An evaluation of community pharmacies' actions under value-based payment.
To determine actions taken by community pharmacies to be successful under a value-based pharmacy program (VBPP). An exploratory sequential mixed methods approach was used to evaluate pharmacies participating in the VBPP, with qualitative data collected and analyzed in the first phase, followed by quantitative measurement through a 30-item survey instrument in the second phase. The qualitative data showed that participating pharmacies were more involved with adherence and cardiovascular and diabetes metrics than with other metrics. Depression metrics received the lowest overall involvement. For total cost of care, different approaches were used; 5 pharmacies used the dashboard to identify likely high-cost patients they could try to manage, and 4 pharmacies monitored adherence to avoid complications that could contribute to increased cost. For the survey response rate was 72.6% (n = 53). The mean perception of level of success was 53.06 ± 20.15 (mean ± SD). Activities with the highest priority were adherence (1.98 ± 0.97) and diabetes care (2.04 ± 0.83), and the activity with the lowest priority was depression care (3.60 ± 1.10). The most frequently mentioned challenge was time availability, and the most common improvement suggestion was better communication between the insurer and providers. In conclusion, this study found that community pharmacies were transforming their practices to be successful under a commercial value-based payment program. The pharmacies tended to build on care processes already established (e.g., medication adherence, patients with diabetes or cardiovascular conditions) and developed new processes to address emerging metrics and associated patient needs (e.g., collecting and documenting blood pressure and hemoglobin A1c levels). Future research is needed to identify best practices for patient care and pharmacy success under broad VBPPs such as the one studied here.


First molecular characterisation and expression analysis of a teleost thioredoxin-interacting protein (TXNIP) gene from rock bream (Oplegnathus fasciatus).
Thioredoxin-interacting protein (TXNIP) is an important regulator of glucose metabolism that functions by inhibiting cellular glucose uptake. The full-length rock bream (Oplegnathus fasciatus) TXNIP (RbTXNIP) cDNA (2499 bp) contains an open reading frame of 1188 bp encoding 396 amino acids. Furthermore, multiple alignments showed that the arrestin domain was well conserved among the other TXNIP sequences tested. RbTXNIP was predicted to contain a PxxP and PPxY motif. Phylogenetic analysis indicated that RbTXNIP is most closely related to Fugu rubripes TXNIP. RbTXNIP was expressed significantly in the RBC, intestine, and spleen. RbTXNIP mRNA expression was also examined in several tissues under conditions of bacterial and viral challenge. Generally, all tissues examined from fish infected with Streptococcus iniae, Edwardsiella tarda and red sea bream iridovirus (RSIV) showed significant downregulation in RbTXNIP expression compared to controls. However, RbTXNIP expression showed significant upregulation in the spleen and kidney after injection of recombinant rock bream TRx1 protein. These findings provide a molecular foundation for functional studies and applications in teleosts.


Simultaneous photocatalytic reduction of Cr(VI) and oxidation of bisphenol A induced by Fe(III)-OH complexes in water.
Simultaneously photocatalytic reduction of Cr(VI) and oxidation of bisphenol A (BPA) in aqueous solution in the presence of Fe(III)-OH complexes were investigated under a 250 W metal halide lamp (lambda>or=365 nm). Synergy effect of the simultaneous photocatalytic oxidation and reduction of both pollutants was achieved. The effects of initial pH value, initial concentration of BPA, Cr(VI) and Fe(III) were preliminarily investigated. The results showed that both photocatalytic reduction of Cr(VI) and degradation of BPA could occur simultaneously in the Fe(III)/Cr(VI)/BPA ternary system, and the rates of photocatalytic reduction of Cr(VI) and the oxidation of BPA were more rapid at a low pH range of 2.0-3.0. The increase of the initial concentration of Fe(III) was favorable to both photocatalytic reduction of Cr(VI) and oxidation of BPA. The reduction efficiency of Cr(VI) decreased with increasing initial concentrations of Cr(VI) and BPA, but the degradation efficiency of BPA was not changed obviously at different Cr(VI) concentrations.


Population Pharmacokinetic and Pharmacodynamic Modeling and Effects on Platelet Counts of Different Dosages of Eltrombopag in Chinese Patients With Chronic Primary Immune Thrombocytopenia.
This study characterized the population pharmacokinetic (pop-PK) and PK/pharmacodynamic (pop-PK/PD) properties of eltrombopag and evaluated platelet count (PLTC) response to different eltrombopag dosages through simulations in Chinese adult patients with chronic primary immune thrombocytopenia (cITP). Pop-PK and pop-PK/PD models were developed from Chinese patients with cITP. Model-based simulations were then performed to predict PLTC response. The pop-PK properties of eltrombopag were described by a 2-compartment model with first-order absorption and elimination and absorption lag time. Steady-state exposure in these Chinese patients was ~55% greater than that in non-East Asian patients. The pop-PK/PD properties of eltrombopag were described by a model with 4 transit compartments where the increase in platelet production rate was linearly related to the plasma eltrombopag concentration. Eleven percent of the patients were identified as nonresponders to eltrombopag. Simulations showed that ~70% to 80% of steady-state PLTC response was achieved at week 2, and the percentages of patients who achieved a PLTC of 50 to 150 × 10(9) cells/L were comparable between weeks 2 and 6 with 12.5-, 25-, 50-, and 75-mg once-daily dosing. The 25-mg once-daily dosage was associated with a more balanced response than were the 12.5-, 50-, and 75-mg once-daily dosages with regard to efficacy (percentages of patients with PLTC 50-150 × 10(9) cells/L, 27% vs 20%, 30%, and 30%, respectively) and the risk for thrombocytosis (percentages of patients with PLTC >250 × 10(9) cells/L, 4% vs 1%, 10%, and 16%). Simulations of PLTCs with the dose-titration regimen showed that ≥42% of patients achieved a PLTC 50 to 150 × 10(9) cells/L at week 6 or later, compared with ≤30% when the 12.5-, 25-, 50-, and 75-mg once-daily fixed doses were given. No more than 5% of patients who underwent dose titration had a PLTC >250 × 10(9) cells/L throughout 24 weeks of treatment, compared with 3%, 7%, 16%, and 24% when the once-daily fixed doses of eltrombopag were given. The pop-PK and pop-PK/PD properties of eltrombopag in these Chinese adult patients with cITP were adequately characterized in the present analyses. The modeling and simulation results support the eltrombopag dose-titration regimen, with 25 mg once daily as a starting dosage and a 2-week titration interval, in Chinese patients with cITP.


[Case report of the problem of diagnosis and therapy of mediastinal tumors with anterior venous obstruction].
At the instance of a patient with upper venous affluence blocking due to a space occupying process in the dorsal and medial mediastinum, the problems of differential diagnostics and therapy of this disease are discussed. In spite of intensive diagnostic efforts, the final diagnosis was only obtained at autopsy. A T-lymphoblastic non-Hodgkin-lymphoma was found.


Mechanical force induced DNA double-strand breaks: Ultrasound.
Since the application of ultrasound for clinical diagnosis and therapeutic purposes has been increased rapidly, the effects of exposure to ultrasound on DNA molecules were studied. In this chapter, we introduced various effects of DNA damages caused by different conditions of exposure of ultrasound. Ultrasound with different sound pressure and pulse transmission conditions have been applied in our study. We discussed the threshold of sound pressure of ultrasound-induced DNA damages. Different kinds of pulses of ultrasound and microbubbles' influences on DNA double-strand breaks were also shown.


Getting it right from the start: Attentional control settings without a history of target selection.
Observers can adopt attentional control settings that regulate how their attention is drawn to salient stimuli in the environment. Do observers choose their attentional control settings voluntarily, or are they primed in a bottom-up manner based on the stimuli that the observer has recently attended and responded to (i.e., target-selection history)? In the present experiment, we tested these two accounts using a long-term memory attentional control settings paradigm, in which participants memorized images of 18 common visual objects, and then searched for those objects in a spatial blink task. Unbeknownst to participants, we manipulated priming by dividing the set of target objects into two subsets: nine objects appeared frequently as targets in the spatial blink task (frequently primed objects), and nine infrequently (infrequently primed objects). We assessed attentional capture by presenting these objects as distractors in the spatial blink task and measuring their effect on task accuracy. We found that both subsets of objects captured attention more than non-studied objects, and frequently primed objects did not capture attention more than infrequently primed objects. Moreover, a follow-up analysis revealed that all studied objects captured attention, even before those objects had appeared as targets in the spatial blink task. These findings suggest that priming through target-selection history plays little-to-no role in long-term memory attentional control settings. Rather, these findings align with a growing body of evidence that attentional control settings are primarily implemented through voluntary control.


Prospective classification of Alzheimer's disease conversion from mild cognitive impairment.
Alzheimer's disease (AD) is emerging as a serious problem with the rapid aging of the population, but due to the unclear cause of the disease and the absence of therapy, appropriate preventive measures are the next best thing. For this reason, it is important to early detect whether the disease converts from mild cognitive impairment (MCI) which is a prodromal phase of AD. With the advance in brain imaging techniques, various machine learning algorithms have become able to predict the conversion from MCI to AD by learning brain atrophy patterns. However, at the time of diagnosis, it is difficult to distinguish between the conversion group and the non-conversion group of subjects because the difference between groups is small, but the within-group variability is large in brain images. After a certain period of time, the subjects of conversion group show significant brain atrophy, whereas subjects of non-conversion group show only subtle changes due to the normal aging effect. This difference on brain atrophy makes the brain images more discriminative for learning. Motivated by this, we propose a method to perform classification by projecting brain images into the future, namely prospective classification. The experiments on the Alzheimer's Disease Neuroimaging Initiative dataset show that the prospective classification outperforms ordinary classification. Moreover, the features of prospective classification indicate the brain regions that significantly influence the conversion from MCI to AD.


