IFNγ-induction of TH1-like regulatory T cells controls antiviral responses.
Regulatory T (Treg) cells are an immunosuppressive population that are required to maintain peripheral tolerance and prevent tissue damage from immunopathology, via anti-inflammatory cytokines, inhibitor receptors and metabolic disruption. Here we show that Treg cells acquire an effector-like state, yet remain stable and functional, when exposed to interferon gamma (IFNγ) during infection with lymphocytic choriomeningitis and influenza A virus. Treg cell-restricted deletion of the IFNγ receptor (encoded by Ifngr1), but not the interleukin 12 (IL12) receptor (encoded by Il12rb2), prevented TH1-like polarization (decreased expression of T-bet, CXC motif chemokine receptor 3 and IFNγ) and promoted TH2-like polarization (increased expression of GATA-3, CCR4 and IL4). TH1-like Treg cells limited CD8+ T cell effector function, proliferation and memory formation during acute and chronic infection. These findings provide fundamental insights into how Treg cells sense inflammatory cues from the environment (such as IFNγ) during viral infection to provide guidance to the effector immune response. This regulatory circuit prevents prolonged immunoinflammatory responses and shapes the quality and quantity of the memory T cell response.


Old World--new territory: European perspectives on intellectual disability.
People with intellectual disability share the mixed fortunes of the diverse countries in that they live, as well as the social and political changes that mark life in Europe at the close of the twentieth century. The European Union exerts its influence through common policies and centrally funded initiatives which promote the social and vocational integration of people with intellectual disabilities. At the same time, many countries in Central and Eastern Europe are building a new and as-yet untested social order. This paper outlines the distinctive features of European identity. Some of the gains already achieved on behalf of Europeans with intellectual disability are presented, as well as some of the problems which continue to threaten their well-being and inclusion. It is suggested that partnerships between countries and regions can help to chart new territory for citizens of the Old World.


Enhanced Home Care Interventions for Community Residing Adults Compared With Usual Care on Health and Cost-effectiveness Outcomes: A Systematic Review.
The need for home care services is expanding around the world with increased attention to the resources required to produce them. To assist decision making, there is a need to assess the cost-effectiveness of alternative programs within home care. Electronic searches were performed in five databases (before February 2020) identifying 3292 potentially relevant studies that assessed new or enhanced home care interventions compared with usual care for adults with an accompanying economic evaluation. From these, 133 articles were selected for full-text screening; 17 met the inclusion criteria and were analyzed. Six main areas of research were identified including the following: alternative nursing care (n = 4), interdisciplinary care coordination (n = 4), fall prevention (n = 4), telemedicine/remote monitoring (n = 2), restorative/reablement care (n = 2), and one multifactorial undernutrition intervention study. Risk of bias was found to be high/weak (n = 7) or have some concerns/moderate (n = 6) rating, in addition to inconsistent reporting of important information required for economic evaluations. Both health and cost outcomes had mixed results. Cost-effective interventions were found in two areas including alternative nursing care and reablement/restorative care. Clinicians and decision makers are encouraged to carefully evaluate the quality of the studies because of issues with risk of bias and incomplete reporting of economic outcomes.


Frequency of Cerebral Venous Thrombosis in Dubai, UAE-A Multicenter, Retrospective Study.
Cerebral venous thrombosis (CVT), also known as cerebral dural venous thrombosis, is not a very common cause of stroke. It has a diverse clinical presentation, with multiple predisposing factors and imaging findings. The incidence of CVT varies in different studies. We hypothesized that the incidence of CVT in Dubai is more than that reported in the West owing to dehydration caused by the high atmospheric temperature. We retrospectively reviewed the medical records of all patients aged more than 13 years with appropriate International Classification of Diseases, 9th Revision, codes for the diagnosis of CVT from January 1, 2010 to December 31, 2018 from three major hospitals with an acute stroke service in Dubai, United Arab Emirates. We identified 138 patients who presented with CVT. The average frequency of CVT was 6.6 per 100,000 population. Fifty percent of the patients presented between May and September, which are considered the hottest months in the UAE. Headache was the most common presentation, followed by seizures. The most important risk factors were the use of oral contraceptive pills, anemia, and polycythemia. Our study showed a higher incidence of anemia, polycythemia, thrombophilia, and abnormal CT brain findings. In our study, CVT was more common during the months of summer. Anemia and polycythemia were strongly associated with CVT. Public awareness about CVT, its higher incidence during summer months and strategies to avoid dehydration might be considered to reduce the incidence of CVT in summer months. However, larger studies are needed to confirm definite associations.


A study of Rose Bengal against a 2-keto-3-deoxy-d-manno-octulosonate cytidylyltransferase as an antibiotic candidate.
Frequent occurrences of multi-drug resistance of pathogenic Gram-negative bacteria threaten human beings. The CMP-2-keto-3-deoxy-d-manno-octulosonic acid biosynthesis pathway is one of the new targets for antibiotic design. 2-Keto-3-deoxy-d-manno-octulosonate cytidylyltransferase (KdsB) is the key enzyme in this pathway. KdsB proteins from Burkholderia pseudomallei (Bp), B. thailandensis (Bt), Pseudomonas aeruginosa (Pa), and Chlamydia psittaci (Cp) have been assayed to find inhibitors. Interestingly, Rose Bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) was turned out to be an inhibitor of three KdsBs (BpKdsB, BtKdsB, and PaKdsB) with promising IC50 values and increased thermostability. The inhibitory enzyme kinetics of Rose Bengal revealed that it is competitive with 2-keto-3-deoxy-manno-octulosonic acid (KDO) but non-competitive against cytidine 5'-triphosphate (CTP). Induced-fit docking analysis of PaKdsB revealed that Arg160 and Arg185 together with other interactions in the substrate binding site seemed to play an important role in binding with Rose Bengal. We suggest that Rose Bengal can be used as the scaffold to develop potential antibiotics.


Rapid determination of the attenuation limit of beer using middle-infrared (MIR) spectroscopy and a multivariate model.
A new approach for the determination of the attenuation limit of beer samples using the specific fingerprint region of middle-infrared (MIR) spectroscopy in combination with multiple regression by partial least-squares (PLS) was developed using an attenuated total reflectance (ATR) module. A specific spectral region between 1200 and 800 cm(-1) was identified as highly informative for the quantification of the limit of attenuation. The absorptions in this region are induced by vibrational bands of ethanol (1080, 1040, and 880 cm(-1)) and dissolved extract, in majority maltotriose (1160-1140 and 1040-980 cm(-1)). The multivariate calibration results in a root mean squared error of calibration (RMSEC) of 0.40% and a validation procedure with independent samples results in a root mean squared error of validation (RMSEV) of 0.50%. A repeatability test, concerning the precision of the developed MIR method as well as the reference method, was analyzed using Student's t test. The test has shown no significant difference between the two random samples.


Polymer Optical Microcavity Sensor for Volatile Organic Compounds with Distinct Selectivity toward Aromatic Hydrocarbons.
A whispering-gallery mode (WGM) optical resonance sensor for volatile organic compounds (VOCs) is developed from polystyrene (PS) microspheres doped with fluorescent β-cyano-appended oligo(p-phenylenevinylene) (β-COPV). The β-COPV-doped PS microspheres (MSCOPV) are formed by the miniemulsion method in a binary solvent. MSCOPV expand upon permeation of VOCs into the PS matrix and exhibit a spectral shift of the WGM resonance peak. The permeation efficiency is highly dependent on the chemical affinity between the analyte and the polymer matrix, with exceptionally high selectivity toward aromatic hydrocarbons such as benzene, toluene, and xylenes (BTXs). The high selectivity and sensitivity of MSCOPV are in clear contrast to those of conventional WGM sensors that just detect VOCs nonpreferentially through adsorption onto the surface.


[Experiences with the FAMACHA-Eye-Colour-Chart for identifying sheep and goats for targeted anthelmintic treatment].
The bloodsuckling abomasal parasite Haemonchus contortus is the most pathogenic worm in sheep and goats. High prevalences of anthelmintic-resistant isolates make H. contortus difficult to control. Detecting the most anaemic animals could support a targeted selective treatment approach. Leaving the rest of the flock untreated would generate a refuge for anthelmintic-sensitive parasites. South-African researchers tried the FAMACHA-Eye-Colour-Chart for anaemic sheep and goats with good success. Field studies, carried out in Northern Germany on naturally infected sheep and goats showed, that at a comparatively low prevalence of H. contortus the FAMACHA-test proved not being sufficient in detecting all animals with high fecal egg counts. Under these conditions there was no satisfying reliability to identify small ruminants for selective deworming only based on the FAMACHAEye-Colour-Test. But if not working hours are the limiting factor, the repeated score could support the selection of pale animals in need to be treated.


INBREEDING DEPRESSION WITH HETEROZYGOTE ADVANTAGE AND ITS EFFECT ON SELECTION FOR MODIFIERS CHANGING THE OUTCROSSING RATE.
The equilibrium level of inbreeding depression in populations with different selfing rates is studied for models with symmetrical or asymmetrical heterozygous advantage at several loci with partial linkage. As for the case of a single locus, the inbreeding depression caused by loci with heterozygous advantage can be higher for partially selfing populations than for complete outcrossing. The spread of modifier alleles at another locus that affects the selfing rate is studied. The stability of outcrossing populations to invasion by alleles that give increased selfing is found to depend on levels of inbreeding depression being greater than one-half, in accordance with earlier models that assumed a fixed level of inbreeding depression. However, in partially selfing populations the spread of such alleles can be checked by smaller levels of inbreeding depression than one-half, so that they do not always spread to fixation. This is interpreted as being due to associations between the genotypes at the modifier locus and the selected loci, together with increasing inbreeding depression as selfing increases, and does not occur if the inbreeding depression is due to mutation-selection balance.


[Surgery of ventral hernia using fascia lata graft].
Severe intraabdominal sepsis sometimes recquires very aggressive surgery with repeated surgical revisions of abdominal cavity. This often leads to large ventral hernia. The authors present one of the possibilities of surgical management of the hernia using fascia lata graft. This method is easy to perform and cost effective because of autologous material, which is most ideal from the point of biological view.


