Estimating the prevalence of chronic hepatitis B virus infection--New York City, 2008.
Chronic hepatitis B virus (HBV) infection is a preventable cause of liver failure, cirrhosis, and liver cancer; estimated chronic HBV infection prevalence is 0.3-0.5% in the U.S.A. Prevalence in New York City (NYC) is likely higher because foreign-born persons, who represent 36% of NYC's population versus 11% nationwide, bear a disproportionate burden of chronic HBV infection. However, because no comprehensive, population-based survey of chronic HBV infection has been conducted in NYC, a reliable prevalence estimate is unavailable. We used two approaches to estimate chronic HBV infection prevalence in NYC: (1) a census-based estimate, combining local and national prevalence data for specific populations, and (2) a surveillance-based estimate, using data from NYC's Department of Health and Mental Hygiene Hepatitis B Surveillance Registry and adjusting for out-migration and deaths. Results from both the census-based estimate and the surveillance-based estimate were similar, with an estimated prevalence of chronic HBV in NYC of 1.2%. This estimate is two to four times the estimated prevalence for the U.S.A. as a whole. According to the census-based estimate, >93% of all cases in NYC are among persons who are foreign-born, and approximately half of those are among persons born in China. These findings underscore the importance of local data for tailoring programmatic efforts to specific foreign-born populations in NYC. In particular, Chinese-language programs and health education materials are critical. Reliable estimates are important for policymakers in local jurisdictions to better understand their own population's needs and can help target primary care services, prevention materials, and education.


Assessing safe and personalised maternity and neonatal care through a pandemic: a case study of outcomes and experiences in two trusts in England using the ASPIRE COVID-19 framework.
The COVID-19 pandemic has resulted in profound and far-reaching impacts on maternal and newborn care and outcomes. As part of the ASPIRE COVID-19 project, we describe processes and outcome measures relating to safe and personalised maternity care in England which we map against a pre-developed ASPIRE framework to establish the potential impact of the COVID-19 pandemic for two UK trusts. We undertook a mixed-methods system-wide case study using quantitative routinely collected data and qualitative data from two Trusts and their service users from 2019 to 2021 (start and completion dates varied by available data). We mapped findings to our prior ASPIRE conceptual framework that explains pathways for the impact of COVID-19 on safe and personalised care. The ASPIRE framework enabled us to develop a comprehensive, systems-level understanding of the impact of the pandemic on service delivery, user experience and staff wellbeing, and place it within the context of pre-existing challenges. Maternity services experienced some impacts on core service coverage, though not on Trust level clinical health outcomes (with the possible exception of readmissions in one Trust). Both users and staff found some pandemic-driven changes challenging such as remote or reduced antenatal and community postnatal contacts, and restrictions on companionship. Other key changes included an increased need for mental health support, changes in the availability and uptake of home birth services and changes in induction procedures. Many emergency adaptations persisted at the end of data collection. Differences between the trusts indicate complex change pathways. Staff reported some removal of bureaucracy, which allowed greater flexibility. During the first wave of COVID-19 staffing numbers increased, resolving some pre-pandemic shortages: however, by October 2021 they declined markedly. Trying to maintain the quality and availability of services had marked negative consequences for personnel. Timely routine clinical and staffing data were not always available and personalised care and user and staff experiences were poorly captured. The COVID-19 crisis magnified pre-pandemic problems and in particular, poor staffing levels. Maintaining services took a significant toll on staff wellbeing. There is some evidence that these pressures are continuing. There was marked variation in Trust responses. Lack of accessible and timely data at Trust and national levels hampered rapid insights. The ASPIRE COVID-19 framework could be useful for modelling the impact of future crises on routine care.


Patient Experience and Preference in Transradial versus Transfemoral Access during Transarterial Radioembolization: A Randomized Single-Center Trial.
To determine patient preference for transradial access (TRA) or transfemoral access (TFA) after experiencing both. A randomized controlled crossover trial was conducted at a single institution. Thirty patients with hepatocellular carcinoma undergoing mapping and transarterial radioembolization (TARE) were enrolled to experience 1 TRA and 1 TFA procedure each, with randomization of which access approach was experienced first. Surveys assessing pain and quality of life (QOL) were administered after each procedure. Access site preference was collected after completion of both procedures. Twenty-two subjects (73.3%) preferred TRA, 4 (13.3%) preferred TFA, and 4 (13.3%) had no preference; 14 (46.7%) reported bruising after TRA, and 17 (53.3%) reported bruising after TFA. TRA was associated with significantly lower pain scores overall during the procedure, at the access site during the procedure, and in the recovery room compared with TFA (2.0 vs 2.9, P = .0046; 2.0 vs 3.0, P = .0004; 2.1 vs 2.9, P = .0357). Pain score after discharge was not significantly different (1.4 vs 1.5, P = .4235). QOL scores were not significantly different between TRA and TFA. No significant differences were found for fluoroscopy time, air kerma, dose-area product, or procedure time between TRA and TFA for either mapping (P = .1442, P = .5871, P = .6667, P = .6131) or radioembolization (P = .8574, P = .2344, P = .1119, P =.8474). For radioembolizations, TRA had significantly shorter recovery times compared with TFA (108 min vs 153 min, P = .0193). Patients exhibited a strong preference for TRA. With TRA, patients experienced less periprocedural pain and shorter recovery times without significant differences in radiation exposure or procedure length.


Allogeneic bone nail for articular fractures.
To investigate the effect of allogeneic bone nail on articular fractures. Ninety-one patients with cancellous bone fracture involved in various joints were fixed with the bone nail or the bone screw. No immunosuppressive agent was used in this series. The average period of follow-up wa s 18 months. All patients except one healed without displacement an d the healing time was within 1-3 months. Joint function was partially limited in 6 patients and others were functioning well. Allogeneic bone nail possesses a good biological compatibility and intensity, thus provides a rigid fixation. Being completely absorbed and ossificated, thus obviating the need for secondary operation, is a suitable internal fixation material for the treatment of articular fractures.


Anaemia and deaths in red deer (Cervus elaphus) fawns associated with heavy infestations of cattle tick (Haemaphysalis longicornis).
In late December/early January 1979/80, deaths occurred in 30 red deer (Cervus elaphus) fawns. Evidence is presented to suggest that these deaths most likely resulted from heavy infestations of ticks (Haemaphysalis longicornis).


A novel multicomponent reaction involving isocyanide, dimethyl acetylenedicarboxylate (DMAD), and electrophilic styrenes: facile synthesis of highly substituted cyclopentadienes.
Alkyl isocyanides, DMAD, and various activated styrenes furnish fully substituted cyclopentadienes in a one-pot three-component reaction. [reaction: see text]


"Distribution of paternal lineages in Mestizo populations throughout Mexico: an in silico study based on Y-STR haplotypes".
The Mexican-Mestizo population arose following European contact with the Americas due to the admixture of principally Spaniards, Native Americans, and Africans around 500 years ago. Because the paternal lineage distribution of the Mexican population has been poorly investigated, this study inferred the haplogroups of ten populations based on 1859 haplotypes (Y-STR data) using two haplogroup predictor programs. In the Mexican population sample, we found predominantly European ancestry (50.1%), followed by Native American (32.5%), Eurasian (13.4%), African (2.1%), East African-South Eurasian (1.3%), and Asian (0.6%) ancestries. In general, our results support a contrary north-to-south gradient throughout the Mexican territory of European and Native-American ancestries, respectively. Moreover, the presence of West-European R1b and Sub-Saharan African E1b1a haplogroups agrees with historical and genetic data of gene flow during the European conquest. This study represents the effort to analyze these paternal lineages on a large scale by taking advantage of Y-STR haplotype data to determine the distribution and ancestry proportions in this country.


Alternative and complementary treatment for food allergy.
Despite increased consumer interest in complementary and alternative medicine (CAM) for the treatment of food allergy, there remains a relative paucity of knowledge regarding the clinical efficacy, mechanisms of action, and safety of most CAM treatments available to consumers. This article focuses on recent advances in CAM for food allergy, including acupuncture, herbal medicine, probiotics, and alternative approaches to allergen immunotherapy. The mechanism of action of several novel approaches to treatment of food allergy is reviewed, but FAHF-2 is the only investigational herbal formulation currently validated for use in human clinical trials.


Clostridium difficile in neonates: serogrouping and epidemiology.
A typing scheme for Clostridium difficile based on serogrouping, toxigenicity and sorbitol fermentation was applied to 270 strains isolated in one neonatal ward during a 6-month prospective study. Two hundred and twenty-three strains were isolated from 377 faecal samples of 114 neonates and 47 from 92 environmental specimens. The isolates were distributed among five different types; 87% of the faecal and 85% of the environmental isolates belonged to two of these types (toxigenic, sorbitol negative, serogroup F and nontoxigenic, sorbitol positive, serogroup A). Nosocomial spread was clearly demonstrated and the environment appeared to be the main source of contamination: most of the neonates were colonized after admission by strains found in their environment; clusters of colonization with unusual isolates were observed following referral of patients from the intensive care unit or from other hospitals. No relation was found between the acquisition or the carriage of C. difficile and any intestinal symptoms. All the strains belonged to types different from those usually found in cases of antibiotic associated colitis (AAC) suggesting differences of pathogenicity among the different types.


Clinical-molecular correlation in 104 mild X-linked muscular dystrophy patients: characterization of sub-clinical phenotypes.
A multidisciplinary study was conducted in order to assess dystrophin expression in a large series of mild X-linked muscular dystrophy patients, with well-defined clinical phenotype. Patients (104) were divided in 4 clinical groups, according to clinical severity: asymptomatic (sub-clinical), benign, moderate and severe, Cardiopathy was also assessed, and dilated cardiomyopathy was found in 47% of sub-clinical and benign cases. Myoglobinuria, cramps and myalgia were also associated with a sub-clinical or benign clinical status. Dystrophin immunohistochemical pattern of labelling and dystrophin amount decreased gradually across clinical groups. Our study showed a significative correlation between: (1) dystrophin amount and immunohistochemical score (p < 0.05); (2) dystrophin amount and clinical score (p < 0.05). Therefore, the combined use of these different techniques for prognosis of mild X-linked muscular dystrophy patients is useful. Our study assesses the prevalence of the various disease courses in a large cohort of mild X-linked muscular dystrophy patients. From our series, up to 30% of patients may be either asymptomatic or have sub-clinical changes.


