (BPBP) is common. Surgical management strategies for BPBP sequelae have the common objectives of decreasing the risk of functional limitations in the long term and improving function. There is no single treatment to deal with the sequelae of BPBP. While there is a myriad of possible clinical presentations, the ages for surgery extend from a 6- to 12-month-old infant to the mature adolescent. Numerous procedures have been described in the literature, ranging from simple soft tissue release to muscular transfers and osteotomies. The indications will depend on a combination of all these factors. In certain cases, an early intervention is recommended to prevent joint deformities, and to allow joint remodeling, often at the shoulder. In other cases, the indications are less clear, thus the expected benefit must be carefully considered. The indications for these operations must meet certain rules to be beneficial for the patient and should only be considered after a comprehensive clinical examination and a commitment from the child and the family to the therapeutic strategy.


Applying radiobiological principles to combined modality treatment of head and neck cancer--the time factor.
Combined modality treatment is indicated for most advanced stage head and neck cancers. It is postulated that the efficacy of combined modality regimens could be enhanced by applying principles derived from radiotherapy fractionation studies to optimize the time factor in treatment scheduling. The premise that tumor clonogens surviving a therapeutic intervention undergo accelerated repopulation in a time-dependent fashion as their numbers are depleted is used as a model to interpret the results of various chemoradiotherapy and postsurgical radiotherapy protocols and to suggest ways in which future combined modality regimens can be more rationally designed. Meta-analyses of chemoradiotherapy trials show the general superiority of concomitant vs. neoadjuvant sequential protocols. There is also emerging evidence that both the duration of postoperative radiotherapy and the delay in its instigation affect treatment outcome. These results are compatible with the hypothesis that the overall duration of the "package deal" of combined modality treatment is an important determinant of outcome. However, a large decrease in duration of the "package deal" does not necessarily translate into a therapeutic gain because the total dose has to be lowered to prevent intolerable acute reactions. In these circumstances tumor control will improve only if the reduced treatment time circumvents more tumor cell regeneration than the cytoreduction that could be achieved by the extra dose tolerable in a longer time period. More modest reductions in treatment time can be accomplished without dose reduction and so avoid this risk. The design of new protocols should take account of the fact that regeneration of tumor clonogens can be predicted to be nonuniform with time. Thus, the greatest therapeutic gain should be achieved by targeting periods of maximal regenerative capacity for shortening or, alternatively, for intensification of treatment. These periods are the latter part of a course of radiotherapy or chemotherapy and the early postoperative phase after surgery. The rational design of combined modality protocols should include principles concerning the time factor derived from radiotherapy fractionation studies. Periods of maximal tumor cell regeneration should be targeted for shortening or for treatment intensification. Any dose sacrifice necessitated by reducing treatment duration must be less than the dose equivalent of regeneration during the same time period.


[Results of determining the sensitivity of hypernephroid cancer to cytostatic agents in vitro and clinically].
Sensitivity of the cells of 57 human hypernephromas was determined with respect to 8 drugs, i.e. tiodipin, fluorbenzotef, mithramycin, cyclophosphan, tiotef, rubomycin, 5-fluoruracyl and olivomycin with the help of the method of primary plasma cultures. Because of the changes introduced earlier into the estimative concentrations used in vitro, coincidence of the results of the sensitivity determined in vitro with the results obtained during the treatment of the same patients in clinics, significantly increased (up to 90 per cent).


Comparison of glycoproteins by two-dimensional mapping of glycosylated peptides.
We describe here a two-dimensional mapping procedure which is capable of resolving glycopeptides isolated by lectin affinity chromatography from radioiodinated tryptic digests of glycoproteins. Glycopeptide maps were successfully produced for the model proteins alpha 1-acid glycoprotein and fetuin, as well as for the two surface glycoproteins gp90 and gp45 from equine infectious anemia virus (EIAV). Differences were detected in the glycopeptide maps obtained for the gp90 and gp45 components from two antigenically distinct strains of EIAV, demonstrating the ability of this procedure to detect variations in glycosylation in closely related glycoproteins. Thus this glycopeptide mapping technique provides a simple, rapid method to study changes in glycopeptides requiring only micrograms of glycoprotein.


[Keratosis palmoplantaris papulosa].
Keratosis palmoplantaris punctata (KPPP) is a rare genodermatosis inherited in autosomal dominant fashion. Clinical findings are multiple, hyperkeratotic, mostly asymptomatic, pinhead-sized papules localized on the palms and soles with progression to hyperkeratotic plaques at pressure sites. A 79-year-old woman presented with a history of hyperkeratotic papules on the palms and soles. Clinical and histopathologic criteria led to the diagnosis KPPP. Identification of causative genes is necessary to permit a better classification and estimation of associated disorders.


Non-hematopoietic STAT6 induces epithelial tight junction dysfunction and promotes intestinal inflammation and tumorigenesis.
Enhanced gut permeability due to dysregulated epithelial tight junction is often associated with inflammatory bowel diseases (IBD), which have a greater risk for developing colorectal cancer. STAT6 activation was detected in inflamed colonic epithelium of active IBD patients, suggesting a role of epithelial STAT6 in colitis development. Here, we demonstrated that non-hematopoietic STAT6, but not hematopoietic STAT6, triggered DSS-induced colitis and subsequent tumorigenesis. This could be due to the enhancing-effect of STAT6 on gut permeability and microbiota translocation via interruption of epithelial tight junction integrity. Mechanistically, long-myosin light-chain kinase (MLCK1) was identified as a target of STAT6, leading to epithelial tight junction dysfunction and microbiota-driven colitis. Furthermore, neutralization of IL-13, which was primarily derived from type 2 innate lymphoid cells (ILC2) in a microbiota-dependent way, inhibited epithelial STAT6 activation and improved gut permeability and DSS-induced colitis. Importantly, pharmacological inhibition of STAT6 reduces murine intestinal tumor formation, and tumoral p-STAT6 levels positively correlated to the clinical stage and poor prognosis of human colorectal cancer. Thus, our study reveals a direct role of STAT6 in the disruption of epithelial tight junction integrity and colitis development, and suggests STAT6 as a potential therapeutic and prophylactic target for IBD and colitis-associated cancer.


Gluten Sensitivity among Egyptian Infants with Congenital Heart Disease.
Gastrointestinal symptoms are a common feature in infants with congenital heart disease. This study was designed to evaluate age-dependent serum levels of antigliadin antibodies among malnourished Egyptian infants with congenital heart disease (CHD) and gastrointestinal symptoms. This case-control study conducted on 60 infants with established congenital heart disease. They were subdivided into cyanotic and acyanotic groups, and each group includes 30 patients compared with thirty apparently healthy infants of matched age, sex, and social class. Serum antigliadin antibodies levels were measured using ELISA. The mean age of introduction of cereals in the diet and appearance of gastrointestinal symptoms were six months. On comparison with controls, patients showed highly significant higher serum levels of antigliadin antibodies (P < 0.000). On analysing risk factors using odds ratio, the age at onset of GIT symptoms, diarrhoea, abdominal pain, and distension had been found to be significantly associated with high serum antigliadin antibodies among malnourished CHD infants with a prediction of 95%. Serum IgA, IgM, and IgG class antibodies to gliadin play a significant role in the pathogenesis of malnutrition in infants with CHD. Gluten containing foods should never be introduced before the end of the six months.


Phosphorylation and Dephosphorylation of Tau Protein by the Catalytic Subunit of PKA, as Probed by Electrophoretic Mobility Retard.
Tau is a microtubule associated protein that regulates the stability of microtubules and the microtubule-dependent axonal transport. Its hyperphosphorylated form is one of the hallmarks of Alzheimer's disease and other tauopathies and the major component of the paired helical filaments that form the abnormal proteinaceous tangles found in these neurodegenerative diseases. It is generally accepted that the phosphorylation extent of tau is the result of an equilibrium in the activity of protein kinases and phosphatases. Disruption of the balance between both types of enzyme activities has been assumed to be at the origin of tau hyperphosphorylation and the subsequent toxicity and progress of the disease. We explore the possibility that, beside the phosphatase action on phosphorylated tau, the catalytic subunit of PKA catalyzes both tau phosphorylation and also tau dephosphorylation, depending on the ATP/ADP ratio. We use the shift in the relative electrophoretic mobility suffered by different phosphorylated forms of tau, as a sensor of the catalytic action of the enzyme. The results are in agreement with the long-known thermodynamic reversibility of the phosphorylation reaction (ATP + Protein = ADP+Phospho-Protein) catalyzed by PKA and many other protein kinases. The results contribute to put the compartmentalized energy state of the neuron and the mitochondrial-functions disruption upstream of tau-related pathologies.


