Notes

System and Effect of Beta-Blockers on Pancreatic Adenocarcinoma: A new Materials Review.
Follicular development can be disturbed due to many factors, including having polycystic ovaries. Aberrant expression of genes involved in steroidogenesis pathway could lead to aberrant oocyte development. In this study, the gene expression levels of a number of genes that is functioning in steroidogenesis pathway were investigated.

The spare oocytes were collected from NEU Hospital IVF Center following controlled ovarian stimulation cycle. RNA was extracted using RNA/DNA Purification Kit (Norgen, Canada) and reverse transcription was performed using TruScript First Strand cDNA Synthesis Kit (Norgen, Canada). Real time PCR was conducted using LightCycler® 480 SYBR Green I Master (Roche, UK).

The expression levels of CYP11, CYP17, CYP19, HSD17B1, HSD3B2 and ACTB were detected in human MII stage oocytes obtained from oocyte donors aged between 18-30 years. The number of follicles and oocytes collected from the patients with polycystic ovaries were slightly higher compared to the control group. The express the patients who do not have polycystic ovaries (p less then 0.05), whereas statistically significant expression levels were observed for CYP17 in the oocytes obtained from patients with polycystic ovaries (p less then 0.05). The expression level of HSD17B1 was also shown to be statistically different in the oocytes (p less then 0.05). The extrapolation of the results indicates that the genes involved in steroidogenesis pathway are altered in cases of polycystic ovaries. Thus, it may have a role in the development of polycystic ovaries.
Elevated extracellular DNA levels are found in the sputum of patients with cystic fibrosis (CF). However, studies investigating the association of extracellular DNA with CF severity are scarce.

To evaluate the association of extracellular DNA levels with pulmonary function, antibiotic use, and hospitalization in CF patients.

This cross-sectional study included CF patients aged ≥5 years who were clinically stable and produced spontaneously expectorated sputum. Extracellular DNA in sputum was quantified, and extracellular DNA networks were seen with immunofluorescence microscopy. Also, cell death profile was assessed. Data on pulmonary function, airway colonization, antibiotic use, and hospitalization in the previous year were collected. Patients were divided into two groups based on median DNA level.

Thirty-three patients were included. Their mean age was 16.3±6.2 years, mean forced expiratory volume in the first second (FEV
) was 67.0±26.7 (% of the predicted), and mean DNA level was 241.9±147.2μg/mL. There were significant correlations of DNA level with FEV
(r=-0.60; p<0.001) and forced vital capacity (r=-0.59; p<0.001). Moreover, patients with higher DNA level (>243.0μg/mL) had lower FEV
(52.1±27.8% vs. 81.1±16.2%; p=0.001) and required more hospitalizations (68.8% vs. 35.3%; p=0.05). Additional findings were the presence of extracellular DNA networks and low rates of necrosis and apoptosis.

Elevated extracellular DNA levels in CF sputum are associated with reduced pulmonary function and increased hospitalizations.
Elevated extracellular DNA levels in CF sputum are associated with reduced pulmonary function and increased hospitalizations.
To investigate the application of graph theory with functional connectivity to distinguish left from right temporal lobe epilepsy (TLE).

Alterations in functional connectivity within several brain networks - default mode (DMN), attention (AN), limbic (LN), sensorimotor (SMN) and visual (VN) - were examined using resting-state functional MRI (rs-fMRI). The study accrued 21 left and 14 right TLE as well as 17 nonepileptic control subjects. The local nodal degree, a feature of graph theory, was calculated foreach of the brain networks. Multivariate logistic regression analysis was performed to determine the accuracy of identifying seizure laterality based on significant differences in local nodal degree in the selected networks.

Left and right TLE patients showed dissimilar patterns of alteration in functional connectivity when compared to control subjects. Compared with right TLE, patients with left TLE exhibited greater nodal degree' (i.e. hyperconnectivity) with right superomedial frontal gyrus (in DMN)n presurgical decision-making in cases of TLE.
Temporomandibular disorders (TMD) are diseases of the temporomandibular joint and masticatory muscles, and are often difficult to be diagnosed because they have various symptoms, pathological conditions and causes.

Herein, we report a 78-year-old male referred to our hospital with a diagnosis of TMD and presenting with facial asymmetry, marked deviation to the right side on vertical mandibular movement and complaints of abnormal perception at the right oral and buccal region. Past medical history revealed that he had undergone a right intracranial trigeminal schwannoma resection 9 years prior. Computed tomography (CT) showed disuse atrophy of the right side of 4 masticatory muscles and 2 suprahyoid muscles controlled by the motor component of the mandibular division (V3) of the trigeminal nerve (TGN). Together with the neurosurgeon, we confirmed that there was no recurrence of the tumor and explained to the patient that the oral and maxillofacial symptoms are after-effects of the operation, and we provided oral hygiene instructions and coordinated cleaning of the inside of the oral cavity.

Although it is difficult to compare treatment methods from case to case, we believe that in our case, the patient's understanding of the cause of his discomfort contributed significantly to the improvement of his quality of life.

We experienced a case of masticatory muscle disuse atrophy during long-term follow-up after resection of intracranial trigeminal schwannoma. Further studies are needed to develop the diagnostic and therapeutic protocols for disuse atrophy.
We experienced a case of masticatory muscle disuse atrophy during long-term follow-up after resection of intracranial trigeminal schwannoma. Further studies are needed to develop the diagnostic and therapeutic protocols for disuse atrophy.
Although an extensive body of work has shown that family functioning is linked to adolescent outcomes, less is known about how the family affects school outcomes and vice versa. The present longitudinal study tested reciprocal relationships between the family environment and school engagement during the middle school years.