Preferential expression of an AAV-2 construct in NOS-positive interneurons following intrastriatal injection.
Most CNS studies using recombinant adeno-associated virus type 2 (rAAV-2) vectors have focused on gene delivery for the purpose of gene therapy. In the present study, we examined the feasibility of using rAAV-2 vectors to study the regulation of preprotachykinin-A (PPT-A) promoter activity in striatal medium spiny projection neurons. An rAAV-2 vector incorporating a PPT promoter fragment (shown previously to confer some cell-specificity of expression in vitro) coupled to a green fluorescent protein (GFP) reporter gene was stereotaxically injected into the rat striatum. Since medium spiny projection neurons represent the predominant neuronal type (90-95%) in the striatum, we predicted that the vast majority of GFP-expressing cells would be of this phenotype. Surprisingly, the transgene was actually expressed in a similar number of medium spiny projection neurons and interneurons, while glial expression of GFP was not observed. A preponderance of GFP-expressing interneurons was immunoreactive for the marker neuronal nitric oxide synthase (nNOS). Our results suggest that viral vector-related events that occur during transduction are the determining factor in the pattern of transgene expression observed, while the influence of the transgene promoter appears to be secondary, at least under the conditions employed.


Myelination in coculture of established neuronal and Schwann cell lines.
Establishing stable coculture systems with neuronal and Schwann cell lines has been considered difficult, presumably because of their high proliferative activity and phenotypic differences from primary cultured cells. The present study is aimed at developing methods for myelin formation under coculture of the neural crest-derived pheochromocytoma cell line PC12 and the immortalized adult rat Schwann cell line IFRS1. Prior to coculture, PC12 cells were seeded at low density (3 × 10(2)/cm(2)) and maintained in serum-free medium with N2 supplement, ascorbic acid (50 μg/ml), and nerve growth factor (NGF) (50 ng/ml) for a week. Exposure to such a NGF-rich environment with minimum nutrients accelerated differentiation and neurite extension, but not proliferation, of PC12 cells. When IFRS1 cells were added to NGF-primed PC12 cells, the cell density ratio of PC12 cells to IFRS1 cells was adjusted from 1:50 to 1:100. The cocultured cells were then maintained in serum-free medium with B27 supplement, ascorbic acid (50 μg/ml), NGF (10 ng/ml), and recombinant soluble neuregulin-1 type III (25 ng/ml). Myelin formation was illustrated by light and electron microscopy performed at day 28 of coculture. The stable PC12-IFRS1 coculture system is free of technical and ethical problems arising from the primary culture and can be a valuable tool to study peripheral nerve degeneration and regeneration.


Administration of anti-interleukin 18 antibody fails to inhibit development of dermatitis in atopic dermatitis-model mice NC/Nga.
Interleukin (IL)-18 has been shown to activate basophils to produce histamine and IL-4 and to induce naive T cells to differentiate into T-helper (Th) 2 cells. However, when expressed together with IL-12, IL-18 induces Th1 cell development and inhibits IgE synthesis. Previously we reported that serum IL-18 levels were elevated in the sera from atopic dermatitis-model mice NC/Nga, prior to the onset and during the development of dermatitis. We studied whether neutralization of IL-18 activity might affect dermatitis in NC/Nga mice, to investigate the role of IL-18 on dermatitis. NC/Nga mice were given weekly anti-IL-18 antibody starting at 5 weeks of age to 13 weeks and development of dermatitis, scratching behaviour and serum IgE concentrations were evaluated. Continuous injections of anti-IL-18 antibody failed to inhibit the onset and development of dermatitis and IgE elevation. The treatment, rather, tended to lead to an exacerbation of dermatitis and scratching behaviour. In addition, the administration of anti-IL-18 antibody did not ameliorate the responsiveness of lymphocytes to IL-4, which was previously demonstrated as an immunological abnormality in the mouse. This study demonstrates that, at least in NC/Nga mice, IL-18, although excessively expressed before the onset of dermatitis, shows antiallergic actions.


Optimal and central-place foraging theory applied to a desert harvester ant, Pogonomyrmex californicus.
Certain predictions of optimal- and central place-foraging theory were tested on the desert harvester ant, Pogonomyrmex californicus. Colonies were offered three different sizes of oat seed and found to maximize net energy intake (ei) over time (t i ) by harvesting the seed sizes with the highest e i /t i rank. Two aspects of t i were measured that were assumed constant in previous studies. The handling components of t i (time required to manipulate the seed and travel time back to the colony with the food) were measured and found to be positively correlated with seed size. The manipulation success rate (the percentage of handled seeds successfully picked up) decreased with increased seed size. These results point out how important it is to measure all parameters of e i /t i rather than to assume constancy with both prey type and foraging distance. The relative abundance of less preferred food types was important in determining the proportion of preferred types in the diet. The food supply of eight colonies was manipulated experimentally over a 25-day period. Four "deprived" colonies were constrained within aluminum enclosures to prevented foraging. The remaining four "satiated" colonies were given food ad libitum. The niche breadths of the treated colonies were then compared to controls, but found not to differ significantly. Seed baits were offered at three distances from the colony to test whether selectivity increased with disance. Contrary to theoretical predictions, all colonies harcested about the same proportion of each seed size at each distance.


On the relation between Pandemic Disease Outbreak News and Crude oil, Gold, Gold mining, Silver and Energy Markets.
Fear of the disease outbreak news (DONs) has shocked commodity markets and raised the likelihood of economic uncertainty and recession globally. This article examines the unprecedented overreaction of investors sentiments in the commodities such as Crude oil, Gold, Gold Mining, Silver, and the Energy sector. The deadly effects of DONs-COVID-19 in the commodities market have been the worst in history; it appeared the first time higher than the common stock's volatility. Covid-19 induced economic uncertainty has impacted severely through all commodities except the safe-haven Gold (GVZ). Importantly, ETF Options based Implied Volatility Index of Crude (OVX), Silver (VXSLV), and Energy (VXXLE) stocks have crossed the peak level what it was prevailing during the global financial crisis 2008. The unparalleled upsurge of the implied volatility index across all commodities indicates higher demand for the hedge funds to protects the commodity portfolio. ETF options on the commodity act as the best hedge against market uncertainty. Overburden on the put option results in an increased risk premium, henceforth higher expected volatility. ETF options truly measure the investor's fear of predominant in the commodity market.


Sex differences in the polygenic architecture of hearing problems in adults.
Hearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated by large-scale genetic studies. Leveraging the UK Biobank, the Nurses' Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program, we conducted a comprehensive genome-wide investigation of HP in 748,668 adult participants (discovery N = 501,825; replication N = 226,043; cross-ancestry replication N = 20,800). We leveraged the GWAS findings to characterize HP polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically correlated traits, and gene interactions with HP environmental risk factors. We identified 54 risk loci and demonstrated that HP polygenic risk is shared across ancestry groups. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HP pathogenesis. The sex-stratified analyses showed several additional associations related to peripheral hormonally regulated tissues reflecting a potential role of estrogen in hearing function. This evidence was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HP associations. Additionally, the genetically informed causal inference analysis showed that HP is linked to many physical and mental health outcomes. The results provide many novel insights into the biology and epidemiology of HP in adults. Our sex-specific analyses and transcriptomic associations highlighted molecular pathways that may be targeted for drug development or repurposing. Additionally, the potential causal relationships identified may support novel preventive screening programs to identify individuals at risk.


Characteristics of nephropathy in severely obese Japanese patients complicated with type 2 diabetes mellitus: a cross-sectional cohort study.
We aimed to investigate the characteristics of kidney disease in severely obese Japanese patients with type 2 diabetes mellitus (T2DM). This was a cross-sectional study of severely obese patients (body mass index ≥35 kg/m2) with T2DM treated at Jinnouchi Hospital, Kumamoto, Japan. A total of 3128 T2DM patients visited the hospital during the survey period, of whom 55 patients (1.7%) were severely obese and 50 patients were enrolled. In terms of diabetic nephropathy (DN), twenty-five patients were stage 1 (non-DN, 50.0%), sixteen were stage 2 (32.0%), five were stage 3 (10.0%), and four were stage 4 (8.0%). There were significant differences in the presence of urinary occult blood (P = 0.01) and history of cardiovascular disease (CVD) (P = 0.04) between patients with DN (stages 2-4) and those without DN (stage 1). The presence of urinary occult blood (odds ratio [OR], 4.96; 95% confidence interval, 1.32-18.6; P = 0.02) was significantly associated with the presence of DN according to multivariate logistic regression analysis with forced inclusion of age, sex, and CVD history. Urinary occult blood may be a significant independent factor associated with the presence of nephropathy in severely obese Japanese patients with T2DM. The presence of urinary occult blood could thus be an important pathogenic factor in obesity-related nephropathy in patients with T2DM.


The role of Mycoplasma ovipneumoniae and Mycoplasma arginini in the respiratory mycoplasmosis of sheep and goats in Italy: Correlation of molecular data with histopathological features.
Mycoplasma infections are commonly found in the respiratory system of small ruminants; the species most commonly detected are Mycoplasma ovipneumoniae and Mycoplasma arginini, associated with the so-called "atypical non-progressive pneumonia". The pathogenic role of M. ovipneumoniae in pneumonia has been demonstrated in sheep but still needs to be verified in goats; on the other hand, the role of M. arginini in sheep is not well understood, while in goats seems to be of low pathogenic value. The present study aims to investigate the aetiology of pneumonia in sheep and goats that died from respiratory disease using anatomopathological, histopathological, and molecular investigations and to clarify the role of respiratory mycoplasmas by the association of molecular data with histopathological features. First, to better understand which histological changes are actually suggestive of atypical pneumonia in sheep and goats, the study identified the histological lesions significantly associated with Mycoplasma spp. infection. Then, the histological score of lesions considered suggestive of atypical pneumonia was used to estimate the pathogenicity of each mycoplasma detected. The results showed that M. ovipneumoniae and M. arginini (alone or in mixed infections) are pathogenic both in sheep, as well as in goats with similar histology and severity of lesions. Moreover, young animals were statistically more susceptible to M.ovipneumoniae and M. arginini infection than adults. Animals appeared more at risk to the development of M. ovipneumoniae and M. arginini infection in summer.


