Notes

Cortical connections with the useful website for hiking as well as operating in posterior parietal cortex regarding galagos.
Although multiple antimicrobial resistance (AMR) determinants can confer the same in vitro antimicrobial susceptibility testing (AST) phenotype, their differing effect on optimal therapeutic choices is uncertain. Using a large population-based collection of clinical strains spanning a 3.5-year period, we applied WGS to detect inhibitor resistant (IR), extended-spectrum β-lactamase (ESBL), and carbapenem resistant (CR) β-lactamase (bla) genes and compared the genotype to the AST phenotype in select isolates. All blaNDM-1 (9/9) and the majority of blaNDM-1/OXA-48 (3/4) containing isolates were resistant to CAZ/AVI as predicted by WGS. The combination of ATM and CAZ/AVI restored susceptibility by disk diffusion assay. Unexpectedly, clinical Kp isolates bearing blaKPC-8 (V240G) and blaKPC-14 (G242 and T243 deletion) did not test fully resistant to CAZ/AVI. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. Presumed phenotypes conferred by AMR determinants need to be tested if therapeutic decisions are being guided by their presence or absence.
Emergence of carbapenem resistance (CR) is a health concern of pertinent importance. Epidemiological surveillance of CR at global and indigenous level (Pakistan) can help to improve infection control and establish pharmacovigilance programs. This study evaluates the prevalence of clinically significant CR isolates, and its genetic variant distribution among geographical regions of Pakistan.

A meta-analysis was conducted to present the current rate of CR infections and prevalence of Metallo-β-lactamases (MBLs). The proposed subject was researched using electronic databases to identify the available literature. Thereafter, relevant data was extracted and statistical analysis was performed using STATA version 14.