A cross-lagged latent model tested these effects in 378 Turkish youth (53.7% males; M=11.73, SD=0.53) evaluated annually (Waves 1, 2, and 3) in grades 6 through 8.

Findings showed the family environment positively predicted developmental changes in school engagement at each time point (β range=0.18 to 0.24); school engagement also positively predicted developmental changes in the family environment (β range=0.12 to 0.28). Follow-up multigroup tests by age, sex, and family structure showed that the reciprocal links between the family environment and school engagement were invariant.

Study findings supported reciprocal longitudinal links between developmental changes of the family environment and school engagement. They extend previous research by highlighting the continued importance of the home environment on developmental changes in academic performance in adolescents, and thus, inform parents, educators, and policymakers on the relevance of the family in promoting academic engagement and achievement in adolescence.
Study findings supported reciprocal longitudinal links between developmental changes of the family environment and school engagement. They extend previous research by highlighting the continued importance of the home environment on developmental changes in academic performance in adolescents, and thus, inform parents, educators, and policymakers on the relevance of the family in promoting academic engagement and achievement in adolescence.
Emotional separation and parental trust are two fundamental components of parent-adolescent relationships across different cultural contexts. Previous research showed that emotional separation hindered adolescents' psychosocial adjustment, while parental trust benefited it. However, research on preadolescence is lacking. Preadolescence is a crucial period, as theories and findings suggest that too early autonomy around puberty had negative consequences for psychosocial adjustment. This study focused on preadolescence and early adolescence and tested two hypotheses that emotional separation would be negatively, and parental trust would be positively, associated with psychosocial adjustment, and that this pattern of associations would be more salient in preadolescence than in early adolescence.

Participants were 856 preadolescent elementary schoolers (49.6% girls; age range 9-12 years, M
=10.79, SD=0.92) and 518 early adolescent junior high schoolers (47.7% girls, age range 12-15 years; M
=13.56, SD=0.98) in Japan, who completed measures of emotional separation, parental trust, and psychosocial adjustment (industry, school adaptation, and daily life behaviors).

Emotional separation was negatively associated with reviewing learning contents and doing homework. Parental trust was positively associated with industry, school adaptation, waking up at regular times, and observing rules at school. These relationships did not differ between age groups.

This study highlights that emotional separation has a negative relationship, and parental trust has a positive relationship, with psychosocial adjustment throughout preadolescence and adolescence.
This study highlights that emotional separation has a negative relationship, and parental trust has a positive relationship, with psychosocial adjustment throughout preadolescence and adolescence.Temperature alterations in neurocritical care settings are common and have a striking effect on brain metabolism leading to or exacerbating neuronal injury. Hyperthermia worsens acute brain injury (ABI) patients outcome. However conclusive evidence linking control of temperature to improved outcome is still lacking. This review article report an update -results from clinical studies published between March 2006 and March 2020- on the relationship between hyperthermia or Target Temperature Management and functional outcome or mortality in ABI patients.
A systematic search of articles in PubMed and EMBASE database was accomplished. Only complete studies, published in English in peer-reviewed journals were included.

A total of 63 articles into 5 subchapters are presented acute ischemic stroke (17), subarachnoid hemorrhage (14), brain trauma (14), intracranial hemorrhage (8), and mixed acute brain injury (10). This evidence confirm and extend the negative impact of hyperthermia in ABI patients on worse functional outcome and higher mortality. In particular "early hyperthermia" in AIS patients seems to have a protective role have as promoting factor of clot lysis but no conclusive evidence is available. Normothermic TTM seems to have a positive effect on TBI patients in a reduced mortality rate compared to hypothermic TTM.

Hyperthermia in ABI patients is associated with worse functional outcome and higher mortality. The use of normothermic TTM has an established indication only in TBI; further studies are needed to define the role and the indications of normothermic TTM in ABI patients.
Hyperthermia in ABI patients is associated with worse functional outcome and higher mortality. The use of normothermic TTM has an established indication only in TBI; further studies are needed to define the role and the indications of normothermic TTM in ABI patients.
Laminectomy and fusion is a standard technique in patients with multilevel degenerative cervical myelopathy (DCM). However, this procedure is associated with a reduction of cervical range of motion. This study examines how patients are subjectively restricted in cervical spine mobility, how they are impaired in activities of daily living (ADLs) and how this affects their quality of life.

In this single-center, retrospective cohort study patients with DCM operated via laminectomy and fusion over at least four segments were included. Clinical outcome was assessed via pain scores, NDI, patient satisfaction index, mJOA and SF-8. The patient-reported restriction of cervical spine mobility and the resulting impairment for various ADLs were acquired by a newly developed five-step score.

53 patients could be evaluated. 75.5 % were satisfied with the treatment. 41.5 % reported a moderate restriction of mobility, followed by severe restriction in 34.0 % and mild restriction in 15.1 %. Of the various directions of movement, flexion was indicated as the least restricted. Overhead work was the most impaired activity (26.4 % severe restriction, 37.7 % complete restriction). 60.4 % experienced none to moderate impairment when driving a car. The mean values for the SF-8 were 37.5 for the physical and 47.8 for the mental component summary.