Involvement of gamma-aminobutyric acid in the control of GTH-1 and GTH-2 secretion in male and female rainbow trout.
The potential role of the neurotransmitter gamma-aminobutyric acid (GABA) in the control of the secretion of the two pituitary fish gonadotropins (GTH-1 and GTH-2) was investigated in male and female rainbow trout (Oncorhynchus mykiss). The presence of glutamate decarboxylase-positive fibers in the neurohypophyseal digitations adjacent to the gonadotropic cells was demonstrated by means of double immunohistochemistry, providing a morphofunctional support for potential GABA-gonadotropin interactions in both sexes. In spermiating males, in vivo treatment with GABA did not affect basal gonadotropin release, but stimulated GTH-1 release when coadministered with a gonadotropin-releasing hormone analogue (GnRHa), and potentiated GnRHa-stimulated GTH-2 release. In vitro, using dispersed pituitary cells, GABA stimulated basal GTH-1 and GTH-2 secretion, in a dose-dependent manner, and potentiated salmon GnRH effect on both hormones. In mature females, GABA induced in vivo a strong elevation of plasma GTH-2 levels after 2- 6 h of injection, but had no effect in vitro. GABA treatment in vivo was also stimulatory in recrudescent females, slightly increasing plasma GTH-2 levels in both saline- and GnRHa-treated fish (GnRHa alone has no effect at this stage). Immature fish were unresponsive to GABA/GnRHa treatments but, after steroid implantation [testosterone (T) or estradiol] for 13 days, injection of GABA stimulated GTH-2 release in vivo (also GTH-1 slightly in T-implanted fish). In conclusion, GABA has an overall stimulatory action on GTH-1 and GTH-2 secretion in rainbow trout, which depends on the sex and the reproductive stage of the fish. The stimulatory action of GABA might be exerted, at least in part, directly onto the gonadotropes, as it stimulates basal and GnRH-induced GTH-1 and GTH-2 secretion from dispersed pituitary cells.


CyberKnife radiosurgery and rituximab in the successful management of sclerosing idiopathic orbital inflammatory disease.
A 26-year-old man presented with symptoms suggesting idiopathic orbital inflammatory disease. After a poor initial response to oral steroids, an orbital biopsy confirmed the diagnosis. A paucicellular lymphocytic infiltrate with areas of fibrosis was seen to replace normal tissue. With the development of exposure keratopathy and diplopia associated with eyelid retraction, lagophthalmos, and decreased motility, increasing doses of steroids and intralesional steroid injections were instituted without effect. On the basis of successful treatment of malignant lymphocytic lesions, he was treated with CyberKnife radiosurgery and rituximab. This resulted in symptom resolution with improved eyelid closure and motility. Eighteen months after treatment, he is essentially symptom-free, with almost complete radiographic regression of his disease process.


11th International Congress on Molecular Plant-Microbe Interactions held at St. Petersburg--a report.
The report is a short summary of the most interesting presentations at the 11th International Congress on Molecular Plant-Microbe Interactions held during July 18-27, 2003 at St. Petersburg, Russia. The key elements from several sessions on the legume-Rhizobium interactions have been discussed.


The prognostic value of human chorionic gonadotropin expression in colorectal adenocarcinomas. An immunohistochemical study of 102 stage B2 and C2 nonmucinous adenocarcinomas.
Several recent studies have detected human chorionic gonadotropin (hCG) expression in colorectal adenocarcinomas and have concluded that its expression is an adverse prognostic indicator. The patient population and length of follow-up has varied. Therefore, we reviewed a defined group of cases with long-term (> 5 years) follow-up. We studied 102 stage B2 and C2 nonmucinous adenocarcinomas immunohistochemically for the production of hCG. Expression of hCG was detected in paraffin sections, including tumor and adjacent mucosa, using immunolabeling with a polyclonal rabbit antibody and the avidin-biotin-peroxidase complex technique. Cytoplasmic positive staining was evaluated semiquantitatively in every low-power microscopic field containing tumor. Expression of hCG was noted in at least one field in 42% (43/102) of the carcinomas. There was no expression in adjacent mucosa. Although the staining was usually focal (< 5% of tumor cells), some cases did stain diffusely. There was no significant correlation of hCG expression with survival, stage, differentiation, age, race, sex, or site of tumor. We therefore conclude that hCG expression is not a significant prognostic indicator in stage B2 and C2 colorectal carcinomas.


Daily physical activity enhances resilient resources for symptom management in middle-aged women.
The aim of the present study was to evaluate the direct and indirect associations between physical activity and menopausal symptoms. Community-dwelling middle-aged women (N = 103; age range 40-60 years) completed daily Internet surveys at the end of the day and wore an accelerometer for the objective assessment of physical activity for 21-days. 1-1-1 multilevel mediation models were estimated to test whether resilient resources (i.e., positive affect and coping efficacy) mediated the association between physical activity and symptom burden at the between- and within-person level. Analyses demonstrated physical activity had an indirect effect (-0.16) on symptom burden through the enhancement of positive affect at the within-person level (p < .05; 95% confidence interval [CI] based on 20,000 Monte Carlo replications [-0.25, -0.08]). In models that tested coping efficacy as the mediator, it was found that the indirect effect of physical activity on symptom burden at the within-person level was -0.08 (p < .05; 95% CI based on 20,000 Monte Carlo replications [-0.14, -0.03]). These effects were nonsignificant at the between-person level, suggesting one route in which physical activity may help a woman to cope with her symptoms is through the enhancement of positive affect and coping efficacy on a day-to-day basis.


T cell dependent B cell activation occurs during the induction of T cell anergy by staphylococcal enterotoxin B in mice.
Staphylococcal enterotoxin B (SEB) can activate specific T cell clones bearing specific TcR V beta domains together with MHC class II ligands on accessory cells. The release of proinflammatory cytokines is the consequence of this activation as well as the main pathological aspect involved in SEB infection. This current study looked at the active role of both T and B cells during the induction of anergy by SEB in vivo. Euthymic and nude BALB/c mice were injected with SEB and over a period of 8 days, cells from the spleen and sera from the blood were collected. After a single injection with SEB (50 micrograms/mouse), a transient increase of CD4+V beta 8+ T cells were detected after 2 days followed by a decrease after 4 days, which persisted until day 8. These clones were rendered anergic upon restimulation in vitro with SEB. Interestingly, cells taken out 2 days after SEB injection, exhibited reduced proliferation in response to Con A. However, this response gradually recovered on days 4, 6 and 8. Furthermore, early IgM antibody production (day 2) was observed after SEB injection. SEB-induced IgM antibody production in euthymic BALB/c was found to have specificity against SEB, cardiolipin (CL) and phosphatidylethanolamine (PE). SEB-treated nude mice did not produce antibody secreting cells in response to SEB, indicating that this process is T cell dependent.


[Cytodiagnostic studies of the laryngeal mucosa in chronic laryngitis].
Cytological diagnostic aids in chronic inflammation of the larynx have been rarely employed so far. A study was conducted to prove whether there is any possibility of larnygeal cytological diagnosis and whether there are any premalignant changes. In view of the results obtained by gynaecological exfoliative cytology, attention was focussed on the metaplastic cells. The frequent incidence of metaplasias was highly significant, whereas dysplasias occurred only in chronic laryngitis besides in tumours. One trend occupying higher cytological diagnostic groups in the Papanicolaou pattern was seen in chronic laryngitis. In our opinion, cytological diagnosis in laryngeal investigation is an aid in the followup control in chronic laryngitis, which is a repeatable procedure without unduly stressing the tissue. Recording of cellular changes in chronic laryngitis can enable a prospective appreciation of morphological changes, which can be useful as diagnostic tool for examining suspicious findings.


Dynamic changes in mental health status related to the COVID-19 pandemic among health care workers and inpatients in China.
Exposure to coronavirus disease 2019 (COVID-19) can cause severe mental health problems, the dynamics of which remain unclear. This study evaluated the mental status of frontline health care workers (FHWs) and suspected infected patients (SIPs) during different periods of the COVID-19 outbreak. Demographic and psychological data were collected through a cross-sectional survey of 409 participants in a hospital from 20 January to 7 August 2020. COVID-19 outbreaks were divided into three periods owing to the time, place, and scale, including the national outbreak period (a nationwide pandemic period from 20 January to 8 April 2020), sporadic period (a stable period from 9 April to 10 June), and local epidemic period (a local pandemic in Beijing from 11 June to 7 August 2020). Acute psychological disorders (APDs), including symptoms of anxiety and depression, were assessed using the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS). A total of 206 FHWs and 203 SIPs completed the electronic questionnaire. Overall, the prevalence rates of anxiety and depression among SIPs were 3.9 and 19.4%, respectively, while significantly higher prevalence rates (17.7 and 25.1%) were found among FHWs, P-value < 0.05. Psychological status among SIPs did not differ significantly across the three periods. The FHWs were more vulnerable, as their SAS and SDS scores and almost all the dimension scores were significantly higher during the local epidemic period than during the national outbreak and sporadic periods (all P-values < 0.001). The prevalence of anxiety (34.41%) and depression (41.94%) was significantly higher during the local epidemic period (P < 0.001). Logistic and linear mixed models showed that age, sex, and doctor-patient ratio especially, independently influenced most dimension scores of SAS and SDS among FHWs (P < 0.05). Compared to the COVID-19 epidemic at the national level, the local epidemic had a greater influence on FHWs' mental health. More attention should be given to the workload of FHWs.


Isolation and amino acid sequence of a dehydratase acting on d-erythro-3-hydroxyaspartate from Pseudomonas sp. N99, and its application in the production of optically active 3-hydroxyaspartate.
An enzyme catalyzing the ammonia-lyase reaction for the conversion of d-erythro-3-hydroxyaspartate to oxaloacetate was purified from the cell-free extract of a soil-isolated bacterium Pseudomonas sp. N99. The enzyme exhibited ammonia-lyase activity toward l-threo-3-hydroxyaspartate and d-erythro-3-hydroxyaspartate, but not toward other 3-hydroxyaspartate isomers. The deduced amino acid sequence of the enzyme, which belongs to the serine/threonine dehydratase family, shows similarity to the sequence of l-threo-3-hydroxyaspartate ammonia-lyase (EC 126.96.36.199) from Pseudomonas sp. T62 (74%) and Saccharomyces cerevisiae (64%) and serine racemase from Schizosaccharomyces pombe (65%). These results suggest that the enzyme is similar to l-threo-3-hydroxyaspartate ammonia-lyase from Pseudomonas sp. T62, which does not act on d-erythro-3-hydroxyaspartate. We also then used the recombinant enzyme expressed in Escherichia coli to produce optically pure l-erythro-3-hydroxyaspartate and d-threo-3-hydroxyaspartate from the corresponding dl-racemic mixtures. The enzymatic resolution reported here is one of the simplest and the first enzymatic method that can be used for obtaining optically pure l-erythro-3-hydroxyaspartate.