A total of 110 relevant studies were identified with 19 meeting the inclusion criteria for the meta-analysis of CR, while 22 for MBLs. Pooled rate for carbapenem resistance was determined to be 0.28 (95% CI 0.26-0.31) with overall significant heterogeneity (I
=99.61%, P<0.001) and significant Delhi Metallo-β-lactamase (NDM)-variants were reported in predominant literature. The prevalence of CR isolates in Pakistan is alarming, associated with MBL production primarily evident from the studies. The study emphasizes the need for regular surveillance, pharmacovigilance and antibiotic stewardship programs to ensure the availability of data to the authorities for preemptive measures of infection control.Tuning of operational variables is a common practice to control the anaerobic digestion process and, in advanced applications, to promote the accumulation of fermentation products. However, process variables are interrelated. In this study, the hydraulic retention time (HRT) was decoupled from the organic loading rate (OLR) in order to isolate the effect of HRT as a selective pressure on process performance, metabolic rates (hydrolytic, acetogenic, and methanogenic) and the microbial community. Four mesophilic anaerobic digesters were subjected to a sequential decrease in HRT from 15 to 8, 4 and 2 days while keeping the OLR constant at chemical oxygen demand of 1 gCOD L r-1 d-1. The results showed that HRT alone was insufficient to washout methanogens from the digesters, which in turn prevented the accumulation of volatile fatty acids (VFA). Methanosaeta was the dominant genus in the four digesters at all HRTs. Metabolic rates showed that process performance was controlled by hydrolysis, with a clear shift in acetogenic rates, from butyrate and propionate degradation to ethanol degradation at 4 and 2d HRT. The change in acetogenic pathways was attributed to a shift in the fermentation pathways co-current with changes in fermentative bacteria. At 2d HRT, biofilm was formed on the walls and paddles of the digesters, probably as a survival strategy. Most of the taxa in the biofilm were also present in the digester media. Overall, it is the combination of HRT with other operational parameters which promotes the washout of methanogens and the accumulation of VFA.Truncated 3'-deoxy- 3', 3' difluororibofuranosyl pyrimidine nucleoside derivatives were synthesized from d-ribose via β-apioribo pyrimidine nucleoside intermediates 11a-c. The synthetic approach signifies that truncation at C3' position of apioribose ring of 13a-c by oxidative cleavage of diols with Pb(OAc)4 and followed by fluorination with DAST as key steps. Cytotoxic evaluation of synthesized truncated nucleoside derivatives 16a-c and 19a-c were tested against MCF7 and MDA-MB-231 breast cancer cell lines. However, only 19a was shown minimal growth suppression activity on MDA-MB-231 cancer cell lines.While full integration of robotic surgery has been achieved in other surgical domains, its transition into neurosurgery has been more prolonged, especially with respect to pituitary surgery. The confined working space and precise maneuvers required in endoscopic endonasal surgery makes development of an efficacious and safe robotic system difficult. Nevertheless, preclinical studies have attempted to demonstrate the feasibility of the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) in both transnasal and transoral approaches. In addition, unique robotics such as the concentric tube robot have been created. This system is optimized specifically for anterior skull base surgery with smaller shaft diameter arms and improved maneuverability in tight corridors. The possible role of concentric tube robotics surgery in skull base pathologies has been explored, and the novel use of telesurgery incorporated into robotic neurosurgery is discussed. An endoscopic endonasal transsphenoidal surgical system has also been developed, integrating computational methods to create a presurgical reconstructive model for surgical planning and automating the line of dissection for an enhanced approach to the sphenoid sinus. While surgical robotics for transsphenoidal surgery remain in its nascency, these preliminary findings are promising and suggest a role for robotic pituitary surgery.Three physiologically mineralizing tissues - teeth, cartilage and bone - have critical common elements and important evolutionary relationships. Phylogenetically the most ancient densely mineralized tissue is teeth. In jawless fishes without skeletons, tooth formation included epithelial transport of phosphates, a process echoed later in bone physiology. Cartilage and mineralized cartilage are skeletal elements separate from bone, but with metabolic features common to bone. Cartilage mineralization is coordinated with high expression of tissue nonspecific alkaline phosphatase and PHOSPHO1 to harvest available phosphate esters and support mineralization of collagen secreted locally. Mineralization in true bone results from stochastic nucleation of hydroxyapatite crystals within the cross-linked collagen fibrils. Mineral accumulation in dense collagen is, at least in major part, mediated by amorphous aggregates - often called Posner clusters - of calcium and phosphate that are small enough to diffuse into collagen fibrils. Mineral accumulation in membrane vesicles is widely suggested, but does not correlate with a definitive stage of mineralization. Conversely mineral deposition at non-physiologic sites where calcium and phosphate are adequate has been shown to be regulated in large part by pyrophosphate. All of these elements are present in vertebrate bone metabolism. A key biological element of bone formation is an epithelial-like cellular organization which allows control of phosphate, calcium and pH during mineralization.Patients with poorly controlled type 2 diabetes mellitus (T2DM) often experience delayed tooth extraction socket (TES) healing. Delayed healing is often associated with an aberrant inflammatory response orchestrated by either M1 pro-inflammatory or M2 anti-inflammatory macrophages. However, the precise mechanism for the attenuated TES healing remains unclear. Here we used diet-induced T2DM mice as a model to study TES. Compared with the control group, the T2DM group showed delayed TES healing and diminished expression of osteogenic and angiogenic genetic profiles. Meanwhile, we detected a more inflammatory profile, with more M1 macrophages and TNF-α expression and less M2 macrophages and PPARγ expression, in TES in the T2DM group when compared to control mice. In vitro co-culture models showed that M1 macrophages inhibited the osteogenic capacity of bone marrow stromal cells and the angiogenic capacity of endothelial cells while M2 macrophages showed an opposite effect. In addition, we constructed a gelatin/β-TCP scaffold with IL-4 to induce macrophage transformation towards M2 polarization. In vitro analyses of the hybrid scaffold revealed sustained release of IL-4 and a phenotype switch to M2 