Metabolomic analysis of Thai Herbal Analgesic Formula based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.
Sahatsatara formula (STF), a Thai herbal medicine formula which has been commonly used as analgesic drugs to relieve musculoskeletal pain and numbness in Thai traditional medicine. The pharmacological studies of its ingredients have represented that have anti-inflammatory and antioxidant properties. However, the quality markers (Q-markers) for STF are still unknown and require further investigation. The primary goal of this study was to establish the chemical profile of STF though metabolomic analysis. Untargeted metabolomics were used to analyze global components and accurately qualify compounds. Multivariate analysis (MVA) was used to classify STF extract at three different concentrations and a quality control sample. Furthermore, samples' characteristics and identification-related markers were observed and compounds matched to the Traditional Chinese medicine library in UNIFI software. According to the results, chemical analysis revealed 63 compounds in positive mode and 33 compounds in negative mode within STF. Notably, 19 potential Q-markers were tentative identified in all three concentrations of STF, including alkaloids, terpenes, phenols, organic acids, disaccharides, fatty acids, glycosides, quinonoids, and steroids. The compounds exhibited pharmacological effects such as anti-inflammatory activity, anti-oxidant activity, and analgesic properties, which correlated to traditional properties of STF. Consequently, this study provides insights into the chemical profiles of the STF and identifies potential markers that can be utilized for qualitative and quantitative quality control of STF. Additionally, the findings can also be useful for further research into STF's anti-inflammatory properties through in vitro assays, as well as exploring its clinical efficacy to support evidence-based medicine for STF.


Displaced ganglion cells in the retina of the rat.
The distribution, laterality of projection, and perikaryal sizes of displaced ganglion cells (DGCs) were examined in whole-mounted retinae after massive unilateral injections of horseradish peroxidase along the optic tract in pigmented rats. The DGCs were found predominantly in the lower temporal periphery of the retina. Nearly all DGCs labeled had contralaterally projecting axons. The sizes of the labeled DGCs spanned the range of ordinary ganglion cells, but few middle-sized DGCs were labeled. The results support the hypothesis that displaced ganglion cells are late-developing neurons that do not complete their migration toward the ganglion cell layer during retinal histogenesis.


Changes in Subjective Sleep Quality Before a Competition and Their Relation to Competitive Anxiety.
The aim of this study was to examine the effects of competitions on subjective sleep quality. Previous studies have been inconclusive and lack differentiated and standardized measurements of subjective sleep quality. Furthermore the temporal relation between precompetitive anxiety and sleep quality was investigated. Anxiety and nervousness associated with competitions are considered to cause sleep impairments. A convenience sample of N = 79 elite male athletes from various sports participated. In a time-to-event paradigm, sleep quality and competitive anxiety were assessed via standardized self-report measurements 4 days before a competition and on the day of the competition. Univariate analyses were used to examine differences between time points. To examine cross-lagged effects between anxiety and sleep quality a latent change score model (LCSM) was specified that tested an effect of anxiety on changes in sleep quality. Evaluations of nocturnal sleep deteriorated significantly from 4 days before competition to the day of competition, but there were no differences regarding perceptions of the restorative value of sleep. LCSM revealed that athletes who reported more intense worry symptoms 4 days before competition also reported greater deterioration in evaluations of nocturnal sleep. The findings support earlier reports of impaired subjective sleep quality before competitions. Precompetitive sleep impairments appear also to be preceded by cognitive anxiety. Whereas interventions should thus address worry-cognitions associated with competition and sleep, research should address the practical importance of these perceptions of sleep impairments.


Measurement of branching fractions and charge asymmetries in B+ decays to eta pi+, eta K+, eta rho+, and eta' pi+, and search for B0 decays to eta K0 and eta omega.
We present measurements of branching fractions and charge asymmetries for six B-meson decay modes with an eta or eta(') meson in the final state. The data sample corresponds to 232 x 10(6) BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) B Factory at SLAC. We measure the branching fractions (in units of 10(-6)): B(B+ -->eta pi(+))=5.1+/-0.6+/-0.3, B(B+ etaK+)=3.3+/-0.6+/-0.3, B(B0-->etaK0)=1.5+/-0.7+/-0.1 (<2.5 at 90% C.L.), B(B+-->eta rho(+))=8.4+/-1.9+/-1.1, B(B0-->eta omiga)=1.0+/-0.5+/-0.2 (<1.9 at 90% C.L.), and B(B+-->eta(')pi(+))=4.0+/-0.8+/-0.4, where the first uncertainty is statistical and second systematic. For the charged modes we also determine the charge asymmetries, all found to be compatible with zero.


Modal reconstruction methods with Zernike polynomials.
To compare the advantages and disadvantages of different techniques for fitting Zernike polynomials to surfaces. Two different methods, Orthogonal Projection and Gram-Schmidt orthogonalization, are compared in terms of speed and performance at fitting a complex object. Orthogonal Projection provides an extremely rapid fitting of a surface, but leaves residual high frequency noise. The Gram-Schmidt technique provides a more accurate fit of the original object, but consumes much more computing time. Orthogonal Projection, and its associated noise, may be tolerated in classifying corneal topography. Orthogonal Projection has a distinct advantage in calculation time over other methods for fitting surfaces. This advantage may be exploited in cases where accurate surface fitting is not necessary, but only general features need to be extracted for classification. If fit accuracy is needed, then slower fitting techniques, such as Gram-Schmidt, should be used.


Improvement of the AOAC 2009.01 total dietary fibre method for bread and other high starch containing matrices.
The dietary fibre (DF) content in wheat grain based food products have been established with both the classical AOAC 985.29 dietary fibre and the new AOAC 2009.01 total dietary fibre protocol. There is a good agreement between the high molecular weight dietary fibre (HMWDF) contents measured with the AOAC 2009.01 method and (DF) content measured with the classical AOAC 985.29 method in wheat grain based food products. With the AOAC 2009.01 method also a significant amount of low molar weight dietary fibre (LMWDF), ranging from 1% to 3% w/w, was measured which is not quantified with the AOAC 985.29 method. With semi-preparative GPC the LMWDF (DP⩾3) fractions in the wheat grain based food products were isolated. The monosaccharide composition of the dissolved LMWDF constituents was determined. Glucose was by far the most abundant monosaccharide present with arabinose, galactose, xylose and mannose as minor constituents. It appeared that the LMWDF contains still not fully converted digestible starch/malto-oligosaccharide fragments with DP⩾3, which are erroneously quantified as LMWDF. By introducing an extra AMG hydrolysis step in the AOAC 2009.01 protocol after evaporation of the ethanol and dissolving the residue in deionised water, these malto-oligosaccharides are fully hydrolysed resulting in that way in a correct and lower LMWDF content.


Cytotoxicity, biocompatibility and osteoinductive profile of an MTA-hydrogel-based cement: An in vitro and animal study.
This study aimed to evaluate the cytotoxicity, biocompatibility and osteoinductive profile of a mineral trioxide aggregate (MTA)-hydrogel-based material (MTA Flow) in comparison with MTA Angelus. Cell viability was evaluated in human periodontal ligament stem cells (hPDLSCs) using the methyl-thiazol-tetrazolium (MTT) colourimetric assay. Polyethylene tubes containing the tested materials and empty polyethylene tubes (control) were implanted in the subcutaneous tissue of Wistar rats. Cellular (lymphocyte infiltration) and extracellular events (ECM; collagen fibres) were analysed in histological sections. Immunohistochemical (collagen I, osteopontin, bone sialoprotein, bone morphogenetic protein4) analyses were also performed. At 24, 48 and 72 h, all tested groups showed cell viability similar to control (p > .05). Regarding biocompatibility, all groups showed similar cellular events represented by a slight inflammatory reaction characterized by hyperaemia and a mild lymphocytic inflammatory infiltrate. The analysis of lymphocytes during the time showed a decrease in these cells in the control group and a significant interaction between MTA Angelus and control (p < .001), with MTA Angelus showing a more extensive inflammatory infiltrate. Regarding fibres, an increase in content was observed in all groups during the experimental time (7, 30 and 60 days), however, no difference was detected among the experimental groups (p = .063). After 60 days, the immunoexpression of bone matrix proteins in the MTA Flow group was similar to or higher than that observed in the MTA Angelus and in the control group. MTA Flow showed a non-cytotoxic behaviour, biocompatibility and ability to stimulate tissue mineralization.


Characterization of a plasmid mutation affecting maintenance, transfer and elimination by novobiocin.
We have isolated a mutant H group plasmid temperature-sensitive for plasmid maintenance. Unlike the wild type plasmid (pSD114), the mutant (pDT4) was eliminated at 37 degrees C and also at 30 degrees C after novobiocin treatment. The mutant plasmid interfered with host cell growth at the non-permissive temperature. Conjugative transfer of the mutant was reduced at 30 degrees C compared to the wild-type plasmid. Introduction of a coumermycin-novobiocin resistance DNA gyrase (cou) mutation into Escherichia coli prevented pDT4 elimination by novobiocin but did not affect the temperature-sensitive phenotype. The evidence indicates that the mutant plasmid used bacterial DNA gyrase for replication. Models to account for the behaviour of this unusual mutant are discussed.


Facilitators and Challenges of Integrating Experts by Experience Activity in Mental Health Services: Experiences from Finland.
This qualitative study examines the facilitators and challenges of integrating Experts by Experience (EbyE) activity in mental health services in the public sector from the perspective of mental health professionals and trained EbyE. The research data consist of four focus group interviews conducted in one hospital district in Finland. In the hospital district, EbyE activity is an established working model in mental health services. The professional focus groups had 9, and the EbyE focus groups had 13 participants. The data were analysed using abductive content analysis. The experiences of professionals and EbyE emphasised the successful integration of EbyE activity. The identified facilitators of integration included an organisational culture that values EbyE activity, facilitating operating structures, and extensive implementation and utilization of EbyE activities. Despite successful integration, certain challenges were described with regard to actors and practices. The findings indicate that the hospital district has overcome many of the obstacles to the integration identified in previous studies. The findings highlight the role of effectively implemented, organised EbyE activity.