Modified Irinotecan Plus Cisplatin and Dexamethasone (ICD) Combination Chemotherapy as Salvage Chemotherapy for Patients with Relapsed/Refractory Diffuse Large Cell Lymphoma.
About 50 % of patients with diffuse large cell lymphoma are candidate for salvage chemotherapy followed by bone marrow transplantation in the selected patients. In the current study we evaluated modified ICD (Irinotecan, Cisplatin, and Dexamethasone with G-CSF support) as salvage chemotherapy in the patients previously treated with R-CHOP or CHOP. In a retrospective study we evaluated 16 patients treated with modified ICD: irinotecan 65 mg/m(2) (max 100 mg)/day plus cisplatin 30 mg/m(2) (max 50 mg)/day and dexamethasone 40 mg/day on days 1 and 8. Prednisolone 200 mg divided in 2 doses was given orally on days 2 and 9. G-CSF (PDgrastim) was administered at 300 μg/day subcutaneously on days 4-6 and 11-13. pre- and post-hydration was given according to our hospital protocol. Overall response rate was 75 % for all of the patients and 90 % for the patients treated as first line salvage. The median overall survival was 23 ± 12 months. There was no grade 3/4 of neutropenia and no cycles of chemotherapy were delayed due to leucopenia. Modified ICD might be an effective salvage regimen for refractory/relapsed lymphoma patients. Unlike original ICD, leucopenia does not seem to be a limiting factor. So we conclude that modified ICD shall be considered as a safe and effective regimen for salvage chemotherapy in refractory/relapsed patients.


Detachable low dead space syringes for the prevention of hepatitis C among people who inject drugs in Bristol, UK: an economic evaluation.
Traditional detachable syringes used by people who inject drugs (PWID) retain larger volumes of blood when the plunger is depressed than syringes with fixed needles-referred to as high (HDSS) and low dead space syringes (LDSS), respectively. Evidence suggests that using HDSS may result in greater hepatitis C virus (HCV) transmission risk than LDSS. We evaluated the cost-effectiveness of an intervention to introduce detachable LDSS in a needle and syringe programme (NSP). HCV transmission and disease progression model with cost-effectiveness analysis using a health-care perspective. Detachable LDSS are associated with increased costs (£0.008) per syringe, yearly staff training costs (£536) and an estimated decreased risk (by 47.5%) of HCV transmission compared with HDSS. The intervention was modelled for 10 years, with costs and health benefits (quality-adjusted life-years: QALYs) tracked over 50 years. Bristol, UK. PWID attending NSP. Gradual replacement of HDSS at NSP, with 8, 58 and 95% of HDSS being replaced by detachable LDSS in 2016, 2017 and 2018, respectively. Comparator was continuing use of HDSS. Net monetary benefit. Benefits were measured in QALYs. Introducing detachable LDSS was associated with a small increase in intervention costs (£21 717) compared with not introducing detachable LDSS, but considerable savings in HCV-related treatment and care costs (£4 138 118). Overall cost savings were £4 116 401 over 50 years and QALY gains were 1000, with an estimated 30% reduction in new infections over the 10-year intervention period. In all sensitivity analyses, detachable LDSS resulted in cost savings and additional QALYs. Threshold analyses suggested that detachable LDSS would need to reduce HCV transmission risk of HDSS by 0.26% to be cost-saving and 0.04% to be cost-effective. Replacing high dead space syringes with detachable low dead space syringes in needle and syringe programmes in the United Kingdom is likely to be a cost-saving approach for reducing hepatitis C virus transmission.


Temporal bone CT-based deep learning models for differential diagnosis of primary ciliary dyskinesia related otitis media and simple otitis media with effusion.
To investigate the diagnostic value of deep learning (DL) in differentiating otitis media (OM) caused by otitis media with effusion (OME) and primary ciliary dyskinesia (PCD), so as to provide reference for early intervention. From January 2010 to January 2021, 31 patients with PCD who had temporal bone computed tomography (TBCT) in the Children's Hospital of Fudan University were retrospectively analyzed. Another 30 age-matched cases of OME with TBCT were collected as the control group. The CT imaging signatures of children were observed. Besides, a variety of DL neural network training models were established based on PyTorch, and the optimal models were trained and selected for PCD screening. The google net-trained model worked best, with an accuracy of 0.99. Vgg16_bn, vgg19_bn, resnet18, and resnet34; having neural networks with fewer layers, better model effects, with an accuracy rate of 0.86, 0.9, 0.86, and 0.86, respectively. Resnet50 and other neural networks with more layers had relatively poor results. DL-based CT radiomics can accurately distinguish OM caused by OME from that induced by PCD, which can be used for screening the PCD.


The effect of national public health measures on the characteristics of trauma presentations to a busy paediatric emergency service in Ireland: a longitudinal observational study.
The SARS-CoV-2 pandemic and government-enforced restrictions have impacted medical practices. The aim of our study was to investigate the impact SARS-CoV-2 and public health restrictions had on trauma presentations to a regional paediatric emergency service. We carried out a multisite retrospective longitudinal study of all paediatric ED attendances from 2018 including 13 March to 7 June 2020. This aligned with the initial government-enforced public health phases: delay phase, mitigation phase and reopening phase 1. There were 7975 total regional attendances during government-enforced restrictions. This represents 17.5% and 15.6% reductions in site attendances when compared with the two previous years. Regional attendances reduced by 52.5% in 2020 compared with 2018 and 50.9% compared with 2019. Following an initial reduction in injury attendances at the beginning of the 'lockdown' (p = 0.076), the number of injuries consistently grew as weeks progressed (p < 0.05), reaching a peak of 44.6% of all attendances. As restrictions eased, the most common location where injuries occurred moved to areas outside the home (p < 0.000). There was a significant change in injury type, final disposition and device-associated injury (p < 0.05). Wheeled recreational devices were associated with over 20% of all injuries by reopening phase 1. This study reveals that total attendances and total injuries reduced during initial phases of the lockdown. This was followed by a significant increase in injury presentations, which reached a peak of 44.6% of all attendances. We identified potential modifiable characteristics of paediatric trauma which can be addressed by future public health strategies.


Prevalence and the associated factors of hepatitis B and hepatitis C viral infections among HIV-positive individuals in same-day antiretroviral therapy initiation program in Bangkok, Thailand.
Viral hepatitis is highly prevalent among people with HIV (PWH) and can lead to chronic liver complications. Thailand started universal hepatitis B vaccination at birth in 1992 and achieved over 95% coverage in 1999. We explored the prevalence of hepatitis B and C viral infections and the associated factors among PWH from same-day antiretroviral therapy (SDART) service at the Thai Red Cross Anonymous Clinic, Bangkok, Thailand. We collected baseline characteristics from PWH enrolled in the SDART service between July 2017 and November 2019. Multivariable logistic regression was performed to determine factors associated with positive hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV). A total of 4011 newly diagnosed PWH who had HBsAg or anti-HCV results at baseline: 2941 men who have sex with men (MSM; 73.3%), 851 heterosexuals (21.2%), 215 transgender women (TGW; 5.4%), and 4 transgender men (0.1%). Median age was 27 years. Overall seroprevalence of HBsAg and anti-HCV were 6.0 and 4.1%, respectively. Subgroup prevalence were 6.2 and 4.7% among MSM, 4.6 and 2.4% among heterosexuals, and 9.3 and 3.7% among TGW, respectively. Factors associated with HBsAg positivity were being MSM, TGW, born before 1992, CD4 count < 200 cells/mm3, and alanine aminotransferase ≥ 62.5 U/L. Factors associated with anti-HCV positivity were being MSM, age > 30 years, alanine aminotransferase ≥ 62.5 U/L, creatinine clearance < 60 ml/min, and syphilis infection. Around 5-10% of newly diagnosed PWH in Bangkok had hepatitis B viral infection after 25 years of universal vaccination. Anti-HCV positivity was found in 4-5% of PWH who were MSM and TGW. As World Health Organization and Thailand national guidelines already support routine screening of hepatitis B and C viral infections in PWH and populations at increased risk of HIV including MSM and TGW, healthcare providers should reinforce this strategy and provide linkage to appropriate prevention and treatment interventions. Catch-up hepatitis B vaccination should be made available under national health coverage.


Fracture of the styloid process of the temporal bone. A case report.
A case of fracture of the styloid process of the temporal bone (Eagle's syndrome) is reported. The differential diagnosis is discussed.


Coronavirus (COVID-19) outbreak: Addictive social media use, depression, anxiety and stress in quarantine - an exploratory study in Germany and Lithuania.
To slow down the spread of the COVID-19 pandemic, governments of many countries introduced various behavioral measures starting March 2020. The measures included domestic quarantine (not leaving home) for infected or potentially infected people. Due to the need for social distancing, online activity increased in spring 2020. This could foster the risk for addictive social media use (SMU). The present study investigated tendencies of addictive SMU and their relationship with depression, anxiety and stress symptoms specifically among individuals who stayed in domestic quarantine due to COVID-19 in Germany and Lithuania. In Germany (N = 529; quarantine group: n = 157, non-quarantine group: n = 372) and in Lithuania (N = 325; quarantine group: n = 54, non-quarantine group: n = 271), data were assessed via online surveys in spring 2020. In both countries, persons in quarantine had higher levels of addictive SMU, depression, anxiety and stress symptoms than individuals who were not in quarantine. The difference was significant only for addictive SMU in the German sample. The significant positive correlations between addictive SMU and symptoms of depression, anxiety and stress were stronger in both quarantine groups than in the non-quarantine groups. The mostly female, young and well-educated composition of both investigated samples limits generalizability of the current findings. Results reveal first evidence that the use of social media during domestic COVID-19 quarantine might contribute to the increase of addictive tendencies and negatively impact well-being. Alternative ways of daily routine during the quarantine are discussed.


