• Heller Omar opublikował 5 miesięcy, 1 tydzień temu

    mallei wild-type strain ATCC 23344 was found to be especially attenuated, as BALB/c mice challenged with the equivalent of 5,350 LD50 completely cleared infection. Based on these findings, we tested the hypothesis that a vaccine containing the Pal protein elicits protective immunity against aerosol challenge. To achieve this, the pal gene was cloned in the vaccine vector Parainfluenza Virus 5 (PIV5) and mice immunized with the virus were infected with a lethal dose of B. mallei. These experiments revealed that a single dose of PIV5 expressing Pal provided 80% survival over a period of 40 days post-challenge. In contrast, only 10% of mice vaccinated with a PIV5 control virus construct survived infection. Taken together, our data establish that the Peptidoglycan-associated lipoprotein Pal is a critical virulence determinant of B. mallei and effective target for developing a glanders vaccine.This study evaluated the efficacy and safety of postoperative acupressure in the recovery of the gastrointestinal system (GIS) after caesarean section. A total of 160 primipara pregnant women delivered by caesarean section under spinal anaesthesia were randomised into four groups group 1 (those who received acupressure), group 2 (coffee was provided three times a day), group 3 (chewed sugar-free gum for 15 min with an interval of 4 h from the second postoperative hour), and group 4 (control group). The first gas outflow and defaecation times of the women were compared among the groups. The first flatus and defaecation exit times of the women in the acupressure group were statistically earlier than those of the other groups. No difference was found among the gum-chewing, coffee, and control groups. Acupressure is effective in reducing the flatus and defaecation exit times due to GIS inactivity after abdominal surgery including caesarean section. Impact statement What is already known about the topic. The slowipuncture or acupressure and should ensure that acupuncture or acupressure practices are converted into a protocol to be implemented in the postoperative period. With this transformation, the treatment methods to increase GIS motility and the reduced medication use can decrease the mother’s and the newborn’s duration of hospital stay and the cost of hospitalisation.

    Sepsis coagulopathy or disseminated intravascular coagulation (DIC) mainly due to progressive endothelial disruption and damage. The glycocalyx is expressed on the endothelial cell surface and contributes to anti-thrombogenicity, anti-inflammatory, and regulates vascular permeability. We aimed to evaluate the clinical utility of plasma glycocalyx components as biomarkers in predicting the onset of DIC in sepsis.

    This was a prospective observational study of 45 patients with sepsis (June to December 2018). Demographic, clinical (Acute Physiology, Age, Chronic Health Evaluation II [APACHE II], Sequential Organ Failure Assessment [SOFA]), and laboratory data from medical records were analyzed. Endothelial glycocalyx components (syndecan-1, heparan sulfate, hyaluronan) were measured using an ELISA kit.

    Among the 45 patients (23, sepsis; 22, septic shock), plasma syndecan-1, heparan sulfate, and hyaluronan levels were higher in those with septic shock and were positively correlated with disease severity as determined by the APACHE II and SOFA scores and lactate levels. Receiver operating characteristic curve analysis revealed high sensitivity and specificity of syndecan-1 for predicting septic shock. Further, these levels were compared between patients with or without the development of DIC. Plasma syndecan-1 and hyaluronan levels were significantly elevated in patients with DIC compared to those in patients without DIC and were strongly associated with activated partial thromboplastin time, prothrombin time, and platelet counts. Area under the curve values for predicting DIC based on syndecan-1 and hyaluronan levels measurements were 0.774 and 0.740, respectively.

    Increased plasma syndecan-1 and hyaluronan levels may be indicators of disease severity and useful predictors for DIC development in sepsis.

    Increased plasma syndecan-1 and hyaluronan levels may be indicators of disease severity and useful predictors for DIC development in sepsis.The extant study aimed to explore the influence of two cytokines TNF-α – 308 and IFN-γ + 874 gene polymorphism on development of renal transplant rejection and to investigate the feasibility of Th1 cytotoxic immune reaction (CD3). It includes 152 kidney recipients were divided into two subgroups 76 stable graft functions (SGF) and 76 allograft dysfunctions (AD) compared with 56 healthy individuals as control group. TNF-α – 308 G > A and IFN-γ + 874 A > T genetic polymorphisms were characterized using ARMS-PCR technique. CD3 protein expression was measured using ELISA Kit. The effect on transplant outcome was analyzed where, statistically significant differences of TNF-a-308 G/A were observed between AD group when compared to SGF group (OR = 0.296, 95% CI = 0.091-0.965, p = .031) in AG genotype (intermediate producer genotype). Also, AD group displayed a statistically significant increase of IFN-γ + 874 TT (high producer genotype) when compared to SGF group (OR = 0.290, 95% CI = 0.127-0.665, p = .003). The expression of CD3+ T lymphocytes in recipients with allograft dysfunction was statistically higher than that with stable allograft function and control groups (732 ± 76, 235 ± 51 and 442 ± 50) respectively and (p ≤ 0.001). In conclusion, IFN-γ + 874 T and TNF-α – 308 A alleles are risk alleles for renal transplant rejection and these two single nucleotide polymorphisms (SNPs) may be implicated in the tendency of rejection after renal transplantation. CD3 may be used as non-invasive biomarker in monitoring of rejection and avoid exposing patients for biopsy risks and sampling error.

    In this study, we investigated whether the Sequential Organ Failure Assessment (SOFA) score performance differs based on the type of infection among patients admitted to the intensive care unit (ICU) with infection.