Circadian rhythms in depression and recovery: evidence for blunted amplitude as the main chronobiological abnormality.
Circadian rhythms of body temperature, plasma cortisol, norepinephrine (NE), thyroid stimulating hormone (TSH), and melatonin were compared in 16 endogenously depressed, 15 recovered (after 3 weeks of anti-depressant treatment), and 16 normal subjects. The depressed patients showed clear circadian rhythm abnormalities, consisting mainly in amplitude reduction. This amplitude reduction was significantly correlated with the patients' Hamilton depression scores. Normal circadian profiles were restored after recovery when amplitude, in particular, was increased. Features of the circadian rhythms observed in remission may be associated with antidepressant drug effects, whereas those observed in depression resemble the circadian rhythms observed in normal subjects living under conditions of temporal isolation and those of blind subjects. Our findings suggest that depression may be related both to a weakening of the coupling processes between internal pacemakers and to an abnormal sensitivity to environmental information.


Demonstration of simultaneous anion-exchange and reversed-phase behavior on a strong anion-exchange column.
We demonstrate in this report that a conventional silica-based strong anion-exchange column can exhibit reversed-phase chromatographic behavior simultaneously with ion-exchange in a methanol-aqueous phthalate mobile phase. Reversed-phase behavior is shown for PAHs in relatively high methanol-content mobile phases, while polar organics exhibit reversed-phase behavior in 0-10% (v/v) methanol-water eluents. At low concentrations (0-10% v/v) methanol has little or no effect on anion retention, while the anions exhibit only slight increases in retention in 60-80% (v/v) methanol at near-neutral pH values. Likewise, pH changes used to manipulate anion retention have essentially no effect on PAH retention, and cause only small decreases in retention for most of the polar organics studied. Little or no pH-effect was seen on a phenyl column (no exchange group) or with acetate mobile phase. It is shown that manipulation of pH and methanol content allows the grouping of neutral organic analytes early in a chromatogram, followed by the anions, with no class overlap. Several example chromatograms are given, including that of a red wine sample. Column efficiency was good for anions but only modest for organics.


Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.
To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible.


Treatment Guideline Nonadherence Pretransport Associated With Need for Higher Level of Care in Children Transferred to a Pediatric Tertiary Care Center for Status Epilepticus.
We sought to investigate the association between adherence to the American Epilepsy Society (AES) 2016 guidelines for management of convulsive status epilepticus (SE) and clinical outcomes among children requiring interhospital transport for SE. We hypothesized that pretransport guideline nonadherence would be associated with needing higher level of care posttransfer. This was a retrospective cohort study of children aged 30 days to 18 years transferred to our pediatric tertiary center from 2017 to 2019 for management of SE. Their care episodes were classified as 2016 American Epilepsy Society guideline adherent or nonadherent. There were 40 referring hospitals represented in this cohort. Of 260 care episodes, 55 (21%) were guideline adherent, 184 (71%) were guideline nonadherent, and 21 (8%) had insufficient data to determine guideline adherence. Compared with the adherent group, patients in the nonadherent care group had longer hospitalizations (32 hours [17-68] vs 21 hours [7-48], P = 0.006), were more likely to require intensive care unit admission (47% vs 31%), and less likely to be discharged home from the emergency department (16% vs 35%; χ 2 test, P = 0.01). Intubation rates did not differ significantly between groups (25% vs 18%, P = 0.37). When we fit a multivariable model to adjust for confounding variables, guideline nonadherence was associated with need for higher level of care (odds ratio, 2.04; 95% confidence interval, 1.04-3.99). Treatment guideline adherence did not improve over the 3-year study period (2017: 22%, 2018: 19%, 2019: 29% [χ 2 test for differences between any 2 years, P = 0.295]). Guideline nonadherence pretransport was associated with longer hospitalizations and need for higher level of care among children transferred for SE at our institution. These findings suggest a need to improve SE guideline adherence through multifaceted quality improvement efforts targeting both the prehospital and community hospital settings.


Decreasing Antibiotic Resistance Trends Nationally in Gram-Negative Bacteria Across United States Veterans Affairs Medical Centers, 2011-2020.
Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria. The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic. Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p < 0.05). The largest decreases were seen in carbapenem-resistant phenotypes of P. mirabilis, Klebsiella, and M. morganii (AAPCs: - 22.9%, - 20.7%, and - 20.6%, respectively). In 2020, percent susceptibility was over 80% for all organisms tested against aminoglycosides, cefepime, ertapenem, meropenem, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. We observed significant decreases in antibiotic resistance for P. aeruginosa and Enterobacterales over the past decade. According to the 2020 antibiogram, in vitro antimicrobial activity was observed for most treatment options. These results may be related to the robust infection control and antimicrobial stewardship programs instituted nationally among VAMCs.


Perilunate Injuries: Current Aspects of Management.
Perilunate dislocations (PLD) and perilunate fracture dislocations (PLFD) are high-energy injuries which can result in long-term complications and significant disability. Early identification of these injuries, followed by prompt, appropriate management is key to optimising patient outcomes. Knowledge of the carpal anatomy is essential in order to understand the varied patterns of injury and plan appropriate definitive management. Emergent reduction and close monitoring of the median nerve, followed by prompt stabilisation or repair of the injured structures remain the mainstay of treatment. In this review, we present a summary of the current evidence regarding the identification and management of these complex injuries.


Central retinal artery occlusion due to infective endocarditis.
We present a case of central retinal artery occlusion (CRAO) in a 59-year-old male suffering from infective endocarditis. The patient was receiving antibiotic treatment for the endocarditis for 5 days prior to the event and received conservative treatment for the CRAO without any improvement. A few days after the event, the patient underwent heart surgery with aortic and mitral valve replacement and eventually recovered without any other side-effects. CRAO is a rare but devastating embolic complication of infective endocarditis and can happen regardless of whether a patient is receiving systemic antibiotic treatment or not. These patients need close observation, because an immediate diagnosis and an urgent therapeutic procedure are mandatory, as the prognosis for vision is poor.


Verification of dioxin formation in a catalytic oxidizer.
Emissions and inlet concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF) have been measured from a catalytic oxidizer and a thermal oxidizer. The catalyst inlet temperature was 427 degrees C. The thermal oxidizer operating temperature was 791 degrees C. Data of the toxic dioxin and furan congeners are reported. Important results of this field study are: (1) the catalytic oxidizer in this study produced an increase in PCDD/PCDF congener concentration of almost 10-fold from the inlet to the outlet (stack), thus verifying results of a previous study that evaluated only PCDD/PCDF emissions. All congeners increased from inlet to the stack. (2) The thermal oxidizer had little effect on PCDD/PCDF levels. There was a decrease in four of the congeners and an increase in 13 congeners. (3) Ambient air was the main source of PCDD/PCDFs in the stack emissions of the thermal oxidizer in this study. Laboratory investigations are needed to understand how PCDD/PCDFs are formed (and emitted) under conditions of this study.


Decreased plasma testosterone concentrations in rams affected by ryegrass staggers.
Feeding ryegrass, cut from pasture that had caused an outbreak of ryegrass staggers, to 10 mature rams caused a significant decrease in plasma testosterone concentrations in six animals. Six rams also developed staggers, but these did not all have decreased testosterone levels. This discrepancy suggests that toxic pasture could cause these two effects independently.


The role of vision on hand preshaping during reach to grasp.
During reaching to grasp objects with different shapes hand posture is molded gradually to the object's contours. The present study examined the extent to which the temporal evolution of hand posture depends on continuous visual feedback. We asked subjects to reach and grasp objects with different shapes under five vision conditions (VCs). Subjects wore liquid crystal spectacles that occluded vision at four different latencies from onset of the reach. As a control, full-vision trials (VC5) were interspersed among the blocked vision trials. Object shapes and all VCs were presented to the subjects in random order. Hand posture was measured by 15 sensors embedded in a glove. Linear regression analysis, discriminant analysis, and information theory were used to assess the effect of removing vision on the temporal evolution of hand shape. We found that reach duration increased when vision was occluded early in the reach. This was caused primarily by a slower approach of the hand toward the object near the end of the reach. However, vision condition did not have a significant effect on the covariation patterns of joint rotations, indicating that the gradual evolution of hand posture occurs in a similar fashion regardless of vision. Discriminant analysis further supported this interpretation, as the extent to which hand posture resembled object shape and the rate at which hand posture discrimination occurred throughout the movement were similar across vision conditions. These results extend previous observations on memory-guided reaches by showing that continuous visual feedback of the hand and/or object is not necessary to allow the hand to gradually conform to object contours.


Ibuprofen: new explanation for an old phenomenon.
Nuclear factor-kappaB (NF-kappaB) translocation from the cytoplasm into the nucleus and the subsequent DNA binding is an essential prerequisite in the up-regulation of many pro-inflammatory genes, e.g. tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). The anti-inflammatory drug ibuprofen, thought to exert its beneficial effects mainly by suppressing the production of eicosanoids, inhibited the up-regulation of the pro-inflammatory cytokines IL-1beta and TNF-alpha. This effect was independent of the described potential of ibuprofen as a cyclooxygenase inhibitor. Ibuprofen inhibited the activation and translocation of the key transcription factor NF-kappaB by blocking the degradation of inhibitor-kappaBalpha, a protein that forms a complex with NF-kappaB, thereby preventing the release and subsequent translocation of NF-kappaB into the nucleus and the expression of inflammatory cytokines. The presented data offer a new explanation for the anti-inflammatory effect of ibuprofen.


Gonadotropin-releasing hormone (GnRH) pharmacokinetics: peptide hormone pharmacokinetics needs clarification.
The plasma level curves of the peptide hormone gonadotropin-releasing hormone (GnRH) after its intravenous, intramuscular, and intraperitoneal administration into rats were fitted according to a two- (i.v.) and one-compartment model (i.m., i.p.), respectively. From the pharmacokinetic parameters it is concluded that urinary excretion and proteolytic degradation by kidney and liver are not sufficient to fully account for the clearance of the hormone and that, therefore, proteolytic degradation by tissues may play a role for the elimination of GnRH. This may be generally true with other short peptide hormones. The GnRH pharmacokinetics is shown as an example to underline that there presently exist problems of interpreting pharmacokinetic data of peptide hormones and that there is a need for a close interplay between biochemical and pharmacokinetic studies on peptide hormones for their pharmacokinetic behaviour to be understood.