The effect of solar UVB doses and vitamin D production, skin cancer action spectra, and smoking in explaining links between skin cancers and solid tumours.
The report of differences between skin cancer rates and solid tumours in sunny versus less sunny countries [Tuohimaa P, Pukkala E, Scelo G, et al. Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: Vitamin D as a possible explanation. Eur J Cancer 2007; 43: 1701-12] raised some important questions regarding the roles of solar ultraviolet (UV) irradiance and cancer risk. The findings can likely be explained based on the effects of UVB dose on cancer risk, the action spectra of different skin cancers, the amount of skin exposed, and the differential effects of smoking on cancer risk. Solar UVB has been found inversely correlated with about 20 types of cancer in ecological and cohort studies in sunny countries. Vitamin D and calcium were recently found to greatly reduce cancer incidence in a prospective double-blind study. Epidemiological studies suggest that the action spectra for skin cancers vary, with solar UVB most important for squamous cell carcinoma, UVA most important for melanoma, and both important for basal cell carcinoma. These differences may explain the different standardised incidence ratios for solid tumours with respect to the different skin cancers in sunny countries. Smoking has been reported as a risk factor for non-melanoma skin cancers, but has been found inversely correlated with melanoma, which may explain some of the differences in standardised incidence ratios for solid tumours linked to smoking with respect to type of skin cancer. In Nordic countries, less skin is generally exposed (in head and neck regions, the most frequent sites of squamous cell carcinoma) resulting in reduced vitamin D production.


A business model for managing system change through strategic financing and performance indicators: a case study.
This article describes how a system of care operated by a county government agency used a fiscal crisis as the opportunity to reform its children's system. A cross-system response to the crisis is outlined that includes a system of care framework coupled with a business model, inter-departmental collaboration and leadership, the use of strategic reinvestment strategies, and a quality improvement system that focuses on key indicators. Implementation of the system change is described with a specific focus on cross-system entry points, financing strategies that re-allocate funds from deep-end programs to community-based services, and management oversight through the use of performance indicators to monitor and support effectiveness. This article examines the results of the system change, including the diversion of youth from system penetration, the reduction in residential treatment bed days, the re-allocation of these savings to community-based services, and the outcomes of children who were diverted from residential care and served in the community. The article offers a number of recommendations for other communities contemplating system change.


Effect of TLR3/dsRNA complex inhibitor on Poly(I:C)-induced airway inflammation in Swiss albino mice.
Rhinovirus infection frequently causes COPD and asthma exacerbations. Impaired anti-viral signaling and reduced viral clearance have both been seen in sick bronchial epithelium, potentially increasing exacerbations. Polyinosinic:polycytidylic acid (Poly(I:C)), a Toll-like receptor-3 (TLR3) ligand, has been shown to cause a viral exacerbation of severe asthma by detecting double-stranded RNA (dsRNA). The purpose of this work was to determine the effect of a TLR3/dsRNA complex inhibitor-Calbiochem drug in the prevention of Poly(I:C)-induced airway inflammation following TLR3 activation and to uncover a potential pathway for the cure of asthma through TLR3 inhibition. Mice were sensitized with Poly(I:C) as an asthma model before being challenged by PBS and ovalbumin (OVA) chemicals. The mice were administered a TLR3/dsRNA complex inhibitor. Throughout the trial, the mice's body weight was measured after each dosage. Biochemical methods are used to analyze the protein as well as enzyme composition in airway tissues. BALF specimens are stained using Giemsa to identify inflammatory cells and lung histopathology to determine morphological abnormalities in lung tissues. By using the ELISA approach, cytokine levels such as TNF-α, IL-13, IL-6, IL-5, and IgE antibody expression in lung tissue and blood serum were assessed. TLR3/dsRNA complex inhibitor drug significantly lowered the number of cells in BALF and also on Giemsa staining slides. It also downregulated the level of TNF-α and IL-6 in contrast to OVA and Poly(I:C) administered in animals. A TLR3/dsRNA complex inhibitor decreased the fraction of oxidative stress markers (MDA, GSH, GPx, and CAT) in lung tissues while keeping the mice's body weight constant during the treatment period. By decreasing alveoli, bronchial narrowing, smooth muscle hypertrophy, and granulocyte levels, the TLR3/dsRNA complex blocker significantly reduced the histopathological damage caused by OVA and Poly(I:C) compounds. In an animal model utilizing ovalbumin, TLR3/dsRNA complex inhibitors similarly reduced the bronchial damage produced by Poly(I:C). A novel TLR3/dsRNA complex inhibitor is expected to be employed in clinical studies since it suppresses airway inflammation without inducing antiviral approach resistance.


The contribution of group prenatal care to maternal psychological health outcomes: A systematic review.
Poor mental health remains a significant cause of morbidity for childbearing women globally. Group care has been shown to be effective in reducing select clinical outcomes, e.g., the rate of preterm birth, but less is known about the effect of Group Prenatal Care (GPC) on mental health outcomes of stress, depression and anxiety in pregnant women. To conduct a systematic review of the current evidence of the effect of group pregnancy care on mental health and wellbeing outcomes (i.e., stress, depression and/or anxiety) in childbearing women. A comprehensive search of published studies in Medline, PsychInfo, CINAHL, ProQuest databases, ClinicalTrials.gov and Google Scholar. Databases were systematically searched without publication period restriction until Feb 2020. Inclusion criteria were randomized controlled trials (including quasi-experimental) and observational studies comparing group care with standard pregnancy care. Included were studies published in English, whose primary outcome measures were stress, depression and/or anxiety. Nine studies met the inclusion criteria, five randomized controlled trials and four observational studies, involving 1585 women (39%) in GPC and 2456 women (61%) in standard (individual) pregnancy care. Although evidence is limited, where targeted education was integrated into the group pregnancy care model, significant reductions in depressive symptoms were observed. In addition, secondary analysis across several studies identified a subset of GPC women, i.e., higher risk for psychological symptoms, who reported a decrease in their depression, stress and anxiety symptoms, postpartum. Due to the diversity of group care structure and content and the lack of outcomes measures universally reported, a comprehensive meta-analysis could not be performed. The evidence suggests improvements in some markers of psychological health outcomes with group pregnancy care. Future research should involve larger well-designed studies encompassing cross-population data using a validated scale that is comparable across diverse childbearing populations and clinical settings to better understand the impact of group pregnancy care.


Gastric Cancer Surgery in the US: a Contemporary Trend Analysis of Lymphadenectomy and the Impact of Minimally Invasive Approaches.
The National Comprehensive Cancer Network guidelines recommend harvesting 16 or more lymph nodes for the adequate staging of gastric adenocarcinoma. This study examines the rate of adequate lymphadenectomy over recent years, its predictors, and its impact on overall survival(OS). The National Cancer Database was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression, Kaplan-Meier survival plots, and Cox proportional hazard regression were utilized. A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Only 50.5% of the patients underwent a lymphadenectomy of ≥ 16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (p < .0001). The main independent predictors of adequate lymphadenectomy included high-volume facility with ≥ 31 gastrectomies/year (OR: 2.71; 95%CI:2.46-2.99), surgery between 2015-2019 (OR: 1.68; 95%CI: 1.60-1.75), and preoperative chemotherapy (OR:1.49; 95%CI:1.41-1.58). Patients with adequate lymphadenectomy had better OS than patients who did not: median survival: 59 versus 43 months (Log-Rank: p < .0001). Adequate lymphadenectomy was independently associated with improved OS (HR:0.79; 95%CI:0.77-0.81). Laparoscopic and robotic gastrectomies were independently associated with adequate lymphadenectomy compared to open, OR: 1.11, 95%CI:1.05-1.18 and OR: 1.24, 95%CI:1.13-1.35, respectively. Although the rate of adequate lymphadenectomy improved over the study period, a large number of patients still lacked adequate lymph node dissection, negatively impacting their OS despite multimodality therapy. Laparoscopic and robotic surgeries were associated with a significantly higher rate of lymphadenectomy ≥ 16 nodes.


Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome.
Nager syndrome, first described more than 60 years ago, is the archetype of a class of disorders called the acrofacial dysostoses, which are characterized by craniofacial and limb malformations. Despite intensive efforts, no gene for Nager syndrome has yet been identified. In an international collaboration, FORGE Canada and the National Institutes of Health Centers for Mendelian Genomics used exome sequencing as a discovery tool and found that mutations in SF3B4, a component of the U2 pre-mRNA spliceosomal complex, cause Nager syndrome. After Sanger sequencing of SF3B4 in a validation cohort, 20 of 35 (57%) families affected by Nager syndrome had 1 of 18 different mutations, nearly all of which were frameshifts. These results suggest that most cases of Nager syndrome are caused by haploinsufficiency of SF3B4. Our findings add Nager syndrome to a growing list of disorders caused by mutations in genes that encode major components of the spliceosome and also highlight the synergistic potential of international collaboration when exome sequencing is applied in the search for genes responsible for rare Mendelian phenotypes.


Confessions of a baboon watcher: from inside to outside the paradigm.
In this "tale" I summarize the major landmarks of my 50-year career watching wild olive baboons (Papio anubis). I review some major discoveries, like baboon hunting and baboon social strategies of competition and defense, that only a creature with a "mind" could manage. My efforts expanded beyond science to include community-based conservation because quite early on these baboons experienced many of the threats of the Anthropocene. My research expanded to include studying crop-raiding by naïve groups of baboons, the first scientific translocation of a primate species, and a detour to study the invasion of a non-indigenous cactus, Opuntia stricta. Throughout I worked with local communities to find solutions to problems that the baboons created, and also to develop new options for their livelihoods. As the baboon research became a long-term project, it depended on a team of Kenyan research assistants who made possible the simultaneous monitoring of up to six baboon troops as well as extensive ecological monitoring. Knowing the ecology, including the impact of the sedentarization of pastoralists in the area, meant we could interpret the process of invasion by a non-indigenous cactus for the first time. Ecological periods allowed comparisons of the same troop over time and different baboon groups during the same ecological phase. Although I began my work before hypothesis testing was the preferred approach, once the paradigm changed, I continued to study and learn what matters to baboons from their perspective. As a result of observing them for 50 years, the baboons showed me that evolution often does not work the way that I had been taught, and it took all my detours and studies to convince me that anecdotes, when they are systematic and comparative, are not stories to be discounted, but evidence, much like Darwin's natural history. Natural history can reassemble the pieces that quantitative hypothesis testing has teased apart to provide its larger meaning. Today, the lone scientist, like me, is an anachronism because no one person has expertise in the many fields needed to understand and save the primates we care about.