    Single-center, retrospective study of adult ICU patients admitted with infection between January 2008 and April 2018 at an urban tertiary care center. Patients were uniquely classified into different infection types based on International Classification of Diseases, Ninth Revision (

    ) and

    codes. Infection types included were pneumonia, meningitis, bacteremia, cellulitis, cholangitis/cholecystitis, intestinal and diarrheal disease, endocarditis, urinary tract infection (UTI), and peritonitis. The SOFA score performance and mortality in relation to SOFA score were compared across infection types.

    A total of 12 283 patients were included. Of these, 50.6% were female and the median age was 70 years (interquartile range 57-82). The most common infection types were pneumonia (32.2%) and UTI (3of sepsis.Exosomes, including human melanoma-derived exosomes (HMEX), are known to suppress the function of immune effector cells, which for HMEX has been associated with the surface presence of the immune checkpoint ligand PD-L1. This study investigated the relationship between the BRAF mutational status of melanoma cells and the inhibition of secreted HMEX exosomes on antigen-specific human T cells. Exosomes were isolated from two melanoma cell lines, 2183-Her4 and 888-mel, which are genetically wild-type BRAFWT and BRAFV600E, respectively. HMEX were isolated using a modified, size-exclusion chromatography (SEC) method shown to reduce co-isolation of non-exosome-associated cytokines compared to ultracentrifugation isolation. The immunoinhibitory effect of the exosomes was tested in vitro on patient-derived NY-ESO-1-specific CD8+ T cells challenged with NY-ESO-1 antigen. HMEX from both cell lines inhibited the immune response of antigen-specific T cells comparably, as evidenced by the reduction of IFN-γ and TNF-α in NY-ESO-1 tetramer-positive cells. This inhibition could be partially reversed by the presence of anti-PD-L1 and anti-IL-10 antibodies. IL-10 has been demonstrated to be a critical pathway for sustaining enhanced tumorigenesis in BRAFV600E mutant cells compared to BRAFWT melanoma cells. Thus, we demonstrate that HMEX inhibit antigen-specific T cell responses independent of the BRAF mutational status of the parent cells. In addition, PD-L1 and IL-10 contribute to the HMEX-mediated immunosuppression of antigen-specific human T cells. The inhibitory capacity of exosomes should be taken into consideration when developing therapies that are reliant upon the potency of customized, antigen-specific effector T cells.This study aims to examine the role of ischaemic-modified albumin (IMA) in predicting clomiphene citrate (CC) resistance in patients with CC-resistant and CC-sensitive infertile polycystic ovary syndrome (PCOS). Sixty women patients admitted to the infertility clinic were evaluated. The patients were divided into two groups. Group 1 comprised 30 infertile PCOS patients with CC resistance; group 2 was the control group comprising 30 infertile PCOS patients with CC sensitivity. Serum IMA levels of PCOS patients with CC resistance were significantly higher than CC sensitivity patients (p  less then  .001). The independent variables BMI and age effects were adjusted according to the logistic regression method with groups. Significant differences were observed between the two groups in the levels of IMA (p = .0005), HOMA-IR (p = .0045), insulin (p = .022), free testosterone (p = .0001) and total testosterone (p = .03) values. By using ROC curve analysis for IMA between study and control groups, cut off point of IMents with CC-resistant PCOS.

    The association between autoimmune bullous dermatoses (AIBD) and serum vitamin D levels has been revealed by some studies, however, inconsistent.

    We aimed to evaluate the difference in vitamin D status between AIBD patients and controls.

    We searched the studies about the vitamin D status of AIBD patients in electronic databases published before January 2020. Mean difference (MD) and 95% confidence intervals (CI) of eligible studies were calculated in meta-analyses of 25(OH)D levels. Pooled odds ratio (OR) and 95%CI were used in analyses of the prevalence of hypovitaminosis D. Different subgroup analyses, sensitivity analyses and publication bias assessment were conducted.

    We included nine case-control studies in the meta-analysis. Vitamin D level was significantly lower in both pemphigus (MD -7.02, 95%CI -10.30 to -3.74) and bullous pemphigoid (BP) (MD -6.37, 95%CI -12.15 to -0.58) patients than that in controls. Active pemphigus patients were at higher risk of presenting hypovitaminosis D (OR 6.95, 95%CI 1.37-35.25).

    Abnormal vitamin D status are more common in AIBD patients than that in general population. Therefore, regular monitoring of vitamin D levels and vitamin D supplementation should be considered as part of the management strategy for AIBD.

    Abnormal vitamin D status are more common in AIBD patients than that in general population. Therefore, regular monitoring of vitamin D levels and vitamin D supplementation should be considered as part of the management strategy for AIBD.

    Onychomycosis is an uncommon condition in children with increasing global prevalence. Health practitioners should confirm the diagnosis through mycology examination and examine family members of affected individuals for onychomycosis and tinea pedis.

    To comprehensively summarize the treatment and management strategies for pediatric onychomycosis.

    We performed a comprehensive literature search in the PubMed database to identify clinical studies on treatment for mycologically-confirmed dermatophyte onychomycosis in children <18 years. The exclusion criteria were combination therapy, case reports, reviews, systematic reviews and duplicate studies.

    Per-weight dosing regimens of systemic antifungal agents such as terbinafine, itraconazole, and fluconazole are found to be safe in children and are used off-label for the treatment of pediatric onychomycosis with high efficacy. Topical antifungal agents such as ciclopirox, efinaconazole, and tavaborole have established safety and efficacy in children. Children respond better than adults to topical therapy due to their thinner, faster growing nails. There is no data on the efficacy of medical devices for onychomycosis in children.