Cloning and characterization of a trypsin-like serine protease gene, a novel regeneration-related gene from Apostichopus japonicus.
Trypsin-like serine protease (TLS) plays an important role in many physiological processes including wound healing, phlogosis reaction, blood clotting, regeneration etc. In this paper, a 1216 bp full-length cDNA sequence of TLS including 39 bp 5' UTR and 355 bp 3'UTR coding for a theoretical 273 amino acids protein was cloned from Apostichopus japonicus by means of the RACE technique for the first time. Bioinformatic analysis revealed that the gene with a 20 residues N-terminal signal peptide and a conserved C-terminal domain belongs to the trypsin-like serine protease superfamily. His78, Asp130 and Ser223 are the principal residues of the catalytic center. In-situ hybridization (ISH) analysis revealed that the TLS gene was widely distributed in different tissues. The expression patterns during different regeneration stages of the TLS gene in the body wall, intestine and respiratory trees were investigated using real-time quantitative PCR. The results show that there was a remarkable and temporary up-regulation of TLS gene expression in the body wall within 1h and subsequent down-regulation of TLS similar to intestine and respiratory trees. With the recovery of tissues, the expression level of the TLS gene was gradually up-regulated and finally reached normal levels. TLS was regulated during different regeneration stages suggesting that TLS is important in the regeneration process of A. japonicus.


Unbridged Rh(ii)-Rh(ii) complexes of N-heterocyclic carbenes and reactions with O2 to form dirhodium(μ-η1:η1-O2) complexes.
Dimeric rhodium(ii) complexes and rhodium(iii) peroxide complexes supported by N-heterocyclic carbenes were synthesized. The treatment of [Ag3(L)2](PF6)3 (L = bis(N-pyridylimidazolylidenyl)methane) with [Rh(COD)Cl] afforded [Rh(L)(CH3CN)]2(PF6)4 in which two [Rh(L)] moieties are bound together via an unsupported Rh-Rh bond. The substitution of axial acetonitrile by phosphines led to the insertion of O2 into the Rh-Rh bond and the isolation of [Rh(L)(PPh3)]2(μ-η1:η1-O2)(PF6)4 and [Rh(L)(PCy3)]2(μ-η1:η1-O2) (PF6)4.


Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption: results of quantitative tissue analysis using real-time RT-PCR method.
The balance between degradation and synthesis of extracellular matrix determines its content in atherosclerotic tissue. To examine the role of expression balance of matrix metalloproteinases (MMPs) to their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and tissue factor pathway inhibitor-2 (TFPI-2) in the development and disruption of atherosclerotic plaque, these gene expressions in human carotid plaque were quantitatively determined by real-time reverse transcription (RT)-polymerase chain reaction (PCR) method. Total RNA for cDNA synthesis was extracted from tissues in 24 patients with carotid endarterectomy. The amounts of cDNAs for MMP-1, -2, -3 and -9, TFPI-2 and TIMP-1, -2 and -3 were determined by real-time RT-PCR method, and normalized with glutaraldehyde 3-dehydrogenase. In plaques, the expression MMP-1 (1.53+/-0.25, mean+/-S.E.M.), MMP-3 (1.99+/-0.59) and MMP-9 (2.00+/-0.51) was augmented compared to those in the adjacent control regions (0.60+/-0.16, 0.46+/-0.18 and 0.58+/-0.21, respectively, p<0.05). The expression of TFPI-2 was lower in plaques (0.32+/-0.08) than in controls (0.94+/-0.23, p<0.01). Although the expression of TIMP-1 was higher in plaques (1.28+/-0.23) than in controls (0.81+/-0.10, p<0.05), the indices of MMP-1/TIMP-1, MMP-3/TIMP-3 and MMP-9/TIMP-1 were still significantly higher in plaques. Interestingly, MMP-9 and the resulting MMP-9/TIMP-1 balance in plaques with disruption were significantly higher (3.36+/-1.52 and 1.66+/-0.12, n=11) than those in non-disrupted plaques (1.11+/-0.52 and 0.76+/-0.12, n=13, p<0.05). With the decreased expression of TFPI-2, upregulation of MMPs in atherosclerotic plaque was disproportional to that of TIMPs, suggesting that imbalanced degradation and synthesis of extracellular matrix persists in advanced lesions, particularly in plaques with disruption.


Umbilicus as the only site of metastasis in recurrent ovarian cancer.
We present 2 rare cases of umbilical metastases (Sister Mary Joseph's nodule) as the first sign of late recurrent ovarian cancer. Two patients with ovarian cancer treated with optimal debulking surgery plus chemotherapy were regularly followed up postoperatively. An isolated umbilical nodule was noted accidentally 8 years and 3 years, respectively, after the initial operation. Abdominal computed tomography (CT) for both patients showed a 1.8-cm mass and a 2.3-cm mass with negative peritoneal tumor seeding. Other tumor surveys, including CA125, showed negative findings. Both patients had exploratory laparotomy and complete excision of the umbilical tumor. The pathology showed an isolated metastatic adenocarcinoma without evidence of other metastases. Both patients were treated with 4-course postoperative adjuvant chemotherapy of carboplatin and paclitaxel. Both patients have been in complete clinical remission for 22 months and 12 months, respectively. In addition to tumor marker CA125, a careful and thorough physical examination, assisted by modern imaging evaluation, is the best method for detecting early recurrence in patients with previously treated ovarian cancer. Although an umbilical metastasis usually indicates advanced disease with disseminating peritoneal spread, it does not always imply inoperable or incurable disease. Intensive treatment can improve the outcome.


Antibodies to a fragment of the Bothrops moojenil-amino acid oxidase cross-react with snake venom components unrelated to the parent protein.
It is widely accepted that immunological cross-reactivity of snake venoms is mediated by antibodies that recognize venom components bearing either amino acid sequence homology or similar biological functions. However, here we demonstrate that polyspecific Bothrops antivenom is a source of cross-reactive antibodies that interact with venom proteins of distinctive primary structures and biological functions. The homoserine lactone derivative of the undecapeptide IQRWSLDKYAM (Ile1-Hse11), excised from the l-amino acid oxidase (LAAO) of the Bothrops moojeni venom, was the ligand of an affinity resin used to isolate specific anti-Ile1-Hse11 antibodies which were instrumental in revealing immunological cross-reactivity among unrelated venom proteins. We examined the extent of the cross-reactivity of these antibodies by probing electroblots of venoms from representative snakes of genera Bothrops, Lachesis, Crotalus and Micrurus, and by unambiguous structural characterization of the affinity-purified proteins of B. moojeni venom recovered from an agarose-anti-Ile1-Hse11 column. Our results indicate that all venoms tested had at least three reactive components toward anti-Ile1-Hse11 antibodies, among which we identified two serine proteases, one phospholipase A2 homologue, and LAAO. We hypothesize that the cross-reactivity of the anti-Ile1-Hse11 antibodies to unrelated venom proteins derives from their mechanism of antigen recognition, whereby complementarity is achieved through reciprocal conformational adaptation of the reacting molecules. Also, we believe these findings have implications both in the development of improved antivenoms and the preparation of immunochemical reagents for diagnostic and scientific investigation purposes in the field of snake venoms.


Human primary motor cortex shows hemispheric specialization for speech.
Hemispheric specialization is a prominent characteristic of the human brain. Should the 'dominant' hemisphere possess differential neural organization for language production in the 'higher order' cortex, it would be rational to consider that the primary motor cortex may also show similar hemispheric specialization for speech production. In order to test this hypothesis, we investigated the spatial distribution of neural activities associated with phonation (M1p), silent tongue motion (M1t), and vocalization (M1v) within the primary motor cortex, utilizing independent component-cross correlation-sequential epoch analysis of high-field functional magnetic resonance imaging time series. While M1t showed no significant differences between the two hemispheres, M1p and M1v exhibited significant hemispheric differences. The study demonstrated direct evidence that human primary motor cortex possesses clear-cut hemispheric specialization similar to that observed for the higher order cortices.


Correction to: Safety and effectiveness of peficitinib (ASP015K) in patients with rheumatoid arthritis: interim data (22.7 months mean peficitinib treatment) from a long-term, open-label extension study in Japan, Korea, and Taiwan.
An amendment to this paper has been published and can be accessed via the original article.


Prenatal diagnosis of ring chromosome 6 in a fetus with cerebellar hypoplasia and partial agenesis of corpus callosum: case report and review of the literature.
Ring chromosome 6 (RC6) is a rare constitutional abnormality, with variable material loss, leading to a variable clinical phenotype: minimal physical anomalies and mild psychomotor retardation to severe physical and mental defects. Among the 22 published cases, only five have been prenatally detected. We describe here a RC6 prenatally diagnosed. Ultrasound follow-up showed growth retardation and cerebellar hypoplasia. Magnetic resonance imaging (MRI) confirmed this, but showed a partial corpus callosum agenesis, leading to amniocentesis and revealing the chromosomal abnormality. Imaging features were correlated with autopsy findings.


Effect of tobacco smoking on tissue protein citrullination and disease progression in patients with rheumatoid arthritis.
The aim of the present work was to study the effect of tobacco smoking on disease progression in rheumatoid arthritis patients and its relation to anti-cyclical citrullinated peptide (anti-CCP) antibodies. The study included 54 patients; 20 non-smokers, 9 ex-smokers, 14 mild to moderate smokers and 11 heavy smokers. Fifteen normal volunteers were also studied as controls. Disease stage was clinically and radiologically determined, rheumatoid factor (RF) and anti-CCP antibodies were measured in serum. Higher percentage of severe disease (stage III) was seen in heavy smoker patients than mild to moderate smokers (54.6% versus 35.7%) and in moderate smokers than ex-smokers (35.7% versus 33.6%). Lowest percentage of severe disease was seen in non-smokers (15%). RF and anti-CCP were significantly higher in smoker than non-smoker and in heavy than mild to moderate smoker patients (p < 0.01, p < 0.05 and p < 0.01, p < 0.001, respectively). In smoker patients, both RF and anti-CCP antibodies correlated significantly and positively with smoking index (r = 0.581, p < 0.001; r = 0.661, p < 0.001). Also, smoking index and anti-CCP correlated significantly and positively with disease stage (r = 0.424, p < 0.05; r = 0.523, p < 0.01). It appears from our results that, tobacco smoking mostly play a role in progression of rheumatoid arthritis through tissue protein citrullination. So all rheumatoid arthritis patients must quit completely to achieve a good control.