Despite multilevel fusion and the reduced physical component summary of the SF-8, more than half of the patients reported only mild to moderate restriction. The concern about a complete impairment in various ADLs is unfounded for the majority of patients.
Despite multilevel fusion and the reduced physical component summary of the SF-8, more than half of the patients reported only mild to moderate restriction. The concern about a complete impairment in various ADLs is unfounded for the majority of patients.Clinician task performance is significantly impacted by the navigational efficiency of the system interface. Here we propose and evaluate a navigational complexity framework useful for examining differences in electronic health record (EHR) interface systems and their impact on task performance. The methodological approach includes 1) expert-based methods-specifically, representational analysis (focused on interface elements), keystroke level modeling (KLM), and cognitive walkthrough; and 2) quantitative analysis of interactive behaviors based on video-captured observations. Medication administration record (MAR) tasks completed by nurses during preoperative (PreOp) patient assessment were studied across three Mayo Clinic regional campuses and three different EHR systems. By analyzing the steps executed within the interfaces involved to complete the MAR tasks, we characterized complexities in EHR navigation. These complexities were reflected in time spent on task, click counts, and screen transitions, and were found to potentially influence nurses' performance. Two of the EHR systems, employing a single screen format, required less time to complete (mean 101.5, range 106-97 s), respectively, compared to one system employing multiple screens (176 s, 73% increase). These complexities surfaced through trade-offs in cognitive processes that could potentially influence nurses' performance. Factors such as perceptual-motor activity, visual search, and memory load impacted navigational complexity. An implication of this work is that small tractable changes in interface design can substantially improve EHR navigation, overall usability, and workflow.
The aim of the study was to identify care home characteristics associated with reported care home influenza outbreaks and factors associated with increased transmission of influenza-like illness (ILI) in care homes in Cheshire and Merseyside during the 2017-2018 influenza season.

This is a matched case-control study comparing characteristics between care homes with and without a declared influenza outbreak and a retrospective risk factor analysis of care home residents with ILI.