Use of an autologous antigen in the serologic testing of patients with erythema migrans of Lyme disease.
We attempted to detect an early rise in antibody titers to Borrelia burgdorferi in the serum of patients with erythema migrans of Lyme disease by utilizing B. burgdorferi isolates obtained from patients' own skin lesions instead of the B31 reference strain. B. burgdorferi was isolated from nine of 23 skin biopsy specimens submitted for culture. Elevated antibody titers were not detected in any of the 23 acute serum samples by immunofluorescence assay. The antigens derived from patient isolates were no more effective than the reference strain in detecting antibodies in patients with early Lyme disease.


Alteration of signal transduction in T cells from cancer patients.
The progressive growth of tumor induces a major alteration in the immune response which could have significant deleterious consequences on the outcome of immunotherapeutic strategies. A more complete understanding of the mechanisms involved and the clinical consequences of these alterations is necessary to determine the importance of such changes. It is possible however, that the analysis of the TCR sigma chain or other signal transduction elements can be a more informative way to monitor the therapeutic effects of a particular treatment than the functional immunologic assays on peripheral blood lymphocytes used presently. Ultimately understanding this phenomenon could help determine the treatment approaches that would prevent or reverse the state of altered immune response, allowing for the development of more effective cancer treatments. It is clear that there are a number of barriers to successful immunotherapy (Table 4-1). Each difficulty has a number of potential solutions. It seem likely that as each of these known barriers is overcome, a larger number of patients will benefit than do now from the current generation of treatment approaches. Of course, it is also likely that there are additional barriers to success yet to be uncovered. It is only through careful observation and monitoring of the clinical effects of our interventions that the remaining obstacles will be defined. And it is only through the close interaction of the laboratory and the clinic that novel solutions will be devised.


Structural analysis revealed a novel conformation of the NTRC reductase domain from Chlamydomonas reinhardtii.
In plant chloroplasts, thiol regulation is driven by two systems. One relies on the activity of thioredoxins through their light dependent reduction by ferredoxin via a ferredoxin-thioredoxin reductase (FTR). In the other system, a NADPH-dependent redox regulation is driven by a NADPH-thioredoxin reductase C (NTRC). While the thioredoxin system has been deeply studied, a more thorough understanding of the function of this plant specific NTRC is desirable. NTRC is a single polypeptide harbouring a thioredoxin domain (Trx) at the C-terminus of a NADPH-dependent Thioredoxin reductase (TrxR). To provide functional and structural insights, we studied the crystal structure of the TrxR domain of the NTRC from Chlamydomonas reinhardtii (CrNTRC, Cre01.g054150.t1.2) and its Cys136Ser (C136S) mutant, which is characterized by the mutation of the resolving cysteine in the active site of the TrxR domain. Furthermore, we confirmed the role of NTRC as electron donor for 2-Cys peroxiredoxin (PRX) also in C. reinhardtii. The structural data of TrxR were employed to develop a scheme of action which addresses electron transfer between TrxR and Trx of NTRC and between NTRC and its substrates.


Effect of calcium and carbonate concentrations on anionic membrane fouling during electrodialysis.
A previous study on electrodialysis of calcium and carbonate high concentration solutions demonstrated that calcium migrated through the cation-exchange membrane (CEM) was blocked by the anion-exchange membrane (AEM) where it formed another fouling. The aim of the present work was to complete the identification of the deposit formed on AEM during electrodialysis and to characterize its physical structure at the interface of the membrane. No fouling was found on the anionic membranes treated without calcium chloride in presence of sodium carbonate, while membranes used during ED process of solutions containing calcium chloride and sodium carbonate were slightly fouled. A thin layer of precipitates was observed on the anionic membrane surface. The appearance of precipitates was typical of a crystalline substance. The size and form of crystal increased in proportion to the concentration of calcium chloride in solution. Large and cubic crystals were the best defined on the membrane treated at 1600 mg/L of CaCl2. The precipitate was identified as calcium hydroxide. However, this fouling was not found to affect significantly the electrical conductivity and the thickness of the membranes. Furthermore, the fouling formed was reversible.


Resolving the Seeming Contradiction between the Superior Rate Capability of Prussian Blue Analogues and the Extremely Slow Ionic Diffusion.
The superior rate capabilities of metal ion battery materials based on Prussian blue analogues (PBAs) are almost exclusively ascribed to the extremely fast solid-state ionic diffusion, which is possible due to structural voids and spacious three-dimensional channels in PBA structures. We performed a detailed electroanalytical study of alkali ion diffusivities in nanosized cation-rich and cation-poor PBAs obtained as particles or electrodeposited films in both aqueous and non-aqueous media, which resulted in a solid conclusion about the exceptionally slow ionic transport. We show that the impressive rate capability of PBA materials is determined solely by the small size of the primary particles of PBAs, while the apparent diffusion coefficients are 3-5 orders of magnitude lower than those reported in earlier studies. Our finding calls for a reconsideration of the apparent facility of ionic transport in PBA materials and deeper analysis of the charge carrier-host interactions in PBAs.


Correlation of immunogenicity with suppression of lymphocyte adenosine 3',5'-monophosphate-dependent protein kinase.
Cyclic-AMP-dependent protein kinase activity was depressed in whole spleen as well as in isolated splenic lymphocytes from 3-methylcholanthrene (MCA), R3230 AdCa mammary adenocarcinoma, N-hydroxy-2-acetylaminofluorene, and 4-dimethylaminoazobenzene (DMAAB) tumor-bearing Fischer rats as compared to control animals. The magnitude of depression increased with the immunogenicity of the tumor. The depressed enzyme activity was the result of a reduced Vmax for adenosine 3',5'-monophosphate (cAMP)-stimulated histone phosphorylation.


Crystal structure of 2,6-bis-(3-hy-droxy-3-methyl-but-1-yn-1-yl)pyridine monohydrate.
In the title pyridine derivative, C15H17NO2·H2O, the two OH groups are oriented in directions opposite to each other with respect to the plane of the pyridine ring. In the crystal, hydrogen bonds between the pyridine mol-ecule and the water mol-ecule, viz. Ohy-droxy-H⋯Owater, Ohy-droxy-H⋯Ohy-droxy, Owater-H⋯Ohy-droxy and Owater-H···Npyridine, result in the formation of a ribbon-like structure running along [011].


NeuroGPU: Accelerating multi-compartment, biophysically detailed neuron simulations on GPUs.
The membrane potential of individual neurons depends on a large number of interacting biophysical processes operating on spatial-temporal scales spanning several orders of magnitude. The multi-scale nature of these processes dictates that accurate prediction of membrane potentials in specific neurons requires the utilization of detailed simulations. Unfortunately, constraining parameters within biologically detailed neuron models can be difficult, leading to poor model fits. This obstacle can be overcome partially by numerical optimization or detailed exploration of parameter space. However, these processes, which currently rely on central processing unit (CPU) computation, often incur orders of magnitude increases in computing time for marginal improvements in model behavior. As a result, model quality is often compromised to accommodate compute resources. Here, we present a simulation environment, NeuroGPU, that takes advantage of the inherent parallelized structure of the graphics processing unit (GPU) to accelerate neuronal simulation. NeuroGPU can simulate most biologically detailed models 10-200 times faster than NEURON simulation running on a single core and 5 times faster than GPU simulators (CoreNEURON). NeuroGPU is designed for model parameter tuning and best performs when the GPU is fully utilized by running multiple (> 100) instances of the same model with different parameters. When using multiple GPUs, NeuroGPU can reach to a speed-up of 800 fold compared to single core simulations, especially when simulating the same model morphology with different parameters. We demonstrate the power of NeuoGPU through large-scale parameter exploration to reveal the response landscape of a neuron. Finally, we accelerate numerical optimization of biophysically detailed neuron models to achieve highly accurate fitting of models to simulation and experimental data. Thus, NeuroGPU is the fastest available platform that enables rapid simulation of multi-compartment, biophysically detailed neuron models on commonly used computing systems accessible by many scientists.


Application of a polyelectrolyte complex based on biocompatible polysaccharides for colorectal cancer inhibition.
Strategies for incorporating water-insoluble photosensitisers (PS) in drug delivery systems have been extensively studied. In this work, we evaluate the formation, characterisation, drug sorption studies, and cytotoxicity of chitosan (CHT)/chondroitin sulphate (CS) polyelectrolyte complexes (PECs) coated with polystyrene-block-poly(acrylic acid) (PS-b-PAA) nanoparticles (NPs) loaded with chloroaluminum phthalocyanine (AlClPc). The PECs were characterised by infrared spectroscopy (FTIR), differential scanning calorimetric (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The PS-b-PAA NPs on the PEC surface was confirmed by scanning electron microscopy (SEM). Additionally, optical images distinguished the PEC structures containing PS-b-PAA or PS-b-PAA/AlClPc from the unloaded PEC. Kinetic and equilibrium studies investigate the sorption capacity of the PEC/PS-b-PAA toward AlClPc. The encapsulation efficiency reached 95% at 190 μg mL-1 AlClPc after only 15 min. The Brunauer-Emmett-Teller (BET) isotherm and pseudo-second-order kinetic fitted well to the experimental data. The PS-b-PAA NPs on the PEC surfaces increase the AlClPc bioavailability and the PEC structure stabilizes the PS-b-PAA/AlClPc nanostructures. The materials were cytocompatible upon healthy VERO (kidney epithelial cells), and cytotoxic against colorectal cancerous cells (HT-29 cells). For the first time, we associate PS-b-PAA/AlClPc with a hydrophilic and cytocompatible polysaccharide matrix. We suggest the use of these materials in strategies to treat cancer by using photodynamic therapy.


Analysis of heterogeneous growth changes in longitudinal height of children.
There have been methodologies developed for a wide range of longitudinal data types; nevertheless, the conventional growth study is restricted if individuals in the sample have heterogeneous growth trajectories across time. Using growth mixture modeling approaches, we aimed to investigate group-level heterogeneities in the growth trajectories of children aged 1 to 15 years. This longitudinal study examined group-level growth heterogeneities in a sample of 3401 males and 3200 females. Data were analyzed using growth mixture modeling approaches. We examined different trajectories of growth change in children across four low- and middle-income countries using a data-driven growth mixture modeling technique. The study identified two-group trajectories: the most male samples group (n = 4260, 69.7%) and the most female samples group (n = 2341, 81.6%). The findings show that the two groups had different growth trajectories. Gender and country differences were shown to be related to growth factors; however, the association varied depending on the trajectory group. In both latent groups, females tended to have lower growth factors (initial height and rate of growth) than their male counterparts. Compared with children from Ethiopia, children from Peru and Vietnam tended to exhibit faster growth in height over time: In contrast, children from India showed a lower rate of change in both latent groups than that of children from Ethiopia. The height of children in four low- and middle-income countries showed heterogeneous changes over time with two different groups of growth trajectories.