Transient 40 °C-shock potentiates cytotoxic responses of Vδ2+ γδ T cell via HSP70 upregulation.
Vδ2+ γδ T cell, one of promising strategies for tumor immunotherapy, recognizes and kills cancer cells in a non-MHC dependent manner. Previously, we pioneeringly proved the clinical safety and efficacy of allogeneic Vδ2+ γδ T cells, in vitro expanded from healthy donors, in the treatment of late-stage cancer patients. Nevertheless, how to profoundly potentiate cytotoxic function of expanded Vδ2+ γδ T cells remains to be further explored. Here, we proposed that 40 °C-Shock could be a simple and reliable approach to in vitro boost the effector function. We found that 40 °C-shock could phosphorylate two MAPK proteins ERK and p38 through HSP70, which facilitated actyl-α-tubulin and actin augments and reorganization, elevated Ki-67 expression and cell surface adhesion, and promoted releases of cytokines IFN-γ, perforin and granzyme B, as well as downregulated LAG3 expression. We also observed 40 °C-shock induced elevations of mitochondrial metabolism. These altogether led to potentiated cytotoxic responses against cancer cells. This proof-of-concept work demonstrated that 40 °C-shock would be probably developed into an effective method to in vitro boost the cytotoxicity of Vδ2+ γδ T cell before applying it in immunotherapy, and provided scientific evidences for the view that fever can activate immune responses of innate immune cells.


Synthetic CT for the planning of MR-HIFU treatment of bone metastases in pelvic and femoral bones: a feasibility study.
Visualization of the bone distribution is an important prerequisite for MRI-guided high-intensity focused ultrasound (MRI-HIFU) treatment planning of bone metastases. In this context, we evaluated MRI-based synthetic CT (sCT) imaging for the visualization of cortical bone. MR and CT images of nine patients with pelvic and femoral metastases were retrospectively analyzed in this study. The metastatic lesions were osteolytic, osteoblastic or mixed. sCT were generated from pre-treatment or treatment MR images using a UNet-like neural network. sCT was qualitatively and quantitatively compared to CT in the bone (pelvis or femur) containing the metastasis and in a region of interest placed on the metastasis itself, through mean absolute difference (MAD), mean difference (MD), Dice similarity coefficient (DSC), and root mean square surface distance (RMSD). The dataset consisted of 3 osteolytic, 4 osteoblastic and 2 mixed metastases. For most patients, the general morphology of the bone was well represented in the sCT images and osteolytic, osteoblastic and mixed lesions could be discriminated. Despite an average timespan between MR and CT acquisitions of 61 days, in bone, the average (± standard deviation) MAD was 116 ± 26 HU, MD - 14 ± 66 HU, DSC 0.85 ± 0.05, and RMSD 2.05 ± 0.48 mm and, in the lesion, MAD was 132 ± 62 HU, MD - 31 ± 106 HU, DSC 0.75 ± 0.2, and RMSD 2.73 ± 2.28 mm. Synthetic CT images adequately depicted the cancellous and cortical bone distribution in the different lesion types, which shows its potential for MRI-HIFU treatment planning. • Synthetic computed tomography was able to depict bone distribution in metastatic lesions. • Synthetic computed tomography images intrinsically aligned with treatment MR images may have the potential to facilitate MR-HIFU treatment planning of bone metastases, by combining visualization of soft tissues and cancellous and cortical bone.


CaMKIIa Neurons of the Ventromedial Hypothalamus Mediate Wakefulness and Anxiety-like Behavior.
Insomnia and anxiety are two common and closely related clinical problems that pose a threat to individuals' physical and mental well-being. There is a possibility that some nuclei and neural circuits in the brain are shared by both insomnia and anxiety. In the present study, using a combination of chemogenetics, optogenetics, polysomnographic recordings and the classic tests of anxiety-like behaviors, we verified that the calmodulin-dependent protein kinase II alpha (CaMKIIa) neurons of the ventromedial hypothalamus (VMH) are involved in the regulation of both wakefulness and anxiety. Chemogenetic manipulation of the VMH CaMKIIa neurons elicited an apparent increase in wakefulness during activation, whereas inhibition decreased wakefulness mildly. It substantiated that the VMH CaMKIIa neurons contribute to wakefulness. Then in millisecond-scale control of neuronal activity, short-term and long-term optogenetic activation induced the initiation and maintenance of wakefulness, respectively. We also observed that mice reduced exploratory behaviors in classic anxiety tests while activating the VMH CaMKIIa neurons and were anxiolytic while inhibiting. Additionally, photostimulation of the VMH CaMKIIa axons in the paraventricular hypothalamus (PVH) mediated wakefulness and triggered anxiety-like behaviors as well. In conclusion, our results demonstrate that the VMH participates in the control of wakefulness and anxiety, and offer a neurological explanation for insomnia and anxiety, which may be valuable for therapeutic interventions such as medication and transcranial magnetic stimulation.


Neonatal mortality and morbidity in preterm infants born from assisted reproductive technologies.
Premature birth is frequent in infants conceived with assisted reproductive technologies (ART). We sought to determine whether neonatal outcome in ART preterm infants differs from that of spontaneously conceived (SC) preterm infants. Data were prospectively collected in infants born ≤ 32 weeks after ART or SC. We calculated a composite index of severe morbidity (based on occurrences of severe necrotizing enterocolitis, severe intraventricular haemorrhage, periventricular leukomalacia or bronchopulmonary dysplasia). Survival rate without severe morbidity was compared between the two groups. Six hundred and twelve preterm infants were hospitalized in our tertiary care centre: 81 in ART group and 521 in SC group. In the ART group, twin pregnancy (69.1% vs. 15.9%, p < 0.001) and inborn delivery (98.8% vs. 90.0%, p < 0.01) were more frequent. Gestational age (29 vs. 28 weeks, p < 0.05) and birth weight (1100 vs. 1020 g, p < 0.001) were also higher. Survival without severe morbidity was significantly higher in ART infants (76.5% vs. 55.2%, p < 0.001), with the difference mainly observed in infants born ≤ 28 weeks (22.9% vs. 55.7%, p < 0.001). Assisted reproductive technologies was not associated with adverse neonatal outcome. Differences in pregnancy and neonatal characteristics probably explain the increased survival without severe morbidity in ART infants.


Contrast echocardiography for assessment of myocardial perfusion.
It has been suggested that the myocardial perfusion can be qualitatively and quantitatively assessed by different ultrasound contrast techniques. It has been reported that the intracoronary or intraaortic administration of the ultrasound contrast agents can be used to visualize perfusion defects or to analyze the coronary flow reserve. The perfusion analysis after intracoronary injection of ultrasound contrast agents seems to be established, but there are a lot of open questions. A topographic (qualitative) perfusion analysis with visualization of perfusion defects and perfusion areas or analysis of collaterals has been demonstrated. A quantitative analysis of myocardial blood flow has been described but the existing studies are inconsistent. It is not known which parameters of the contrast wash-out curves should be used for perfusion analysis and if the Stewart-Hamilton curve analysis can be transferred to all ultrasound contrast agents as a model for quantitative myocardial blood flow assessment. The development of the transpulmonary contrast agents for echocardiographic evaluation of left ventricular cavity has the impact for myocardial perfusion imaging. The increase of myocardial intensity does not mean that a qualitative or quantitative perfusion analysis can be clinically used. In this field we have to differentiate between the possibilities of qualitative discrimination of perfusion defects and quantitative perfusion (myocardial blood flow) analysis. The different scanning conditions, the poor transthoracic ultrasound window and insufficient enhancement of the myocardial intensity make it problematic to quantify the myocardial perfusion. At the moment myocardial intensity will be increased after intravenous injection of transpulmonary contrast agents, but the value for perfusion analysis has not been shown. New ultrasound technologies such as second harmonic imaging, power-mode and raw data analysis have to show the clinical importance of these techniques for perfusion analysis in daily clinical routine. The open questions of the perfusion analysis by contrast echocardiography will be discussed in this review article.


Medical rapid prototyping technologies: state of the art and current limitations for application in oral and maxillofacial surgery.
We describe state-of-the-art software and hardware requirements for the manufacture of high quality medical models manufactured using medical rapid prototyping. The limitations of medical models, the source of artefacts, and their physical appearance are illustrated along with remedies for their removal. Medical models were built using predominantly stereolithography and fused deposition modeling at both institutions over a period of 6 years. A combined total of 350 models have been produced for a range of maxillofacial, neurosurgical, and orthopedic applications. Stereolithography, fused deposition modeling, computerized numerical milling, and other technologies are described along with computer software requirements. A range of unwanted artefacts that create distortions on medical models have been identified. These include data import, computed tomography gantry distortion, metal, motion, surface roughness due to support structure removal or surface modeling, and image data thresholding. The source of the artefact has been related to the patient, imaging modality performance, or the modeling technology. Discussion as to the significance of the artefacts on clinical use is provided. It is recommended that models of human anatomy generated by medical rapid prototyping are subject to rigorous quality assurance at all stages of the manufacturing process. Clinicians should be aware of potential areas for inaccuracies within models and review the source images in cases where model integrity is in doubt.