Routinely collected outbreak surveillance data on symptomatic residents and staff, antiviral prophylaxis and influenza vaccination history, which were reported to Public Health England, were extracted from health protection electronic records. Further care home characteristics were extracted from the Care Quality Commission (CQC) website. Care homes with declared influenza outbreaks were matched with care homes without outbreaks. Chi-squared tests and logistic regression were used to examine associations between care home factorivation of antiviral prophylaxis were associated with an increased risk of ILI. Further research is needed, particularly focussing on temporality between provision of prophylactic antivirals and the onset of ILI.This review analyses the fundamental thermodynamic theory of the crude oil-brine-rock (COBR) interface and the underlying rock-brine and oil-brine interactions. The available data are then reviewed to outline potential mechanisms responsible for increased oil recovery from low salinity waterflooding (LSWF). We propose an approach to studying LSWF and identify the key missing links that are needed to explain observations at multiple length scales. The synergistic effect of LSWF on other chemical enhanced oil recovery methods such as surfactant, alkaline, nanoparticle and polymer flooding are also outlined. We specifically highlight key uncertainties that must be overcome to fully implement the technique in the field.The aim of this study was to use a combined in vitro-in silico approach to develop a physiologically based pharmacokinetic model (PBPK) that predicts the bioavailability of albendazole (ABZ), a BCS class II/IV lipophilic weak base, and simulates its main metabolite albendazole sulphoxide (ABZSO) after oral administration of the current marketed dose of 400 mg in the fasted state. In vitro data was collected from solubility and dissolution tests performed with biorelevant media and transfer tests were carried out to evaluate the supersaturation and precipitation characteristics of ABZ upon gastric emptying. These in vitro results were used as biopharmaceutical inputs together with ABZ physicochemical properties including also permeability and in vitro metabolism data and information gathered from different clinical trials reported in the literature, were used to enable PBPK models to be developed using GastroPlus™ (version 9.7). As expected for this weak base with pKa = 3.6, ABZ exhibited a pronounced pH depennfirm that ABZ behaves as a BCS class IV compound.Flurbiprofen (FB) is an analgesic and anti-inflammatory drug, but its low water solubility (BCS Class II) limits its dermal bioavailability. The aim of this study is to develop a FB nanosuspension (NS) based gel and to evaluate its analgesic and anti-inflammatory activities in rats. FB-NS was produced by the wet milling method with Plantacare 2000Ⓡ, as stabilizer. The FB-NS was then incorporated in different carrier gels such as hydroxypropyl methyl cellulose (HPMC), polycarbophil, oleogel, and chitosan. To select the optimum gel type, visual examinations, pH and rheological property measurements, texture profile analysis, in vitro release and ex vivo permeation studies were performed. Following these tests, the analgesic and anti-inflammatory activities of the optimum NS based gel were evaluated using the tail flick and carrageenan-induced paw edema methods consecutively. The NS was successfully prepared with the wet milling method, and the PS, PDI and ZP values were found to be 237.7 ± 6.8 nm, 0.133±0.030, and -30.4 ± 0.7 mV; respectively. Among the NS-based gels, HPMC gel showed more suitable rheological and mechanical properties, also the percentage of permeated FB and the flux value observed for HPMC gel were higher for HPMC than for the other gels. Thus, HPMC gel was selected as a carrier gel for in vivo pharmacodynamics studies. The anti-inflammatory activity of FB-NS HPMC gel was higher than that of the physical mixture gel and that of the coarse suspension gel. Results of our analgesic activity studies showed that, in the 180th min of FB nanosuspension treatment, the latency time was significantly prolonged compared to that of the control group (p less then 0.05). As a conclusion, while nanosuspensions increased the in vivo pharmacodynamics effect of FB by means of nanosized particles and a large surface area, the HPMC gel as a carrier prolonged the contact time of NSs with skin and eased the dermal application.Inflammatory bowel disease (IBD) is a group of chronic, relapsing disorders of the gastrointestinal (GI) tract that significantly affect patient's quality of life. The main goals of IBD treatment are long-lasting clinical remission without serious adverse events. The lack of fully effective treatment urges researchers to seek for new therapeutic strategies and design of novel anti-inflammatory compounds. In this review, we focus on the latest advances in the IBD therapy. We characterize the clinical efficacy and mechanism of action of stem cell-, antibody- and small molecule-based methods of treatment that already reached clinic or are currently evaluated in clinical studies. The scope of this article is on agents targeting interleukin 12 and 23, integrins α4β7 and αEβ7, mucosal vascular addressin cell adhesion molecule, janus kinases, sphingosine-1-phosphate and toll-like receptor 9. We also describe recent advances in the discovery of biomarkers in IBD.Learning to act to receive reward and to withhold to avoid punishment has been found to be easier than learning the opposite contingencies in young adults. To what extent this type of behavioral adaptation might develop during childhood and adolescence and differ during aging remains unclear. We therefore tested 247 healthy individuals across the human life span (7-80 years) with an orthogonalized valenced go/no-go learning task. Computational modeling revealed that peak performance in young adults was attributable to greater sensitivity to both reward and punishment. However, in children and adolescents, we observed an increased bias toward action but not reward sensitivity. By contrast, reduced learning in midlife and older adults was accompanied by decreased reward sensitivity and especially punishment sensitivity along with an age-related increase in the Pavlovian bias. These findings reveal distinct motivation-dependent learning capabilities across the human life span, which cannot be probed using conventional go/reward no-go/punishment style paradigms that have important implications in lifelong education.In periodontal treatment, topical adjunctive therapy with antimicrobials or anti-inflammatory agents is frequently applied. However, currently available drug carrier biomaterials often exhibit poor perfusion into small crevices, such as the deep and irregular periodontal pockets, due to relatively high viscosity. Moreover, high polymer concentrations of the polymer can potentially be cytotoxic upon confined local administration. This study aimed to formulate an antimicrobial and anti-inflammatory treatment option, by incorporating doxycycline (DOX) and/or lipoxin A4 (LXA4) into 0.5 wt% thermo-reversible polyisocyanopeptide (PIC). PIC can form hydrogels upon low polymer concentration, and we hypothesized that the thermo-reversible nature of the material would allow for application into the periodontal pocket. The formulations were characterized in vitro and finally tested in dogs with naturally occurring periodontitis, which were not euthanized afterward. Results showed that PIC/DOX/LXA4 hydrogel could be easily prepared and injected into periodontal pockets. The PIC hydrogel facilitated the release of DOX or LXA4 for around 4 days in vitro. When applied in dogs, the hydrogel exerted no local or systemic adverse effects. Gels loaded with LXA4 and/or DOX reduced the subgingival bacterial load and pro-inflammatory interleukin-8 level. In addition, PIC-DOX and PIC-DOX+LXA4 improved gingival clinical attachment by 0.6 mm compared with conventional periodontal treatment alone (i.e. mechanical debridement). In