[Sarcomatoid renal cell carcinoma].
The objective was to perform a systematic review of literature concerning epidemiology, clinical and biological data, prognosis and therapy of sarcomatoid renal cell carcinomas. Data on sarcomatoid renal cell carcinomas have been sought by querying the server Medline with MeSH terms following or combination of them: "renal carcinoma", "renal cell carcinoma," "renal cancer", "sarcomatoid" "sarcomatoid transformation" and "sarcomatoid differentiation." The articles obtained were selected according to their methodology, the language in English or French, the relevance and the date of publication. Twenty papers were selected. According to the literature, a sarcomatoid contingent can be observed in all subtypes of renal cell carcinomas, with a frequency of 1 to 15% of cases. The median age at diagnosis was 60 years with a majority of symptomatic patients (90%), mainly with abdominal pain and hematuria. These tumors were often found in patients with locally advanced or metastatic (45-77%). The imaging was not specific for the diagnosis and biopsy had a low sensitivity for identifying a sarcomatoid contingent. The treatment was based on a combination of maximal surgical resection whenever possible and systemic therapy for metastastic disease. Pathological data often showed large tumors, Furhman 4 grades, combined biphasic carcinomatous contingent (clear cell carcinoma in most cases) and sarcomatoid. Genetically, there was no specific abnormality but a complex association of chromosomal additions and deletions. The prognosis was pejorative with a specific median survival of 5 to 19 months without any impact of the sarcomatoid contingent rate. Sarcomatoid renal cell carcinoma is a form not to ignore despite its rarity. Mainly symptomatic and discovered at an advanced stage, it has a poor prognosis, requiring multidisciplinary management quickly and correctly.


Patterns in Wing Morphology and Fluctuating Asymmetry in Eulaema nigrita along an Altitudinal Gradient in the Brazilian Rupestrian Grassland.
Mountain ecosystems experience abrupt abiotic changes that represent environmental filters for many organisms, shaping their phenotypic expressions. However, little is known about the morphological and symmetric adjustments of native bees along altitudinal gradients. We evaluated the changes on wing morphology, wing size, and vein fluctuating asymmetry (FA) of Eulaema nigrita Lepeletier (Apidae: Euglossini) associated with climatic variables along an altitudinal gradient in the rupestrian grassland (known also as campo rupestre or rupestrian field) of Serra do Cipó, Brazil. Seven sampling points along the altitudinal gradient were selected and distributed among 800 and 1400 m.a.s.l., and then, 40 individuals of E. nigrita were collected per each altitudinal point to determine the FA levels and the morphological changes using geometric morphometric techniques. We found that the wing size of E. nigrita decreased with increasing altitude. At the highest altitudes, the levels of FA of the wing veins were greater compared to bees from lower altitudes. We detected significant changes in wing morphology along the altitudinal gradient; bees of lower altitudes showed longer and wider wings than bees of higher altitudes, which had narrower and less elongated wings. Our results show a set of morphological adjustments and phenotypic expressions in E. nigrita associated with the variation in environmental conditions along the altitudinal gradient. We highlight the importance of environmental variables as insect-stressor factors, and that FA and geometric morphometric can be excellent tools for monitoring and evaluating environmental stresses.


Optimal fed-batch operation of recombinant cells subject to plasmid instability and death.
Optimal feed rate strategy is studied for fed-batch culture of recombinant cells with plasmid instability and with different death rates for the plasmid-free cells (PFC) and plasmid-bearing cells (PBC). Most of the fed-batch fermentation is known to have first-order singularity and therefore a single singular arc. However, this study shows that a singular arc with second-order singularity and therefore two distinct singular arcs are possible for a recombinant cell process if PFC and PBC are subjected to death, and their specific growth rates are proportional to each other. Two types of singular arcs are elucidated and analyzed. The optimal policies over the singular arcs are theoretically explored as these findings reveal qualitative information on the singular arc, which is critically important in providing the optimal initial conditions in numerical computation of optimal feed rate profile.


Effects of low intensity noise from aircraft or from neighbourhood on cognitive learning and electrophysiological stress responses.
The effects of low intensity noise on cognitive learning and autonomous physiological processes are of high practical relevance but are rarely addressed in empirical investigations. This study investigated the impact of neighbourhood noise (of 45 dB[A], n=20) and of noise coming from passing aircraft (of 48 dB[A] peak amplitude presented once per minute; n=19) during computer based learning of different texts (with three types of text structure, i.e. linear text, hierarchic hypertext, and network hypertext) in relation to a control group (35 dB[A], n=20). Using a between subjects design, reproduction scores, heart rate, and spontaneous skin conductance fluctuations were compared. Results showed impairments of reproduction in both noise conditions. Additionally, whereas in the control group and the neighbourhood noise group scores were better for network hypertext structure than for hierarchic hypertext, no effect of text structure on reproduction appeared in the aircraft noise group. Compared to the control group, for most of the learning period the number of spontaneous skin conductance fluctuations was higher for the aircraft noise group. For the neighbourhood noise group, fluctuations were higher during pre- and post task periods when noise stimulation was still present. Additionally, during the last 5 min of the 15 min learning period, an increased heart rate was found in the aircraft noise group. Data indicate remarkable cognitive and physiological effects of low intensity background noise. Some aspects of reproduction were impaired in the two noise groups. Cognitive learning, as indicated by reproduction scores, was changed structurally in the aircraft noise group and was accompanied by higher sympathetic activity. An additional cardiovascular load appeared for aircraft noise when combined with time pressure as indicated by heart rate for the announced last 5 min of the learning period during aircraft noise with a peak SPL of even 48 dB(A). Attentional mechanisms (attentional control) like being threatened by passing aircraft approaching the airport, higher demands of selective filtering, and difficulties in changing cognitive strategies during noise are discussed as underlying mechanisms.


Induction of cytosolic NADPH-diaphorase/nitric oxide synthase in reactive microglia/macrophages after quinolinic acid lesions in the rat striatum: an electron and light microscopical study.
Induction of nitric oxide synthase and increased production of nitric oxide in microglia may play a crucial role in neuronal damage and neurodegenerative disorders. In the present study we have used light and electron microscopical NADPH-diaphorase histochemistry as the visualization procedure for nitric oxide synthase to investigate the time-course and subcellular patterns of NADPH-diaphorase expression in microglia/macrophages of quinolinic acid-lesioned rat striatum. For light microscopy, NADPH-diaphorase histochemistry sections were stained with nitroblue tetrazolium, while for ultrastructural analysis the tetrazolium salt 2-(2'-benzothiazolyl)-5-styryl-3(4'-phthalhydrazidyl) tetrazolium chloride (BSPT) was applied. Light microscopical inspection revealed a progressively increasing number of positive cells with increasing intensity of NADPH-diaphorase staining in microglia/macrophages from day 1 after quinolinic acid injection onward. Electron microscopical examination revealed a membrane bound NADPH-diaphorase in quiescent microglia as well as in activated microglia/macrophages through all stages of the lesion studied. Predominantly membranes of the nuclear envelope and the endoplasmic reticulum were labeled with BSPT-formazan, while in advanced stages selective membrane portions of mitochondria, Golgi apparatus and plasmalemma were also stained. From day 5 onward after lesion induction, a very distinctive type of NADPH-diaphorase was observed, forming accumulations of electron-dense grains that were distributed differentially throughout cytoplasmic areas and phagocytic vacuoles. Dynamics of expression, unique cytosolic localization and occurrence exclusively in activated microglia/macrophages suggest that this particular NADPH-diaphorase activity probably reflects the inducible isoform of nitric oxide synthase, whereas the membrane-bound precipitate may represent the neuronal and/or the endothelial isoform of the enzyme.


Sodium/Potassium homeostasis in the cell.
All animals are characterized by steep gradients of Na(+) and K(+) across the plasma membrane, and in spite of their highly similar chemical properties, the ions can be distinguished by numerous channels and transporters. The gradients are generated by the Na(+),K(+)-ATPase, or sodium pump, which pumps out Na(+) and takes up K(+) at the expense of the chemical energy from ATP. Because the membrane is more permeable to K(+) than to Na(+), the uneven ion distribution causes a transmembrane voltage difference, and this membrane potential forms the basis for the action potential and for much of the neuronal signaling in general. The potential energy stored in the concentration gradients is also used to drive a large number of the secondary transporters responsible for transmembrane carriage of solutes ranging from sugars, amino acids, and neurotransmitters to inorganic ions such as chloride, inorganic phosphate, and bicarbonate. Furthermore, Na(+) and K(+) themselves are important enzymatic cofactors that typically lower the energy barrier of substrate binding.In this chapter, we describe the roles of Na(+) and K(+) in the animal cell with emphasis on the creation and usage of the steep gradients across the membrane. More than 50 years of Na(+),K(+)-ATPase research has revealed many details of the molecular machinery and offered insights into how the pump is regulated by post-translational modifications and specific drugs.


[Resistance testing for urinary tract infections. A barrier to guideline implementation].
Urinary tract infections (UTI) are among the most common reasons for antibiotic prescriptions. Due to increasing resistance rates, antibiotic therapy should be targeted and based on evidence-based recommendations. Test results and recommendations by medical laboratories have a relevant impact on the choice of antibiotics. The extent to which medical laboratories consider antibiotics recommended by evidence-based treatment guidelines in microbiological testing is unclear. The aim of the present study is to assess whether guideline recommendations for antibiotic therapy of UTI are taken into account by medical laboratories in northern Germany. A standardized and piloted questionnaire was used in our telephone survey. All microbiological laboratories in northern Germany (Hamburg, Bremen, Lower Saxony, Schleswig-Holstein, and Mecklenburg-Western Pomerania; n = 82) were asked about their standards in diagnosing and microbiological testing of urine cultures. A total of 71 of the 82 contacted laboratories perform microbiological tests, whereby 40 of these participated (56 %). Most of the laboratories (43 %) routinely perform microbiological testing when bacterial counts were ≥ 10(4) colony forming units per ml (CFU/ml), 15 % ≥ 10(5) CFU/ml, 17 % ≥ 10(3) CFU/ml, and 8 % ≥ 10(2) CFU/ml. Antibiotic testing includes ciprofloxacin (95 %), cotrimoxazole (87.5 %), trimethoprim (57 %), fosfomycin (85 %), and nitrofurantoin (72 %). The diagnostic threshold recommended in evidence-based guidelines (10(3) CFU/ml) is used only by a few laboratories. Antibiotics recommended as a first line therapy are only partly taken into account in microbiological testing. This variance in different diagnostic thresholds and microbiological testing is a barrier to guideline implementation.