Renal tuberculosis and hypertension: value of the renal vein renin ratio.
We applied the central renal vein renin ratios in a group of patients with unilateral renal tuberculosis and hypertension to see whether the diseased kidney was involved in the pathogenesis of the elevated blood pressure. Of 20 patients 11 were nephrectomized, 7 had positive renal vein renin ratios and normal peripheral plasma renin activity; only 2 kept their blood pressure in control without medication. From 5 without a positive index, only 1 kept his blood pressure in control without medicine 1 year after surgery. The renal vein renin ratio has to be interpreted in light of other parameters, such as blood pressure, peripheral renin--if high the more the chance of being significant--and global renal function. The renal vein renin ratio alone per se gives poor information on the pressor role of a unilateral tuberculous kidney.


Novel Small Molecules in IBD: Current State and Future Perspectives.
Biologicals have dominated the therapeutic scenery in inflammatory bowel diseases (IBDs), namely ulcerative colitis (UC) and Crohn's disease (CD), for the past 20 years. The development of tofacitinib was the starting point for an era of small molecules after the era of biologicals. These new agents may challenge the use of biological agents in the future. They share properties that appeal to both patients and physicians. Low production costs, a lack of immunogenicity, and ease of use are only some of their benefits. On the other hand, patients and their physicians must manage the potential side effects of small molecules such as JAK inhibitors or S1P1R modulators. Here, we present agents that have already entered the clinical routine and those that are still being investigated in clinical trials.


Prevalence of Capillaria plica in Danish wild carnivores.
Capillaria plica is a parasitic nematode belonging to the family Capillariidae. The adult parasites reside in the urinary tract of wild and domestic canines. The infection is most often asymptomatic, but can cause a wide range of symptoms including urinary bladder inflammation, pollacisuria, dysuria and hematuria. Canines acquire the infection by ingesting the intermediate host, the earthworm (Lumbricidae). Epidemiological studies on C. plica infection in wildlife are few and only one previous Danish study examined the prevalence in red foxes, while studies on prevalence in other animals are limited. We examined the urine sediment or urinary bladder from 375 Raccoon dogs (Nyctereutes procyonoides), 247 red foxes (Vulpes vulpes), 20 beech martens (Martes foina), 16 wild mink (Neovison vison), 14 otters (Lutra lutra), nine European polecats (Mustela putorius), three European badgers (Meles meles) and one golden jackal (Canis aureus) received as a part of Danish wildlife surveillance. Capillaria plica was detected in 73.7% of red foxes, 20.0% of beech martens, 0.5% of raccoon dogs, and in the Golden jackal. Red foxes originating from all 5 regions of Denmark were infected, although with a significantly higher prevalence in the three regions in Jutland compared to Region Zealand.


Workplace violence prevention policies in home health and hospice care agencies.
Workplace violence in the home health industry is a growing concern, but little is known about the content of existing workplace violence prevention programs. The authors present the methods for this study that examined workplace violence prevention programs in a sample of 40 California home health and hospice agencies. Data was collected through surveys that were completed by the branch managers of participating facilities. Programs were scored in six different areas, including general workplace violence prevention components; management commitment and employee involvement; worksite analysis; hazard prevention and control; safety and health training; and recordkeeping and program evaluation. The results and discussion sections consider these six areas and the important gaps that were found in existing programs. For example, although most agencies offered workplace violence training, not every worker performing patient care was required to receive the training. Similarly, not all programs were written or reviewed and updated regularly. Few program differences were observed between agency characteristics, but nonetheless several striking gaps were found.


Higher energy states in the CO dimer: millimeter-wave spectra and rovibrational calculations.
New extensive millimeter-wave measurements of the 12C16O dimer have been made, and more than 300 new spectral transitions have been observed in the frequency range 81-135 GHz. A joint analysis of these and previous millimeter-wave data yielded the precise location of 33 new energy levels of A+ symmetry and 20 levels of A- symmetry. These energy levels are located at 8-18 cm(-1) above the zero-point level. Some of them belong to already known stacks, and others make up 9 new stacks of the dimer. Newly determined stacks have K=0, 1, and, for the first time, 2, where K is the projection of the total angular momentum on the intermolecular axis. The energy levels from accompanying rovibrational calculations with the use of a recently developed hybrid CCSD(T)/DFT-SAPT potential are in very good agreement with experiment. Analysis of the calculated wave functions revealed that two new stacks of A+ symmetry with K=2 correspond to overall rotation of the dimer while the other newly observed stacks belong to the geared bend overtone modes. The ground vibrational states of the two "isomers" found are more or less localized at the two minima in the potential surface, whereas all the geared bend excited states show a considerable amount of delocalization.


Post liposuction infections by rapidly growing mycobacteria.
Rapidly growing mycobacteria (RGM) are recognized agents of surgical site infections. Recently, RGM skin and soft tissue infections have been increasingly reported. As symptoms, clinical signs and disease latency remain non-specific and microbiological detection requires targeted growth media, RGM diagnosis remains challenging for clinicians. Appropriate management is often delayed due to lack of awareness of these infections. RGM infections after plastic surgery have also been described in the setting of interventions performed in developing countries, a growing phenomenon commonly known as medical tourism. We describe a case of Mycobacterium chelonae/abscessus infection following liposuction and liposculpture procedures performed in the Dominican Republic and review the literature on this subject.


Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen-driven affinity selection.
The analysis of molecular signatures of antigen-driven affinity selection of B cells is of immense use in studies on normal and abnormal B cell development. Most of the published literature compares the expected and observed frequencies of replacement (R) and silent (S) mutations in the complementarity-determining regions (CDRs) and the framework regions (FRs) of antibody genes to identify the signature of antigenic selection. The basic assumption of this statistical method is that antigenic selection creates a bias for R mutations in the CDRs and for S mutations in the FRs. However, it has been argued that the differences in intrinsic mutability among different regions of an antibody gene can generate a statistically significant bias even in the absence of any antigenic selection. We have modified the existing statistical method to include the effects of intrinsic mutability of different regions of an antibody gene. We used this method to analyse sequences of several B cell-derived monoclonals against T-dependent antigens, T-independent antigens, clones derived from lymphoma and amyloidogenic clones. Our sequence analysis indicates that even after correcting for the intrinsic mutability of antibody genes, statistical parameters fail to reflect the role of antigen-driven affinity selection in maturation of many clones. We suggest that, contrary to the basic assumption of such statistical methods, selection can act both for and against R mutations in the CDR as well as in the FR regions. In addition we have identified different methodological difficulties in the current uses of such statistical analysis of antibody genes.


Development of an Intranasal Gel for the Delivery of a Broadly Acting Subunit Influenza Vaccine.
Influenza virus is a major cause of death on a global scale. Seasonal vaccines have been developed to combat influenza; however, they are not always highly effective. One strategy to develop a more broadly active influenza vaccine is the use of multiple rounds of layered consensus buildings to generate recombinant antigens, termed computationally optimized broadly reactive antigen (COBRA). Immunization with the COBRA hemagglutinin (HA) can elicit broad protection against multiple strains of a single influenza subtype (e.g., H1N1). We formulated a COBRA H1 HA with a stimulator of interferon genes agonist cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) into a nasal gel for vaccination against influenza. The gel formulation was designed to increase mucoadhesion and nasal retention of the antigen and adjuvant to promote a strong mucosal response. It consisted of a Schiff base-crosslinked hydrogel between branched polyethyleneimine and oxidized dextran. Following a prime-boost-boost schedule, an intranasal gel containing cGAMP and model antigen ovalbumin (OVA) led to the faster generation of serum IgG, IgG1, and IgG2c and significantly greater serum IgG1 levels on day 42 compared to soluble controls. Additionally, OVA-specific IgA was detected in nasal, vaginal, and fecal samples for all groups, except the vehicle control. When the COBRA HA was given intranasally in a prime-boost schedule, the mice receiving the gel containing the COBRA and cGAMP had significantly higher serum IgG and IgG2c at day 41 compared to all groups, and only this group had IgA levels above the background in vaginal, nasal, and fecal samples. Overall, this study indicates the utility of an intranasal gel for the delivery of COBRAs for the generation of serum and mucosal humoral responses.


Toward an affirmative lesbian, gay, bisexual, and transgender leadership paradigm.
This article presents an affirmative paradigm for understanding the leadership of sexual minorities-that is, lesbian, gay, bisexual, and transgender (LGBT) people. Although research on LGBT issues in leadership to date is almost nonexistent, there are several bodies of literature that can contribute to an understanding of the unique leadership challenges faced by sexual minority people. These include the literatures on stigma and marginalization, leadership in particular status groups (e.g., college students, women), and LGBT vocational issues (especially workplace climate and identity disclosure). We propose a new, multidimensional model of LGBT leadership enactment that incorporates sexual orientation (particularly regarding identity disclosure), gender orientation (including leader gender), and the situation (conceptualized here as group composition); the model also is embedded in context, the most relevant factors that affect the enactment of leadership being stigma and marginalization. We explicate this model with findings and concepts from relevant literatures, and we conclude the article with recommendations for building a scholarly literature in LGBT leadership.


Diopside-tricalcium phosphate bioactive ceramics for osteogenic differentiation of human adipose stem cells.
Ti scaffolds combined with autologous human adipose-derived mesenchymal stem cells (hASCs) have been successfully applied for regenerative cranio-maxillofacial bone therapies. Future challenges reside in regeneration of larger bone defects and displacement of the permanent Ti structure, thus, advanced resorbable scaffolds are needed. Composites of β-Ca3 (PO4 )2 with 80 and 60 wt % of CaMg(SiO3 )2 with improved mechanical properties compared to tricalcium phosphate (TCP) materials are presented. Synthetic CaMg(SiO3 )2 and a precursor of Ca3 (PO4 )2 were used to fabricate the composites and a reference β-Ca3 (PO4 )2 material by uniaxial pressing and solid state sintering. Optimum sintering temperature of 1225°C was selected. Microstructural analysis and Weibull distributions of tensile strengths determined by the diametral compression of discs test are reported. Thermodynamic simulation of the dissolution process in simulated body fluid body fluid was done. The biological response with hASCs was analyzed using basic and osteogenic media. Viability and osteogenic potential-LIVE/DEAD assay; alkaline phosphatase activity and collagen type-I production-were characterized. The composites have higher tensile strength (>3×) than TCP materials, for similar reliability, and support viability and osteogenic differentiation of hASCs. Resorption of the high strength phase diopside is the slowest. The promising results reported here suggest possible uses of these bioactive β-Ca3 (PO4 )2 -CaMg(SiO3 )2 ceramics together with hASCs in bone tissue engineering.