conclusion, the thermo-reversible PIC hydrogel is a safe and effective vehicle for periodontal drug delivery.Nanoparticle (NP)-based drug delivery systems accumulate in the disrupted epithelium of inflamed colon tissue in ulcerative colitis. However, premature early drug release and uptake or degradation of NPs during their passage through the harsh gastric or intestinal environment compromise their therapeutic outcomes. This study aimed to develop an advanced colitis-targeted hybrid nanoparticles-in-microparticles (NPsinMPs) drug delivery system to overcome the aforementioned challenges. First, sustained drug releasing poly(lactic-co-glycolic acid) NPs were generated and further encapsulated in pH-sensitive Eudragit FS30D MPs to ensure complete drug protection in a gastric-like pH and for selective delivery of NPs to the colon. SEM and confocal microscopy for the NPsinMPs revealed successful NP encapsulation. NPsinMPs prevented drug release in an acidic gastric-like and intestinal-like pH and presented a sustained release thereafter at an ileal and colonic pH, indicating the degradation of the outer pH-sensitive MPs and release of NPs. Furthermore, in vivo imaging of gastrointestinal tract of a colitis mouse orally administered with fluorescent NPsinMPs revealed higher fluorescence intensities selectively in the colon, demonstrating the release of loaded NPs and their concomitant accumulation at the site of colon inflammation. NPsinMPs markedly mitigated experimental colitis in mice indicated by improved histopathological analysis, decreased myeloperoxidase activity, neutrophils and macrophage infiltration, and expression of proinflammatory cytokines in colonic tissues compared with NP-treated mice. The present results show the successful formulation of an NPsinMP-based drug delivery system and provide a platform to improve NP-based colon-targeted drug delivery through improved protection of encapsulated NPs and their payload in the early small intestine.Multivalent antibodies such as sIgA can crosslink motile entities such as sperm and bacteria, creating agglomerates that are too large to permeate the dense mucin matrix in mucus, a process commonly referred to as immune exclusion. Unfortunately, sIgA remains challenging to produce in large quantities, and easily aggregates, which prevented their use in clinical applications. To develop sIgA-like tetravalent antibodies that are stable and can be easily produced in large quantities, we designed two IgGs possessing 4 identical Fab domains, with the Fabs arranged either in serial or in the diametrically opposite orientation. As a proof-of-concept, we engineered these tetravalent IgG constructs to bind a ubiquitous sperm antigen using a Fab previously isolated from an immune infertile woman. Both constructs possess at least 4-fold greater agglutination potency and induced much more rapid sperm agglutination than the parent IgG, while exhibiting comparable production yields and identical thermostability as the parent IgG. These tetravalent IgGs offer promise for non-hormonal contraception and underscores the multimerization of IgG as a promising strategy to enhance antibody effector functions based on immune exclusion.A better understanding of bone nanostructure around the bone-implant interface is essential to improve longevity of clinical implants and decrease failure risks. This study investigates the spatio-temporal evolution of mineral crystal thickness and plate orientation in newly formed bone around the surface of a metallic implant. Standardized coin-shaped titanium implants designed with a bone chamber were inserted into rabbit tibiae for 7 and 13 weeks. Scanning measurements with micro-focused small-angle X-ray scattering (SAXS) were carried out on newly formed bone close to the implant and in control mature cortical bone. Mineral crystals were thinner close to the implant (1.8 ± 0.45 nm at 7 weeks and 2.4 ± 0.57 nm at 13 weeks) than in the control mature bone tissue (2.5 ± 0.21 nm at 7 weeks and 2.8 ± 0.35 nm at 13 weeks), with increasing thickness over healing time (+30 % in 6 weeks). These results are explained by younger bone close to the implant, which matures during osseointegration. Thinner mineral crystals parallel to the implant surface within the first 100 µm indicate that the implant affects the ultrastructure of neighbouring bone , potentially due to heterogeneous interfacial stresses, and suggest a longer maturation process of bone tissue and difficulty in binding to the metal. The bone growth kinetics within the bone chamber was derived from the spatio-temporal evolution of bone tissue's nanostructure, coupled with microtomographic imaging. The findings indicate that understanding mineral crystal thickness or plate orientation can improve our knowledge of osseointegration.Opsonization of nanocarriers is one of the most important biological barriers for controlled drug delivery. The typical way to prevent such unspecific protein adsorption and thus fast clearance by the immune system is the covalent modification of drug delivery vehicles with poly(ethylene glycol) (PEG), so-called PEGylation. Recently, polyphosphoesters (PPEs) were identified as adequate PEG substitutes, however with the benefits of controllable hydrophilicity, additional chemical functionality, or biodegradability. Here, we present a general strategy by non-covalent adsorption of different nonionic PPE-surfactants to nanocarriers with stealth properties. Polyphosphoester surfactants with different binding motifs were synthesized by anionic ring-opening polymerization of cyclic phosphates or phosphonates and well-defined polymers were obtained. They were evaluated with regard to their cytotoxicity, protein interactions, and corona formation and their cellular uptake. We proved that all PPE-surfactants have lower cytotoxicity as the common PEG-based surfactant (Lutensol® AT 50) and that their hydrolysis is controlled by their chemical structure. Two polymeric nanocarriers, namely polystyrene and poly(methyl methacrylate), and bio-based and potentially biodegradable hydroxyethyl starch nanocarriers were coated with the PPE-surfactants. All nanocarriers exhibited reduced protein adsorption after coating with PPE-surfactants and a strongly reduced interaction with macrophages. This general strategy allows the transformation of polymeric nanocarriers into camouflaged nanocarriers and by the chemical versatility of PPEs will allow the attachment of additional moieties for advanced drug delivery.Resistance to β-lactam antibiotics in Gram-negatives producing metallo-β-lactamases (MBLs) represents a major medical threat and there is an extremely urgent need to develop clinically useful inhibitors. We previously reported the original binding mode of 5-substituted-4-amino/H-1,2,4-triazole-3-thione compounds in the catalytic site of an MBL. Moreover, we showed that, although moderately potent, they represented a promising basis for the development of broad-spectrum MBL inhibitors. Here, we synthesized and characterized a large number of 4-amino-1,2,4-triazole-3-thione-derived Schiff bases. Compared to the previous series, the presence of an aryl moiety at position 4 afforded an average 10-fold increase in potency. Among 90 synthetic compounds, more than half inhibited at least one of the six tested MBLs (L1, VIM-4, VIM-2, NDM-1, IMP-1, CphA) with Ki values in the μM to sub-μM range. Several were broad-spectrum inhibitors, also inhibiting the most clinically relevant VIM-2 and NDM-1. Active compounds geners MBLs.
Mothers of infants hospitalized in neonatal intensive care units (NICUs) need to be recognized as essential partners of the care team as their presence and involvement are key to infants' health and developmental outcomes. Addressing mothers' perceived needs is beneficial for the improvement of supportive nursing care; however, little qualitative research on their unmet needs has been conducted in South Korea. This study assessed mothers' perspectives on their NICU experiences and their unmet needs within the South Korean cultural context.