Growth hormone deficiency and central precocious puberty in Klinefelter syndrome: report of a case and review of KIGS database.
Growth hormone deficiency (GHD) and central precocious puberty (CPP) have each, individually, been described in patients with Klinefelter syndrome. However, the combination of GHD, CPP, and Klinefelter syndrome has never been reported. We described a Klinefelter syndrome patient who developed GHD at age 2 10/12 years and CPP at 8 6/12 years. Despite CPP, GnRH agonist therapy was not initiated because of his excellent predicted adult height. At 11 8/12 years, his height was 164.6 cm, close to his mid-parental target height of 165 cm. We report an additional nine patients with Klinefelter syndrome and GHD from the Pfizer International Growth Study (KIGS) database, none of whom had CPP. We conclude that the combination of GHD and CPP is very rare in Klinefelter syndrome and that CPP is unlikely to compromise final adult height.


Histopathological findings concerning the morphogenesis of mixed carcinoma of the uterine cervix.
The morphological and functional glandular characteristics of cervical cancers have been studied in terms of the degree of mucous reaction and glandular structure and the morphogenesis of such lesions has been discussed. Among 128 cases of frank invasive carcinoma of the uterine cervix, glandular structure was found in 42 cases (32.8%) and a positive mucous reaction without glandular structure was found in 43 cases (33.6%). Adenocarcinoma was defined as all frank invasive carcinoma with more than 80% glandular structure (R greater than 80%). Lesions with less than 5% glandular structure (R less than or equal to 5%) and a negative mucous reaction were defined as epidermoid carcinoma, and all remaining lesions were defined as mixed carcinoma. Following these definitions, the percentages of adenocarcinoma and mixed and epidermoid carcinomas among the frank invasive carcinoma cases were 10.2 (13 cases), 12.5 (16 cases), and 77.3% (99 cases). The histological structure of the 16 cases of mixed carcinoma included 3 cases of acanthomatous change adenocarcinoma, 4 cases of collision pattern of adenocarcinoma and epidermoid carcinoma, and 9 cases where the lesion is thought to develop by bipotential differentiation together with the neoplastic changes of reserve cells.


Cerebral and ocular hemodynamic effects of sumatriptan in the nitroglycerin headache model.
Sumatriptan is a selective 5-hydroxytryptamine1d (5-HT1d)-receptor agonist, highly effective in the short-term treatment of migraine headaches. However, the mechanism underlying the action of sumatriptan is not yet completely understood. To further characterize the vascular effects of sumatriptan, we studied the effects on cerebral and ocular circulation in the well-established nitroglycerin headache model. In a double-blind, placebo-controlled, randomized, two-way crossover study in 10 healthy male subjects, we administered either placebo plus nitroglycerin or sumatriptan plus nitroglycerin. Blood flow velocity in the middle cerebral artery and the ophthalmic artery, as well as ocular fundus pulsations and systemic hemodynamic parameters, were measured after sumatriptan and placebo and during the following infusion of nitroglycerin. After infusion of nitroglycerin, blood flow velocity in the middle cerebral decreased by -13.3% versus baseline after placebo pretreatment, but by only -2.2% after sumatriptan (treatment effect, +10.8%; p < 0.05). In contrast, sumatriptan had no effect in the ophthalmic artery. Ocular fundus pulsations, which estimate local pulsatile ocular blood flow, were slightly reduced after sumatriptan. Moreover, sumatriptan partially prevented the increase in fundus pulsations during nitroglycerin infusion (treatment effect, -5.4%; p < 0.05). Sumatriptan prevents the effect of nitroglycerin-induced vasodilation in the middle cerebral artery but not in the ophthalmic artery, which strongly supports the concept that sumatriptan directly vasoconstricts distended basal cerebral arteries. Measurement of ocular fundus pulsations indicates that sumatriptan also has a small vasoconstrictor action on resistance vessels.


Abscess in infective endocarditis: the value of transesophageal echocardiography and outcome: a 5-year study.
In patients with infective endocarditis (IE), detection of abscess remains difficult. We investigated abscess detection by transesophageal echocardiography (TEE) and predictors of abscess and death in patients with IE. A 5-year study included 115 patients with definite IE according to the modified Duke criteria who underwent TEE and cardiac surgery. Abscess was found perioperatively in 44 patients (38%). Twenty-one abscesses (48%) were detected by TEE. Sixty-one percent of missed abscesses were localized on the posterior mitral annulus. In 64% of unrecognized mitral valve abscesses, the abscess was localized around calcification in the posterior mitral annulus. Fourteen patients (54%) had prosthetic valve dehiscence, and 8 (57%) had abscess as well. Overall 6-month mortality was 17% and predictable by age (odds ratio 1.1, 95% CI 1-1.001, P = .01), abscess (odds ratio 5.3, 95% CI 1.5-19, P = .01), and the causative microorganism (P = .035), in particular staphylococci. In patients with a missed abscess, surgical delay was significantly longer (P = .04) and mortality was nonsignificantly higher (P = .2) than in patients with a preoperatively detected abscess. Detection of abscess by TEE seemed to be underestimated. In most cases, abscess was missed in the presence of calcification in the posterior mitral annulus. Age, abscess, and staphylococcal infection predicted 6-month mortality. Early surgery may improve outcome in patients with an abscess.


Reduction of nitrous oxide contamination in a paediatric hospital.
Ambient nitrous oxide concentrations were recorded in an operating room during delivery of the gas at low and medium flow-rates, with and without the application of simple scavenging devices. Residual background levels of nitrous oxide were still present more than one hour after disconnection of the flowmeters and use of the room. Scavenging reduced concentrations ten-fold. Adjacent corridors and the post-anaesthetic recovery room were contaminated with nitrous oxide from the operating rooms and from patients. A vigorous programme of checking for leaks and repairing and maintaining equipment, coupled with the use of suction scavenging, can reduce atmospheric contamination with nitrous oxide below 30 p.p.m., which is well within the limit suggested by the U.S. National Institute for Occupational Safety and Health.


The impact of beta-receptor blocker addition to high-dose angiotensin-converting enzyme inhibitor-nitrate therapy in heart failure.
The natural history of heart failure is one of continued worsening of cardiac function. Beta-receptor blocker therapy has been effective in improving clinical status and left ventricular function in patients with heart failure. Similarly, high doses of angiotensin-converting enzyme (ACE) inhibitors with nitrates partially reverse the ventricular remodeling of heart failure. We tested the hypothesis that beta-blocker therapy added to high-dose ACE inhibitor-nitrates would potentiate the reversal of heart failure. Thirteen patients, aged 52 +/- 8 years, with moderate to severe heart failure, 12 of whom were referred for transplant consideration, with heart failure duration of 4.8 +/- 2.2 years, were prospectively followed for 12 months. Baseline echocardiographic ejection fraction was 19 +/- 8%, and presenting New York Heart Association class was 2.9 +/- 0.7. Angiotensin-converting enzyme inhibitors and nitrates were uptitrated over 6 months to a final dose of lisinopril 53 +/- 31 mg/day, and isosorbide dinitrate 217 +/- 213 mg/day. At 6 months, beta-blocker therapy with atenolol was initiated and titrated to a final dose of 46 +/- 23 mg/day. Two-dimensional Doppler echocardiography and metabolic stress testing were performed at baseline, at 6 months on lisinopril-nitrates only, and at 12 months on combined ACE inhibitor-nitrate and beta-blocker therapy. New York Heart Association classification improved from 2.9 +/- 0.7 to 1.8 +/- 0.8 on lisinopril-nitrates (p < 0.05), and to 1.5 +/- 0.5 with the addition of beta blockade (p = NS). On follow-up, peak oxygen consumption rose from 17 +/- 7 ml O2/kg/min at baseline to 21 +/- 5 ml O2/kg/min at 6 months on lisinopril-nitrates (p = 0.06) without further change on beta blockade. Ejection fraction rose from 19 +/- 8 to 33 +/- 14% on lisinopril-nitrates at 6 months (p = 0.005) and to 36 +/- 18% on beta blockade at 12 months (p = NS). High-dose ACE inhibitor-nitrate therapy significantly improved patient clinical status and left ventricular systolic function in heart failure. The addition of beta-receptor blockade over and above high-dose ACE inhibitor-nitrates was well tolerated but had no further impact on symptomatic status, exercise tolerance, or left ventricular systolic function. The potential for pharmacologic reversal of heart failure remodeling may be finite despite the use of complementary therapies. Larger placebo-controlled and randomized trials of beta-receptor blockade added to high-dose ACE inhibitor-nitrate therapy are needed to confirm these observations.


Response of extracellular and intracellular alkaline phosphatase in Microcystis aeruginosa to organic phosphorus.
Cyanobacterial blooms caused by Microcystis have become a menace to public health and water quality in the global freshwater ecosystem. Alkaline phosphatases (APases) produced by microorganisms play an important role in the mineralization of dissolved organic phosphorus (DOP) into orthophosphate (Pi) to promote cyanobacterial blooms. However, the response of extracellular and intracellular alkaline phosphatase activity (APA) of Microcystis to different DOP sources is poorly understood. In this study, we compared the growth of M. aeruginosa on two DOP substrates (β-glycerol-phosphate (β-GP) and lecithin (LEC)) and monitored the changes of P fractions and the extra- and intracellular APA under different P sources and concentrations. M. aeruginosa can utilize both β-GP and LEC to sustain its growth, and the bioavailability of LEC was greater than β-GP. For the β-GP treatment, there was no significant difference in the algal growth at different concentrations (P > 0.05), while the algal growth in the LEC treatment groups was significantly affected by concentrations (P < 0.05). The results showed that intracellular APA of M. aeruginosa could be detected in all DOP treatment groups and generally higher than extracellular APA. In addition, the intracellular APA per cell increased first and then decreased in all DOP treatment groups. Compared with the β-GP treatment, M. aeruginosa in the LEC groups could secret more extracellular APA.