The organization of the gene for the human cerebroside sulfate activator protein.
The organization of 14 exons covering 97% of the cDNA sequence of human cerebroside sulfate activator protein precursor has been determined from two overlapping EMBL-4 human genomic clones extending over 17 kb. All exons and exon/intron splice junctions and five introns were sequenced. Exon 8 consists of only 9 bp and is involved in alternative splicing which generates three different mRNAs of cerebroside sulfate activator precursor.


Characterization and inhibition of four fungi producing citrinin in various culture media.
This study aimed to investigate the effects of different fermentation conditions (culture medium, temperature, incubation time, pH value and additive) on citrinin production by four fungi. Among the culture media, potato dextrose medium had lowest citrinin production, followed by yeast sucrose medium and monosodium glutamate medium. The lowest citrinin contents were produced by Monascus anka (M. anka) in potato dextrose medium and yeast sucrose medium, Aspergillus oryzae AS3.042 (A. oryzae) produced the lowest citrinin production in monosodium glutamate medium. The optimum fermentation temperatures for citrinin production by Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were at 30 °C, whereas those by M. anka and A. oryzae were at 35 °C. Citrinin synthesis by four fungi were completely inhibited with a pH value of less than 5.4. By adding ethylene diamine tetraacetic acid (EDTA) or triammonium citrate into monosodium glutamate medium, citrinin production by A. oryzae and A. niger were totally inhibited. Ammonium sulfate completely inhibited citrinin production by A. oryzae, M. anka and P. citrinum, and ammonium nitrate completely inhibited citrinin production by A. oryzae. These results indicated that the suitable fermentation conditions could make considerable contributions to the reduction of citrinin production. This study provided an effective way for decreasing the citrinin production.


Bradykininase and protease inhibitors in seminal plasma of fertile and infertile men.
The level of protease acrosin in the seminal plasma of oligozoospermic men was significantly higher than that of normozoospermic men. The amount of bradykininase in the seminal plasma was very high in both normozoospermic and oligozoospermic patients. When the acrosin and kininase content was referred to one million spermatozoa, seminal plasma kininase was significantly enhanced in oligozoospermic men, while the acrosin activity was similar in normozoospermic fertile men and infertile men. Human seminal plasma inhibitor I (HUSI I) increased along with sperm count. Human seminal plasma inhibitor II (HUSI II) showed no change. The motility of spermatozoa was depressed in oligozoospermic patients.


3D convolutional neural networks for detection and severity staging of meniscus and PFJ cartilage morphological degenerative changes in osteoarthritis and anterior cruciate ligament subjects.
Semiquantitative assessment of MRI plays a central role in musculoskeletal research; however, in the clinical setting MRI reports often tend to be subjective and qualitative. Grading schemes utilized in research are not used because they are extraordinarily time-consuming and unfeasible in clinical practice. To evaluate the ability of deep-learning models to detect and stage severity of meniscus and patellofemoral cartilage lesions in osteoarthritis and anterior cruciate ligament (ACL) subjects. Retrospective study aimed to evaluate a technical development. In all, 1478 MRI studies, including subjects at various stages of osteoarthritis and after ACL injury and reconstruction. 3T MRI, 3D FSE CUBE. Automatic segmentation of cartilage and meniscus using 2D U-Net, automatic detection, and severity staging of meniscus and cartilage lesion with a 3D convolutional neural network (3D-CNN). Receiver operating characteristic (ROC) curve, specificity and sensitivity, and class accuracy. Sensitivity of 89.81% and specificity of 81.98% for meniscus lesion detection and sensitivity of 80.0% and specificity of 80.27% for cartilage were achieved. The best performances for staging lesion severity were obtained by including demographics factors, achieving accuracies of 80.74%, 78.02%, and 75.00% for normal, small, and complex large lesions, respectively. In this study we provide a proof of concept of a fully automated deep-learning pipeline that can identify the presence of meniscal and patellar cartilage lesions. This pipeline has also shown potential in making more in-depth examinations of lesion subjects for multiclass prediction and severity staging. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:400-410.


Perinatal intracranial hemorrhage due to severe neonatal alloimmune thrombocytopenic purpura (NAITP) associated with anti-Yukb (HPA-4a) antibodies.
Neonatal alloimmune thrombocytopenic purpura (NAITP) is one of the causes of thrombocytopenia in the newborn period. The thrombocytopenia is caused by maternal transplacental antiplatelet alloantibodies. We report a case of NAITP in a newborn infant having subarachnoid hemorrhage. Examination of platelet antibodies revealed anti-Yukb, that is, human platelet antigen (HPA)-4a incompatibility. Cranial ultrasound and brain magnetic resonance imaging revealed subarachnoid hemorrhage in the temporal region inferior to the cephalohematoma. The lesion seemed to have been sustained during delivery. The patient was treated with high-dose gamma-globulin and several transfusions of random donor platelets and showed a good clinical course. This is the second reported case of NAITP associated with the Yuk antigen system having intracranial hemorrhage.


Effect of rapamycin treatment on oocyte in vitro maturation and embryonic development after parthenogenesis in yaks.
Autophagy plays an important role in mammalian oocyte maturation and early embryonic development and rapamycin is well known for inducing autophagy. Although previous studies have reported the effects of rapamycin on oocytes in vitro maturation (IVM) in different species, few studies have been reported on the role of rapamycin in yak oocytes IVM and embryonic development. Therefore, the objective of this study was to examine the effect of rapamycin treatment on yak oocytes IVM and early embryonic development. Specifically, immature yak oocytes during IVM or parthenogenetic (PA) embryos were treated with different rapamycin concentrations to select an optimal dose. Then evaluated its effect on maturation rates, cleavage, and blastocyst formation rates, mitochondrial membrane potential, ROS levels. Related genes and proteins expression in matured oocytes and blastocysts were also evaluated. The results show that 10 nM rapamycin treatment during IVM significantly improved oocyte maturation rates of oocytes and blastocyst formation rates. Treatment with 10 nM rapamycin reduced ROS level but increased mitochondrial membrane potential. Correspondingly, mRNA and protein expressions of LC3, Beclin-1, and Bcl-2 up-regulated while Bax down-regulated in matured yak COCs. When parthenogenetic embryos were treated with different rapamycin concentrations, 10 nM rapamycin treatment showed higher 8-cell and blastocyst formation rates. Also, CDX2, POU5F1, SOX2, and Nanog levels in blastocysts were upregulated. In summary, our findings demonstrate that rapamycin treatment improves oocytes maturation probably by increasing mitochondrial membrane potential, reducing ROS levels, and regulating the apoptosis in mature yak oocytes. Rapamycin treatment also improves embryonic developmental competence in the yak.


Translating human genetics into novel treatment targets for schizophrenia.
Human genetics is a rational starting point for target identification in drug discovery, yet this approach has found little application in neuroscience. Recent large-scale analyses have begun to identify robust genetic loci for schizophrenia, providing an opportunity to derive novel drug targets. Here, we summarize a strategy for applying human genetics to neuroscience drug discovery.


[The use of cimetidine in the prevention and therapy of gastroduodenal hemorrhage in resuscitation. Preliminary results].
The Authors report on 85 patients hospitalized in the resuscitation department, suffering from serious acute conditions and treated prophylactically with cimetidine. In comparison with analogous group of not treated patients, a marked diminution of digestive bleeding complications, typical in these patients, was noted.


Lessons from other fields of medicine, Part 2: Cystic fibrosis.
Cystic fibrosis (CF), first described in 1938, is a common, life-limiting monogenetic disease. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 was crucial in advancing our understanding of disease pathogenesis and paving the road for treatment aimed at the fundamental molecular defect. With the delineation of over 2000 variations in the CFTR gene, a sound understanding of the individual variations in cell biology, and electrophysiological abnormalities conferred by the most common defects propelled the advent of targeted disease-modifying therapeutics beginning in 2012. Since then, CF care has transformed beyond just symptomatic treatment to include a variety of small-molecule therapies that address the basic electrophysiologic defect and cause profound improvements in physiology, clinical manifestations, and long-term outcomes, designed to differentially address six genetic/molecular subtypes. This chapter illustrates the progress made toward how fundamental science and translational initiatives enabled personalized, mutation specific treatment. We highlight the importance of preclinical assays and mechanistically-driven development strategies that were coupled with sensitive biomarkers and a clinical trial cooperative to provide a platform for successful drug development. This convergence of academic and private partnerships, and formation of multidisciplinary care teams directed by evidence-based initiatives provide a seminal example of addressing the needs of individuals with a rare, but fatal genetic disease.


Study on pollution evolution law of coal and rock mixed dust in coal-oil shale fully mechanized mining face: a study case.
To better understand the dust dispersion and pollution laws in coal-oil shale fully mechanized mining faces, the airflow distribution and coal and oil shale mixed dust emission law was simulated, and the simulation results are analyzed and verified in combination with the field measured data. The research results showed that in the area 0-10 m on the leeward side of the front drum, most of the coal dust particles with a large particle size stay near the roof of the hydraulic support and the height of the breathing zone, while most of the oil shale dust particles with a large particle size stay in the area below the height of the breathing zone. In the height of the breathing belt, oil shale and coal dust particles seriously polluted the 0-6-m and 0-13-m areas on the leeward side of the front drum of the shearer, respectively. According to the different distribution of coal dust and oil shale dust, a wet dust collector and multi-nozzle atomization set are designed to remove dust. The field test results show that the dust removal rates of the two kinds of dust reach 83.4% and 87.5% respectively after the dust removal device is opened.