macrophages. Finally, we demonstrated that sustained IL-4 release significantly increased expression of osteogenic and angiogenic genetic profiles and improved TES healing in T2DM mice. Together, we report that increased M1 and decreased M2 macrophage polarization may be responsible for delayed TES healing in T2DM patients through abnormal expression of TNF-α and PPARγ. This imbalance negatively influences osteogenesis and angiogenesis, two of the most important biological factors in bone wound healing. Enhancing M2 macrophage polarization with IL-4 delivery system may represent a potential strategy for promoting the healing of TES in T2DM patients.Bone nonunion caused by bacterial infection accounts for bone fractures, bone trauma and bone transplantation surgeries. Severe consequences include delayed unions and amputation and result in functional limitations, work disability, and poor quality of life. However, the mechanism of bone nonunion remains unknown. In this study, we aimed to screen the miRNA biomarkers of bacterial bone infection and investigated whether miRNAs regulate the osteoblasts and thus contribute to bone nonunion. We established a miRNA-mRNA network based on high-throughput RNA sequencing to compare the model rabbits infected with Staphylococcus aureus with the control rabbits. After validation experiments, miRNA-331-3p and fibroblast growth factor 23 (FGF23) were found to be inversely correlated with the pathways of osteoblast mineralization and pathology of infected bone nonunion. In in vitro experiments, miRNA-331-3p was downregulated and FGF23 was upregulated in lipopolysaccharide (LPS)-induced mouse calvarial osteoblasts. Further studies of the mechanism showed that mutated of putative miRNA-331-3p can bind to FGF23 3'-untranslated region sites. MiRNA-331-3p acted as an osteoblast mineralization promoter by directly targeting FGF23. Downregulation of miRNA-331-3p led to inhibition of osteoblast mineralization by regulating the DKK1/β-catenin mediated signaling. Thus, we established an improved animal model and identified new bone-related biomarkers in the infected bone nonunion. The miRNA-331-3p biomarker was demonstrated to regulate osteoblast mineralization by targeting FGF23. The novel mechanism can be used as potential diagnostic biomarkers and therapeutic targets in the infected bone nonunion and other inflammatory bone disorders.To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis. It included oxidative phosphorylation spectrophotometric assays, western blots, structural analysis, ATP production, glycolysis and cell proliferation evaluation. We demonstrated the deleterious nature of three original mutations. Striking gradation in severity of the mutations consequences and differences between muscle, fibroblasts and cybrids implied a likely under-diagnosis of human complex V defects.BACs-on-Beads (BoBs) assay and copy number variation sequencing (CNV-seq) are two frequently used methods in today's prenatal diagnosis. Several studies were conducted to investigate the performance of each approach, but they were never compared side by side. In this article, a comprehensive comparison of BoBs and CNV-seq was conducted using 1876 amniotic fluid and umbilical cord blood samples collected from Fujian Provincial Maternity and Children's Hospital between 2015 and 2019. Karyotyping was used as the gold standard for chromosome structure variation, and chromosomal microarray analysis was performed to validate inconsistent results. Overall, 174 cases of confirmed chromosome anomalies were detected, including 73 chromosomal aneuploidies, 10 mosaics, 30 pathogenic CNVs, and 61 other structural anomalies. BoBs and CNV-seq achieved a 100% concordance in all 55 pathogenic euchromosome aneuploidies, but CNV-seq had a higher detection rate in sex chromosome aneuploidy and mosaic identification. For CNV detection, all of the 20 pathogenic CNVs discovered by the BoBs assay also were identified by CNV-seq and 10 additional pathogenic CNVs were observed by CNV-seq. The results of this study showed that CNV-seq was a reliable and more favorable method in terms of detection rate, costs, and disease range. In combination with karyotyping, CNV-seq could improve the efficiency and accuracy of a prenatal diagnosis to alleviate maternal emotional anxiety and deduce birth defects.The detection and characterization of cell-free DNA (cfDNA) in peripheral blood from neuroblastoma patients may serve as a minimally invasive approach to liquid biopsy. Major challenges in the analysis of cfDNA purified from blood samples are small sample volumes and low cfDNA concentrations. Droplet digital PCR (ddPCR) is a technology suitable for analyzing low levels of cfDNA. Reported here are two quadruplexed ddPCR assay protocols that reliably quantify MYCN and ALK copy numbers in a single reaction together with the two reference genes, NAGK and AFF3, and accurately estimate ALKF1174L (exon 23 position 3522, C>A) and ALKR1275Q (exon 25 position 3824, G>A) mutant allele fractions using cfDNA as input. The separation of positive and negative droplets was optimized for detecting two targets in each ddPCR fluorescence channel by the adjustment of the probe and primer concentrations of each target molecule. The quadruplexed assays were validated using a panel of 10 neuroblastoma cell lines and paired blood plasma and primary neuroblastoma samples from nine patients. Accuracy and sensitivity thresholds in quadruplexed assays corresponded well with those from the respective duplexed assays. Presented are two robust quadruplexed ddPCR protocols applicable in the routine clinical setting and that require only minimal plasma volumes for the assessment of MYCN and ALK oncogene status.Tau is a microtubule-associated protein involved in Alzheimer's disease. However, little is known on its physiological function in the healthy central nervous system. Here, we observed that the expression of Tau isoforms was modulated by neuronal maturation and visual experience in the mouse retina and in the visual cortex. The visual function of wild-type (WT) and Tau knockout (KO) mice was evaluated using the optokinetic reflex (OKR), an innate visuomotor behavior, and by electroretinography. Visual tests did not reveal functional impairments in young adult and old Tau KO animals. Moreover, monocular deprivation (MD) was used to increase OKR sensitivity, a plasticity phenomenon depending on the visual cortex. MD-induced OKR sensitivity enhancement was significantly stronger in Tau KO than in WT mice suggesting that Tau restricts visual plasticity. In addition, human Tau expression did not affect visual function and plasticity in a mouse tauopathy model, relative to WT controls. Our results unveil a novel function for Tau in the adaptive mechanisms of plasticity operating in the adult brain subjected to sensory experience changes.
To describe the distribution and determinants of choroidal thickness (CT) in participants in a population study based on spectral-domain (SD)-OCT measurements.