    Efinaconazole topical solution 10% and tavaborole topical solution 5% are FDA approved for the treatment of onychomycosis in children ≥6 years; ciclopirox topical solution 8% nail lacquer is approved in children ≥12 years.

    Efinaconazole topical solution 10% and tavaborole topical solution 5% are FDA approved for the treatment of onychomycosis in children ≥6 years; ciclopirox topical solution 8% nail lacquer is approved in children ≥12 years.

    This is the first comprehensive review to focus on currently available evidence regarding maternal, fetal and neonatal mortality cases associated with Coronavirus Disease 2019 (COVID-19) infection, up to July 2020.

    We systematically searched PubMed, Scopus, Google Scholar and Web of Science databases to identify any reported cases of maternal, fetal or neonatal mortality associated with COVID-19 infection. The references of relevant studies were also hand-searched.

    Of 2815 studies screened, 10 studies reporting 37 maternal and 12 perinatal mortality cases (7 fetal demise and 5 neonatal death) were finally eligible for inclusion to this review. All maternal deaths were seen in women with previous co-morbidities, of which the most common were obesity, diabetes, asthma and advanced maternal age. Acute respiratory distress syndrome (ARDS) and severity of pneumonia were considered as the leading causes of all maternal mortalities, except for one case who died of thromboembolism during postpartum period. Fetal and neonatal mortalities were suggested to be a result of the severity of maternal infection or the prematurity, respectively. Interestingly, there was no evidence of vertical transmission or positive COVID-19 test result among expired neonates.

    Current available evidence suggested that maternal mortality mostly happened among women with previous co-morbidities and neonatal mortality seems to be a result of prematurity rather than infection. However, further reports are needed so that the magnitude of the maternal and perinatal mortality could be determined more precisely.

    Current available evidence suggested that maternal mortality mostly happened among women with previous co-morbidities and neonatal mortality seems to be a result of prematurity rather than infection. However, further reports are needed so that the magnitude of the maternal and perinatal mortality could be determined more precisely.Background High-density lipoprotein (HDL) cholesterol has inverse association with cardiovascular disease. HDL possesses anti-inflammatory properties in vitro, but it is unknown whether this may be protective in individuals with inflammation. Methods and Results The functional capacity of HDL to inhibit oxidation of oxidized low-density lipoprotein (ie, the HDL inflammatory index; HII) was measured at baseline and 12 months after random allocation to rosuvastatin or placebo in a nested case-control study of the JUPITER (Justification for the Use of Statins in Prevention An Intervention Evaluating Rosuvastatin) trial. There were 517 incident cases of cardiovascular disease and all-cause mortality compared to 517 age- and sex-matched controls. Multivariable conditional logistic regression was used to examine associations of HII with events. Median baseline HII was 0.54 (interquartile range, 0.50-0.59). Twelve months of rosuvastatin decreased HII by a mean of 5.3% (95% CI, -8.9% to -1.7%; P=0.005) versus 1.3% (95% CI, -6.5% to 4.0%; P=0.63) with placebo (P=0.22 for between-group difference). HII had a nonlinear relationship with incident events. Compared with the reference group (HII 0.5-1.0) with the lowest event rates, participants with baseline HII ≤0.5 had significantly increased risk of cardiovascular disease/mortality (adjusted hazard ratio, 1.53; 95% CI, 1.06-2.21; P=0.02). Furthermore, there was significant (P=0.002) interaction for HDL particle number with HII, such that having more HDL particles was associated with decreased risk only when HDL was anti-inflammatory. Conclusions In JUPITER participants recruited on the basis of chronic inflammation, HII was associated with incident cardiovascular disease/mortality, with an optimal anti-inflammatory HII range between 0.5 and 1.0. This nonlinear relationship of anti-inflammatory HDL function with risk may account in part for the HDL paradox. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT00239681.Thalassemia is a great health burden in mainland China. Carrier screening and prenatal diagnosis (PND) are essential for its prevention. The aim of this study was to describe the trend in the timing of PND for thalassemia in at-risk families in mainland China. All women who were at-risk for thalassemia and received PND at a mainland Chinese tertiary obstetric center between 2011 and 2019 were included. Information required for the survey was obtained from the database of the institute. In total, 4045 women underwent PND for thalassemia, including 1720 for β-thalassemia (β-thal) and 2325 for α-thalassemia (α-thal). The median gestational age for the PND procedure was 13 weeks. The number of PNDs performed increased year by year over this period. For both β-thal and α-thal, the proportion of women undergoing early PND also increased along with the time span. A total of 428 cases was diagnosed prenatally to be affected with β-thal major (β-TM) and 769 were affected with Hb Bart’s disease. Most of the β-TM pregnancies and all of the Hb Bart’s disease pregnancies were terminated. With the implementation of effective screening measures, births of affected infants have been dramatically avoided, and early PND has become the main approach, thus allowing the possibility of obtaining results at an earlier stage of pregnancy.Intimate partner violence (IPV) is a major international public health concern that poses significant mental and physical health risks for affected individuals. To improve prevention efforts, it is imperative that researchers and government bodies understand risk factors for IPV. One such risk factor concerns the extent to which violence is intergenerational, such that exposure to violence predisposes individuals to engage in violence toward intimate partners. The purpose of this research is to assess childhood exposure to violence as a risk factor for perpetration of IPV in adulthood, and to evaluate the Dark Tetrad personality traits as mediators in this relationship. We recruited 153 men and 246 women (age range = 18-73, Mage = 33.50, SDage = 10.26) through Amazon’s Mechanical Turk to complete a series of questionnaires and an open-ended IPV perpetration assessment. Results showed no relationship between IPV perpetration and childhood IPV exposure, indicating that mediation analyses were not possible. Possible explanations are discussed. Follow-up exploratory analyses demonstrated that gender moderated the relationships between childhood IPV exposure and levels of Factor 1 psychopathy and Machiavellianism. Specifically, men who were exposed to IPV in childhood were more likely to develop higher levels of Factor 1 psychopathy and Machiavellianism, whereas women were not. Overall, our findings highlight the importance of providing researchers and clinicians with a greater understanding of environmental events preceding maladaptive trait development. It is also important for researchers and clinicians to consider gender differences in pathways between exposure to IPV and subsequent development of dark personality traits. Theoretical and practical implications are discussed.