Ferulago angulata flower and leaf extracts inhibit angiogenesis in vitro through reducing VEGF-A and VEGFR-2 genes expression.
Ferulago angulata (Apiacea) has been used in Iranian traditional medicine since ancient times and its various health care and pharmacological benefits have been demonstrated recently. In this study, for the first time, we have investigated the effects of F. angulata flower and leaf ethanol extracts on angiogenesis, as the key process in tumor growth, invasion and metastasis. Cytotoxic effects of different concentrations (20-140 µg/mL) of each extract were assessed on human umbilical vein endothelial cells (HUVECs) using neutral red uptake assay. After evaluating the less toxic concentrations (up to 80 µg/mL), we performed three-dimensional angiogenesis, tube formation and migration assays to assess the key properties of HUVECs, including the angiogenesis process, in response to the extracts. Finally, quantitative gene expression analysis of VEGF-A and VEGFR-2, two critical mediators of angiogenesis, was performed using real-time RT-PCR. Both flower and leaf extracts exhibited concentration-dependent inhibition of sprouting, tube formation and migration capacities of HUVECs. For the flower extract, the respective IC50 values were 25.79, 26.52 and 38.92 µg/mL while for the leaf extract, the corresponding IC50 values were 34.18, 41.24 and 28.69 µg/mL. Both flower and leaf extracts downregulated VEGF-A and VEGFR-2 genes relative to the GAPDH gene as the internal control at concentrations of 60 and 80 µg/mL, respectively. These findings suggest that both flower and leaf extracts may contain anti-angiogenic compounds and may have the capacity to be utilized in tumor anti-angiogenic therapy strategies.


Treatments for Persistent Genital Arousal Disorder in Women: A Scoping Review.
Persistent genital arousal disorder (PGAD) is characterized by elevated discomfort associated with persistent genital arousal in the absence of sexual desire. To perform a scoping review of the proposed treatments for PGAD and their efficacy. A scoping review was carried out (PRISMA-Scr) that included articles on PGAD as the main disorder, only in women, which explained, in detail, the treatment and its efficacy, was empirical, was written in English and Spanish. No prior filtering by years was performed. Three different effective treatments were found (Physical therapies, pharmacological therapies, and psychotherapeutics in combination with other therapies). Thirty-eight articles were selected. From physical therapies, treatments using neuromodulation, transcutaneous electrical stimulation, Botox, surgery, electroconvulsive therapy, manual therapy, pelvic floor therapy, dietary changes, and transcranial magnetic stimulation showed effectiveness. Using the pharmacological approach, paroxetine, duloxetine, pramipexole, ropinirole, and clonazepam treatments were effective. Psychotherapy treatments showed effectiveness only in combination with other types of treatments, specifically a combination of cognitive-behavioral strategies with pharmacological treatment. Pharmacological treatment, specifically SSRIs, have proven to be the therapy of choice for different subtypes of patients. This study analyzed treatment effectiveness with different approaches and took into consideration those articles where psychotherapy was used as a combination treatment with pharmacological and physical therapy. The main limitation is that it was focused exclusively on women, and the results cannot be generalized to include men. To date, a combination of pharmacological interventions with physical therapy and, in some occasions, with psychological therapy is main strategy followed to accomplish effective treatment of PGAD. Martín-Vivar M, Villena-Moya A, Mestre-Bach G, et al. Treatments for Persistent Genital Arousal Disorder in Women: A Scoping Review. J Sex Med 2022;19:961-974.


Synchrotron Mössbauer source: trade-off between intensity and linewidth.
A synchrotron Mössbauer source (SMS) enables conventional (energy-domain) Mössbauer spectroscopy at synchrotron radiation facilities. In comparison with radioactive sources, SMS provides a beam of several micrometres in size, permitting studies of extremely small samples. The SMS linewidth can be narrowed at the expense of its intensity by varying the angular position and temperature of the key element of the SMS - an iron borate 57FeBO3 crystal. Here, in order to optimize the SMS performance, the angular and temperature dependencies of the SMS parameters have been studied and the optimal angular position and temperature of the crystal have been determined for highest intensity at specified source width. The results show that, when accepting broadening of the source width up to ∼6 natural widths, the intensity of the SMS at the European Synchrotron reaches more than 105 γ-quanta s-1. In the opposite extreme, the width of the source approaches the natural width with intensity decreasing to about 103 γ-quanta s-1. These changes of intensity up to two orders of magnitude take place over a temperature range of about 0.5°C. For all temperature and angular conditions, the instrumental function of the source was derived; we also analyzed the modification of its shape when passing from the `low-width' to `high-intensity' extremes of SMS operation. Finally, we estimated the influence of the temperature instability and mosaicity of the iron borate crystal on the SMS performance.


Humans modulate arm stiffness to facilitate motor communication during overground physical human-robot interaction.
Humans can physically interact with other humans adeptly. Some overground interaction tasks, such as guiding a partner across a room, occur without visual and verbal communication, which suggests that the information exchanges occur through sensing movements and forces. To understand the process of motor communication during overground physical interaction, we hypothesized that humans modulate the mechanical properties of their arms for increased awareness and sensitivity to ongoing interaction. For this, we used an overground interactive robot to guide a human partner across one of three randomly chosen paths while occasionally providing force perturbations to measure the arm stiffness. We observed that the arm stiffness was lower at instants when the robot's upcoming trajectory was unknown compared to instants when it was predicable - the first evidence of arm stiffness modulation for better motor communication during overground physical interaction.


Pituitary apoplexy after joint arthroplasty.
Pituitary apoplexy is a rare but potentially life-threatening condition caused by the sudden enlargement of a pituitary adenoma secondary to infarction and hemorrhage. The clinical syndrome is characterized by sudden onset of headache, ocular palsies, visual disturbances, and altered state of consciousness. We report 2 patients who had postoperative pituitary apoplexy after total hip and total knee arthroplasty. Asymptomatic pituitary adenomas are difficult to diagnose preoperatively. Its existence is an unlikely suspect until the clinical symptoms develop after surgery. This is the first reported case following total hip arthroplasty.


Knocking down the expression of the molecular motors, myosin A, C and F genes in Toxoplasma gondii to decrease the parasite virulence.
Toxoplasmosis is a serious parasitic infection and novel therapeutic options are highly demanded to effectively eliminate it. In current study, Toxoplasma gondii myosin A, C and F genes were knocked down using small interference RNA (siRNA) method and the parasite survival and virulence was evaluated in vitro and in vivo. The parasites were transfected with specific siRNA, virtually designed for myosin mRNAs, and co-cultured with human foreskin fibroblasts. The transfection rate and the viability of the transfected parasites were measured using flow cytometry and methyl thiazole tetrazolium (MTT) assays, respectively. Finally, the survival of BALB/c mice infected with siRNAs-transfected T. gondii was assessed. It was demonstrated that a transfection rate of 75.4% existed for siRNAs, resulting in 70% (P = 0.032), 80.6% (P = 0.017) and 85.5% (P = 0.013) gene suppression for myosin A, C and F in affected parasites, respectively, which was subsequently confirmed by Western blot analysis. Moreover, lower parasite viability was observed in those with knocked down myosin C with 80% (P = 0.0001), followed by 86.15% (P = 0.004) for myosin F and 92.3% (P = 0.083) for myosin A. Considerably higher mouse survival (about 40 h) was, also, demonstrated in mice challenged with myosin siRNA-transfected T. gondii, in comparison with control group challenged with wild-type parasites. In conclusion, myosin proteins knock down proposes a promising therapeutic strategy to combat toxoplasmosis.


Fluorescent derivative of cysteine-10 reveals thyroxine-dependent conformational modifications in human serum prealbumin.
Fluorescence studies on the N-(iodoacetyl)-N'-(5-sulfo-1-naphthyl)ethylenediamine-labeled cysteine-10 residue of human prealbumin were carried out to detect conformational changes induced by the binding of the ligand thyroxine to the two structurally identical binding sites. A red shift of the spectrum was observed and the total change was confined to the first ligand. This was interpreted as resulting from a conformational change which increases the exposure of the fluorescent probe moiety. Thyroxine also alters the effect of the collisional quencher, acrylamide, confirming the greater exposure of the probe. This modification in structure is associated with changes in relaxation time which indicate that when thyroxine is bound there is an increase in the rotational freedom of the segment or domain of prealbumin which contains the fluorescent probe.


Reductive assembly of cyclobutadienyl and diphosphacyclobutadienyl rings at uranium.
Despite the abundance of f-block-cyclopentadienyl, arene, cycloheptatrienyl and cyclo-octatetraenide complexes, cyclobutadienyl derivatives are unknown in spite of their prevalence in the d-block. Here we report that reductive [2+2]-cycloaddition reactions of diphenylacetylene and (2,2-dimethylpropylidyne)phosphine with uranium(V)-inverted sandwich 10π-toluene tetra-anion complexes results in the isolation of inverted sandwich cyclobutadienyl and diphosphacyclobutadienyl dianion uranium(IV) complexes. Computational analysis suggests that the bonding is predominantly electrostatic. Although the ψ4 molecular orbital in the cyclobutadienyl and diphosphacyclobutadienyl ligands exhibits the correct symmetry for δ-bonding to uranium, the dominant covalent contributions arise from π-bonding involving ψ2 and ψ3 orbital combinations. This contrasts with uranium complexes of larger arenes and cyclo-octatetraenide, where δ-bonding dominates. This suggests that the angular requirements for uranium to bond to a small four-membered ring favours π-bonding, utilizing 5f- instead of 6d-orbitals, over δ-bonding that is favoured with larger ligands, where 6d-orbitals can become involved in the bonding.


Vascularized free radius transfer for clavicle reconstruction concurrent with below elbow amputation.
In the course of a below elbow amputation, forearm composite tissue that would routinely be discarded was used as a microvascular free-tissue transfer for distant reconstruction. The principle of "spare part" microsurgical reconstruction should routinely be considered during the planning of an ablative operation.