Excitation energy transfer in Chlamydomonas reinhardtii deficient in the PSI core or the PSII core under conditions mimicking state transitions.
The efficient use of excitation energy in photosynthetic membranes is achieved by a dense network of pigment-protein complexes. These complexes fulfill specific functions and interact dynamically with each other in response to rapidly changing environmental conditions. Here, we studied how in the intact cells of Chlamydomonas reinhardtii (C.r.) the lack of the photosystem I (PSI) core or the photosystem II (PSII) core affects these interactions. To that end the mutants F15 and M18 (both PSI-deficient) and FUD7 (PSII-deficient) were incubated under conditions known to promote state transitions in wild-type. The intact cells were then instantly frozen to 77K and the full-spectrum time-resolved fluorescence emission of the cells was measured by means of streak camera. In the PSI-deficient mutants excitation energy transfer (EET) towards light-harvesting complexes of PSI (Lhca) occurs in less than 0.5 ns, and fluorescence from Lhca decays in 3.1 ns. Decreased trapping by PSII and increased fluorescence of Lhca upon state 1 (S1)→state 2 (S2) transition appears in the F15 and less in the M18 mutant. In the PSII-deficient mutant FUD7, quenched (0.5 ns) and unquenched (2 ns) light-harvesting complexes of PSII (LHCII) are present in both states, with the quenched form more abundant in S2 than in S1. Moreover, EET of 0.4 ns from the remaining LHCII to PSI increases upon S1→S2 transition. We relate the excitation energy kinetics observed in F15, M18 and FUD7 to the remodeling of the photosynthetic apparatus in these mutants under S1 and S2 conditions.


Biological information.
In computer science, we can theoretically neatly separate transmission and processing of information, hardware and software, and programs and their inputs. This is much more intricate in biology. Nevertheless, I argue that Shannon's concept of information is useful in biology, although its application is not as straightforward as many people think. In fact, the recently developed theory of information decomposition can shed much light on the complementarity between coding and regulatory, or internal and environmental information. The key challenge that we formulate in this contribution is to understand how genetic information and external factors combine to create an organism, and conversely how the genome has learned in the course of evolution how to harness the environment, and analogously how coding, regulation and spatial organization interact in cellular processes.


Control of proliferation by Bcl-2 family members.
The anti-proliferative effect of Bcl-2 acts mainly at the level of the G0/G1 phase of the cell cycle. Deletions and point mutations in the bcl-2 gene show that the anti-proliferative activity of Bcl-2, can in some cases, be dissociated from its anti-apoptotic function. This indicates that the effect of Bcl-2 on cell cycle progression can be a direct effect and not only a consequence of its anti-apoptotic activity. Bcl-2 appears to mediate its anti-proliferative effect by acting on both signal transduction pathways (NFAT, ERK) and on specific cell cycle regulators (p27, p130).


Improvement of rice blast resistance by developing monogenic lines, two-gene pyramids and three-gene pyramid through MAS.
Rice blast caused by Magnaporthe oryzae (M. oryzae) is one of the most destructive diseases in rice production. Development of resistant varieties through pyramiding of resistant (R) genes is considered as an effective strategy to cope with the disease. However, is it really essential to pyramid more R genes in a specific ecological regions? To answer this question, a set of rice improved lines were developed in this study. Afterwards, the blast disease resistance and agronomic traits of the recurrent parent (RP), donor parents (DPs) and improved lines were investigated. We developed seven improved lines, comprising three monogenic lines, three two-gene pyramids and one three-gene pyramid, by introgression of R gene(s) into a common genetic background using marker-assisted backcross breeding (MABB). Based on 302 SSR markers, the recurrent genome of the seven improved lines reached a range of 89.1 to 95.5%, with the average genome recovery of 92.9%. The pathogenicity assays inoculated with 32 different blast isolates under artificial conditions showed that the resistance spectrum of all the improved lines was significantly broadened. The assays further showed that the two-gene pyramids and the three-gene pyramid exhibited wider resistance spectrum than the monogenic lines. At natural nurseries, the three monogenic lines still showed high ratios of infected panicles, whereas the two-gene pyramids and the three-gene pyramid showed high level of panicle blast resistance. However, the two-gene pyramid R504 reached the similar resistance effect of the three-gene pyramid R507 considering resistance spectrum under artificial conditions and panicle blast resistance under field conditions. Generally, the improved lines showed comparable agronomic traits compared with the recurrent parent (RP), but the three-gene pyramid showed reduced grain yield per plant. All the improved lines conferred wider resistance spectrum compared with the RP. Yet, the three monogenic lines did not work under field conditions of the two nurseries. Given the similar performances on the main agronomic traits as the RP, the two-gene pyramids have achieved the breeding goals of broad resistance spectrum and effective panicle blast resistance. Whereas, the three-gene pyramid harboring Pi2, Pi46 and Pita seems superfluous considering its reduced yield, although it also showed displayed high level of blast resistance. Thus, rational use of R genes rather than stacking more R genes is recommended to control the disease.


Progressive balloon dilatation following hepaticojejunostomy improves outcome of bile duct stricture after iatrogenic biliary injury.
Iatrogenic biliary stricture (IBS) is a disastrous complication of cholecystectomy. Although the endoscopic treatments are well accepted as initial attempts for IBS, surgical hepaticojejunostomy (HJ) is often necessary for a considerable proportion of patients. However, the anastomotic stricture after HJ also occurs. In the present study, a new procedure, progressive balloon dilation following HJ (HJPBD), was designed and utilized in the IBS treatment. We retrospectively compared HJPBD with the traditional HJ in term of the outcomes when used for IBS treatment. Between January 1997 and December 2009, 112 patients with IBS attributed to cholecystectomy enrolled in our hospital were treated with surgical reconstruction with either HJ (n=58) or HJPBD (n=54). Of the 58 patients in HJ group, 48 patients (82.8%) had a successful outcome, while 52 out of 54 patients (96.3%) in HJPBD group achieved success. The successful surgical reconstruction rates were significantly different between these two groups, with a further improved outcome in patient undergone progressive balloon dilation following HJ. Additionally, 8 of the 10 failure cases in HJ group were successfully rescued by HJPBD procedure. Our findings suggest that the new procedure of HJPBD could be successfully applied to IBS patients, and significantly improve the outcome of IBS reconstruction.


Plasma IgA, IgG and IgM and their relationship to breast cancer in British, Japanese and Hawaiian-Japanese women.
The plasma levels of immunoglobulins IgA, IgG and IgM have been measured in 35 British, 44 Hawaiian-Japanese and 37 Japanese healthy adult women. Previous investigations showed that the mean levels of all three immunoglobulins were higher in Japanese than in British normal women. The present study finds that Hawaiian-Japanese women have "Japanese" levels of IgA, "British" levels of IgM and are intermediate for IgG. Thus, plasma IgM concentrations correlate with breast cancer incidence rates in the three racial groups and the reduced amounts of plasma IgM found in Japanese patients with breast cancer support this association.


Non-invasive vagus nerve stimulation in a hungry state decreases heart rate variability.
Vagus nerve signals from the gut to brain carry information about nutrients and drive food reward. Such signals are disrupted by consuming large amounts of high-calorie foods, necessitating greater food intake to elicit a similar neural response. Non-invasive vagus nerve stimulation (nVNS) via a branch innervating the ear is a candidate treatment for obesity in humans. There is disagreement on the optimal location of nVNS in the ear for experimental and clinical studies. There are also no studies comparing nVNS in hungry and post-prandial states. We aimed to compare ear position(s) for nVNS and explore the effects of nVNS during hungry and post-prandial states on proxies for autonomic outflow (heart-rate variability) and efferent metabolism (gastric wave frequency and resting energy expenditure). In a within-subject design, 14 participants (10 women, on average 29.4 +/- 6.7 years old) received nVNS in four different locations (cymba conchae, tragus, earlobe, or tragus AND cymba conchae) on separate days. In each session, participants were asked to consume a palatable chocolate flavored milk. With electrography on the abdomen and indirect calorimetry in a canopy, we measured electro-cardiogram, electro-gastrogram and resting energy expenditure for 15 min before and at least 35 min after consumption of the palatable drink. We also collected ratings of the palatable drink and internal and other states. Pre-drink consumption (in a hungry state) we observed no differences in the effect of location of acute nVNS on resting energy expenditure and gastric wave measures. However, nVNS in cymba conchae decreases heart-rate variability (relative to sham) and ratings of how much participants want to consume the drink (relative to tragus AND cymba conchae and a trend relative to sham). After drink consumption and with continued nVNS, gastric wave frequency is unchanged, and resting energy expenditure increases regardless of stimulation location. Heart-rate variability decreases in all locations, except cymba conchae. We also observe a trend for an increase in gastric wave amplitude in late post-drink consumption time-points in cymba conchae. We observe no support for the combined stimulation of tragus AND cymba conchae being more effective than either of the individual locations. These results suggest that nVNS in the cymba conchae in a hungry state has a similar acute effect on vagal tone as food consumption: to decrease heart rate variability. This effect then negates the usual postprandial effects of a decrease in heart rate variability as seen in the other nVNS locations. These preliminary observations suggest that nVNS in cymba conchae may act primarily on vagal afferent autonomic (and only modestly on metabolic output) in a similar way as food consumption does.


Mixed-Poisson Point Process with Partially-Observed Covariates: Ecological Momentary Assessment of Smoking.
Ecological Momentary Assessment is an emerging method of data collection in behavioral research that may be used to capture the times of repeated behavioral events on electronic devices, and information on subjects' psychological states through the electronic administration of questionnaires at times selected from a probability-based design as well as the event times. A method for fitting a mixed Poisson point process model is proposed for the impact of partially-observed, time-varying covariates on the timing of repeated behavioral events. A random frailty is included in the point-process intensity to describe variation among subjects in baseline rates of event occurrence. Covariate coefficients are estimated using estimating equations constructed by replacing the integrated intensity in the Poisson score equations with a design-unbiased estimator. An estimator is also proposed for the variance of the random frailties. Our estimators are robust in the sense that no model assumptions are made regarding the distribution of the time-varying covariates or the distribution of the random effects. However, subject effects are estimated under gamma frailties using an approximate hierarchical likelihood. The proposed approach is illustrated using smoking data.