[Markers of thyroid function (I). Assessment of glandular activity].
Thyroid hormones have a fundamental role in the metabolism, and are active in all organs and systems. Thyroid dysfunction (TD) is an important public health problem that concerns 10% of the general population. Diagnosis of TD is currently carried out on the basis of serum hormone levels determined by laboratory analysis. The results are classified into clinical (TSH and thyroid hormones out of normal range) and subclinical (isolated TSH disorder) dysfunction. The development of third generation assays in the TSH test represents a great step forward in the diagnosis of TD. However, the debate about the pathological significance of subclinical TD has intensified. There is as yet no agreement on the best approach for diagnosis and treatment of this common condition. It is currently impossible to know which subjects with subclinical TD will develop the typical complications of clinical dysfunction. In this setting, it is feasible that a number of subclinical hypothyroid subjects may in some cases be overtreated with thyroxin, while others remain undertreated with increased iatrogenic morbidity as a consequence.


Leveraging Traditional Ecological Knowledge and Access to Nutrient-Rich Indigenous Foods to Help Achieve SDG 2: An Analysis of the Indigenous Foods of Sauria Paharias, a Vulnerable Tribal Community in Jharkhand, India.
Indigenous food systems of traditional communities are potentially sustainable, have nutrient rich food sources and can enhance dietary diversity. Sauria Paharias, are one of the particularly vulnerable tribal groups of Jharkhand India, who despite residing in rich biodiverse environment and possessing traditional ecological knowledge, lag behind various health, and nutritional indicators. Our study explored their traditional ecological knowledge around indigenous foods (IFs), their routine consumption, access, and nutritive values. A cross-sectional mixed methods study was carried out in 18 villages of Godda district, Jharkhand. Free list of all IFs known to the community was developed using focus group discussions. This was followed by enumerating commonly consumed as well as little or historically used IFs. Following the taxonomic classification of these foods, their nutritive values were searched in literature or food samples were analyzed in accredited laboratories. Reasons for consumption and non-consumption of specific IFs were explored. The community was aware of a large number of IFs (n = 193) but only 50% of these were routinely consumed. Rest were either little used or historically consumed. About 47.6% IFs (n = 92) were identified using taxonomic classification; of which 87 IFs were classified based on their common names in secondary literature and five food items were collected, herbariums were prepared and identified. Nutritive values were documented for 84 IFs (this included both routinely consumed as well as little used); out of which 55 foods were found to have nutritive values in existing literature and 29 foods were analyzed in laboratory. Many of these IFs were rich in micronutrients like calcium, iron, zinc, folic acid, vitamin A, and vitamin C. Common reasons for preferences or non-consumption of specific IFs included taste, availability, access seasonality, opportunity cost of access and processing time. Promoting adequate intake of commonly accessed nutrient rich IFs and revival of little used IFs while addressing the causes of non-consumption and mainstreaming them into the daily diets could be an effective strategy to increase the intake of micronutrients. Policies focusing on incorporation of nutrient rich IFs into dietary diversification strategies and ongoing supplementary feeding programs can help address malnutrition in the community.


[Quantitative spectral evaluation of vocal hypofunction].
The purpose of this study was to explore the interaction between voice asthenicity and the acoustic prediction of vocal hypofunction. One hundred and seven phonatory samples of Reinke's edema were categorized by listeners using GRBAS scale. Seven frequency and time domain parameters were used to predict perceptual severity of asthenicity. Logistic regresion analysis showed that a useful measure for the prediction of asthenicity was the loss of harmonic components in the middle and upper portion of the spectrum. A spectral classification of vocal hypofunction is proposed.


Evaluation and Management of Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Generalized Hypermobility Spectrum Disorder: Protocol for a Pilot and Feasibility Randomized Controlled Trial.
Dyspnea is a prevalent symptom in individuals with hypermobile Ehlers-Danlos Syndrome (hEDS) and generalized hypermobility spectrum disorder (G-HSD), yet its contributors have not been identified. One known contributor to dyspnea is respiratory muscle weakness. The feasibility and effectiveness of inspiratory muscle training (IMT) in combination with standard-of-care rehabilitation (aerobic, resistance, neuromuscular stabilization, and balance and proprioception exercises) in improving respiratory muscle strength and patient-reported outcomes in patients with hEDS or G-HSD have not been evaluated. This study aims to evaluate dyspnea, respiratory muscle strength, and patient-reported outcome measures (PROMs) in hEDS or G-HSD compared with healthy controls and to assess the feasibility of a randomized controlled trial of IMT and standard-of-care rehabilitation for improving respiratory muscle strength, exercise capacity, and PROMs compared with standard-of-care rehabilitation in hEDS and G-HSD. The study will include 34 participants with hEDS or G-HSD and 17 healthy, age- and sex-matched controls to compare respiratory muscle structure and function and PROMs. After baseline assessments, participants with hEDS or G-HSD will be randomized into the intervention group and provided IMT combined with Ehlers-Danlos Syndrome standard-of-care rehabilitation or into the usual care group, and provided only standard-of-care rehabilitation for 8 weeks. The intervention group will be prescribed IMT in their home environment using the POWERbreathe K5 IMT device (POWERbreathe International Ltd). IMT will comprise 2 daily sessions of 30 breaths for 5 days per week, with IMT progressing from 20% to 60% of the baseline maximal inspiratory pressure (MIP) over an 8-week period. Feasibility will be assessed through rates of recruitment, attrition, adherence, adverse events, and participant satisfaction. The primary pilot outcome is MIP change over an 8-week period in hEDS or G-HSD. Secondary outcomes will include the evaluation of dyspnea using Medical Research Council Scale and 18-point qualitative dyspnea descriptors; diaphragmatic thickening fraction using ultrasound; respiratory muscle endurance; pulmonary function; prefrontal cortical activity using functional near-infrared spectroscopy; aerobic capacity during cardiopulmonary exercise testing; quality of life using Short Form-36; and scores from the Depression, Anxiety, and Stress scale-21. These measures will also be performed once in healthy controls to compare normative values. Multivariable regression will be used to assess the contributors to dyspnea. Paired 2-tailed t tests will be used to assess the changes in MIP and secondary measures after 8 weeks of IMT. Study recruitment began in August 2021 and, with several disruptions owing to COVID-19, is expected to be completed by December 2023. This study will provide a better understanding of the factors associated with dyspnea and the feasibility and effectiveness of IMT combined with standard-of-care rehabilitation. IMT may be a novel therapeutic strategy for improving respiratory muscle function and patient-reported outcomes in individuals with hEDS or G-HSD. ClinicalTrials.gov NCT04972565; https://clinicaltrials.gov/ct2/show/NCT04972565. DERR1-10.2196/44832.


Case Report of a Small Gastric Neuroendocrine Tumor in a Deep Layer of Submucosa With Diagnosis by Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Treatment With Laparoscopic and Endoscopic Cooperative Surgery.
Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by enterochromaffin-like cells of the stomach. Optimal management of GNETs has not yet been definitively determined. Endoscopic resection is approximately recommended for small GNETs associated with hypergastrinemia. However, endoscopic resection might present risk of perforation or positive vertical margin because neuroendocrine tumors occur in the deep mucosa, with some invading the submucosa. In this case, a patient with type A chronic atrophic gastritis had a small subepithelial lesion in a deep submucosal layer, and we diagnosed it as GNET using endoscopic ultrasound-guided fine-needle aspiration biopsy using a forward-viewing and curved linear-array echoendoscope. Moreover, our results show that laparoscopic and endoscopic cooperative surgery with regional lymph node dissection is a safe and feasible procedure for GNETs, especially those that cross to the muscularis propria. We suggest this approach as one therapeutic option for GNETs because it safely minimizes resection and is less invasive.


Prevention of acute aspirin-induced gastric mucosal injury by 15-R-15 methyl prostaglandin E2: an endoscopic study.
The deleterious effects of aspirin on gastric mucosa have been well documented in experimental and clinical studies. Prostaglandins offer a potential method by which this injury may be prevented. In these studies, we developed a single-dose endoscopic assay system of aspirin-induced gastric mucosal injury in normal volunteers. With this system, 27 of 30 volunteers (90%) demonstrated severe mucosal injury after ingestion of aspirin. Subsequently, we evaluated whether pretreatment with 15-R-15 methyl prostaglandin E2 prevented severe injury after ingestion of aspirin. Following an initial dose-response study, a double-blind crossover trial was performed using pretreatment with placebo or with 10-micrograms doses of 15-R-15 methyl prostaglandin E2 for 24 h before treatment with aspirin. The results of this trial indicate that prostaglandin pretreatment significantly prevented the occurrence of endoscopically visible severe gastric mucosal injury after single-dose aspirin administration.


[Hemangioma of the liver: often an incidental finding].
Hemangioma is the most frequent benign liver tumor with an incidence of 0.4-7.3%. The tumors are typically small, asymptomatic and detected accidentally by ultrasound or CT. Hemangiomas extending a diameter of 2-3 cm can be proved by dynamic contrast CT or scintigraphy with 99-m Tc erythrocytes. Hemangiomas with a diameter less than 2 cm are a diagnostic dilemma. In case of a typical ultrasonic picture (small white tumor) in an asymptomatic patient, a consequent ultrasonic follow-up is indicated. It is yet unclear whether MRI will be an additional diagnostic tool to identify small hemangiomas.


Optosensor for cinchona alkaloids with C18 silica gel as a substrate.
A flow-through optosensor for cinchona alkaloids with C18 silica gel as a substrate is proposed. The sensor is developed in conjunction with a flow-injection analysis system and is based on the retention of the cinchona alkaloids on a C18 column and the enhancement of their fluorescence. The analytical performance characteristics of the proposed sensor for the detection and quantification of these alkaloids were as follows: the detection limits of quinine, cinchonine, quinidine and cinchonidine were 2.3, 31.6, 2.3 and 31.6 ng ml-1, respectively, with relative standard deviations of 0.9% for quinine and quinidine (20 ng ml-1, n = 7) and 1.1% for cinchonine and cinchonidine (4.0 micrograms ml-1, n =7), respectively. Most of the common species did not interfere. The recommended method has been successfully tested for determination of quinine in pharmaceutical preparations and soft drinks.