Extent of HCV NS3 protease variability and resistance-associated mutations assessed by next generation sequencing in HCV monoinfected and HIV/HCV coinfected patients.
HCV quasispecies variability represents the background for the selection of mutations and for the development of drug resistance. Natural aminoacid changes in NS3, associated with reduced protease inhibitor susceptibility, have been observed in treatment-naïve patients. Massively parallel sequencing has been used to analyze NS3 quasispecies in patients infected with HCV genotype 1, naive to anti-HCV treatment, with/without HIV-coinfection, to establish the genetic heterogeneity and the presence of amino acid substitutions at positions responsible for drug resistance. Genomes carrying substitutions represented either predominant or minority components of viral quasispecies, and were observed in 85.7% of patients. Multiple substitutions, frequently associated on the same haplotype, were observed in 46.4% of patients. High resistance combinations were not detected, neither on the same genome, nor in the whole quasispecies. Heterogeneity of HCV NS3 was lower in HIV-coinfected as compared to HCV-monoinfected patients, but factors underlying this difference remain to be established. Although the relevance of naturally occurring mutations with respect of resistance development and probability of success of direct acting antivirals is questioned, UDPS may be beneficial to help understanding viral dynamics, providing high resolution view of viral diversity.


Correction to: Quantitative analysis of PET microplastics in environmental model samples using quantitative 1H-NMR spectroscopy: validation of an optimized and consistent sample clean-up method.
The original version of this article contained a mistake.


The dorsal occult ganglion of the wrist and ultrasonography.
In five cases of suspected occult ganglion on the back of the wrist, an ultrasonographic examination was performed. This revealed a small hypoechogenic area on the dorsal aspect between the scaphoid and the lunate or just dorsal to the lunate. Exploration of this area in three cases confirmed the presence of an occult ganglion. In the other two cases, further aspiration revealed traces of mucinous jelly at the tip of the needle.


Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome.
A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS). At the beginning, all patients were steroid sensitive but received more than one steroid course (median 4). Following several relapses, they became steroid dependent or steroid resistant. Group 1 consisted of 22 children [3 focal segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received cyclophosphamide (CP) orally for 2.5 +/- 0.5 months. Group 2 consisted of 15 children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28 +/- 15 months. The level of proteinuria decreased significantly and remained low during the follow-up. The relapse-free period was significantly longer in the CP group (CP 30 +/- 21.5; CSA 26.2 +/- 18 months, p < 0.001). The relapse rate decreased significantly in both groups and remained in this lower level during the follow-up (from 3.4 +/- 2.8 to 0.1 +/- 0.2/year in group 1, and from 3.7 +/- 3.1 to 0.6 +/- 0.8/year in group 2). At the end of the 5-year follow-up, 20/22 patients (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2 respectively, with or without treatment (p < 0.05). In the long term, both CP and CSA is effective second-line therapy following steroid monotherapy in INS patients, but the relapse rate was lower and the relapse free period was significantly longer in the CP-treated group.


Succinylation-associated lncRNA signature to predict the prognosis of colon cancer based on integrative bioinformatics analysis.
Colon cancer (CC) has a poor 5-year survival rate though the treatment techniques and strategies have been improved. Succinylation and long noncoding RNAs (lncRNAs) have prognostic value for CC patients. We analyzed and obtained succinylation-related lncRNA by co-expression in CC. A novel succinylation-related lncRNA model was developed by univariate and Least absolute shrinkage and selection operator (Lasso) regression analysis and we used principal component analysis (PCA), functional enrichment annotation, tumor immune environment, drug sensitivity and nomogram to verify the model, respectively. Six succinylation-related lncRNAs in our model were finally confirmed to distinguish the survival status of CC and showed statistically significant differences in training set, testing set, and entire set. The prognosis of with this model was associated with age, gender, M0 stage, N2 stage, T3 + T4 stage and Stage III + IV. The high-risk group showed a higher mutation rate than the low-risk group. We constructed a model to predict overall survival for 1-, 3-, and 5-year with AUCs of 0.694, 0.729, and 0.802, respectively. The high-risk group was sensitive to Cisplatin and Temozolomide compounds. Our study provided novel insights into the value of the succinylation-related lncRNA signature as a predictor of prognosis, which had high clinical application value in the future.


Look into my eyes: What can eye-based measures tell us about the relationship between physical activity and cognitive performance?
There is a growing interest to understand the neurobiological mechanisms that drive the positive associations of physical activity and fitness with measures of cognitive performance. To better understand those mechanisms, several studies have employed eye-based measures (e.g., eye movement measures such as saccades, pupillary measures such as pupil dilation, and vascular measures such as retinal vessel diameter) deemed to be proxies for specific neurobiological mechanisms. However, there is currently no systematic review providing a comprehensive overview of these studies in the field of exercise-cognition science. Thus, this review aimed to address that gap in the literature. To identify eligible studies, we searched 5 electronic databases on October 23, 2022. Two researchers independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX scale, for interventional studies) and the critical appraisal tool from the Joanna Briggs Institute (for cross-sectional studies). Our systematic review (n = 35 studies) offers the following main findings: (a) there is insufficient evidence available to draw solid conclusions concerning gaze-fixation-based measures; (b) the evidence that pupillometric measures, which are a proxy for the noradrenergic system, can explain the positive effect of acute exercise and cardiorespiratory fitness on cognitive performance is mixed; (c) physical training- or fitness-related changes of the cerebrovascular system (operationalized via changes in retinal vasculature) are, in general, positively associated with cognitive performance improvements; (d) acute and chronic physical exercises show a positive effect based on an oculomotor-based measure of executive function (operationalized via antisaccade tasks); and (e) the positive association between cardiorespiratory fitness and cognitive performance is partly mediated by the dopaminergic system (operationalized via spontaneous eye-blink rate). This systematic review offers confirmation that eye-based measures can provide valuable insight into the neurobiological mechanisms that may drive positive associations between physical activity and fitness and measures of cognitive performance. However, due to the limited number of studies utilizing specific methods for obtaining eye-based measures (e.g., pupillometry, retinal vessel analysis, spontaneous eye blink rate) or investigating a possible dose-response relationship, further research is necessary before more nuanced conclusions can be drawn. Given that eye-based measures are economical and non-invasive, we hope this review will foster the future application of eye-based measures in the field of exercise-cognition science.


Mn-mediated coupling of alkyl iodides and ketimines: a radical addition route to alpha,alpha-disubstituted alpha-aminoesters.
Coupling of primary and secondary alkyl iodides with N-acylhydrazonoesters via Mn-mediated photolysis conditions affords access to tert-alkyl amines.


Rotational Profiler: A Fast, Automated, and Interactive Server to Derive Torsional Dihedral Potentials for Classical Molecular Simulations.
Rotational Profiler provides an analytical algorithm to compute sets of classical torsional dihedral parameters by fitting an empirical energy profile to a reference one that can be obtained experimentally or by quantum-mechanical methods. The resulting profiles are compatible with the functional forms in the most widely used biomolecular force fields (e.g., GROMOS, AMBER, OPLS, and CHARMM). The linear least-squares regression method is used to generate sets of parameters that best satisfy the fitting. Rotational Profiler is free to use, analytical, and force field/package independent. The formalism is herein described, and its usage, in an interactive and automated manner, is made available as a Web server at http://rotprof.lncc.br.


Osteoporosis and transforming growth factor-beta-1 gene polymorphism in Chinese men and women.
Transforming growth factor-beta-1 (TGF-Beta(1)) has been implicated in bone mineral density (BMD) determination. We investigated the relationship between the TGF polymorphism, BMD, and vertebral fractures in 588 Chinese men and women. No association between TGF polymorphism and BMD was observed in postmenopausal women (aged 55-59 years), elderly men (aged 70-79 years), or elderly women (aged 70-79 years) at the hip, spine, or total body ( P >> 0.05 by two-way ANOVA). In all study groups, there was no effect of an interaction between TGF polymorphism and calcium intake on BMD ( P >> 0.05 for the interaction effects by two-way ANOVA). No statistical significant association was observed between TGF polymorphism and vertebral fracture in elderly men or women ( P >> 0.05 by the chi-square test), even though men of the TT and TC genotypes seem to have more vertebral fractures. Contrary to previous studies that found an association between BMD and TGF polymorphism in the Japanese, we found no association between TGF polymorphism and BMD of elderly Chinese men or women. This finding could result from different sampling methods between the previous and current studies and environmental factors and ethnic differences between the two populations.


Women's right to health and Ireland's abortion laws.
The provision of the Irish Constitution that guarantees "the unborn" a right to life equal to that of a pregnant woman has consequences for access to abortion and the care of women in pregnancy generally. Long-awaited legislation to give effect to the narrow constitutional right to abortion was enacted into law in 2013. In 2014, a guidance document for health professionals' implementation of the legislation was published. However, the legislation and guidance document fall far short of international human rights bodies' recommendations: they fail to deliver effective procedural rights to all of the women eligible for lawful abortion within the state and create new legal barriers to women's reproductive rights. At the same time, cases continue to highlight that the Irish Constitution imposes an unethical and rights-violating legal regime in non-abortion-related contexts. Recent developments suggest that both the failure to put guidelines in place and the development of guidelines that are not centered on women or based on rights further reduce women's access to rights and set unacceptable limitations on women's reproductive autonomy. Nevertheless, public and parliamentary scrutiny of cases involving Ireland's abortion laws is increasingly focusing on the need for reform.