    Intensive care unit-acquired weakness (ICUAW) can manifest as muscle weakness or neuropathy-like symptoms, with diagnosis remaining a challenge. Uncertainties surround the long-term cause and sequelae. Therefore, the purpose was to assess incidence, time course and long-term influence on quality of life (QoL) of symptoms in ICU survivors.

    After ethical approval and registration (www.drks.de DRKS00011593), in a single-center cohort study all patients admitted to the ICU in 2007-2017 in a German university hospital were screened. Out of 1,860 patients (≥7d ICU care including ventilation support for ≥72 h, at least 6mo-10y after ICU) 636 were deceased, 912 survivors were contacted.

    149 former patients (age 63.5 ± 13.1y; males 73%; duration in ICU 20.8 ± 15.7d; duration of ventilation 16.5 ± 13.7 h; time post-ICU 4.4 ± 2.7y, 5-10y 43%) consented to be interviewed concerning occurrence, duration, recovery and consequences of ICUAW-associated muscle weakness or neuropathy-like symptoms after ICU. In 75% at lewww.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011593, registration number DRKS00011593.

    ICUAW symptoms were disturbingly common in the majority of long-term survivors, indicating that symptoms persist up to 10y and frequently impair QoL. However, only a small number of patients had been diagnosed with ICUAW. Trial registry Deutsches Register Klinischer Studien (DRKS), https//www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011593, registration number DRKS00011593.Hypertrophic scar (HS) has been considered as a great concern for patients and a challenging problem for clinicians as it can cause functional debility, cosmetic disfigurement and psychological trauma. Although many methods have been developed to prevent and treat HS, the scarless healing is still a worldwide medical problem. In this study, palmatine-loaded poly(ε-caprolactone)/gelatin nanofibrous scaffolds (PCL/GE/PALs) were fabricated by electrospinning, and their effects on wound healing and HS formation were investigated. These nanofiber mats exhibit good antibacterial and antioxidant activities. In vitro studies indicate PCL/GE/PAL scaffolds can facilitate the adhesion, spreading and proliferation of L929 fibroblasts. In vivo tests demonstrate the full-thickness wounds treated with PCL/GE/PAL scaffolds heal about 3.5 days earlier than those in the control group. Scar elevation index measurements and histological analyses reveal PCL/GE/PAL scaffolds significantly inhibit HS formation, with the decrease in the thickness of dermis and epidermis, the number of fibroblasts, as well as the density of collagen and microvascular. Accelerating wound healing and inhibiting HS formation of these scaffolds are contributed to the sustained release of palmatine. The present work validates the potential use of palmatine-loaded electrospun nanofibrous scaffold PCL/GE/PALs as a functional wound dressing for healing wounds and preventing HS formation.Ureteral stents have been widely used as biomedical devices to treat some urological diseases for several decades. However, the encrustation complications hamper the long-time clinical use of the ureteral stents. In this work, a new type of biodegradable material for the ureteral stents, methoxypoly(ethylene glycol)-block-poly(L-lactide-ran-Ɛ-caprolactone) (mPEG-PLACL), is evaluated to overcome this problem. The results show that the hydrophilicity and degradation rate in artificial urine of mPEG-PLACL are both significantly increased. It is worth noting that the mPEG-PLACL shows a lower amount of encrustation after immersing the stents in the dynamic urinary extracorporeal circulation (DUEC) model for 7 days. In addition, 71% Ca and 92% Mg are inhibited in vivo by quantitative analysis. Pathological analysis exhibit that the mPEG-PLACL cause less diffuse mucosal hyperplasia after 7 weeks of implantation. All the results indicate that this new type of biodegradable material had an excellent potential for the ureteral stents in the future.Introduction Double-J ureteral stents are subject to encrustation. Studies have shown that the encrustation onset is linked with indwelling time. In prevention, it is admitted that the Double-J stent indwelt for medium or long term should be replaced periodically. However, in the absence of guidelines, indwelling durations vary with centers’ habits, stent indication, and stent materials. Our target was to evaluate the actual ureteral stent medium-/long-term indwelling times and related encrustation rates perceived by urologists in daily practice. Methods An observational retrospective study was performed over six European centers. All data of all consecutive removed stents of the same material implanted for more than 2 months within a same 2-year referred period were collected. Three stent types of various materials, with/without coating, were evaluated. Encrustation rates were analyzed according to indwelling times and stent indication. Results Four hundred seventy-three stents were recorded with indwelling times between 60 and 679 days. An unexpected number of long-term indwelling times were noticed globally one-third more than 6 months, and 9% more than 1 year. In case of malignant indication, these rates were, respectively, 44% and 17%. For nonstone indication, clinically significant encrustation rates stayed extremely low before 4 months (1.3%) and quite low before 6 months (5.2%), increasing with time to reach around 10% in the long term. However, as expected, the rate was higher for stone indication with a marked increase after 4 months (8% before 4 months, nearly 17% after). Conclusion Our data confirm a higher encrustation risk for stone patients. Long indwelling times in nonstone patients beyond 6 months or even 12 months appear to be still requested and relatively well supported in usual practice by this population.