A cross-sectional, multicentered, secondary analysis study was conducted using the written responses to an open-ended questionnaire. Of the 344 NICU-experienced mothers, 232 throughout South Korea (seven cities and five provinces) voluntarily completed the questionnaire via smartphone-based or web-based surveys. Their narrative responses were analyzed using thematic content analysis guided by the critical incident technique.

Four themes emerged. NICU-experienced motheto NICU staff.
The aim of this study is to evaluate the psychometric properties of the Turkish version of the Health Professionals Communication Skills Scale (HP-CSS).

The HP-CSS was translated into Turkish following an international instrument translation guideline. A convenience sample of 394 health professionals participated in this study. Internal consistency reliability, content validity, test-retest reliability, and convergent validity were assessed. A confirmatory factor analysis was conducted to evaluate the construct validity.

The Turkish version of HP-CSS comprised four factors (empathy, informative communication, respect, and social skill). The HP-CSS-TR demonstrated adequate internal consistency (Cronbach'sα values .72-.79). In terms of the content validity, the scale-level content validity index (CVI) was .94, and the item-level CVI ranged from .83 to 1.00. The HP-CSS-TR showed good test-retest reliability (intraclass correlation coefficients were above .82). No statistically significant difference was found between the applications. There was a good agreement between the HP-CSS-TR and communication skills inventory (CSI) scales. Confirmatory factor analysis results (χ2/df, GFI, AGFI, IFI, TLI, CFI, RMSEA, and SRMR) showed a good fit for the original four-factor model.

Results showed that the Turkish version of the HP-CSS is a valid and reliable tool for the assessment of communication skills of health professionals in Turkey. The use of the HP-CSS-TR measure in clinical settings could be useful in enhancing the quality of care by identifying inadequacies and improving communication skills.
Results showed that the Turkish version of the HP-CSS is a valid and reliable tool for the assessment of communication skills of health professionals in Turkey. The use of the HP-CSS-TR measure in clinical settings could be useful in enhancing the quality of care by identifying inadequacies and improving communication skills.Details of incident cases of porcine reproductive and respiratory syndrome (PRRS) in United States breeding herds were obtained from the Morrison's Swine Health Monitoring Project. Herds were classified as cases if they reported an outbreak in a given season of the year and non-cases if they reported it in a season other than the case season or if they did not report a PRRS outbreak in any season. The geographic distribution of cases and non-cases was compared in each season of the year. The density of farms that had a PRRS outbreak during summer was higher in Southern Minnesota and Northwest-central Iowa compared to the density of the underlying population of non-case farms. This does not mean that PRRS outbreaks are more frequent during summer in absolute terms, but that there was a geographical clustering of herds breaking during summer in this area. Similar findings were observed in autumn. In addition, the density of farms reporting spring outbreaks was higher in the Southeast of the United States compars throughout the year. We showed that not only the spatial risk of PRRS varies regionally according to the season of the year, but also that the effect of swine density, herd size and air filtering on PRRS incidence may also vary according to the season of the year. Further studies should investigate regional and seasonal drivers of disease. Breeding herds should maintain high biosecurity standards throughout the year.Determination of steroid hormones synthesized by the human body plays an important role in various fields of endocrinology. Neurosteroids (NS) are steroids that are synthesized in the central (CNS) or peripheral nervous system (PNS), which is not only a source but also a target for neurosteroids. They are discussed as possible biomarkers in various cognitive disorders and research interest in this topic raises continuously. Nevertheless, knowledge on functions and metabolism is still limited, although the concept of neurosteroids was already introduced in the 1980s. Until today, the analysis of neurosteroids is truly challenging. The only accessible matrix for investigations of brain metabolism in living human beings is cerebrospinal fluid (CSF), which therefore becomes a very interesting specimen for analysis. However, neurosteroid concentrations are expected to be very low and the available amount of cerebrospinal fluid is limited. Further, high structural similarities of endogenous neurosteroids challenges analysis. Therefore, comprehensive methods, highly selective and sensitive for a large range of concentrations for different steroids in one aliquot are required and under continuous development. Although research has been increasingly intensified, still only few data are available on reference levels of neurosteroids in human cerebrospinal fluid. In this review, published literature of the last twenty years, as a period with relatively contemporary analytical methods, was systematically investigated. Considerations on human cerebrospinal fluid, different analytical approaches, and available data on levels of in analogy to periphery conceivable occurring neurosteroids, including (pro-) gestagens, androgens, corticoids, estrogens, and steroid conjugates, and their interpretation are intensively discussed.Coronary artery aneurysms (CAAs) are infrequent but not rare. Because of the lack of supportive data and a substantial knowledge gap in this field, clinicians are in a dilemma how to manage patients with coronary artery aneurysms. Most often, CAAs are discovered incidentally, while symptomatic patients present with diverse complications of unstable angina, myocardial infarction, arrhythmias, or sudden cardiac death. Therapeutical approaches consist of surgical procedure, percutaneous coronary intervention (PCI), and medical management. Because of the scarcity of randomized trials or large-scale data on symptomatic and asymptomatic patients with coronary artery aneurysms, the management of these patients poses considerable challenges for the cardiologists. This review summarizes the current literature, a proposed algorithm for the management of CAAs is highlighted in the text. In view of the majority of current proposal information based on small series of case reports or observational studies, an individualized therapeutic regimen should be on the basis of the location, expansion by time, morphology, complications, and etiologies of the coronary artery aneurysms, the clinical presentations, and the patient's characteristics.Recently the role of metabolic signaling pathways has emerged as playing a critical role in dictating the outcome of T cell responses. The uptake and metabolism of the amino acid glutamine is essential for effector T cell activation. Since the growth and expansion of tumor cells relies on similar anabolic and metabolic requirements, we hypothesized that glutamine blockage might represent a promising strategy to promote allograft survival while inhibit tumor growth. 6-Diazo-5-oxo-L-norleucine (DON) was used as a glutamine antagonist. First, an in vitro study of T cell proliferation was performed to examine the ability of glutamine antagonism to inhibit T cell proliferation. Then we investigated whether DON could prolong allograft survival and inhibit tumor growth by using a fully MHC-mismatched mice full thickness skin transplantation model and a mice TC-1 tumor-bearing model. The proliferation study demonstrated that DON inhibited effector T cells proliferation in a dose-dependent manner. We found a marked prolonged graft median survival time and significant tumor inhibition for mice that received DON compared to those that received no treatment. These results highlight that targeting glutamine metabolism can promote allograft acceptance in a long tumor-free period.
A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid.