Clone mixtures and a pacemaker: new facets of Red-Queen theory and ecology.
Host-parasite antagonistic interaction has been proposed as a potential agent to promote genetic polymorphism and to favour sex against asex, despite its twofold cost in reproduction. However, the host-parasite gene-for-gene dynamics often produce unstable cycles that tend to destroy genetic diversity. Here, we examine such diversity destroying coevolutionary dynamics of host and parasite, which is coupled through local or global migration, or both, between demes in a metapopulation structure. We show that, with global migration in the island model, peculiar out-of-phase islands spontaneously arise in the cluster of islands converging to a global synchrony. Such asynchrony induced by the 'pacemaker islands' serves to restore genetic variation. With increasing fraction of local migration, spots of asynchrony are converted into loci or foci of spiral and target patterns, whose rotating arms then cover the majority of demes. A multi-locus analogue of the model reproduces the same tendency toward asynchrony, and the condition arises for an advantage of asexual clones over their sexual counterpart when enough genetic diversity is maintained through metapopulation storage-migration serves as a cheap alternative to sex.


rac-Methyl 3-(2-meth-oxy-phen-yl)-3a,4-di-hydro-3H-chromeno[4,3-c]isoxazole-3a-carboxyl-ate.
The title compound, C19H17NO5, comprising two stereogenic C atoms of the same configuration, crystallizes in a centrosymmetric space group as a racemate. The pyran ring adopts a half-chair conformation, while the isoxazole ring adopts an envelope conformation with the C atom bonded to the meth-oxy-phenyl group as the flap. The dihedral angle between the mean plane of the pyran ring and the adjacent benzene ring is 5.86 (5)°. In the crystal, mol-ecules are linked by a weak C-H⋯O hydrogen bond, forming a chain along the a axis.


Residential traffic exposure and lymphohematopoietic malignancies among children in the city of São Paulo, Brazil: An ecological study.
Despite widespread evidence that air pollution is carcinogenic, there is little evidence from low-middle income countries, especially related to childhood malignancies. We examined the role of traffic related pollution on lymphohematopoietic malignancies among under-14 s in Sao Paulo. All incident cases between 2002 and 2011 were collected from a population-based registry. Exposures were assigned on residential address at diagnosis via traffic density database (for the year 2008) and a satellite derived NO2 land use regression model (averaged between 1997 and 2011). Incidence rate ratios (IRRs) were calculated via Poisson Regression adjusted by age, gender and socioeconomic status (SES), with additional stratification by SES. A positive association between traffic and NO2 with some lymphohematopoietic malignancies was observed with the degree of effect differing by SES. For example, lymphoid leukemia IRRs in the lower SES group were 1.21 (95 % CI: 1.06, 1.39) for traffic density and 1.38 (95 % CI: 1.13, 1.68) for NO2. In the higher group they were 1.06 (95 % CI: 1.00, 1.14) and 1.37 (95 % CI: 1.16, 1.62). NO2 and traffic density were associated with Hodgkin lymphoma and lymphoid leukemia among children in São Paulo. Differing IRRs by gender and SES group indicate differences in underlying risk and/or exposure profiles.


Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo.
Recruitment of mononuclear leukocytes within atherosclerotic lesions is a critical step in atherogenesis. Mice lacking the chemokine receptor CCR2, highly expressed on macrophages but also on T lymphocytes, show a striking reduction of atherosclerotic lesion formation. The chemokine receptor CXCR3 is a marker of activated T helper type 1 lymphocytes, the principal T lymphocyte type detected within atheroma. We investigated whether the deletion of both of these 2 important receptors expressed on the principal inflammatory cells present in atheroma would further affect atherogenesis in vivo. We crossed ApoE(-/-) mice with either CCR2(-/-) or CXCR3- mice and crossed ApoE(-/-) CCR2(-/-) mice with the ApoE(-/-) CXCR3- mice to generate a triple knockout strain. Analysis of atherosclerosis development after 10 weeks of high-cholesterol diet revealed differential effects on early atherosclerotic lesions in the abdominal aorta and on advanced lesions in aortic roots. ApoE(-/-) CXCR3- mice, but not the triple knockout mice, displayed significantly reduced atherosclerotic lesion development within abdominal aortas compared with ApoE(-/-) CCR2(-/-) and ApoE(-/-) mice. This reduction of lesion formation correlated with an upregulation of antiinflammatory molecules such as interleukin-10, interleukin-18BP, and endothelial nitric oxide synthase and with an increased number of regulatory T lymphocytes within atherosclerotic lesions. In contrast, lesion size development within the aortic roots was more enhanced in ApoE(-/-) and ApoE(-/-) CXCR3- mice compared with ApoE(-/-) CCR2(-/-) and triple knockout mice. Blocking chemokine signaling in vivo through deletion of the chemokine receptors CCR2 and CXCR3 has differential effects during atherogenesis. In addition, our results point to an important role of regulatory T lymphocytes during early atherogenesis.


Autophagy modulates miRNA-mediated gene silencing and selectively degrades AIN-1/GW182 in C. elegans.
MicroRNAs (miRNAs) post-transcriptionally repress gene expression via the miRNA-induced silencing complex (miRISC), which includes miRNA, Argonaute and a GW182 family member. Here we show that in Caenorhabditis elegans, miRNA-mediated gene silencing is modulated by macroautophagy, a lysosome-mediated degradation process. Loss of autophagy activity suppresses developmental defects caused by partially impaired silencing of miRNA targets including the let-7 family and lsy-6. The C. elegans GW182 homolog AIN-1 is itself selectively degraded by autophagy and colocalizes with the p62 homolog SQST-1 in autophagy mutants. Thus, autophagy activity modulates miRNA-mediated gene silencing and degrades a core miRISC component.


Application of permanents of square matrices for DNA identification in multiple-fatality cases.
DNA profiling is essential for individual identification. In forensic medicine, the likelihood ratio (LR) is commonly used to identify individuals. The LR is calculated by comparing two hypotheses for the sample DNA: that the sample DNA is identical or related to a reference DNA, and that it is randomly sampled from a population. For multiple-fatality cases, however, identification should be considered as an assignment problem, and a particular sample and reference pair should therefore be compared with other possibilities conditional on the entire dataset. We developed a new method to compute the probability via permanents of square matrices of nonnegative entries. As the exact permanent is known as a #P-complete problem, we applied the Huber-Law algorithm to approximate the permanents. We performed a computer simulation to evaluate the performance of our method via receiver operating characteristic curve analysis compared with LR under the assumption of a closed incident. Differences between the two methods were well demonstrated when references provided neither obligate alleles nor impossible alleles. The new method exhibited higher sensitivity (0.188 vs. 0.055) at a threshold value of 0.999, at which specificity was 1, and it exhibited higher area under a receiver operating characteristic curve (0.990 vs. 0.959, P = 9.6E-15). Our method therefore offers a solution for a computationally intensive assignment problem and may be a viable alternative to LR-based identification for closed-incident multiple-fatality cases.


Nuclear enlargement and DNA synthesis in mouse epidermis treated with carcinogen and promotor.
An autoradiographic investigation was made into the causes of nuclear size increase observed in the mouse epidermis within a few days of topical benzpyrene treatment. The effects of croton oil pretreatment of posttreatment in combination with benzpyrene were examined to see what effect a growth stimulus had on this response. The degree of nuclear size increase induced in the epidermis suggested that some ploidy level increase resulted from combined croton oil and benzpyrene treatment and evidence was found of a G2 block occurring in association with this. Enhancement of nuclear size increase by croton oil highlighted the importance of a growth stimulus in carcinogen induced nuclear enlargement and the implications of this are discussed. Disappearance of enlarged nuclei was seen when mice were kept for 5 days after combined croton oil and benzpyrene treatment in spite of a reduced cell loss compared with croton oil treatment alone.


Survival of metastatic germ cell cancer patients assessed by international germ cell consensus classification in Japan.
As a risk classification system of metastatic germ cell tumors, the International Germ Cell Consensus (IGCC) classification was proposed in 1997 and has received broad approval. Since the IGCC classification was based on patients treated between 1975 and 1990, we aimed to investigate whether survival has improved for more recently treated Japanese patients. We analyzed 296 patients with metastatic germ cell tumors treated at seven hospitals in Japan between 1990 and 2001. These cases are classified as good, intermediate or poor prognosis groups by the IGCC classification. The 5-year progression-free and the 5-year overall survivals were calculated for each prognosis group. The median follow-up period of all patients was 53 months. In 227 non-seminomatous germ cell tumor cases, the 5-year progression-free survival (95% confidence interval) for good (n = 55), intermediate (n = 106) and poor (n = 66) prognosis was 96% (91-100), 71% (62-80) and 52% (39-65) (P < 0.001), respectively. The 5-year overall survival was 94% (88-100), 81% (73-89) and 61% (49-73) (P < 0.001), respectively. In 69 seminoma cases, the 5-year progression-free survival for good (n = 64) and intermediate (n = 5) prognosis was 78% (67-89) and 80% (45-100) (P = 0.98), respectively. The 5-year overall survival was 90% (82-99) and 80% (45-100) (P = 0.49), respectively. There was a trend of increase in survival for any risk groups and, in particular, large increase in survival for patients with a poor prognosis. This increase is most likely attributed to more effective chemotherapy regimens and more extensive care in the experienced institutes.


Innervation of nonmystacial vibrissae in the adult rat.
Vibrissal follicle-sinus complexes (F-SCs) in the mystacial pad of rodents are heavily innervated by different types of sensory nerve endings. One site in mystacial F-SCs, the inner conical body (ICB), is uniquely well innervated only in those species, such as the rat, that rhythmically whisk their mystacial vibrissae. In this study, we examined the innervation of rat nonmystacial F-SCs, which are not whisked. Supraorbital, posteroorbital, lateral cervical, median cervical, submental, and carpal forelimb F-SCs were cut on a cryostat and were either prepared for anti-human protein gene product (PGP 9.5) immunofluorescence or stained using the Winkelmann silver technique. Much of the innervation of the nonmystacial F-SCs is similar to that of mystacial F-SCs. All are innervated by a large deep vibrissal nerve (DVN) and several smaller superficial vibrissal nerves (SVNs). As in the mystacial pad, the SVNs show a distribution of Merkel and free nerve endings qualitatively similar to the rete ridge collar of all the nonmystacial F-SCs as well as provide circumferentially oriented endings to the ICBs to all but median-cervical and carpal F-SCs. Not only was the ICB innervation relatively sparse in median-cervical and carpal F-SCs, but a large portion of the carpal ICB innervation also ascended from the DVNs, which make only a small ICB contribution in other locations. Similar to mystacial pad F-SCs, the DVNs provided Merkel and lanceolate endings to the level of the ring sinus as well as reticular and irregular lanceolate-like endings to the level of the cavernous sinus. However, all but the posteroorbital F-SCs have relatively few lanceolate endings. Carpal F-SCs also have relatively few ring-sinus Merkel endings, which are diffusely distributed, are limited to the superficial portion of the outer root sheath. They also lack reticular and irregular lanceolate-like endings in the cavernous sinus. However, carpal F-SCs have a unique set of corpuscular endings in the ICB, ring sinus, and cavernous sinus that are rarely seen in other F-SCs. PGP 9.5 immunofluorescence also revealed two sets of fine-caliber profiles at the level of the ICB and ring sinus that were not previously seen in mystacial F-SCs. Although there was no correlation between ICB innervation and whisking, the regional variations in F-SC innervation suggest that functional differences may exist between vibrissae at different locations in the body.