Population-based, cross-sectional study.

Ethnic Chinese, Indian, and Malay adults aged more than 50 years without any retinal diseases (e.g., diabetic retinopathy, macular edema, age-related macular degeneration, central serous chorioretinopathy) that might affect the CT were recruited from the Singapore Epidemiology of Eye Diseases Study.

Choroidal imaging was performed by SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany) in enhanced depth imaging (EDI) mode. Subfoveal choroidal thickness (SFCT) was measured on the foveal line scan by 2 retinal experts independently (YS and KT), and the average was used in the analyses. In Chinese and Indian cohorts in whom macular raster scans were captured, the manufacturer-supplied research software (Heyex SP-X version 6.4.8.116; Heidelberg Engineering) was used to obtain automated segmentati wide range in physiologic limits. These data may be used as a reference in future studies.
Subfoveal choroidal thickness is influenced by age, gender, and ethnicity along with regional differences even within individual eyes. Subfoveal choroidal thickness also shows a wide range in physiologic limits. These data may be used as a reference in future studies.
Germline mutations of either the endothelial cell-specific tyrosine kinase receptor TIE2 or the glomulin (GLMN) gene are responsible for rare inherited venous malformations. Both genes affect the hepatocyte growth factor receptor c-Met, inducing vascular smooth muscle cell migration. Germline mutations of hepatocyte growth factor are responsible for lymphatic malformations, leading to lymphedema. The molecular alteration leading to the abnormal mixed vascular anomaly defined as lymphovenous malformation has remained unknown.

A group of 4 patients with lymphovenous malformations were selected. Plasma was obtained from both peripheral and efferent vein samples at the vascular malformation site for cell-free DNA extraction. When possible, we analyzed tissue biopsy samples from the vascular lesion.

We have demonstrated that in all four patients, an activating MET mutation was present. In three of the four patients, the same pathogenic activating mutation, T1010I, was identified. The mutation was found at thssues. Although a wider cohort of patients is necessary to confirm its causative role in lymphovenous malformations, these data suggest that lymphovenous malformations could result from postzygotic somatic mutations in genes that are key regulators of lymphatic development. The noninvasiveness of the method avoids any risk of bleeding and can be easily performed in children. We are confident that the present pioneering results have provided a viable alternative in the future for lymphovenous malformation diagnosis, allowing for subsequent therapy tailored to the genetic defect.
Catheter-directed interventions (CDIs) have been increasingly used for selected patients with acute intermediate-risk (submassive) pulmonary embolism (sPE) to prevent decompensation, mortality, and potentially long-term sequelae. The purpose of the present study was to determine whether the choice of anesthetic during these interventions has an effect on the postprocedural outcomes.