[Metronidazole for treatment of puerperal mastitis (author's transl)].
Pathogenic anaerobic bacteria may be among the causes of puerperal mastitis which, therefore, was treated by the authors with metronidazole (Vagimid) and with antibiotics, such as penicillin, oxacillin, erythromycin, and oxytetracycline. Best results were obtained by administration of metronidazole to patients in early mastitis. The frequency of incisions was reduced. The therapeutic results obtained from the use of metronidazole on patients with advanced mastitis were identical with those obtained from antibiotics.--Metronidazole concentrations were equal in serum and milk. No side effects were observed.


Hospital readmission after coronary artery bypass grafting: are women doing worse?
In studies of gender effects on outcome after coronary artery bypass grafting, early mortality has consistently tended to be higher among women, whereas long-term results have varied. The aim of this study was to identify predictors of hospital readmission and assess the effect of gender. Between 1987 and 1996, 7,493 patients were discharged alive after primary coronary artery bypass grafting and were followed up to the first readmission, date of death, or December 31, 1996. The hazard ratios for the risk factors found were used to calculate a readmission risk score. A total of 4,780 (63.8%) patients were readmitted. The fraction not readmitted within 1, 5, and 10 years were 61%, 29%, and 14% (95% confidence intervals = 60 to 62, 28 to 30, and 12 to 16), respectively. The risk of readmission was highest early after operation and then gradually decreased. Older age, active smoking, diabetes, previous myocardial infarction, unstable angina, dyspnea, severe left ventricular dysfunction, advanced New York Heart Association functional class, bypass time of 2 hours or more, and length of stay all independently increased the risk of readmission. Female sex was a significant risk factor in univariate but not in multivariate analysis. In all age groups, women had a one unit higher risk score. Given the same risk score, the risk of readmission was similar between sexes. This study showed an acceptable risk of readmission after coronary artery bypass grafting. Women more often had risk factors related to readmission. However, given identical disease severity, the risk was similar in men and women.


[Pharmacokinetics of ampicillin in patients with gastric and duodenal ulcers and patients having undergone Billroth II gastric resection].
It has been shown that exacerbation of gastric and duodenal ulcers results in a more complete absorption of ampicillin administered per os. Pyloric stenosis retarded ampicillin absorption. Billroth II stomach resection does not change the drug kinetics in the blood.


[Rapid screening of Chemical Weapons Convention-related chemicals in oil matrix by headspace solid-phase microextraction and gas chromatography-mass spectrometry].
The Chemical Weapons Convention (CWC) requires verification of a large number of compounds with different types and properties. The results of the verification are of great political and military sensitivity. However, the sources of verification samples are complex and diverse, and the contents of the target compounds in these samples are usually very low. These issues increase the likelihood of missed or false detection. Thus, establishing rapid and effective screening methods for the accurate identification of CWC-related compounds in complex environmental samples are of great importance. In this study, a fast and simple procedure based on headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-electron ionization mass spectrometry (GC-EI/MS) in full-scan mode was developed to determine CWC-related chemicals in oil matrix. A total of 24 CWC-related chemicals with different chemical characteristics were selected to simulate the screening procedure. The selected compounds were divided into three groups based on their properties. The first group included volatile and semi-volatile CWC-related compounds with relatively low polarity, which could be extracted by HS-SPME and directly analyzed by GC-MS. The second group included moderately polar compounds with hydroxyl or amino groups; such compounds are related to nerve, blister, and incapacitating agents. The compounds in the third group included non-volatile CWC-related chemicals with relatively strong polarity, such as alkyl methylphosphonic acids and diphenyl hydroxyacetic acid. These compounds must be derivatized into vaporizable derivatives prior to extraction by HS-SPME and analysis by GC-MS. Variables that influence the SPME process, such as fiber type, extraction temperature and time, desorption time, and derivatization protocol, were optimized to improve the sensitivity of the method. The screening procedure for CWC-related compounds in the oil matrix samples included two main steps. First, low-polarity volatile and semi-volatile compounds (i. e. the first group) were extracted by HS-SPME with divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fibers and analyzed in split-injection mode (split ratio, 10∶1) using GC-MS. The use of a large split ratio can reduce the solvent effect, which is conducive to the detection of low-boiling-point compounds. If necessary, the sample could be extracted once more and analyzed in splitless mode. The derivatization agent bis(trimethylsilyl)trifluoroacetamide (BSTFA) was then added to the sample. Mid- and high-polarity compounds (i. e. the second and third groups) were extracted with polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibers after derivatization and analyzed in splitless mode using GC-MS. The established method exhibited good repeatability and sensitivity. The detection limits for the compounds in the first group ranged from 0.5 ng/mL to 100 ng/mL, whereas the detection limits for the compounds in the second and third groups ranged from 20 ng/mL to 300 ng/mL. Except for compounds with extremely high boiling points and a few compounds that are not suitable for derivatization with BSTFA, the method can be used to analyze most CWC-related compounds in oil matrix samples. In particular, it greatly shortened the preparation time of the oil matrix samples and reduced the loss of low-boiling-point compounds owing to the sample concentration process, thereby avoiding missed detection. The method was successfully applied to the Organization for the Prohibition of Chemical Weapons (OPCW) proficiency tests and proved to be a useful technique for the rapid screening of trace levels of CWC-related chemicals in oil matrix.


The radial artery forearm flap: an anomaly of the radial artery.
The radial forearm flap derives its blood supply from the radial artery. Anatomical variations of this vessel are uncommon. This report describes an anomaly which has relevance for the radial forearm flap.


Analysis of the role of the COL1 domain and its adjacent cysteine-containing sequence in the chain assembly of type IX collagen.
The mechanisms of chain selection and assembly of type IX collagen, a heterotrimer alpha 1(IX)alpha 2(IX)alpha 3(IX), must differ from that of fibrillar collagens since it lacks the characteristic C-propeptide of these latter molecules. We have tested the hypothesis that the information required for this process is contained within the C-terminal triple helical disulfide-bonded region (LMW). The reassociations of the purified LMW fragments of pepsinized bovine type IX collagen were followed by the formation of disulfide-bonded multimers. Our data demonstrate that only three triple helical assemblies form readily, (alpha 1)3, (alpha 2)3 and alpha 1 alpha 2 alpha 3. The information required for chain selection and assembly is thus, at least in part, contained in the studied fragments. Molecular stoichiometries different from the classical heterotrimer may thus also form under certain conditions.


Carbon dots and AuNCs co-doped electrospun membranes for ratiometric fluorescent determination of cyanide.
Due to the extremely toxic nature of cyanide, the World Health Organization (WHO) has set 1.9 μM as the maximum acceptable level in drinking water. Therefore, methods for facile screening and on-site detection of cyanide is urgently needed. In this work, a ratiometric fluorescent method for cyanide detection was developed based on blue-emitting carbon dots (CDs) and red-emitting AuNCs. To suit an on-site detection, the two fluorophores were incorporated into a nanofibrous membrane through electrospinning, yielding the core-shell structure of CDs/AuNCs-PVA@CA. Upon reaction with cyanide, the red fluorescence of AuNCs was quenched but the blue fluorescence of CDs was retained, resulting in ratiometric fluorescence change. Besides, both CDs and AuNCs can be excited with a handheld UV lamp (365 nm), and the resultant visible fluorescence color change could be visualized with naked eye. The proposed ratiometric method provided a limit of detection (LOD) 0.15 μM for cyanide, which was far lower than 1.9 μM. The membrane was further employed for screening analysis of cyanide in tap water samples. After collection of 500 analytical results, only 5.6% of the results located outside the X¯±2s criteria, while for the X¯±3s criteria, there is no outlier. The statistical results indicated that the proposed method may be potentially useful for screening analysis of cyanide in water samples.


The clinical effect of early enteral nutrition in liver-transplanted patients: a systematic review and meta-analysis.
Appropriate nutritional support is critical for patients undergoing liver transplantation (LT). Early enteral nutrition (EEN) has been considered effective in critically ill patients. However, the clinical effect of EEN on liver-transplanted patients is unclear. To evaluate the clinical effect of early enteral nutrition in patients receiving a liver transplant. A systematic search was performed on the Cochrane Library, PubMed, CINAHL, EMBASE, Web of Science, WanFang database, Chinese Biomedical Literature Database and China National Knowledge Infrastructure to collect relevant studies up to January, 2020. The results of these studies were pooled to calculate relative risk and mean differences with 95% confidence intervals for dichotomous data and continuous data. All statistical analysis was carried out by Review Manager 5.3. 9 RCTs and 10 cohort studies with 1300 patients were included in this meta-analysis. Compared with TPN, EEN reduced postoperative infection rates, ICU hours, length of hospitalization, and the duration of bowel ventilation as well as strengthening the nutritional status and liver function of LT patients. There is no difference in mortality rates, blood glucose levels or gastrointestinal complications. Compared to TPN, the combined EN + PN method more effectively prevented infection. For patients undergoing liver transplantation, early enteral nutrition with or without combination may considered as a better nutritional therapy than total parenteral nutrition.