An exhaustive comprehension of the role of herbal medicines in Pre- and Post-COVID manifestations.
The coronavirus disease (COVID-19) has relentlessly spread all over the world even after the advent of vaccines. It demands management, treatment, and prevention as well with utmost safety and effectiveness. It is well researched that herbal medicines or natural products have shown promising outcomes to strengthen immunity with antiviral potential against SARS-COV-2. Our objective is to provide a comprehensive insight into the preventive and therapeutic effects of herbal medicines and products (Ayurvedic) for pre-and post-COVID manifestations. The database used in the text is collected and compiled from Scopus, PubMed, Nature, Elsevier, Web of Science, bioRxiv, medRxiv, American Chemical Society, and clinicaltrials.gov up to January 2022. Articles from non-academic sources such as websites and news were also retrieved. Exploration of the studies was executed to recognize supplementary publications of research studies and systematic reviews. The keywords, such as "SARS-COV-2, coronavirus, COVID-19, herbal drugs, immunity, herbal immunomodulators, infection, herbal antiviral drugs, and WHO recommendation" were thoroughly searched. Chemical structures were drawn using the software Chemdraw Professional 18.104.22.168 (PerkinElmer Informatics, Inc.). A plethora of literature supports that the use of herbal regimens not only strengthen immunity but can also treat SARS-COV-2 infection with minimal side effects. This review summarizes the mechanistic insights into herbal therapy engaging interferons and antibodies to boost the response against SARS-COV-2 infection, several clinical trials, and in silico studies (computational approaches) on selected natural products including, Ashwagandha, Guduchi, Yashtimadhu, Tulsi, etc. as preventive and therapeutic measures against COVID. We have also emphasized the exploitation of herbal medicine-based pharmaceutical products along with perspectives for unseen upcoming alike diseases. According to the current state of art and cutting-edge research on herbal medicines have showed a significant promise as modern COVID tools. Since vaccination cannot be purported as a long-term cure for viral infections, herbal/natural medicines can only be considered a viable alternative to current remedies, as conceived from our collected data to unroot recurring viral infections.


Vascular effects of glycoprotein130 ligands--part II: biomarkers and therapeutic targets.
Glycoprotein130 (gp130) ligands are defined by the use of the common receptor subunit gp130 and comprise interleukin (IL)-6, oncostatin M (OSM), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), IL-27 and neuropoietin (NP). In part I of this review we addressed the pathophysiological functions of gp130 ligands with respect to the vascular wall. In part II of this review on the vascular effects of gp130 ligands we will discuss data about possible use of these molecules as biomarkers to predict development or progression of cardiovascular diseases. Furthermore, the possibility to modulate circulating levels of gp130 ligands or their tissue expression by specific antibodies, soluble gp130 protein, renin-angiotensin-aldosterone system (RASS) inhibitors, statins, agonists of peroxisome proliferator-activated receptors (PPAR), hormone replacement therapy, nonsteroidal anti-inflammatory drugs (NSAID) or lifestyle modulating strategies are presented. Recent knowledge about the application of recombinant cytokines from the gp130 cytokine family as therapeutic agents in obesity or atherosclerosis is also summarized. Thus the purpose of this review is to cover a possible usefulness of gp130 ligands as biomarkers and targets for therapy in cardiovascular pathologies.


Metal ion binding in triclinic lysozyme.
The binding sites of Mn2+, Co2+, and Gd3+ have been determined in triclinic lysozyme at pH 4.5 to 4.6. Mn2+ and Co2+ bind a site approximately 2.5 A from 1 of the oxygen atoms of the Glu-35 chain. The occupancy of the Mn2+ site is 0.22, corresponding to 1 bound ion for each 4.6 protein molecules. The occupancy of the Co2+ site is much lower, about 0.048. Gd3+ appears to be bound at two sites, the main one 2.5 A from an oxygen atom of the Glu-35 side chain, the other 3.1 A from an oxygen atom of the Asp-52 chain. The occupancy of both Gd3+ sites is low, 0.036 and 0.016, the latter being so low that the presence of the ion at this site is in doubt. The binding site of Mn2+ in the di(N-acetylglucosamine)-lysozyme complex has also been determined. It does not differ significantly from the Mn2+ binding site in the native protein, but the occupancy is lower, 0.16.


Efficacy and safety of a novel synergistic drug candidate, CRx-102, in hand osteoarthritis.
The novel synergistic drug candidate CRx-102 comprises dipyridamole and low dose prednisolone and is in clinical development for the treatment of immunoinflammatory diseases. The purpose of this clinical study was to examine the efficacy and safety of CRx-102 in patients with hand osteoarthritis (HOA). The study was conducted as a blinded, randomised, placebo-controlled trial at four centres in Norway. Eligibility criteria included being of age 30-70 years, at least one swollen and tender joint, a Kellgren-Lawrence (K-L) score of 2 or higher on radiographs, and a score of at least 30 mm pain on the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) visual analogue pain scale (VAS). The primary endpoint was a reduction in pain from baseline to day 42 on the AUSCAN pain subscale. Two-sided p values for the differences in least squares (LS) means adjusted for baseline are presented. The mean age of the 83 patients with HOA was 60 years and 93% were females. CRx-102 was statistically superior to placebo at 42 days for changes in AUSCAN pain (LS mean -14.2 vs -4.0) and for clinically relevant secondary endpoints (joint pain VAS (-18.6 vs -6.3), patient global VAS (-15.9 vs -4.2)) in the intention to treat population. The most frequently reported adverse event during the study was headache (52% in CRx-102 vs 15% in the placebo group). The novel synergistic drug candidate CRx-102 demonstrated efficacy by statistically reducing pain compared to placebo in HOA and was generally well tolerated.


Cushing's disease.
Cushing's disease (CD) is the most prevalent cause of endogenous hypercortisolism. CD is responsible for multiple co-morbidities and increased mortality. Accurate and prompt diagnosis and optimal treatment are essential to improve the prognosis of CD. However, the diagnosis of CD is probably one of the most difficult in endocrinology and, therefore, diagnostic workup should be performed in an experienced center. Transsphenoidal surgery performed by an expert surgeon is the only therapeutic option that can offer definitive cure and remains the first-line treatment in most patients. Second-line treatments include pharmacotherapy, pituitary radiotherapy and bilateral adrenalectomy. The second-line therapeutic strategy is complex, must be individualized and performed in a multidisciplinary expert center. Symptomatic treatments of persisting co-morbidities after remission, which are responsible for increased mortality and impaired quality of life is an important part of medical management.


Seasonal biochemical plasticity of a flight muscle in a bat, Murina leucogaster.
Cellular and biochemical responses of the pectoral muscle to variation in seasonal activity were studied in the bat, Murina leucogaster ognevi. We collected bats in mid-hibernation (February), end-hibernation (April), and mid-summer (August) to track major activity periods in their annual cycle. Our findings indicated that myofiber cross-sectional area decreased to 68% between mid- and end-hibernation, but returned to the winter level in mid-summer. Total soluble protein and total RNA concentrations were not altered over these sampling periods. Oxidative potential gauged by citrate synthase activity increased 1.47-fold from mid- to end-hibernation and then remained at the similar level in mid-summer. Glycolytic potential gauged by lactate dehydrogenase activity changed little between mid- and end-hibernation but increased 1.42-fold in summer, compared with the winter level. Thus, the myofibers underwent disuse atrophy during hibernation, while enzymatic catalytic function recovered towards the level of mid-summer.


Formulation, characterization of Quercus infectoria (Olivier) emulsions, and in vitro, in vivo evaluation as cosmeceutical formulation.
Pharmacological properties of Quercus infectoria Olivier (galls) have been determined to be astringent, antidiabetic, antipyretic, anti-tremor, local anesthetic, and anti-parkinsonism. The galls of Quercus infectoria have been used for millennia in traditional oriental medicine in Asian nations to treat inflammatory illnesses. The study's objective was to create a Quercus infectoria Olivier gall extract in stable water in oil (w/o) emulsion and to check its effects on the mechanical properties of skin and antiaging effects. The galls were macerated in absolute methanol. Quercus infectoria Olivier gall extract's antioxidant property was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) technique. Stearic acid, cetyl alcohol, KOH, glycerin, and distilled water were used to create the emulsion. The test (with extract) and control (without extract) emulsions were made, respectively, using the same process. Stability tests (color, liquefaction, microscopy, phase separation, and pH) are performed in in vitro, lasted 72 days at four distinct storage temperatures that is 8°C, 25°C, 40°C, and 40°C + 75% RH for both the control and test formulations. By using spectrophotometry, the (SPF) sun protection factors of the two formulations were calculated at various concentrations. Extract from Quercus infectoria underwent phytochemical investigation as well. The results showed that Quercus infectoria Olivier has antioxidant and (SPF) sun protection properties, reduce sebum, increases elasticity and stable emulsion containing 04% Quercus infectoria gall extract which might be used as topical antiaging formulation.


Gamma probe-guided sentinel node biopsy--optimal timing for injection.
We initiated a Phase I feasibility study using a gamma-detecting probe (GDP) and radiolabelled colloid to localize the sentinel lymph node (SLN) in breast cancer. The aim of the study was to establish the ideal timing for injection and examine any possible exclusion criteria for this method. Thirty breast cancer patients diagnosed by fine needle aspiration (FNA) were included in this study. All were injected with 60 MBq rhenium colloid labelled with 99mTc (Tck-17). Scintigraphy was done 20 min, 2, 6 and 25 hours post-injection. Patients were then taken to surgery where they were injected with patent blue dye. During surgery, the SLN was located with a GDP (Neoprobe Model 1000). In 28 patients, the SLN was identified by scintigraphy 2 hours after injection, identical to the images seen after 24 hours. In all 28 patients, the SLN was found by the GDP during surgery. In 26 patients the SLN was dyed blue. The two patients with no SLN localization had received prior radiation. Pathology disclosed SLNs with metastases in seven patients. Two patients had a negative SLN but had an axillary lymph node replaced by tumour. Two to 24 hours prior to surgery is suitable timing for injection. Previous radiotherapy predicts failure for this procedure. Further studies are needed to find the exact false-negative rate of this method for breast cancer.