Repeated premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans.
We explored the aftereffects of two premotor 1 Hz rTMS sessions on motor cortex excitability in healthy humans. In experiment 1, 11 healthy right-handed volunteers received 20-min submotor threshold 1 Hz rTMS trains over the left premotor cortex on 2 consecutive days. Left motor cortex excitability was determined at baseline, immediately after, 30, 60, 120 min, and 24 h after each rTMS session. We measured motor thresholds, amplitudes of motor-evoked potentials, silent periods, and paired-pulse excitability at interstimulus intervals (ISI) of 3-7, 10, and 15 ms. In experiment 2, 5 volunteers received two identical rTMS trains on Days 1 and 7. Measurements were carried out on Day 1 (first rTMS train), Day 2, and Day 7 (second rTMS train). In experiment 1 there was a selective increase of paired pulse facilitation at an ISI of 7 ms after rTMS lasting for less than 30 min on Day 1. This effect was also present after rTMS on Day 2. However, it persisted for at least 2 h. In experiment 2 the same extra facilitation was induced by rTMS on Days 1 and 7 but not on Day 2. It lasted for less than 30 min on both Day 1 and Day 7. We conclude that 1 Hz premotor rTMS leads to cumulative plastic changes of intrinsic motor cortex excitability when repeated within 24 h but not after 1 week, implying the formation of memory after the first rTMS train lasting more than a day but less than a week.


Effect of ischemic preconditioning on repeated sprint ability in team sport athletes.
This study investigated whether ischemic preconditioning (IPC) in a trained population affected repeated sprint performance. A secondary aim was to assess responses according to gender. Sixteen (nine females and seven males) well trained team sport athletes took part in a randomised crossover study design. Participants underwent an IPC and placebo treatment involving three periods of 5 min occlusion applied unilaterally (3 × 5 min occlusion to each leg) at either 220 mmHg or 50 mmHg. Each period of occlusion was followed by 5 min reperfusion. Following treatment 5 × 6 s maximal effort sprints were undertaken on a cycle ergometer against 7.5% body mass, each interspersed by 24 s recovery. Measured parameters included peak power, total power, percentage decrement, post-exercise blood lactate and ratings of perceived exertion. Nor within subject main effect for IPC was observed, neither was there an interaction effect with gender. Effect sizes were trivial (ES < 0.2) with the exception of a moderate (ES < 1.2) change in post-exercise blood lactate in the female cohort (1.6 ± 0.4 mmol⁻¹ lower following IPC). Results suggest no benefit to team sport players in utilising IPC as a means of enhancing repeated sprint performance. A lower blood lactate response in female participants following IPC may suggest improved blood flow through vasodilation.


Are drug metabolites able to cause T-cell-mediated hypersensitivity reactions?
Adverse drug reactions with an immune pathogenesis are a problem in the clinic and an impediment to drug development. T lymphocytes are believed to play a role in the pathogenesis; however, the nature of the drug interaction with immune receptors remains an area of debate. This article reviews recent advances in our understanding of drug hypersensitivity focusing specifically on the way in which drugs are displayed in MHC molecules. Most drugs associated with a high incidence of reactions have been shown to form protein-reactive metabolites. Hence, the relationship between drug metabolism and T-cell activation is discussed in detail. The role of metabolism in pathogenesis of immunological drug reactions has only been studied with a small number of drugs where synthetic metabolites are available for functional studies. In each case, metabolite-responsive T cells have been detected. However, the field is skewed by the fact that most research is conducted using the parent compound in metabolically inert cell systems. We propose that research efforts are directed towards the synthesis of drug metabolites and/or drug-protein conjugates. Furthermore, analytical methods need to be developed to relate metabolite exposure to the T-cell response. For now, our understanding of the chemical basis of drug hypersensitivity is incomplete.


Acuity and case management: a healthy dose of outcomes, part III.
This is the third of a 3-part series presenting 2 effective applications--acuity and dosage--that describe how the business case for case management (CM) can be made. In Part I, dosage and acuity concepts were explained as client need-severity, CM intervention-intensity, and CM activity-dose prescribed by amount, frequency, duration, and breadth of activities. Concepts were presented that related the practice of CM to the use of evidence-based practice (EBP), knowledge, and methods and the development of instruments that measure and score pivotal CM actions. Part I also featured a specific exemplar, the CM Acuity Tool, and described how to use acuity to identify and score the complexity of a CM case. Part II further explained dosage and 2 acuity instruments, the Acuity Tool and AccuDiff. Part III presents linkage to EBP and practical applications. The information contained in the 3-part series applies to all CM practice settings and contains ideas and recommendations useful to CM generalists, specialists, supervisors, and business and outcomes managers. The Acuity Tools Project was developed from frontline CM practice in one large, national telephonic CM company. Dosage: A literature search failed to find research into dosage of a behavioral intervention. The Huber-Hall model was developed and tested in a longitudinal study of CM models in substance abuse treatment and reported in the literature. Acuity: A structured literature search and needs assessment launched the development of the suite of acuity tools. A gap analysis identified that an instrument to assign and measure case acuity specific to CM activities was needed. Clinical experts, quality specialists, and business analysts (n = 7) monitored the development and testing of the tools, acuity concepts, scores, differentials, and their operating principles and evaluated the validity of the acuity tools' content related to CM activities. During the pilot phase of development, interrater reliability testing of draft and final tools for evaluator concordance, b testing for content accuracy and appropriateness, and representative sample size testing were done. Expert panel reviews occurred at multiple junctures along the development pathway, including the 5 critical points after initial tool draft and both before and after b-test (n = 5) and pilot-test (n = 28) evaluations. The pilot testing body (n = 33) consisted of a team of case managers (n = 28) along with quality analysts (n = 2), supervisory personnel (n = 2), and the lead product analyst (the developer). Product evaluation included monitoring weekly reports of open cases for the 28 case managers for 3 months (June-August 2000). The Acuity Tools Suite was used to calculate individual case acuity, overall caseload acuity profiles, case length, and acuity differentials. Normal distributions and outliers were analyzed and the results were used for internal quality improvement and outcomes monitoring. To show value, case managers need to access the evidence base for practice, use tools to capture quantities of intervention intensity, and precisely specify the activities that produce better outcomes. Acuity and dosage can help case managers explore and fully describe their own practice in ways that can be measured, and thus provide data and evidence that contributes to the accumulating body of definitive proof regarding the exceptional worth of CM. Proving business and professional worth in CM through EBP is a clarion call that case managers must heed and an innovation that all case managers can practice.


Natural killer cell function in HIV-1 infected patients.
A cross-talk between dendritic cells (DC) and resting natural killer (NK) cells leads to the activation of both cell populations, a process requiring cell-cell contact. When the number of activated NK cells overwhelms surrounding DC, they became able to kill specifically immature DC, a feedback mechanism to shut off DC-mediated immune responses. DC, at the mucosal site, can capture HIV and transfer it to CD4+ T lymphocytes present in the regional lymph node thus giving rise to a productive infection; on the other hand, NK cells represent the first line of defence against viral infection. Our preliminary results suggest that during the early phases of an HIV infection, NK cell activity is not functionally compromised, but that infected cells might escape natural immune surveillance through several mechanisms, including a reduced lysis of autologous DC.


[Self-perceived health status in health workers 3 and 6 months after a SARS-CoV-2 infection (COVID-19).]
After the acute period of infection by the SARS-CoV-2 virus (COVID-19), multi-organ signs and symptoms may remain. This study tried to compare the perception of the state of health and the sequelae in Navarra-Osasunbidea health workers after COVID-19, with the previous situation through the Health Survey. Through a descriptive cross-sectional study, using a reduced questionnaire from the 2017 National Health Survey sent to health workers from the Navarre-Osasunbidea Health Service COVID-19 cases after 3 and 6 months, from April to July 2021 and compared with 2017. Differences were described through means, percentages and prevalence ratio, with 95% confidence intervals. Of 938 surveys sent, 93 of 3 months (46.3%) and 305 of 6 months (41.4%) were received, 87% of women and 13% of men and 43 years of average age and 64.3% were from nursing and 19.1% from medicine. The percentage that assessed their health status as good or very good was significantly lower at 6 months than health workers and the general population in 2017 (70.2% vs 80.4% and 75.5%), the limitation for the habitual activity (39.8% and 35.1% vs 18.3%), headache 2.7 times more frequent, the days of activity restriction (41.5 and 26.7 vs 7.5) and on bed. Mental health problems, concentration (45.2% and 43.9%), loss of sleep (44.1% and 43.3%) and consumption of tranquilizers and antidepressants (2 and 3 times more) stood out, although not of medical consultations. Navarre health workers diagnosed with COVID-19 in 2020 and early 2021 refer to the worst assessment of their health status at 3 and 6 months, greater limitation for usual activities, more frequent headaches and mental health problems, compared to the pre-pandemic period.


High complete response in advanced nasopharyngeal carcinoma with bleomycin, epirubicin, and cisplatin before radiotherapy.
Undifferentiated carcinoma of nasopharyngeal type (UCNT) is a geographically endemic, Epstein-Barr virus-related carcinoma of epidermoid origin with reported 5-year survival rates of 15%-40% when treated with radiotherapy alone. Although UCNT can be well controlled locally by radiation therapy, in advanced nodal stage N3 [International Union Against Cancer-American Joint Committee on Cancer (UICC-AJCC, 1987)] the survival rate is below 20%, primarily because of metastatic spread in 80% of the fatalities. We report a pilot study of 41 patients with nonmetastatic, locoregionally advanced disease (85% of the patients had a nodal status greater than or equal to N2C-N3; 43% had T4 primaries), during which we used a combination of 100 mg of cisplatin/m2 on day 1, 15 mg of bleomycin by intravenous push and 12 mg/m2 by continuous infusion on days 1-5, and 70 mg of epirubicin/m2 on day 1 every 21 days for three cycles before definitive radiation therapy with 70 Gy for 7 weeks. Twenty-seven of 41 patients (66%; 95% confidence interval = 52.5%-80.5%) achieved a clinical complete response, and 40 of 41 (98%) had a major objective response after chemotherapy. Two deaths were treatment related, but side effects were moderate, and the overall treatment sequence was feasible. At the end of radiation therapy, all 39 assessable patients were in complete response, with a median follow-up of 21+ months (greater than 10-greater than 31); 33 (80%) patients had no evidence of disease. We believe that such a complete response rate in a high-volume disease with the use of combined modality treatment indicates a therapeutic gain in UCNT. Researchers performing a multicenter international controlled trial will test this hypothesis and compare local control, disease-free, and overall survival of the therapeutic sequence presented here with radiotherapy alone.