Patients who had undergone CDI for acute sPE from 2009 to 2019 were identified and grouped according to the intraprocedural use of propofol. The primary outcome was in-hospital intra- or postprocedural major adverse events, defined as the need for intubation, progression to massive pulmonary embolism, and in-hospital death. Major bleeding events (ie, intracerebral hemorrhage, transfusion of ≥2 U, the need for reintervention) were also assessed. Multivariate logistic regression analysis was used to evaluate the predictors of the studied outcomes.

During the study period, 340 patients (age, 58.74 ± 15.22years; 51.2% men) had uer procedure-related events, including stroke in 4 (1.17%), coronary sinus perforation in 1, tricuspid valve rupture in 1, and the need for transfusion in 10 patients. The type of intervention (ie, standard thrombolysis, ultrasound-assisted thrombolysis, suction thrombectomy) was not a predictive factor for any studied outcome.

CDIs are low-risk procedures with minimal postoperative morbidity and mortality in the setting of acute sPE. However, the use of propofol for intraprocedural sedation should be avoided because it can have detrimental effects.
CDIs are low-risk procedures with minimal postoperative morbidity and mortality in the setting of acute sPE. However, the use of propofol for intraprocedural sedation should be avoided because it can have detrimental effects.Chlorinated ethanes are environmental pollutants found frequently at many contaminated industrial sites. 1,1,1-Trichloroethane (1,1,1-TCA) can be dechlorinated and detoxified via abiotic transformation or biologically by the action of dechlorinating microorganisms such as Dehalobacter (Dhb). At a field site, it is challenging to distinguish abiotic vs. biotic mechanisms as both processes share common transformation products. In this study, we evaluated using the Dhb 16S rRNA gene and specific reductive dehalogenase genes as biomarkers for 1,1,1-TCA and 1,1-dichloroethane (1,1-DCA) dechlorination. We analyzed samples from laboratory groundwater microcosms and from an industrial site where a mixture of granular zero valent iron (ZVI) and guar gum was injected for 1,1,1-TCA remediation. Abiotic and biotic transformation products were monitored and the changes in dechlorinating organisms were tracked using quantitative PCR (qPCR) with primers targeting the Dhb 16S rRNA gene and two functional genes cfrA and dcrA encoding enzymes that dechlorinate 1,1,1-TCA to 1,1-DCA and 1,1-DCA to chloroethane (CA), respectively. The abundance of the cfrA- and dcrA-like genes confirmed that the two dechlorination steps were carried out by two distinct Dhb populations at the site. The biomarkers used in this study proved useful for monitoring different Dhb populations responsible for step-wise dechlorination and tracking biodegradation of 1,1,1-TCA and 1,1-DCA where both abiotic (e.g., with ZVI) and biotic processes co-occur.The effects of phosphonates, the heavily-used antiscalants in reverse osmosis systems, on microalgae are controversial, although they are harmless to most aquatic organisms. Herein, we assessed the inhibitory effects of etidronic acid (HEDP) and diethylenetriamine penta(methylene phosphonic acid) (DTPMP) on algal growth and revealed the mechanisms involved in both intrinsic toxicity and complexation. The phosphonates showed weak influences on Scenedesmus sp. LX1 in the first 4 d of cultivation. In contrast, a significant growth inhibition was observed subsequently with half maximal effective concentrations of 57.6 and 35.7 mg/L for HEDP and DTPMP, respectively, at 10 d. The phosphonates had little effect on cellular energy transfer and oxidative stress, quantified by adenosine triphosphate level and superoxide dismutase activity, respectively, demonstrating weak intrinsic toxicities to algal cells. Phosphonates blocked the algal assimilation of iron ions through complexation. Severe iron deficiency limited photosynthetic activity and caused chlorophyll decline, resulting in a functional loss of the photosystem followed by complete algal growth inhibition at the late cultivation stage. Our findings point to a potential ecological impact wherein harmful algal blooms are induced by the natural degradation of phosphonates due to the release of both iron and phosphate ions that stimulate algal regrowth after disinhibition.
To examine associations between area-level characteristics (socioeconomic status, racial or ethnic characteristics, age, and any other characteristics that may be associated with vulnerability) and the prices of tobacco products and electronic nicotine delivery systems (ENDS).