Peritoneal and serum concentrations of caspofungin, micafungin and anidulafungin were analysed in surgical patients with suspected candida peritonitis. After 4 days of starting therapy, serum and peritoneal samples (through peritoneal drainage) were obtained at baseline, 1, 6, 12 and 24 h of drug administration. Micafungin and anidulafungin concentrations were determined using high-performance liquid chromatography (HPLC/F), whereas caspofungin concentrations were established by bioassay.

Twenty-three critically ill patients with suspected abdominal fungal infection who were receiving an echinocandin were prospectively recruited. No specific criteria were applied to prescribe one specific echinocandin. No special clinical differences were observed among the three groups of patients. All were receiving antibiotic therapy, 80% required inotropic dnged treatment with echinocandins and suboptimal control of abdominal infection.
Glucagon is well known to regulate blood glucose but may be equally important for amino acid metabolism. Plasma levels of amino acids are regulated by glucagon-dependent mechanism(s), while amino acids stimulate glucagon secretion from alpha cells, completing the recently described liver-alpha cell axis. The mechanisms underlying the cycle and the possible impact of hepatic steatosis are unclear.

We assessed amino acid clearance invivo in mice treated with a glucagon receptor antagonist (GRA), transgenic mice with 95% reduction in alpha cells, and mice with hepatic steatosis. In addition, we evaluated urea formation in primary hepatocytes from ob/ob mice and humans, and we studied acute metabolic effects of glucagon in perfused rat livers. We also performed RNA sequencing on livers from glucagon receptor knock-out mice and mice with hepatic steatosis. Finally, we measured individual plasma amino acids and glucagon in healthy controls and in two independent cohorts of patients with biopsy-verified non-alcoeduced after diet-induced reduction in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, a marker of hepatic steatosis).

Glucagon regulates amino acid metabolism both non-transcriptionally and transcriptionally. Hepatic steatosis may impair glucagon-dependent enhancement of amino acid catabolism.
Glucagon regulates amino acid metabolism both non-transcriptionally and transcriptionally. Hepatic steatosis may impair glucagon-dependent enhancement of amino acid catabolism.A novel coronavirus related to severe acute respiratory syndrome virus, (SARS-CoV-2) is the causal agent of the COVID-19 pandemic. Despite the genetic mutations across the SARS-CoV-2 genome being recently investigated, its transcriptomic genetic polymorphisms at inter-host level and the viral gene expression level based on each Open Reading Frame (ORF) remains unclear. Using available High Throughput Sequencing (HTS) data and based on SARS-CoV-2 infected human transcriptomic data, this study presents a high-resolution map of SARS-CoV-2 single nucleotide polymorphism (SNP) hotspots in a viral population at inter-host level. Four throat swab samples from COVID-19 infected patients were pooled, with RNA-Seq read retrieved from SRA NCBI to detect 21 SNPs and a replacement across the SARS-CoV-2 genomic population. Twenty-two RNA modification sites on viral transcripts were identified that may cause inter-host genetic diversity of this virus. In addition, the canonical genomic RNAs of N ORF showed higher expression in transcriptomic data and reverse transcriptase quantitative PCR compared to other SARS-CoV-2 ORFs, indicating the importance of this ORF in virus replication or other major functions in virus cycle. Phylogenetic and ancestral sequence analyses based on the entire genome revealed that SARS-CoV-2 is possibly derived from a recombination event between SARS-CoV and Bat SARS-like CoV. Ancestor analysis of the isolates from different locations including Iran suggest shared Chinese ancestry. These results propose the importance of potential inter-host level genetic variations to the evolution of SARS-COV-2, and the formation of viral quasi-species. The RNA modifications discovered in this study may cause amino acid sequence changes in polyprotein, spike protein, product of ORF8 and nucleocapsid (N) protein, suggesting further insights to understanding the functional impacts of mutations in the life cycle and pathogenicity of SARS-CoV-2.
One of the most common mental disorders in the perinatal period is postpartum depression (PPD), which is associated with impaired emotional functioning due to alterations in different cognitive aspects including thought and facial emotion recognition (FER). Emotional impairments may affect the interaction and care offered to infants and their later development and therefore interventions with potential to minimize impairments associated with PPD are opportune. Oxytocin (OXT) was shown to have therapeutic properties associated with the promotion of affiliative and pro-social behaviors in different mental disorders. Few studies have assessed its therapeutic potential in PPD.