Brucella melitensis VirB12 recombinant protein is a potential marker for serodiagnosis of human brucellosis.
The numerous drawbacks of current serological tests for diagnosis of brucellosis which mainly results from cross reactivity with LPS from other gram-negative bacteria have generated an increasing interest to find more specific non-LPS antigens. Previous studies had indicated that Brucella VirB12 protein, a cell surface protein and component of type IV secretion system, induces antibody response during animal infection. However, this protein has not yet been tested as a serological diagnostic marker in human brucellosis. Recombinant VirB12 protein was prepared and evaluated the efficacy of it in an indirect enzyme-linked immunosorbent assay (ELISA) for brucellosis with sera collected from different region of Iran and the results were compared with a commercial ELISA kit. Sera from human brucellosis patients strongly reacted to the purified recombinant VirB12. The sensitivity, specificity, accuracy, negative predictive value and positive predictive value of recombinant VirB12-based ELISA related to the commercial-ELISA method were 87.8, 94, 90, 80 and 96.6% respectively. We concluded that antigenic VirB12 have a property value that can be considered as a candidate for using in serodiagnostic tests for human brucellosis.


Upper gastrointestinal bleeding from gastric antral vascular ectasia following cocaine use: case presentation and review of literature.
Gastric antral vascular ectasia (GAVE), also known as "Watermelon stomach", is a rare cause of upper gastrointestinal bleeding (UGIB). It is characterized by an endoscopic appearance of flat red blood vessels traveling from the pylorus to the antrum. Patients often present with chronic blood loss resulting in iron deficiency anemia, or, less commonly, with acute gastropathy resulting in massive hemorrhage. The etiology of GAVE is unknown but the disorder has been more commonly observed in patients with cirrhosis, especially with portal hypertension, as well as in those with systemic sclerosis and other connective tissue disease. There is no definitive cure for GAVE, but the condition can be managed with a variety of endoscopic techniques, including heater probes, bipolar probes, plasma coagulators, laser therapy, and radiofrequency ablation. In rare cases, patients also require blood transfusions. Here we present an interesting case of upper GI bleeding resulting in symptomatic anemia in a 69-year-old female patient with GAVE following cocaine use. The patient was initially admitted for fatigue and shortness of breath and required multiple units of pRBCs. She was also found to have a urine drug screen positive for cocaine. Following stabilization, she underwent endoscopy which revealed the characteristic "watermelon stomach" appearance consistent with GAVE syndrome. The patient was discharged on an oral proton-pump inhibitor with instructions to follow-up outpatient with Gastroenterology. This case is presented as an example of a risk factor for acute exacerbation of a rare cause of UGIB. This patient presentation also represents an example of the importance of strict follow-up for those with risk factors for exacerbation of chronic GI conditions.


Pathological and Prognostic Impacts of FGFR2 Overexpression in Gastric Cancer: A Meta-Analysis.
Fibroblast growth factor receptor-2 (FGFR2) protein expression by immunohistochemistry has been reported in up to 60% of patients with gastric cancer (GC). However, the clicopathological impacts of high FGFR2 expression have not been consistent among studies. We conducted this meta-analysis to evaluate the pathological and prognostic significance of FGFR2 overexpression in patients with GC. A systematic search of the electronic databases including PubMed, PMC, EMBASE, and Google Scholar was performed. From ten studies, 4,294 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for pathological features and hazard ratios (HRs) with 95% CIs for overall survival according to the FGFR2 expression status. Compared with tumors showing low FGFR2 expression, GCs with FGFR2 overexpression revealed deeper depth of invasion (pT3-4) (OR = 2.63, 95% CI: 1.70-4.06, p < 0.0001), higher rate of lymph node metastasis (OR = 1.87, 95% CI: 1.31-2.67, p < 0.0001), and more advanced stage (III-IV) (OR = 1.78, 95% CI: 1.07-2.96, p = 0.03). In addition, patients with FGFR2-overexpressed GC showed significantly worse survival than those with FGFR2-low tumor (HR = 1.40, 95% CI: 1.25-1.58, p < 0.00001). In conclusion, this meta-analysis indicates that FGFR2 overexpression is associated with poor pathological features and prognosis in patients with GC.


Effect of supplementation of fennel seed powder on intake, growth performance, gut health and economics in goats.
The aim of this study was to evaluate the effect of fennel seed powder (FSP) at varying levels on intake, growth, gut health, body condition, body measurements and economics in post weaned male goats. For this experiment a total of 30 post weaned male kids of Barbari goats with statistically similar body weight (P = 0.575) and age (3-4 months) were randomly distributed in three comparable groups each having 10 kids. Three groups viz. control (no supplementation), T1 (0.5% of DM in diet) and T2 (1.0% of DM in diet) were formed and the study continued up to 5 months. Statistical analysis of results showed significant effect of FSP supplementation on intake, growth, body condition, and gut health and body measurements in goats of treatment groups. Significantly highest body weight (BW), average daily gain (ADG) and dry matter intake (DMI) (P < 0.001) was reported in T2 group, followed by T1 than control group goats. Further, feed conversion ratio (FCR), feed conversion efficiency (FCE%) and body condition score of treatment groups (T1 and T2) was improved significantly (P < 0.001) than control group goats. However, FCR and FCE% in T1 and T2 differed non- significantly (P > 0.05). Analysis of fecal samples indicated significantly higher (P < 0.001) fecal dry matter (FDM%), fecal consistency score (FS) in T1 and T2 group than control group whereas parasitic fecal egg count per gram (EPG) was significantly lower in T1 and T2 group than control group. However, EPG in T1 and T2 differed non- significantly (P > 0.05). Body measures differed significantly (P < 0.05) among groups. Economic evaluation of FSP supplemented showed that T1 and T2 group fetched INR 462 and 501 per goat on selling over control group (1USD = 82.54 INR). It can be concluded from this study that supplementation of FSP @ 1.0% of DM in diet may economically improve intake, growth, gut health, body condition, body measurements and economics in post weaned male Barbari goats.


Denture identification using individual national identification number of Saudi Arabia: An innovative inclusion method of casted metal.
Forensic odontology is one of the branches of dentistry, which played a very important role in identification of individuals in accident, natural and mass disaster, and civil unrest and in genocide crimes. In the absence of natural teeth, marking or labeling of denture plays a vital role in the personal identification. Various types of marking or labeling methods are reported. However, many are not according to the criteria put forth by American Dental Association or other professional association. Majority of these techniques may be time consuming and expansive, may not be standardized, long lasting and do not permit the incorporation of a large amount of information. The aim of this study is to find out a denture identification technique that should be easy, less expensive, long lasting, and standardized. This article illustrates an inclusion denture casted metal technique of the individual national identification number printed in the patient's residence number or iquama or national identity card issued by the ministry of interior, Kingdom of Saudi Arabia is used as a denture marker in the lingual surface of mandibular denture. The label in this method is durable and can withstand high temperature, less chances of deterioration, visible radiographically, and provide all important information about individual that is standardized, reliable, and also accessible from any remote location. Hence, the proposed technique is an easy, less expensive, long lasting, radiographically visible, and standardized method of identification.


Continuous vs. Targeted Medication in Older Schizophrenic Outpatients.
The authors compared targeted as opposed to continuous neuroleptic medication for the treatment of older (over age 50) schizophrenic outpatients. Patients in the continuous medication group (n = 17) received maintenance neuroleptic medication throughout the 12-month study period. Those in the targeted group (n = 14) received medication only during periods of prodrome. Significantly fewer maintenance patients had at least one prodromal episode, and fewer experienced relapse, compared to the targeted medication group. No significant differences were found in the rate of hospitalization between the groups. Patients in the targeted group took, cumulatively, less medication. There were no significant differences between the two groups on measures of symptoms, side effects, or quality of life. A targeted medication approach was therefore judged inferior to maintenance medication for older schizophrenic outpatients.


A random amplified polymorphic DNA (RAPD) primer to assist the identification of a selected strain, aizu K-111 of Panax ginseng and the sequence amplified.
Panax ginseng is widely used as a Chinese medicine, but it takes a long time to reach harvest and to establish its qualified strains. In the course of searching high quality Panax ginseng, we found a useful random amplified polymorphic DNA (RAPD) primer, which showed a 725 base pair band for a selected elite strain Aizu K-111 (now called Kaishusan) including its cultured tissues, while the other strains did not necessarily show this band. We sequenced the DNA fragment amplified and designed primers to improve electrophoretic profiles, based on the sequence.


Screening and treatment of childhood type 1 and type 2 diabetes mellitus in Japan.
A large number of children with type 2 diabetes mellitus (T2DM) and a small number with a slowly progressive form of type 1 diabetes mellitus (SPT1DM) have been detected by a urine glucose screening program conducted at Japanese schools since 1974. The incidence of T2DM in children has increased over the last 3 decades and is estimated to be approximately 3.0/100,000/year, which is twice as that of T1DM. In contrast, SPT1DM in children is more prevalent in Asians, particularly Japanese, and exhibits unique clinical features that differ from those of the rapid onset form of T1DM, usually seen in Caucasians. In the first part of this review, we summarize the urine glucose screening program conducted at Japanese schools and clinical characteristics of the 2 diabetic subtypes in Japanese children. In recent years, concerns regarding childhood diabetes in Asian countries, including Japan, have risen, and medical care for the same is exceedingly developing. Intensive insulin therapy such as basal-bolus therapy by multiple daily insulin injections and pump therapy, both using insulin analogs, has been increasing in pediatric patients with T1DM. In addition, various antidiabetic medications have been introduced for children with T2DM. In the second part of this review, we describe treatment of Japanese children with T1DM and T2DM and changes in glycemic control as a result of development of the treatment.