    High blood pressure effects heart and vessels. Development of pathogenesis is the result of oxidative stress. We aimed to investigate the antioxidant effects of propolis, caffeic acid phenethyl ester (CAPE), and pollen on the hearts of rats which chronic nitric oxide synthase (NOS) inhibited through Nω-nitro-L-arginine methyl ester (L-NAME). Paraoxonase 1 (PON1), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), asymmetric dimethylarginine (ADMA), and nuclear factor-κB (NF-κB) were analyzed on the heart.

    Sprague-Dawley rats were divided five groups of seven rats in every group; Group I Control, Group II L-NAME, Group III L-NAME+propolis, Group IV L-NAME+CAPE and Group V L-NAME+pollen. L-NAME become dissolved in regular saline (0.9% NaCl w/v). The ethanolic extract of propolis (200 mg/kg/days, gavage), pollen (100 mg/kg/days, by gavage), CAPE (50µM/kg/days, intraperitoneally), and the NOS inhibitor L-NAME (40 mg/kg, intraperitoneally) had been administered.

    Blood pressure (BP) of rats treated with propolis, CAP,E and pollen statistically significant decreased. Decreasing in BP of the rats of pollen group was more than CAPE and propolis groups (

    <.05). PON1 and TAS levels decreased in L-NAME-treated groups (

    <.05), but ranges have been better in propolis, CAPE and pollen groups. TOS, ADMA and NF-κB levels increased (

    <.05) in L-NAME group; however, these parameters were lower (

    <.05) in propolis and CAPE groups (

    <.05).

    Vasorelaxant properties and free radical scavenging actions of propolis, CAPE, and pollen may reduce the oxidative stress and blood pressure in the rats chronic NOS inhibited through L-NAME.

    Vasorelaxant properties and free radical scavenging actions of propolis, CAPE, and pollen may reduce the oxidative stress and blood pressure in the rats chronic NOS inhibited through L-NAME.The benefits of pulmonary rehabilitation (PR) for chronic obstructive pulmonary disease (COPD) are restricted by poor uptake and completion. Lay health workers (LHWs) have been effective in improving access to treatment and services for other health conditions. We have successfully shown the feasibility of this approach in a PR setting and its acceptability to the LHWs and COPD patients. We present here the feasibility of assessment, and the fidelity of delivery of LHW support achieved for COPD patients referred for PR. LHWs, volunteer COPD patients experienced in PR, received training in the intervention including communication skills, confidentiality and behaviour change techniques (BCTs). Interactions between LHWs and patients were recorded, transcribed and coded for delivery style and BCTs. Inter-rater agreement on the coding of delivery style and BCTs was high at >84%. LHWs built rapport and communicated attentively in over 80% of interactions. LHWs most consistently delivered BCTs concerning information provision about the consequences of PR often making those consequences salient by referring to their own positive experience of PR. Social support BCTs were also used by the majority of LHWs. The use of BCTs varied between LHWs. The assessment of intervention delivery fidelity by LHWs was feasible. LHW training in the setting of PR should add emphasis to the acquisition of BCT skills relating to goal setting and action planning.This is a retrospective study carried out at a tertiary care cancer center to assess weight loss in patients of head and neck cancers (HNCs) during treatment with chemoradiotherapy (CRT) and study various factors affecting it. Treatment and follow-up records of 77 patients of HNCs were studied and assessed for demographic, disease-specific variables, treatment parameters, weight loss during CRT, as well as survival at 2 years after treatment completion. A statistical analysis was conducted to assess the association of study variables with weight loss. It was also assessed if a correlation existed between weight loss during treatment and patient survival at 2 years. Of the study patients, 62.3% (48) suffered 5% or more weight loss during CRT while 23.4% (18) suffered a weight loss of 10% or more. No particular factor was identified having a statistically significant association with weight loss. Nutritional impairment is an important factor affecting the morbidity and possibly the mortality of patients of HNCs undergoing CRT. More robust studies are required to identify which factors affect weight loss during treatment and whether weight loss can be used as a parameter to prognosticate patients.Issue In medical education, teaching is currently viewed as an intervention that causes learning. The task of medical education research is seen as establishing which educational interventions produce the desired learning outcomes. This 'medical model’ of education does not do justice to the dynamics of education as an open, semiotic, recursive system rather than a closed, causal system. Evidence Empirical 'evidence’ of 'what works’ – that is, what is supposed to affect 'learning’ – has become the norm for medical educational improvements, where generalized summary outcomes of research are often presented as must-follow guidelines for myriad future educational situations. Such investigations of educational processes tend to lack an explicit engagement with the purposes of medical education, which we suggest to understand in terms of qualification (the acquisition of knowledge, skills, and understanding), socialization (becoming a member of the professional group) and subjectification (becoming a thoughtful, ievaluation should be reoriented to include and integrate all three purposes in educational practice. It also means that medical education research findings cannot be applied in just any teaching context without carefully considering the value of the suggested courses of actions toward the particular educational aims and teaching setting. In addition, medical educational research would need to investigate all three purposes and recognize the openness, semiotic nature, and recursivity of education in offering implications for teaching practice.