To assess the effects of the acute administration of intranasal OXT (24IU) on FER of baby faces and negative thoughts after delivery in mothers with and without PPD.

We conducted a randomized double-blind, placebo-controlled trial with a crossover design involving mothers with PPD (N=20) and without PPD (N=35) in the puerperium. Participants completed a static task of FER of baby faces and a questionnaire of post-natal negative thoughts.

Mothers with PPD had increased scores of negative thoughts about motherhood/infants, but no impairments in FER, when compared to healthy mothers. OXT had no effects on the rates of correct judgments or response times in the FER task, but was associated with response biases to facial happiness and the reduction of negative thoughts in mothers with PPD.

OXT may have positive effects on maternal affiliative behavior, maternal care, and mother-infant interactions as suggested by changes found in different cognitive aspects, thus minimizing the deleterious effects of PPD on child development.
OXT may have positive effects on maternal affiliative behavior, maternal care, and mother-infant interactions as suggested by changes found in different cognitive aspects, thus minimizing the deleterious effects of PPD on child development.Disruptions in reward processing and anhedonia have long been observed in Anorexia Nervosa (AN). Interoceptive deficits have also been observed in AN, including reduced tactile pleasure. However, the extent to which this tactile anhedonia is specifically liked to an impairment in a specialised, interoceptive C-tactile system originating at the periphery, or a more top-down mechanism in the processing of tactile pleasantness remains debated. Here, we investigated differences between patients with and recovered from AN (RAN) and healthy controls (HC) in the perception of pleasantness of touch delivered in a CT-optimal versus a CT-non-optimal manner, and in their top-down, anticipatory beliefs about the perceived pleasantness of touch. To this end, we measured the anticipated pleasantness of various materials touching the skin and the perceived pleasantness of light, dynamic touch applied to the forearm of 27 women with AN, 24 women who have recovered and 30 HCs using C Tactile (CT) afferents-optimal (slow) and non-optimal (fast) velocities. Our results showed that both clinical groups anticipated tactile experiences and rated delivered tactile stimuli as less pleasant than HCs, but the latter difference was not related to the CT optimality of the stimulation. Instead, differences in the perception of CT-optimal touch were predicted by differences in top-down beliefs, alexithymia and interoceptive sensibility. Thus, tactile anhedonia in AN might persist as a trait even after otherwise successful recovery of AN and it is not linked to a bottom-up interoceptive deficit in the CT system, but rather to a learned, defective top-down anticipation of tactile pleasantness.Hyperglycemia is common and associated with poor outcome in acute ischemic stroke patients. Neutrophil extracellular traps (NETs) are increased either in diabetes or ischemic stroke. We aimed to determine the role of NETs in acute ischemic stroke with hyperglycemia as it has not been clarified. NETs were observed in thrombi retrieved from ischemic stroke patients undergoing endovascular treatment. Citrullinated histone H3 was much more abundant in thrombi from hyperglycemic patients than in those from normoglycemic patients. BKS-db/db and wild-type mice injected with glucose were used to establish the permanent middle cerebral artery occlusion model with hyperglycemia. NETs induced by hyperglycemia were detected in the peri-ischemic brain tissue. Inhibition of NET formation decreased the infarction volume both in db/db and wild-type mice with hyperglycemia. Neurological function deficits were alleviated by blocking NET formation. These findings suggest that NETs increased by hyperglycemia play a role in exacerbation of ischemic brain damage.Auditory neuronal responses are modified by background noise. Inferior colliculus (IC) neuronal responses adapt to the most frequent sound level within an acoustic scene (adaptation to stimulus statistics), a mechanism that may preserve neuronal and behavioral thresholds for signal detection. However, it is still unclear whether the presence of foreground stimuli and/or task involvement can modify neuronal adaptation. To investigate how task engagement interacts with this mechanism, we compared the response of IC neurons to background noise, which caused adaptation to stimulus statistics, while macaque monkeys performed a masked tone detection task (task-driven condition) with responses recorded when the same background noise was presented alone (passive listening condition). In the task-dependent condition, monkeys performed a Go/No-Go task while 50-ms tones were embedded within an adaptation-inducing continuous background noise whose levels changed every 50 ms and were drawn from a probability distribution.al, midbrain auditory neurons of behaving animals.Unaccustomed eccentric (ECC) exercise induces muscle fatigue as well as damage and initiates a protective response to minimize impairments from a subsequent bout (i.e., repeated bout effect; RBE). It is uncertain if the sexes differ for neuromuscular responses to ECC exercise and the ensuing RBE. Twenty-six young adults (13 females) performed 2 bouts (4 weeks apart) of 200 ECC maximal voluntary contractions (MVCs) of the dorsiflexors. Isometric (ISO) MVC torque and the ratio of ISO torque in response to low- versus high-frequency stimulation (10100 Hz) were compared before and after (2-10 min and 2, 4, and 7 days) exercise. The decline in ECC and ISO MVC torque and the 10100 Hz ratio following bout 1 did not differ between sexes (P > 0.05), with reductions from baseline of 31.5% ± 12.3%, 24.1% ± 15.4%, and 51.3% ± 12.2%, respectively. After bout 2, the 10100 Hz ratio declined less (45.0% ± 12.4% from baseline) and ISO MVC torque recovered sooner compared with bout 1 but no differences between sexes were evident for the magnitude of the RBE (P > 0.
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