Alendronate (ALN) combined with osteoprotegerin (OPG) significantly improves mechanical properties of long bone than the single use of ALN or OPG in the ovariectomized rats.
Alendronate (ALN) is the most common form of bisphosphonates used for the treatment of osteoporosis. Osteoprotegerin (OPG) has also been shown to reduce osteoporotic changes in both humans and experimental animals after systemic administration. The aim of this current study was to test if the anti-resorption effects of ALN may be enhanced when used in combination with OPG. To investigate the effects of ALN, OPG or combined on bone mass and bone mechanical properties in ovariectomized (OVX) rats. OVX rats were treated with ALN, OPG-Fc, or OPG-Fc and ALN. Biochemical markers, trabecular bone mass, biomechanics, histomorphometry and RANKL expression in the bone tissues were examined following the treatments. The treatment of ALN, OPG-Fc and ALN+OPG-Fc all prevented bone loss in the OVX-rats, there was no statistical difference among the three treatment groups in terms of vertebrae BMD, mineralizing surfaces, mineral apposition rate, BFR/BS. The ALN+OPG-Fc treatment group had significantly increased the mechanical strength of lumber vertebral bodies and femoral shafts when compared to the ALN and OPG-Fc treatment groups. The RANKL protein expression in the vertebral bones was significantly decreased in the ALN and ALN+OPG-Fc treatment groups, suggesting the combined use of OPG-Fc and ALN might have amplified inhibition of bone resorption through inhibiting RANKL-dependent osteoclastogenesis. The combined use of OPG-Fc and ALN may be a new treatment strategy for reversing bone loss and restoring bone quality in osteoprotic disorders.


Long-term survival of patients with intermediate and high grade lymphoma treated with COMLA/ABP.
Between September 1983 and April 1985, 15 patients with previously untreated intermediate and high grade lymphoma were treated with COMLA/ABP (cyclophosphamide, vincristine, cytarabine, methotrexate, leucovorin, adriamycin, bleomycin, prednisone). There were nine males and six females; age ranged between 36 and 77 years (median, 58). Histologic diagnoses included five patients with diffuse large cell, six patients with immunoblastic, three patients with composite, and one patient with follicular large cell with diffuse areas. Following therapy, 10 patients (67%; 95% confidence interval (Cl), 43-91%) achieved a complete remission (CR) including five of six patients with immunoblastic; three patients (20%) had a partial remission, and two patients (14%) had no response. Toxicity was acceptable. After a minimum follow up of 4 years, there has been only one relapse which occurred 7 months after CR. The 4-year survival for all 15 patients is 65% (95% Cl, 40-89%). The COMLA/APB program produced a high rate of complete and durable remissions especially among patients with immunoblastic lymphoma.


Beliefs Related to Mental Illness Stigma Among California Young Adults.
This study examines mental illness stigma and related beliefs among young adults in California, especially whether levels of stigma are higher or lower than those observed in older adults.


Mortality in dementia is predicted by older age of onset and cognitive presentation.
Survival information in dementia is important for future planning and service provision. There have been limited Australian data investigating survival duration and risk factors associated with mortality in younger-onset dementia. This was a cross-sectional retrospective study investigating survival in inpatients with a diagnosis of dementia admitted to a tertiary neuropsychiatry service from 1991 to 2014. The Australian Institute of Health and Welfare National Death Index was used to obtain mortality information. A total of 468 inpatients were identified, of which 75% had symptom onset at ⩽65 years of age (defined as younger-onset dementia). Dementia was categorised into four subtypes, Alzheimer's dementia, frontotemporal dementia, vascular dementia and other dementias; 72% of the patients had died. Overall median survival duration was 10.6 years with no significant differences in duration within the dementia subtypes (p = 0.174). Survival in older-onset dementia (symptom onset at >65 years of age) was about half of that in younger-onset dementia (median survival 6.3 years compared to 12.7 years, respectively). Independent predictors of mortality were having older-onset dementia (hazard ratio: 3.2) and having initial presenting symptoms being cognitive in nature (hazard ratio: 1.5). Females with an older-onset dementia had longer survival compared to males with an older-onset dementia, and this was reversed for younger-onset dementia. Older-onset dementia and younger-onset dementia conferred 3 and 6 times, respectively, increased risk of death compared to the general population. This is the largest Australian study to date investigating survival and risk factors to mortality in dementia. We report important clinical information to patients with dementia and their families about prognosis which will assist with future planning. Our findings suggest that for both older-onset dementia and younger-onset dementia, 'new onset' psychiatric symptoms precede the cognitive symptoms of a neurodegenerative process. This, and sex differences in survival depending on the age of onset of the dementia warrant further investigation.


Analysis of postoperative vaginal vault radiotherapy of stage I endometrial cancer with different radionuclides.
A total of 213 patients in stage I grade 1 endometrial cancer were treated postoperatively with either radium or caesium vaginal applicators. The rate of complication and the incidence of second malignancies were studied in both groups. The frequency of grades 2 and 3 vaginal complications was higher among patients treated with caesium applicators but not statistically significant. The observed number of second malignancies was significantly higher than expected in the radium-treated group, in which the observed number of second malignancies with distant location was also significantly higher than expected, which could not be found in the caesium group.


Time-of-flight neutral particle analyzer and calibration.
A time-of-flight diagnostic has been implemented on the Irvine field reversed configuration (IFRC) to obtain an energy distribution function from charge-exchanged neutral hydrogen. The diagnostic includes a 13 cm radius slotted disk rotating at 165 Hz in vacuum which chops the emitted neutrals at a rate of 26 kHz. In situ timing verification was performed with a dc xenon discharge lamp with an uncertainty less than 100 ns for a 38 micros chopping period. Energy calibration was accomplished with a singly ionized lithium source in the range of 300-1500 eV, achieving an average energy uncertainty, DeltaE/E, of 0.11. The diagnostic has measured neutrals in the range of 20-80 eV from the IFRC and the corresponding energy distribution function has been obtained.


A Library for fMRI Real-Time Processing Systems in Python (RTPSpy) With Comprehensive Online Noise Reduction, Fast and Accurate Anatomical Image Processing, and Online Processing Simulation.
Real-time fMRI (rtfMRI) has enormous potential for both mechanistic brain imaging studies or treatment-oriented neuromodulation. However, the adaption of rtfMRI has been limited due to technical difficulties in implementing an efficient computational framework. Here, we introduce a python library for real-time fMRI (rtfMRI) data processing systems, Real-Time Processing System in python (RTPSpy), to provide building blocks for a custom rtfMRI application with extensive and advanced functionalities. RTPSpy is a library package including (1) a fast, comprehensive, and flexible online fMRI image processing modules comparable to offline denoising, (2) utilities for fast and accurate anatomical image processing to define an anatomical target region, (3) a simulation system of online fMRI processing to optimize a pipeline and target signal calculation, (4) simple interface to an external application for feedback presentation, and (5) a boilerplate graphical user interface (GUI) integrating operations with RTPSpy library. The fast and accurate anatomical image processing utility wraps external tools, including FastSurfer, ANTs, and AFNI, to make tissue segmentation and region of interest masks. We confirmed that the quality of the output masks was comparable with FreeSurfer, and the anatomical image processing could complete in a few minutes. The modular nature of RTPSpy provides the ability to use it for a simulation analysis to optimize a processing pipeline and target signal calculation. We present a sample script for building a real-time processing pipeline and running a simulation using RTPSpy. The library also offers a simple signal exchange mechanism with an external application using a TCP/IP socket. While the main components of the RTPSpy are the library modules, we also provide a GUI class for easy access to the RTPSpy functions. The boilerplate GUI application provided with the package allows users to develop a customized rtfMRI application with minimum scripting labor. The limitations of the package as it relates to environment-specific implementations are discussed. These library components can be customized and can be used in parts. Taken together, RTPSpy is an efficient and adaptable option for developing rtfMRI applications. Code available at: https://github.com/mamisaki/RTPSpy.


Isolation of anti-inflammatory fractions and compounds from the root of Astragalus membranaceus.
Foot ulceration, if not treated properly, will eventually result in amputation. Inflammation may impede the wound healing process if not properly controlled. The root of Astragalus membranaceus (AR) is one of the Chinese herbs commonly found in Chinese herbal formulae used for treating foot ulcer. In this study, we aimed to identify the active fractions and/or compounds from AR aqueous extract, which are responsible for the anti-inflammatory effect using in vitro bioassay-guided fractionation. The anti-inflammatory effect was monitored by the inhibition of nitric oxide (NO) released from lipopolysaccharide-stimulated mouse macrophage RAW 264.7 cells after treated with AR aqueous extract or its fractions and isolated components. Two major active fractions (P2-3-2-2-2 and P2-3-2-2-3) were found to significantly inhibit NO production at 0.156 mg/mL (p < 0.01). In addition, three chemical components (formononetin, calycosin and astragaloside IV) were successfully isolated from P2-3-2-2-3. Only formononetin could significantly inhibit NO production (p < 0.01), whereas the other two components had no significant effects at concentrations ranging from 0.039 to 0.156 mg/mL. In conclusion, two major anti-inflammatory active fractions that may enhance wound healing were identified, and formononetin was one of the active ingredients in the active fractions.


Patient experiences in making PTSD treatment decisions.
Although there is a range of effective posttraumatic stress disorder (PTSD) treatments, the number of patients who receive those treatments is disappointingly low (Finley et al., 2015; Maguen et al., 2018). Very little research has examined the patient experience of deciding on a PTSD treatment option and how that experience influences treatment preference and selection. In a sample of 12 veterans and 10 providers, we recorded the sessions in which providers discussed PTSD treatment options with their patients and then interviewed patients to ask their impressions of those same sessions. Specifically, using qualitative analysis, we sought to understand (a) patient preferences and experiences of choosing a PTSD treatment option, (b) what information patients retain from treatment planning sessions, and (c) why patients chose a given treatment. Almost all the patients in this sample chose an evidence-based psychotherapy but could remember little about the options afterward. Patients reported that providers presented options neutrally and that they made shared decisions with their providers. Most could talk through their reasons for coming to a decision and felt comfortable with the decision, but decisions were often made heuristically rather than deliberatively. Surprisingly, a few patients had a hard time explaining why they chose a specific treatment, were not conscious of their exact reasons for choosing a treatment, or seemed unable to remember why they chose a treatment. We also noticed subtle ways in which providers' discussions influenced treatment choice. Implications for practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Metabolic reconstruction of the human pathogen Candida auris: using a cross-species approach for drug target prediction.
Candida auris is an emerging human pathogen, associated with antifungal drug resistance and hospital candidiasis outbreaks. In this work, we present iRV973, the first reconstructed Genome-scale metabolic model (GSMM) for C. auris. The model was manually curated and experimentally validated, being able to accurately predict the specific growth rate of C. auris and the utilization of several sole carbon and nitrogen sources. The model was compared to GSMMs available for other pathogenic Candida species and exploited as a platform for cross-species comparison, aiming the analysis of their metabolic features and the identification of potential new antifungal targets common to the most prevalent pathogenic Candida species. From a metabolic point of view, we were able to identify unique enzymes in C. auris in comparison with other Candida species, which may represent unique metabolic features. Additionally, 50 enzymes were identified as potential drug targets, given their essentiality in conditions mimicking human serum, common to all four different Candida models analysed. These enzymes represent interesting drug targets for antifungal therapy, including some known targets of antifungal agents used in clinical practice, but also new potential drug targets without any human homolog or drug association in Candida species.