    Data on infant human milk intakes in low- and middle-income countries are limited, although the deuterium oxide dose-to-mother method (DTM) is an accurate tool for its estimation.

    We assessed human milk intakes of Thai infants during the first 6 months comparing exclusive breastfeeding (EBF), predominant breastfeeding (PBF), and partial breastfeeding (PartBF).

    One hundred and ten healthy Thai lactating mother-infant pairs were followed from birth. Human milk intakes were determined at 6 weeks, 3 months, and 6 months using the DTM method. Daily energy and protein intakes were assessed using 3-day nonconsecutive 24-hour recalls. Sociodemographic characteristics were collected using a questionnaire. To compare breastfeeding practices, one-way analysis of variance with Tukey post hoc test assessed normally distributed data, while the Kruskal-Wallis test with Mann-Whitney

    test was used for not normally distributed data.

    No difference existed in human milk intakes during the first 6 months between EBF (7ov as NCT04020640.

    In 2020, due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronavirus disease (COVID-19) has become a pandemic. As of 11 August 2020, the cumulative number of confirmed cases worldwide had reached 19 million, with 700,000 reported deaths, indicating this pandemic’s significant global impact.

    We reviewed the application of rehabilitation therapy in the clinical treatment of COVID-19 patients. A systematic search was performed using PubMed, Springer, CNKI, and Wanfang Data of database up to 1 August 2020. The search terms included the English terms and their Chinese equivalents 'COVID-19,’ 'ARDS,’ 'rehabilitation,’ 'critically ill patients,’ 'physiotherapy,’ 'respiratory rehabilitation,’ 'traditional Chinese medicine,’ and 'psychotherapy.’

    Rehabilitation research concerning patients with COVID-19 remains ongoing. Rehabilitation guidance for such patients with COVID-19 is based on previous experience. However, as different patients have differing degrees of dysfunction, personalized plans need to be designed according to the patients’ age, sex, lifestyle, hobbies, occupation, and physical conditions. The rapid development of remote devices that can monitor patients’ real-time physical conditions post-discharge may encourage better adherence to rehabilitation training.

    Rehabilitation research concerning patients with COVID-19 remains ongoing. Rehabilitation guidance for such patients with COVID-19 is based on previous experience. However, as different patients have differing degrees of dysfunction, personalized plans need to be designed according to the patients’ age, sex, lifestyle, hobbies, occupation, and physical conditions. The rapid development of remote devices that can monitor patients’ real-time physical conditions post-discharge may encourage better adherence to rehabilitation training.The dark triad (DT) traits are differentially related to psychometrically assessed life history strategy (LHS), such that psychopathy is strongly associated with a faster LHS, whereas narcissism appears to be, if anything, a slow LHS indicator. However, the research supporting these generalizations has been based largely on undergraduate samples in which LHS has been measured using the Arizona Life History Battery (ALHB; or its short version the Mini-K), an instrument that arguably lacks adequate coverage of low-extroversion content linked to a slower LHS. In this study, 929 U.S. MTurk workers completed a set of DT instruments, a 10-item Big Five Inventory, a 42-item version of the ALHB (K-SF-42), and the life history rating form (LHRF), which is less weighted toward high extroversion content than the ALHB. Factor analysis of the DT instruments yielded factors corresponding to callousness, secondary psychopathy, and socially adaptive narcissism (leadership/authority and grandiose exhibitionism). Callousness and secondary psychopathy were fast LHS indicators with respect to both LHS instruments. Socially adaptive narcissism appeared as a slow LHS indicator with respect to the K-SF-42 but as a fast LHS indicator with respect to the LHRF. Variation in extroversion accounted entirely for the K-SF-42’s positive association with socially adaptive narcissism. This study suggests that narcissism’s apparent status as a slow LHS indicator may be more a matter of measurement than of substance.The beneficial impacts of the ketogenic diet and metabolic reprograming were recently reported for ovarian cancer patients. In this study, the effects of glucose restriction with or without beta-hydroxybutyrate (bHB) enrichment were studied in drug-resistant CD133high A2780CP and CD133low SK-OV-3 ovarian cancer cells to scrutinize the impact of experimental ketosis on ATP production, epithelial to mesenchymal transition (EMT), and related signaling pathways including Wnt, Hippo, and Hedgehog. Cells were adapted and maintained for a month with restricted levels of glucose (250 mg/l) with or without the therapeutic concentration of bHB (5 mM). Quantitative PCR, Western blot analysis, flow cytometry, chemiluminescence, and wound healing assay were used in this study. Glucose restriction and bHB enrichment reduced the stemness marker and diminished In Vitro migration in both cell lines. Glucose restriction significantly reduced ATP levels in both cells, but bHB enrichment was partially compensated for the ATP levels solely in SK-OV-3 cells. Glucose restriction mainly inhibited the Wnt pathway in the CD133high A2780CP cells, but the Hedgehog pathway was the main target in CD133low SK-OV-3 cells. In Conclusion, Prior targeted evaluations of key genes’ expression would help to predict the distinctive impacts of metabolic fuels and to optimize the efficacy of ketogenic diets.

    This study was designed to evaluate the possible association between an exaggerated blood pressure (BP) response to exercise and subclinical vascular impairment in normotensive individuals.