Chemical identification and determination of sulfonamides in n-component solid mixtures within THz-region--solid-state Raman spectroscopic and mass spectrometric study.
The identification and quantitative determination of sulfonamidesin solid-state as n-component mixtures is performed. The limits of detection (LODs), accuracy, precision and repeatability are obtained and discussed, using the Raman spectra within 200-30 cm(-1) region (6.00-0.9 THz). The excitations, corresponding to H-bonding deformations, lattice vibrations, as well as coupling modes are used for determination. The validation of the statistical and mathematical tools for procedure of the spectroscopic patterns is performed. The possibilities of baseline correction methods, smoothing procedures, and non-linear curve fitting method for quantitative analysis within THz-region for complex spectroscopic patterns of n-component mixtures (n=1-5) are discussed. The hybrid HPLC tandem mass spectrometry (MS/MS) and powder XRD are applied as independent physical methods for analysis of the studied systems.


The prevalence of neuropsychiatric disorders in a nursing home population.
The prevalence of neuropsychiatric disorders and other medical illnesses was investigated in 65 nursing home residents. The authors found neuropsychiatric disorders to be present in 94% of the sample. The neuropathologic causes of these syndromes were found to be more diverse than in previous studies. The most frequent causes were degenerative, vascular, and toxic. The most common psychiatric syndromes that resulted from these neuropathologic disorders were dementia syndrome (72%), organic personality syndrome (14%), and organic psychotic disorders (12%). The most common behavioral problems, agitation and aggression, most likely reflected the high prevalence of frontal lobe damage and affected 48% of the sample. Other non-neuropsychiatric medical problems were significantly less common. While only 4% of the sample had no neuropsychiatric diagnosis, 39% had no other non-neuropsychiatric diagnosis. These results suggest that the nursing home is not used as a referral source for chronic medical conditions in general but almost exclusively for the care of chronic neuropsychiatric disorders.


Quantum-chemical and empirical calculations on phospholipids, III. Hydration of the dimethylphosphate anion.
The binding of water to the dimethylphosphate anion (DMP-) was calculated using the PCILO method. We found binding energies of 25.95 kcal-mol-1 in the O1-P-O3 plane bridgeing the anionic oxygen atoms and 19.3 kacl-mol-1 for the one-site association of a water molecule to an anionic oxygen atom of DMP-. In this range on water molecule added to DMP- in the O1...O3 bridged configuration has a significantly higher binding energy to DMP- than water molecules added to other binding sites. The total binding energy of 5 water molecules to DMP- is 92 kcal-mol-1, a quantity which is about 10% less than the sum of the binding energies of the corresponding monohydrates.


Studies on an isolated West Indies population. VII. Genetic linkage studies of hearing loss.
Linkage analysis was performed between the locus of sensorineural hearing loss and 14 polymorphic genetic markers on 108 informative families with a total of 721 individuals in the island of Saint-Barthélémy. No significant linkage was found, and only for Gm could tight linkage be excluded.


Vestibular Schwannoma Cerebellopontine Angle Position Impacts Facial Outcome.
To determine the impact of vestibular schwannoma (VS) position relative to the internal auditory canal (IAC) on postoperative facial nerve function and extent of surgical resection. Retrospective chart review. Retrospective review of patients undergoing resection of large (≥25 mm) VSs. Outcome measures included early (≤1 month) facial function, long-term (≥1 year) facial function and extent of resection. Tumor measurements included the greatest dimension, dimension anterior to the IAC axis, dimension posterior to the IAC axis, and a ratio of posterior-to-anterior dimension (PA ratio). A total of 127 patients met inclusion criteria. In early follow-up, 60% patients had good (House-Brackmann I-II), and 40% patients had poor (House-Brackmann III-VI) facial function. In long-term follow-up, 71% patients had good, and 29% patients had poor facial function. A total of 72% of patients underwent gross total resection (GTR) of their tumors. Patients with good facial function had significantly larger PA ratios than patients with poor function both early and long term; however, greatest dimension was the more clearly significant independent predictor of facial outcomes. A larger PA ratio was observed in patients in whom GTR was achieved, but this association was potentially confounded by surgeon preferences and was not statistically significant after controlling for surgical site. This study demonstrates that VS position relative to the IAC axis can be used along with tumor size to predict postoperative facial outcomes. A greater proportion of tumor posterior to the IAC axis was associated with significantly better facial outcomes. 4 Laryngoscope, 132:1093-1098, 2022.


Estimating the cost of implementing district mental healthcare plans in five low- and middle-income countries: the PRIME study.
An essential element of mental health service scale up relates to an assessment of resource requirements and cost implications. To assess the expected resource needs of scaling up services in five districts in sub-Saharan Africa and south Asia. The resource quantities associated with each site's specified care package were identified and subsequently costed, both at current and target levels of coverage. The cost of the care package at target coverage ranged from US$0.21 to 0.56 per head of population in four of the districts (in the higher-income context of South Africa, it was US$1.86). In all districts, the additional amount needed each year to reach target coverage goals after 10 years was below $0.10 per head of population. Estimation of resource needs and costs for district-level mental health services provides relevant information concerning the financial feasibility of locally developed plans for successful scale up.


Radiotherapy in Current Neuro-Oncology: There Is Still Much to Reveal.
Radiation therapy (RT) has a pivotal role in the treatment of Central Nervous System (CNS) neoplasms and is routinely employed for both benign and malignant lesions [...].


Application of triazine "superactive esters" in the repetitive synthesis of oligopeptides. Part 2. Synthesis of N-terminal hexapeptide of emerimicin III.
N-terminal fragment of emerimicin III has been synthesized by the repetitive method in solution, involving triazine ,,superactive esters". The synthetic protocol, equivalent to the classic REMA procedure, has been applied in the step by step approach, and in the fragment coupling affording all the peptide bonds. By monitoring the progress of the synthesis by FAB-MS, 1H-NMR and HPLC, the structure and high purity of the final products have been confirmed.


Phosphatidylethanolamine N-methyltransferase in human red blood cell membrane preparations. Kinetic mechanism.
The successive methylations of phosphatidylethanolamine to form phosphatidylcholine were measured using exogenously added intermediates and membrane preparations from human red blood cells. The addition of phosphatidylethanolamine resulted in no increase in methylation rate over that with endogenous substrate; however, the addition of monomethylphosphatidylethanolamine (PME) and dimethylphosphatidylethanolamine (PDE) markedly increased the reaction rate and allowed studies into the kinetic mechanism for the second and third methylation reactions. The data are consistent with catalysis of the last two methylations being by a single enzyme with a random Bi-Bi sequential mechanism. Analysis of PDE:phosphatidylcholine product ratios indicates that the enzyme can conduct multiple methylations of enzyme-bound phospholipid. The nature of the acyl chain (16:0 versus 18:1) of the phospholipid had only a small effect on the value of the kinetic constants. The maximal velocities obtained with the 18:1 substrate were less than 5% lower than those obtained with the 16:0 substrate. The Km values for the two phospholipids were 20-45 and 10-14 microM for the methylation of PME and PDE, respectively. The Km for S-adenosylmethionine (AdoMet) was 5-9 microM with PME and 4 microM with PDE as substrates. Depending on the acyl chain and the phospholipid, the Ki(AdoMet) varied from 8 to 19 microM, the Ki(PME) from 41 to 82 microM, and the Ki(PDE) from 35 to 61 microM. The Ki for S-adenosylhomocysteine (AdoHcy) was between 1.0 and 1.4 microM depending upon the variable substrate. The endogenous concentrations of PME and PDE in red blood cell membranes were estimated to be 0.49 and 0.24 mumol/liter packed cells, respectively. The product from the utilization of AdoMet, S-adenosylhomocysteine (AdoHcy), was shown to be a competitive inhibitor of its precursor, AdoMet, and a noncompetitive inhibitor of the two phospholipid substrates.


Methylene blue and indocyanine green artifactually lower pulse oximetry readings of oxygen saturation. Studies in dogs.
The effects of fluorescein, methylene blue, and indocyanine green on hemodynamic variables and on pulse oximetry and co-oximetry measurements of arterial hemoglobin oxygen saturation (SaO2) and oxyhemoglobin percentage (% HbO2) were evaluated in 16 anesthetized dogs in vitro by co-oximetry (% HbO2) and in vivo by pulse oximetry (SaO2). The light absorbance (optical density) in plasma (range 500 to 800 nm) was measured by a spectrophotometer. Fluorescein did not affect oximetry measurements, plasma light absorbance in the range measured, or hemodynamic variables. Methylene blue caused dose-dependent decreases in measurements made with both forms of oximetry for up to 30 minutes, the decrease being greater and longer lasting with pulse oximetry (P less than 0.05). Hemodynamic measurements in 5 dogs showed that methylene blue (1 to 5 mg/kg) increased arterial pressure transiently, after which cardiac output, stroke index, and left ventricular stroke work index decreased and left ventricular end-diastolic pressure and systemic and pulmonary vascular resistances increased (P less than 0.05 with 5 mg/kg). Methemoglobin concentration measured by co-oximetry increased significantly (to 19.9 +/- 1.4%, P less than 0.05) 1 minute after 5 mg/kg of methylene blue was injected. Methylene blue had a dose- and time-dependent effect on plasma light absorbance, and this effect peaked in the 660- to 670-nm range. The data do not distinguish the relative contributions of physiology (hemodynamic change), chemistry (methemoglobin production), and physics (optical properties) to the decrease in pulse oximetry and co-oximetry measurements that follows injection of methylene blue. Indocyanine green affected neither hemodynamic variables nor co-oximetry readings but decreased pulse oximetry readings for up to 10 minutes dose dependently.(ABSTRACT TRUNCATED AT 250 WORDS)


Procedural accidents: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will cover procedural accidents, including perforation repairs, separated instrument, and accidents with irrigants and endodontic materials.