Independent and combined effects of sepiolite and palygorskite on humus spectral properties and heavy metal bioavailability during chicken manure composting.
The effects of the independent and combined addition strategies of sepiolite and palygorskite on humification and heavy metals (HMs) during chicken manure composting were evaluated. Results showed that clay mineral addition showed a favorable effect on composting, prolonged the duration of the thermophilic phase (5-9 d) and improved the TN content (14%-38%) compared to CK. Independent strategy enhanced the humification degree in equal measures with the combined strategy. Carbon nuclear magnetic resonance spectroscopy (13C NMR) and fourier transform infrared spectroscopy (FTIR) confirmed that aromatic carbon species increased by 31%-33% during composting process. Excitation-emission matrix (EEM) fluorescence spectroscopy showed that humic acid-like compounds increased by 12%-15%. In addition, the maximum passivation rate of Cr, Mn, Cu, Zn, As, Cd, Pb and Ni were 51.35%, 35.98%, 30.39%, 32.46%, -87.02%, 36.61% and 27.62%, respectively. The independent addition of palygorskite exhibits the most potent effects for most HMs. Pearson correlation analysis indicated that pH and aromatic carbon were the key determinants of the HMs passivation. This study provided preliminary evidence and perspective of the application of clay minerals on the humification and safety of composting.


The effects of aggregation, protein binding and cellular incorporation on the photophysical properties of benzoporphyrin derivative monoacid ring A (BPDMA).
Absorption, fluorescence and laser flash photolysis spectroscopies were used to investigate the effects of self-aggregation, binding to human serum albumin and incorporation in cancer cells on the photophysics of benzoporphyrin derivative monoacid ring A (BPDMA). Aggregation of BPDMA has been studied in mixtures of methanol and phosphate-buffered saline (PBS). The extent of aggregation was dependent on dye concentration and solvent composition, becoming particularly marked in mixtures containing less than 30% methanol. A dimerization constant Kd or 9 x 10(6) M-1 was determined by fluorescence experiments for BPDMA in pure PBS. In addition to spectral modifications, aggregation induces a lowering of the fluorescence and intersystem crossing quantum yields. Human serum albumin binds BPDMA with an association constant Kb of 5.2 x 10(5) M-1 in PBS. When bound to HSA, BPDMA displays photophysical properties very similar to the monomer in organic solvents. The molar ratio [HSA]/[BPDMA] corresponding to complete binding of the dye was determined to be approximately 10. Efficient generation of the triplet state of BPDMA was also observed from aqueous cellular suspensions containing incorporated photosensitizer.


Isolation of rat bone marrow stem cells.
Stem cell research has become an important field of study for molecular, cellular, and clinical biology as well as pharmaco-toxicology. Indeed, stem cells have a strong proliferative and unlimited self-renewal potential and are multipotent. In vivo as well as in vitro studies have confirmed the differentiation of adult bone marrow stem cells into muscle cells, adipocytes, cardiomyocytes, neuroectodermal cells, osteoblasts, chondroblasts, and so on. Recently, it has been shown that, under appropriate culture conditions, adult bone marrow stem cells may also differentiate into hepatocyte-like cells. Because of their extensive proliferative capacity and pluripotency, adult bone marrow stem cells could serve in the future as an unlimited source of hepatocytes for pharmaco-toxicological research and testing. We describe a protocol for isolation of mononuclear cells from adult rat bone marrow.


Efficacy of induction regimens for cryptococcal meningitis in HIV-infected adults: a systematic review and network meta-analysis.
Cryptococcal meningitis (CM) is the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority of 1-week amphotericin B deoxycholate (AmphB) + flucytosine (5-FC) regimen over other antifungals in the management of HIV patients with CM (HIV-CM patients). We aimed to evaluate the differences in efficacy and tolerability of different antifungal agents in HIV-CM patients by conducting a current network meta-analysis NMA. Overall, 19 randomized controlled trials were included with 2642 participants. A regimen indicated a possibly lower early mortality rate, namely, AmphB + 5-FC + Azole (OR = 1.1E-12, 95% CIs = 1.3E-41 to 0.06) comparing to AmphB + 5-FC. The current NMA provides evidence that AmphB + 5-FC + Azole are superior to all the investigated treatments for induction regimen in HIV-CM patients.


Therapy With Local Anesthetics to Treat Vulvodynia. A Pilot Study.
Vulvodynia (chronic vulvar pain) is a sexually debilitating disorder with a prevalence of ∼10%. To investigate the effectiveness of therapy with local anesthetics (TLA) in women with severe vulvodynia, we conducted a prospective, non-controlled observational study. 45 patients with severe chronic vulvodynia (primary and secondary vulvodynia, 0-10 numeric analogue scale (NAS) ≥6, median 7.9, duration ≥6 months, median 65.2 months) in an outpatient practice in Germany were treated with TLA in 3-12 sessions using procaine 1% as local anesthetic. Effectiveness was analyzed with Wilcoxon signed rank tests and Wilcoxon rank sum tests. Therapeutic success as a reduction of pain to ≤4 NAS lasting for ≥6 months after end of therapy. TLA successfully reduced vulvodynia in 36 of 45 patients (80 %, responders). The NAS reduction was from 7.9 to 2.4 (P < .001). Even patients denominated as non-responders experienced a significant reduction in NAS (P = .03). In responders, long-term success was observed for 6.8-125 months (median 24.1 months). No adverse events occurred. A promising new treatment for a hard-to-treat chronic female pain disorder. Limitation: Monocentric, non-controlled observational design; Strength: the high number of patients treated. The high success rate of TLA in this investigation offers new perspectives on the etiology of vulvodynia as a complex pain syndrome affecting several nerves of the pelvic floor, and also provides early insight into the effectiveness of TLA in women with vulvodynia. Weinschenk S, Benrath J, Kessler E, et al. Therapy With Local Anesthetics to Treat Vulvodynia. A Pilot Study. Sex Med 2022;10:100482.


Thermodynamics of the conversion of fumarate to L-(-)-malate.
The thermodynamics of the conversion of aqueous fumarate to L-(-)-malate has been investigated using both heat conduction microcalorimetry and a gas chromatographic method for determining equilibrium constants. The reaction was carried out in aqueous Tris-HCl buffer over the pH range 6.3-8.0, the temperature range 25-47 degrees C, and at ionic strengths varying from 0.0005 to 0.62 mol kg-1. Measured enthalpies and equilibrium ratios have been adjusted to zero ionic strength and corrected for ionization effects to obtain the following standard state values for the conversion of aqueous fumarate 2- to malate 2- at 25 degrees C: K = 4.20 +/- 0.05, delta G degrees = -3557 +/- 30 J mol-1, delta H degrees = -15670 +/- 150 J mol-1, and delta C degrees p = -36 +/- J mol-1 K-1. Equations are given which allow one to calculate the combined effects of pH and temperature on equilibrium constants and enthalpies of this reaction.


Increased ecological risk due to the hyperaccumulation of As in Pteris cretica during the phytoremediation of an As-contaminated site.
Ecological risk due to the hyperaccumulation of As in Pteris cretica during phytoremediation was evaluated at an abandoned As-contaminated site. Five receptor groups representing terrestrial invertebrates, avian insectivores, small mammals, herbivores, and omnivores were selected as potentially affected ecological receptors. Soil and food ingestion were considered as major exposure pathways. Phytoremediation was performed with P.cretica only and with both P.cretica and siderophores to enhance plant uptake of As. Ecological hazard index (EHI) values for the small mammal greatly exceeded 1.0 even after three weeks of growth regardless of siderophore application, probably due to its limited home range. For the mammalian herbivore, which mainly consumes plant foliage, the EHI values were greater than 5.73 after seven weeks without siderophore application, but the value increased sharply to 29.3 at seven weeks when siderophores were applied. This increased risk could be attributed to the facilitated translocation of As from roots to stems and leaves in P.cretica. Our results suggest that, when a phytoremediation strategy is considered for metals remediation, its ecological consequences should be taken into account to prevent the spread of hyperaccumulated heavy metals throughout the food chain of ecological receptors. Uncertainties involved in the ecological risk assessment process were also discussed.