    The study participants consisted of 92 untreated normotensive men (aged 42±9years) without a history of cardiovascular disease or stroke. A graded exercise test was conducted using a bicycle ergometer, and the mean arterial pressure (MAP) during submaximal exercise was evaluated. The brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. The second peak of radial systolic BP (SBP2) was used as an estimate of central BP. The albumin-to-creatinine ratio (ACR) values were determined as the mean of two nonconsecutive spot urine specimens.

    Compared with individuals with a normal response (MAP z-score < +1.0,

    =60), those with an exaggerated BP response to exercise (MAP z-score ≥ +1.0,

    =32) exhibited significantly higher baPWV (1412±158 vs. 1250±140 cm/s), radial SBP2 (122±11 vs. 106±13mmHg), and greater log-ACR (0.93±0.30 vs. 0.59±0.23 mg/gCre). Multiple regression analysis revealed that an exaggerated BP response to exercise was significantly associated with baPWV (

    =0.198,

    =.043), radial SBP2 (

    =0.156,

    =.049), and log-ACR (

    =0.276,

    =.006) independent of potential confounding factors.

    These results suggest that subclinical vascular impairment is associated with an exaggerated increase in BP during exercise even in the absence of clinical hypertension.

    These results suggest that subclinical vascular impairment is associated with an exaggerated increase in BP during exercise even in the absence of clinical hypertension.Innovation Procurement Strategies (IPS) strive for purchasing healthcare solutions that do not yet exist on the market and are increasingly being advocated to improve health outcomes while managing escalating healthcare costs. Due to the newness of IPS, there are limited resources available to healthcare organizations and professionals looking to engage in IPS. The purpose of this study was to develop an evidence-based clinical framework to guide healthcare organizations and professionals. Adopting a qualitative grounded theory approach, we interviewed participants with experience in innovation procurement to understand the skills, resources, and supports needed to initiate and oversee an IPS project. Using thematic design and open coding, three overarching themes emerged from the data and formed the basis of our IPS clinical framework. By describing the components, skills, and supports and resources necessary for engaging in IPS, our framework addresses the knowledge gap in healthcare organizations and professionals wishing to implement IPS.

    Retrospective study.

    Previous studies have demonstrated that increased implant density (ID) results in improved coronal deformity correction. However, low-density constructs with strategically placed fixation points may achieve similar coronal correction. The purpose of this study was to identify key zones along the spinal fusion where high ID statistically correlated to improved coronal deformity correction. Our hypothesis was that high ID within the periapical zone would not be associated with increased percent Cobb correction.

    We identified patients with Lenke type 1 curves with a minimum 2-year follow up. The instrumented vertebral levels were divided into 4 zones (1) cephalad zone, (2) caudal zone, (3) apical zone, and (4) periapical zone. High and low percent Cobb correction groups were compared, high percent Cobb group was defined as percent correction >67%. Total ID, total concave ID, total convex ID, and ID within each zone of the curve were compared between the groups. A multivariable analyn each spinal zone was associated with improved percent Cobb correction. The ability to achieve coronal balance was not statistically influence by ID. The results of this study support that increasing ID along the entire length of the construct improves percent Cobb correction.

    Increased ID for the entire construct, the entire convex side, the entire concave side, and within each spinal zone was associated with improved percent Cobb correction. The ability to achieve coronal balance was not statistically influence by ID. The results of this study support that increasing ID along the entire length of the construct improves percent Cobb correction.Pharmaceutical cocrystals are still gaining the interest of the researchers due to their potential to alter physicochemical, mechanical, and pharmacokinetic properties of active pharmaceutical ingredients without negotiating therapeutic action. The diverse new applications of cocrystals, like taste masking, reduced toxicity, patenting opportunities, commercial potential, etc. act as driving force to the rising interest of the pharmaceutical industries. Initially, cocrystals from the view of regulatory authorities, design strategies, cocrystal preparation in brief with special emphasis on scalable and solvent-free hot melt extrusion method, and practical guide to characterization have been provided. The special focus has been given to the biopharmaceutical attributes of the cocrystal. Finally, challenges before and after cocrystal preparation are presented in this review along with some commercial examples of the cocrystals.Objective The objective of this study is to compare the use of three-dimensional (3D) vision systems with traditional two-dimensional systems in laparoscopic urological surgery, analyzing the benefits, limitations, and impact of introducing this medical technology with regard to surgical performance and the surgeon’s ergonomics. Methods A systematic review with a structured bibliographic search was conducted in the electronic libraries (PubMed and EMBASE) until August 2019 and with no language restrictions. Studies on 3D visualization technology in laparoscopic urologic surgery, randomized controlled trials, and observational comparative studies were included. Relevant data were extracted and analyzed. Results A total of 25 articles were obtained, of which 4 were clinical studies with patients, 2 studies were carried out in experimental animal models, and the remaining 19 were conducted in simulated environments. Regarding the European training program in basic laparoscopic urological skills, the results showecreased stress and workloads during 3D vision with no differences in potential side effects.Efforts to identify mutations that underlie inherited genetic diseases combined with strides in the development of gene therapy vectors over the last three decades have culminated in the approval of several adeno-associated virus (AAV)-based gene therapies. Genetic diseases that manifest in the lung such as cystic fibrosis (CF) and surfactant deficiencies, however, have so far proven to be elusive targets. Early clinical trials in CF using AAV serotype 2 (AAV2) achieved safety, but not efficacy endpoints; however, importantly, these studies provided critical information on barriers that need to be surmounted to translate AAV lung gene therapy toward clinical success. Bolstered with an improved understanding of AAV biology and more clinically relevant lung models, next-generation molecular biology and bioinformatics approaches have given rise to novel AAV capsid variants that offer improvements in transduction efficiency, immunological profile, and the ability to circumvent physical barriers in the lung such as mucus. This review discusses the principal limiting barriers to clinical success in lung gene therapy and focuses on novel engineered AAV capsid variants that have been developed to overcome those challenges.We report new consensus models estimating acute toxicity for algae, Daphnia and fish endpoints. We assembled a large collection of 3680 public unique compounds annotated by, at least, one experimental value for the given endpoint. Support Vector Machine models were internally and externally validated following the OECD principles. Reasonable predictive performances were achieved (RMSEext = 0.56-0.78) which are in line with those of state-of-the-art models. The known structural alerts are compared with analysis of the atomic contributions to these models obtained using the ISIDA/ColorAtom utility. A benchmarking against existing tools has been carried out on a set of compounds considered more representative and relevant for the chemical space of the current chemical industry. Our model scored one of the best accuracy and data coverage. Nevertheless, industrial data performances were noticeably lower than those on public data, indicating that existing models fail to meet the industrial needs. Thus, final models were updated with the inclusion of new industrial compounds, extending the applicability domain and relevance for application in an industrial context. Generated models and collected public data are made freely available.