The ouabain receptor in animal tissues and its endogenous ligand.
Cardiac glycosides bind to the Na+,K+-ATPase and inhibit its activity. Low concentrations (less than 10(-7) M) of ouabain stimulate the activity of Na+,K+-ATPase in whole homogenates of rat brain. The magnitude of this stimulation varies from 5 to 70%. The concentration of ouabain which induces maximal stimulation is also highly variable and ranges between 10(-9) to 10(-7) M. This stimulation may be explained by the presence of an endogenous ouabain-like compound (OLC) in the brain homogenate. Mammalian tissues and body fluids including brain, heart, kidney, plasma, urine and cerebrospinal fluid contain a unidentified OLC. An endogenous OLC was also demonstrated in toad skin and plasma. This compound was purified to homogeneity and identified using UV, NMR and Mass spectroscopies to be 3-hydroxy-14, 15-epoxy-20,22-dienolide glycoside (resibufogenin). Several reports have suggested that unsaturated fatty acids are the ouabain-like regulators of the Na+,K+-ATPase. Furthermore, Saline infusion to WKY rats, which was shown to increase OLC in the plasma causes also an elevation of free fatty acids. Thus, the interaction of fatty acids with several plasma membrane components was studied. Ouabain binding, opiate binding and binding to the beta-adrenergic receptor were all inhibited by micromolar concentrations of the unsaturated fatty acids, linoleic, oleic and arachidonic. Binding to the opiate receptor was inhibited with IC50 of 40-90 microM and binding to beta-adrenergic receptor with IC50 of 350-450 microM.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of Kinesitherapy on Balance Reactions in Patients with Ischemic Stroke in the Chronic Period.
The study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on balance reactions in patients with ischemic stroke in the chronic period (ISChP). A prospective, multicenter study with 56 patients with ISChP. Evaluation of balance reactions using Berg Balance Scale - BBS, includes implementation of 14 tasks with increasing difficulty reflecting the usual activities of everyday life. The first 5 assignments are used to assess the main balance potential and the remaining 9 (6th to 14th task) include more sophisticated balance tasks. The patients were found with a significant improvement in balance opportunities, according to the scale of Berg. Compared to initial data there is a significant increase in the number of points in the measured indicators for functional and static balance. In absolute terms, positive change is most pronounced during the 1st month with a level of significance of p <0.001. The applied specialized kinesitherapeutic methodology continued later as adapted exercise program at home, and significantly improved equilibrium reactions in patients with postural disorders because of ischemic stroke and is with a supportive prolonged exposure.


Reduction of Escherichia coli O157:H7 in Biofilms Using Bacteriophage BPECO 19.
Biofilm formation is a growing concern in the food industry. Escherichia coli O157:H7 is one of the most important foodborne pathogens that can persists in food and food-related environments and subsequently produce biofilms. The efficacy of bacteriophage BPECO 19 was evaluated against three E. coli O157:H7 strains in biofilms. Biofilms of the three E. coli O157:H7 strains were grown on abiotic (stainless steel, rubber, and minimum biofilm eradication concentration [MBECTM ] device) and biotic (lettuce) surfaces at different temperatures. The effectiveness of bacteriophage BPECO 19 in reducing preformed biofilms on these surfaces was further evaluated by treating the surfaces with a phage suspension (108 PFU/mL) for 2 h. The results indicated that the phage treatment significantly reduced (P < 0.05) the number of adhered cells in all the surfaces. Following phage treatment, the viability of adhered cells was reduced by ≥3 log CFU/cm2 , 2.4 log CFU/cm2 , and 3.1 log CFU/peg in biofilms grown on stainless steel, rubber, and the MBECTM device, respectively. Likewise, the phage treatment reduced cell viability by ≥2 log CFU/cm2 in biofilms grown on lettuce. Overall, these results suggested that bacteriophages such as BPECO 19 could be effective in reducing the viability of biofilm-adhered cells.


Clinical aspects of augmentation enterocystoplasties.
Augmentation enterocystoplasty was performed in 28 patients with tuberculous, interstitial, radiation and chronic bacterial cystitis and hypertonic neurogenic bladder. Better results were observed in tuberculous contracted bladders where the extent of bladder resection and the bowel segment used were not related to the surgical outcome. In the other forms, the ileocecal segment is preferable. In our experience patients with neurogenic bladder did not benefit from the procedure. Radiographic and urodynamic studies are valuable for an accurate follow-up; radioisotope scan is also useful in selected cases. Anatomical and surgical causes of failure are discussed. Pharmacologic treatment is useful in partial surgical failure and provides indications for further bladder neck surgery.


Renal mechanisms of salt-sensitive hypertension: contribution of two steroid receptor-associated pathways.
Although salt is a major environmental factor in the development of hypertension, the degree of salt sensitivity varies widely among individuals. The mechanisms responsible for this variation remain to be elucidated. Recent studies have revealed the involvement of two important signaling pathways in renal tubules that play key roles in electrolyte balance and the maintenance of normal blood pressure: the β2-adrenergic stimulant-glucocorticoid receptor (GR)-with-no-lysine kinase (WNK)4-Na(+)-Cl(-) cotransporter pathway, which is active in distal convoluted tubule (DCT)1, and the Ras-related C3 botulinum toxin substrate (Rac)1-mineralocorticoid receptor (MR) pathway, which is active in DCT2, connecting tubules, and collecting ducts. β2-Adrenergic stimulation due to increased renal sympathetic activity in obesity- and salt-induced hypertension suppresses histone deacetylase 8 activity via cAMP/PKA signaling, increasing the accessibility of GRs to the negative GR response element in the WNK4 promoter. This results in the suppression of WNK4 transcription followed by the activation of Na(+)-Cl(-) cotransporters in the DCT and elevated Na(+) retention and blood pressure upon salt loading. Rac1 activates MRs, even in the absence of ligand binding, with this activity increased in the presence of ligand. In salt-sensitive animals, Rac1 activation due to salt loading activates MRs in DCT2, connecting tubules, and collecting ducts. Thus, GRs and MRs are independently involved in two pathways responsible for renal Na(+) handling and salt-sensitive hypertension. These findings suggest novel therapeutic targets and may lead to the development of diagnostic tools to determine salt sensitivity in hypertensive patients.


A Simple Method for the Assessment of Fusarium Head Blight Resistance in Korean Wheat Seedlings Inoculated with Fusarium graminearum.
Fusarium head blight (FHB; scab) caused mainly by Fusarium graminearum is a devastating disease of wheat and barley around the world. FHB causes yield reductions and contamination of grain with trichothecene mycotoxins such as deoxynivalenol (DON) which are a major health concern for humans and animals. The objective of this research was to develop an easy seed or seedling inoculation assay, and to compare these assays with whole plant resistance of twenty-nine Korean winter wheat cultivars to FHB. The clip-dipping assay consists of cutting off the coleoptiles apex, dipping the coleoptiles apex in conidial suspension, covering in plastic bag for 3 days, and measuring the lengths of lesions 7 days after inoculation. There were significant cultivar differences after inoculation with F. graminearum in seedling relative to the controls. Correlation coefficients between the lesion lengths of clip-dipping inoculation and FHB Type II resistance from adult plants were significant (r=0.45; P<0.05). Results from two other seedling inoculation methods, spraying and pin-point inoculation, were not correlated with adult FHB resistance. Single linear correlation was not significant between seed germination assays (soaking and soak-dry) and FHB resistance (Type I and Type II), respectively. These results showed that clip-dipping inoculation method using F. graminearum may offer a real possibility of simple, rapid, and reliable for the early screening of FHB resistance in wheat.


The relationship between NMDA receptors and microwave-induced learning and memory impairment: a long-term observation on Wistar rats.
Abstract Purpose: To investigate whether high power microwave could cause continuous disorders to learning and memory in Wistar rats and to explore the underlying mechanisms. Eighty Wistar rats were exposed to a 2.856 GHz pulsed microwave source at a power density of 0 mW/cm(2) and 50 mW/cm(2) microwave for 6 min. The spatial memory ability, the structure of the hippocampus, contents of amino acids neurotransmitters in hippocampus and the expression of N-methyl-D-aspartic acid receptors (NMDAR) subunit 1, 2A and 2B (NR1, NR2A and NR2B) were detected at 1, 3, 6, 9, 12 and 18 months after microwave exposure. Our results showed that the microwave-exposed rats showed consistent deficiencies in spatial learning and memory. The level of amino acid neurotransmitters also decreased after microwave radiation. The ratio of glutamate (Glu) and gammaaminobutyric acid (GABA) significantly decreased at 6 months. Besides, the hippocampus showed varying degrees of degeneration of neurons, increased postsynaptic density and blurred synaptic clefts in the exposure group. The NR1 and NR2B expression showed a significant decrease, especially the NR2B expression. This study indicated that the content of amino acids neurotransmitters, the expression of NMDAR subunits and the variation of hippocampal structure might contribute to the long-term cognitive impairment after microwave exposure.


Should Immigration Status Information Be Included in a Patient's Health Record?
The documentation of immigration status in patient records poses a challenge to clinicians. On one hand, recording this social determinant of health can facilitate continuity of care and improved communication among clinicians. On the other, it might expose patients or their family members to immediate and unforeseen risks, such as being stigmatized and discriminated against by nonimmigrant-friendly clinicians or being exposed to immigration enforcement if staff contact immigration officials in violation of patient confidentiality. Patients may raise concerns about the purpose and risks of such documentation alongside fears about potential data sharing and violations of privacy and confidentiality. This commentary explores clinicians' options for documenting immigration status within the context of ethical, legal, and historical considerations in caring for stigmatized populations in changing political landscapes.