Perceived changes in the mental well-being among Nigerians due to Ramadan Intermittent Fasting during the COVID-19 pandemic.
Muslims fast every year during the month of Ramadan from dawn until dusk. This study examined mental well-being and correlating factors among Nigerian adults who observed Ramadan intermittent fasting (RIF). A validated generalized anxiety disorder-2 and Patient Health Questionnaire-2, the four-item spiritual well-being index, and the Islamic intrinsic religiosity questionnaire were used to collect data about mental well-being (depression, anxiety), spirituality, and intrinsic religiosity through a web-based survey between the May 9, 2021 (27th of Ramadan, 1442) and the June 4, 2021 (29th of Shawwal, 1442). We studied the mental well-being of respondents over a period of 4 weeks before Ramadan (BR) and during the 4 weeks of Ramadan between the April 12, 2021 and the May 12, 2021(DR). Multinomial regression analysis was used to determine the factors associated with depression and anxiety. This research did not receive any grant or funding. A total of 770 adult Nigerians who observed RIF study were included in this cross-sectional study. When compared to mental well-being BR, observing RIF by Nigerian adult respondents was associated with a significant improvement in their mental well-being. A higher proportion of respondents felt less depressed DR (61.3% vs. 56.5%. < .001). Interest and pleasure in doing things improved DR than BR (p= 0.007) and respondents felt less nervous and anxious (60.7% vs. 57.1%, respectively; p <.001). Mental well-being was independently associated with sociodemographic characteristics, physical activity, and perceived relationships. This study found significant improvement in mental well-being DR compared to BR despite the ongoing COVID-19 pandemic. The effect of RIF on mental well-being needs further research with multicentric studies among different sets of ethnic populations.


Evaluation of an interactive web-based programme on relapse management for people with multiple sclerosis (POWER@MS2): study protocol for a process evaluation accompanying a randomised controlled trial.
Process evaluations accompanying complex interventions examine the implementation process of the underlying intervention, identify mechanisms of impact and assess contextual factors. This paper presents the protocol for a process evaluation conducted alongside the randomised controlled trial POWER@MS2. The trial comprises the evaluation of a web-based complex intervention on relapse management in 188 people with multiple sclerosis conducted in 20 centres. The web-based intervention programme focuses on relapse treatment decision making and includes a decision aid, a nurse-led webinar and an online chat. With the process evaluation presented here, we aim to assess participants' responses to and interactions with the intervention to understand how and why the intervention produces change. A mixed methods design is used to explore the acceptance of the intervention as well as its use and impact on participants. Participants are people with multiple sclerosis, neurologists, nurses and stakeholders. Quantitative semistandardised evaluation forms will be collected throughout the study. Qualitative semistructured telephone interviews will be conducted at the end of the study with selected participants, especially people with multiple sclerosis and neurologists. Quantitative data will be collected and analysed descriptively. Based on the results, the qualitative interviews will be conducted and analysed thematically, and the results will be merged in a joint display table. The process evaluation has received ethical approval from the Ethical Committee of the University of Lübeck (reference 19-024). Findings will be disseminated in peer-reviewed journals, at conferences, meetings and on relevant patient websites. NCT04233970.


Acquired immunodeficiency syndrome with subacute sclerosing panencephalitis.
A 7-year-old boy with acquired immunodeficiency syndrome, receiving antiretroviral drugs for 2 years, presented with a recent onset of myoclonic jerks and cognitive deterioration. On examination, he manifested myoclonic jerks once every 10-15 seconds. His electroencephalogram indicated periodic complexes, and his cerebrospinal fluid tested positive for measles antibodies.


Cytochrome P450 reconstitution systems.
Human liver microsomes contain multiple forms of cytochrome P450 (CYP or P450) that catalyze oxidation of a number of xenobiotic and endobiotic chemicals. Individual P450 forms have unique, but overlapping, substrate specificities. It is necessary to determine which P450s play more important roles in the oxidation of these chemicals. A good way of studying the roles of P450s in the metabolism of these chemicals is to reconstitute the activities by mixing purified P450s and nicotinamide adenine dinucleotide phosphate-cytochrome P450 reductase in the membranes of phospholipid vesicles. However, our studies have suggested that the conditions for reconstitution of activities vary depending on the P450 enzymes used. For example, some reactions catalyzed by P450s require cytochrome-b5 and a particular phospholipid environment for exerting their full catalytic activities. In this chapter, we describe optimal conditions that have been determined in our laboratories for the reconstitution of drug oxidation activities catalyzed by purified human CYP1A2, 2C9, 2E1, and 3A4.


Family medicine ethical issues regarding physician-patient interactions from patients' perspectives: A qualitative study.
The physician-patient relationship is important because the patient's satisfaction affects trust in physician and accepting physician's recommendations in medical treatment decisions. Understanding a patient's opinion about a trustworthy and friendly physician as well as ethical issues regarding family medicine, therefore, gains double importance. This paper attempts to provide a comprehensive evaluation of the subject. In summer 2018, a conventional qualitative content analysis was done on 21 participants who were referred to family physicians in the North of Iran. Data were collected by means of purposive sampling and semi-structured face to face individual interviews. Participants shared their experiences about ethical considerations in family medicine. All interviews were recorded and transcribed word for word, data were analyzed using qualitative content analysis. Data analysis resulted in the extraction of 7 categories and 21 sub-categories from the 71 initial codes. The categories include "responsibility", "patient's privacy", "informed consent", "respect and dignity of patient", "effective physician-patient communication", "trust in physician" and "conflict of interests". There are some differences between the participants' perceptions of ethical considerations in family medicine and opinions of medical ethics curriculum designers in Iran and particularly in the world. Some shared elements including "resource allocation", "the beginning and end of life", "research ethics", "substitute decision-making", etc. - all of them are main titles of ethics curriculum - could not be weighed as major ethical issues from the patients' perspectives. The patient's satisfaction and, therefore, the enhancement of mutual trust is essential. Patients' comments should be considered when providing ethical guidelines.


Effect of virtual reality distraction on pain and anxiety during infiltration anesthesia in pediatric patients: a randomized clinical trial.
Different distraction techniques have been used in dentistry and have shown great results in managing anxious pediatric patients specially during local anesthesia administration. One of the recently invented techniques is virtual reality. The purpose of the study was to evaluate the effect of virtual reality distraction on anxiety and pain during buccal infiltration anesthesia in pediatric patients. Healthy, cooperative 6- to 12-year-old children requiring buccal infiltration anesthesia were randomly assigned to a test or control group. In the test group, local anesthesia was administered while the subjects were watching a cartoon video using virtual reality goggles. Subjects in the control group watched a cartoon video on a screen during the administration of local anesthesia. To assess anxiety in both groups, heart rate was recorded using a pulse oximeter at five time points: (1) once the subject sets on the dental chair as a baseline; (2) when video is on; (3) at topical anesthesia application; (4) during needle insertion; (5) after the administration of local anesthesia. The face, legs, activity, cry, consolability (FLACC) behavioral pain assessment scale and the Wong-Baker FACES pain rating scale were used to assess pain. A total of 50 subjects were included with a mean age of 8.4 ± 1.46 years. Twenty-nine (58.0%) of the subjects were females. The mean heart rate at all time points except baseline was significantly higher among the test group compared to the control group. Multiple regression analysis showed that younger subjects and females had higher mean FLACC behavioral pain assessment scale scores (P = 0.034 and P = 0.004, respectively) regardless of the distraction technique used. Younger subjects and subjects with higher baseline heart rate reported higher mean Wong-Baker FACES pain rating scale score (P = 0.031 and P = 0.010, respectively), controlling for all other variables. Female subjects and the younger age group were more likely to report higher pain scores during local anesthesia administration regardless of the type of distraction used. The study was retrospectively registered in ClinicalTrials.gov with the identifier: NCT04483336 on 23/07/2020.


Synthesis and biological properties of Zn-incorporated micro/nano-textured surface on Ti by high current anodization.
It is acknowledged that ideal implant coatings should possess micro/nano-textured surface, have good interfacial bonding, and can release bioactive elements. In this study, we fabricated a Zn-incorporated micro/nano-textured surface by one-step high current anodization (HCA) in an aqueous solution with 10g/L of NaOH and different concentrations of Zn(NO3)2 (4, 7, and 12g/L). The control group of Zn-free was fabricated in the electrolyte of 7g/L Zn(NO3)2. Scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and inductively coupled plasma mass spectroscopy (ICP-MS) were used to analyze the morphology, composition, microstructure, and Zn+ release kinetics of the micro/nano-textured coatings. The biological properties of the surface structure were evaluated by cytotoxicity assay, cell viability, cytoskeletal assembly and alkaline phosphatase activity. Our results show the micro/nano-textured surface is composed of TiO2 mesoporous arrays, into which the Zn is demonstrated to be incorporated in the form of ZnO. The Zn content in the surface and release level of Zn2+ can be tailored through varying Zn(NO3)2 concentration in the electrolyte. In addition, the surface oxide layers show good interfacial bonding strength to the substrate. Compared with pure Ti and anodized Zn-free samples, the Zn-incorporated surface can upregulate osteoblast functions such as proliferation and alkaline phosphatase activity, which are assayed by MTT and ALP staining experiments, respectively. Collectively, this micro/nano-textured structure combined with high interfacial bonding strength and release of Zn2+ render the material surface promising as orthopedic implant coatings.