    Dravet syndrome (DS), a prototypic developmental and genetic epileptic encephalopathy (DEE), is characterized by an early onset of treatment-refractory seizures, together with impairments in motor control, behavior, and cognition. Even with multiple conventional anti-epileptic drugs, seizures remain poorly controlled, and there has been a considerable unmet need for effective and tolerable treatments.

    This targeted literature review aims to highlight recent changes to the therapeutic landscape for DS by summarizing the most up-to-date, evidence-based research, including pivotal data from the clinical development of stiripentol, cannabidiol, and fenfluramine, which are important milestones for DS treatment, together with the latest findings of other pharmacotherapies in development. In phase III, double-blind, placebo-controlled randomized controlled trials stiripentol, cannabidiol, and fenfluramine have shown clinically relevant reductions in convulsive seizure frequency, and are generally well tolerated. Stiripentol was associated with responder rates (greater than 50% reduction in convulsive seizure frequency) of 67%-71%, when added to valproic acid and clobazam; cannabidiol was associated with responder rates of 43%-49% (48%-63% in conjunction with clobazam), and fenfluramine of 54%-68% across studies. Therapies in development include soticlestat, ataluren, verapamil, and clemizole, with strategies to treat the underlying cause of DS, including gene therapy and antisense oligonucleotides beginning to emerge from preclinical studies.

    Despite the challenges of drug development in rare diseases, this is an exciting time for the treatment of DS, with the promise of new efficacious and well-tolerated therapies, which may pave the way for treatment advances in other DEEs.

    Despite the challenges of drug development in rare diseases, this is an exciting time for the treatment of DS, with the promise of new efficacious and well-tolerated therapies, which may pave the way for treatment advances in other DEEs.The CD47-Signal regulatory protein α (SIRPα) singling axis acts as a crucial regulator that limits the phagocytic activity of professional phagocytes such as macrophages. Recent studies have demonstrated that the interaction between CD47 on tumor cells and SIRPα on macrophages is implicated in the ability of tumors to evade immunosurveillance. Targeting the CD47-SIRPα interaction is therefore considered to be a promising approach for cancer therapy. Herein, we review some of studies displaying the potential clinical application of antibodies and other modalities that target the CD47-SIRPα interaction. Current limitations of the CD47-SIRPα-targeted immunotherapeutic approaches are also discussed as well as other avenues for future study to improve the current strategies in targeting the CD47-SIRPα signaling axis for cancer immunotherapy.

    Prospective study.

    To study the increasing divergence between targeted and achieved distractions observed with magnetically controlled growing rod (MCGR)lengthening, and the relationship of this reduced rate of achieved lengthening with remaining rod length.

    Patients with early onset scoliosis (EOS) who underwent MCGRs with minimum 2-year follow-up were consecutively enrolled. Targeted and achieved lengths were compared. Correlation between percentage of lengthening achieved from targeted length was identified with the timing of rod exchanges.

    A total of 20 patients fulfilled the inclusion criteria. The mean age at index surgery was 9.5 years and mean postoperative follow-up was 68 ± 28 months. Of these, 8 patients had at least one rod exchange that occurred at 23 ± 4 months. A decrease in rate of achieved lengthening was observed when compared with targeted distractions. The achieved lengthening drops from 86% of targeted length at the first distraction to only 58.8% at the 21st distraction episode for the first set of rods. After rod exchange, the average achieved lengthening went back up to 81.3% of the targeted length but subsequently had a gradual reduction to 35% at the 19th distraction episode.

    We propose a „law of temporary diminishing distraction gains” that MCGR users should be aware of when monitoring rod lengthening. Diminishing distraction length gains is observed as the rod is lengthened and is a phenomenon independent of patient factors. It is only temporary as the rates of achieved lengthening returns to baseline after rod exchange.

    We propose a „law of temporary diminishing distraction gains” that MCGR users should be aware of when monitoring rod lengthening. Diminishing distraction length gains is observed as the rod is lengthened and is a phenomenon independent of patient factors. It is only temporary as the rates of achieved lengthening returns to baseline after rod exchange.

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