Effect of bovine somatotropin and food deprivation on beta-adrenergic and A1 adenosine receptor binding in adipose tissue of lactating cows.
Lactating Holstein cows were used to assess the effect of bovine somatotropin (bST; n = 8) and fasting (FAST; n = 4) on ligand binding to beta-adrenergic (BAR) and Type-1 adenosine (A1R) receptors in adipose tissue. Cows received exogenous bST (sometribove; 40 mg/d) or no hormone (control) for 4 d in a single-reversal design with a 7-d interval between treatment periods. Subcutaneous adipose tissue biopsies were taken on day 4 of each treatment. Eight d after the bST regimen, 4 cows were fasted for 3 d and adipose biopsies were taken. Ligand binding was quantified with a postnuclear, total adipose tissue membrane preparation (100,000 x g pellet). Binding to BAR and A1R was assessed with the antagonists [125I]iodocyanopindolol (ICP) and [3H]8-cyclopentyl-1,3-dipropylxanthine (DCPCX), respectively. The binding affinity (Kd) of BAR for ICP was not affected by bST but was enhanced by FAST; maximal binding (Bmax) was increased with bST treatment (P < 0.06) and reduced by FAST (61%, P < 0.01). Kd values for DCPCX binding to A1R were not changed by bST or FAST. bST did not affect Bmax for A1R; however, FAST reduced the Bmax by 38%. Data highlight the differential regulation of BAR and A1R by bST and FAST.


Safety of current antiviral drugs for chronic hepatitis B.
Oral nucleos(t)ide analogues (NUCs) are recommended as first-line therapy for chronic hepatitis B (CHB) due to higher HBV-DNA suppression rates and safety profile. Long-term treatment with NUCs is often necessary to achieve durable viral suppression. This review provides an overview of the long-term safety data that have become available since entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were first approved, and recent data on tenofovir alafenamide (TAF) in patients with CHB. NUCs generally show remarkable safety in patients taking them for long periods. Nevertheless, renal and bone toxicity may occur in a minority of patients on TDF therapy. These effects have been overcome by the recent release of TAF. Moreover, the currently available data do not allow firm conclusions on the superiority of TDF on ETV about hepatocellular carcinoma (HCC) risk reduction. Observational studies involving more homogeneous cohorts are therefore needed; furthermore, long-term studies assessing the impact of TAF on this important topic are warranted.


The modified prostate health index (PHI) outperforms PHI density in the detection of clinical prostate cancer within the PSA grey zone.
To compare the accuracy of several volume and diameters modified prostate health index (mPHI) models with PHI density (PHID), PHI, and other prostate-specific antigen (PSA) derivatives in detecting PSA grey zone prostate cancer (PCa). Between August 2020 and September 2021, a consecutive cohort of 214 suspected PCa patients with elevated total PSA values ranged from 4.0 to 10.0 ng/mL were prospectively recruited and received PHI detections and transrectal ultrasonography (TRUS) measurements, followed by systematic prostate biopsies confirmation. Among the 214 patients enrolled in the project, a total of 80 were diagnosed with PCa. In univariate analysis for the training cohort, the area under curve (AUC) of mPHI-2 [Formula: see text] was 0.8310, which outperformed PHID in identifying PSA grey zone PCa (P ≤ 0.0001) and showed the best net benefit in decision curve analysis (DCA). By a threshold of 0.2835, the sensitivity and specificity in the prediction of PCa were 78.9% and 90.3%, while the positive predictive value (PPV) and negative predictive value (NPV) were 78.3% and 78.6%, respectively. According to our present single-center experience, the mPHI-2 risk predictor outperformed PHID or other classical parameters alone in the PCa detection with a grey zone PSA level in Asian males.


Oral form identification as a measure of cortical sensory dysfunction in apraxia of speech and aphasia.
Oral form identification scores were obtained for nine anterior and nine posterior left-hemisphere brain lesion subjects exhibiting speech apraxic behavior and aphasia. An objective measure of speech apraxic difficulty and a standardized aphasia assessment were obtained for each subject. Despite the traditional association of a cortical sensory deficit including asterognosis in posterior brain-injured patients, oral form identification scores did not differ significantly for the two subject groups. However, a previously reported heterogeneity of performance was observed in the present data. The oral form identification deficit was unrelated to the severity of apraxia but exhibited its highest correlation value with a task of linguistic symbol discrimination. Results were interpreted to suggest that oral form identification deficits are most probably not causally related to motor speech programming problems nor should such deficits in this population be viewed as a valid indicator of cortical sensory dysfunction.


Vitamin B3 confers resistance to sulfa drugs in Saccharomyces cerevisiae.
Sulfa drugs are ubiquitous antibiotics used to treat bacterial infections and diseases caused by eukaryotes, such as Pneumocystis carinii, the leading cause of pneumonia (PCP) in HIV patients. A daily regimen of sulfonamides and multivitamins including vitamin B3 is also recommended for persons with HIV. We show that exogenous vitamin B3 (nicotinate) confers resistance to sulfa drugs in Saccharomyces cerevisiae, a model for P. carinii. We propose a model of metabolic rerouting in which increased nicotinate leads to increased intracellular concentration of p-aminobenzoate, thus leading to sulfonamide resistance.


The influence of synesthesia on eye movements: no synesthetic pop-out in an oculomotor target selection task.
Recent research on grapheme-colour synesthesia has focused on whether visual attention is necessary to induce a synesthetic percept. The current study investigated the influence of synesthesia on overt visual attention during an oculomotor target selection task. Chromatic and achromatic stimuli were presented with one target among distractors (e.g. a '2' (target) among multiple '5's (distractors)). Participants executed an eye movement to the target. Synesthetes and controls showed a comparable target selection performance across conditions and a 'pop-out effect' was only seen in the chromatic condition. As a pop-out effect was absent for the synesthetes in the achromatic condition, a synesthetic element appears not to elicit a synesthetic colour, even when it is the target. The synesthetic percepts are not pre-attentively available to distinguish the synesthetic target from synesthetic distractors when elements are presented in the periphery. Synesthesia appears to require full recognition to bind form and colour.


Circadian variation in sudden cardiac death: effects of age, sex, and initial cardiac rhythm.
Previous studies based on data obtained from vital statistics records have demonstrated circadian variation in the occurrence of sudden cardiac death. The purpose of this study was to examine the effects of age, sex, and initial cardiac rhythm on circadian variability in sudden cardiac death. This study employed a retrospective analysis of the records of adult patients with witnessed cardiac arrest who underwent resuscitation in an urban paramedic system during a 5-year period. The records of 2,250 consecutive patients with witnessed cardiac arrest were reviewed. Spectral analysis was used to decompose the data into frequency components. A circadian variation in the occurrence of sudden cardiac death was demonstrated, with a low occurrence rate between midnight and 6 AM and a 2.4-fold increase between the rate at 6 AM and the rate at noon. The same circadian pattern was noted among both men and women, among both patients aged 18 to 70 and those older than 70 years, and among patients with various initial cardiac arrest rhythms (ventricular tachycardia or fibrillation, asystole, and electromechanical dissociation). However, the outcome of resuscitation in these patients (ie, the rate of successful resuscitation and the rate of survival) did not demonstrate circadian variation. Witnessed out-of-hospital sudden cardiac death demonstrated circadian variation, and this variability was observed regardless of the patient's age, sex, or initial cardiac arrest rhythm. The outcome of resuscitation did not show circadian variability. These results suggest a common pathophysiologic mechanism leading to sudden cardiac death.


Standard SPECT myocardial perfusion estimation from half-time acquisitions using deep convolutional residual neural networks.
The purpose of this work was to assess the feasibility of acquisition time reduction in MPI-SPECT imaging using deep leering techniques through two main approaches, namely reduction of the acquisition time per projection and reduction of the number of angular projections. SPECT imaging was performed using a fixed 90° angle dedicated dual-head cardiac SPECT camera. This study included a prospective cohort of 363 patients with various clinical indications (normal, ischemia, and infarct) referred for MPI-SPECT. For each patient, 32 projections for 20 seconds per projection were acquired using a step and shoot protocol from the right anterior oblique to the left posterior oblique view. SPECT projection data were reconstructed using the OSEM algorithm (6 iterations, 4 subsets, Butterworth post-reconstruction filter). For each patient, four different datasets were generated, namely full time (20 seconds) projections (FT), half-time (10 seconds) acquisition per projection (HT), 32 full projections (FP), and 16 half projections (HP). The image-to-image transformation via the residual network was implemented to predict FT from HT and predict FP from HP images in the projection domain. Qualitative and quantitative evaluations of the proposed framework was performed using a tenfold cross validation scheme using the root mean square error (RMSE), absolute relative error (ARE), structural similarity index, peak signal-to-noise ratio (PSNR) metrics, and clinical quantitative parameters. The results demonstrated that the predicted FT had better image quality than the predicted FP images. Among the generated images, predicted FT images resulted in the lowest error metrics (RMSE = 6.8 ± 2.7, ARE = 3.1 ± 1.1%) and highest similarity index and signal-to-noise ratio (SSIM = 0.97 ± 1.1, PSNR = 36.0 ± 1.4). The highest error metrics (RMSE = 32.8 ± 12.8, ARE = 16.2 ± 4.9%) and the lowest similarity and signal-to-noise ratio (SSIM = 0.93 ± 2.6, PSNR = 31.7 ± 2.9) were observed for HT images. The RMSE decreased significantly (P value < .05) for predicted FT (8.0 ± 3.6) relative to predicted FP (6.8 ± 2.7). Reducing the acquisition time per projection significantly increased the error metrics. The deep neural network effectively recovers image quality and reduces bias in quantification metrics. Further research should be undertaken to explore the impact of time reduction in gated MPI-SPECT.