We searched MEDLINE, EconLit and Scopus, unpublished and grey literature, hand-searched four specialty journals, examined references of relevant studies, and contacted key informants.

We considered all studies that quantitatively examined area-level variations in the prices of tobacco products and ENDS. We included all studies that examined any area-level measures regardless of the geographic location, language or time of publication. At least two reviewers independently screened the articles. We identified 20 studies.

At least two reviewers independently extracted the characteristics, methods, and main results and assessed the quality of each included study.

Overall, cigarette prices were found to be lower in lower socioeconomatic monitoring of tobacco prices and ENDS is warranted.
Fatigue is a common and disabling symptom in chronic inflammatory diseases. To the best of our knowledge, there are no studies evaluating fatigue thoroughly in patients with chronic spontaneous urticaria (CSU).

To evaluate fatigue and its drivers in patients with CSU, and to compare patients with healthy controls in terms of fatigue.

One hundred and three patients with CSU and 35 age- and gender-matched healthy control subjects were evaluated for fatigue with the Fatigue Severity Scale (FSS) and visual analog scale-fatigue. Patients were also assessed for their duration, activity, and control of disease, as well as anxiety, depression, and quality of life (QoL).

There were no significant associations between disease activity, disease control scores, and FSS (P > .05). Although there were no significant differences in terms of antinuclear antibody positivity and IgE levels between fatigued and nonfatigued patients with CSU, C-reactive protein levels were higher in fatigued patients (P= .009). A significant correlation was noted between total FSS score and both Chronic Urticaria-QoL (r= 0.246, P= .013) and Dermatology Life Quality Index (r= 0.302, P= .002) in patients with CSU. In regression analyses, female gender and the presence of disturbed sleep were found to be significant predictors of fatigue in patients with CSU (P= .008; odds ratio [OR] 9.02, and P=.001; OR 8.35).

Fatigue is a common and important symptom in patients with CSU and adversely affects QoL. While evaluating patients with CSU, it is important to assess fatigue, especially in female gender patients and in those having sleep disturbance.
Fatigue is a common and important symptom in patients with CSU and adversely affects QoL. While evaluating patients with CSU, it is important to assess fatigue, especially in female gender patients and in those having sleep disturbance.
Recent studies highlight the immunoregulatory potential of bacterial lysates, indicating their potential use in the prevention and treatment of allergic diseases.

To investigate the clinical efficacy of polyvalent mechanical bacterial lysates (PMBLs) in children with grass pollen-induced allergic rhinitis.

Seventy children with seasonal allergic rhinitis were enrolled to this study and were randomly assigned to the PMBL and placebo groups. Severity of seasonal allergic rhinitis symptoms was assessed by the total nasal symptom score, total ocular symptom score, and visual analogue scale. During 3 visits, peak nasal inspiratory flow was measured, and nasal smears for the presence of eosinophils and nasal lavage fluids for the presence of allergen-specific IgE against timothy grass pollen allergens were sampled.

A statistically significant decrease in total nasal symptom score (P= .001), total ocular symptom score (P=.04), and visual analogue scale score for nasal and eye symptoms (P < .001 and P <ensitized to grass pollen allergens. PMBLs probably affect mucosal immunity, weakening the response of TH2 cells.
Cognitive deficits are associated with asthma globally; however, the association between cognitive function and asthma has not been fully elucidated.

To assess the relationship between asthma and cognitive function.

A total of 202 patients with asthma aged older than 18 years were analyzed retrospectively from August 2019 to February 2020. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) test. We compared the associations of clinical parameters with cognitive function (MoCA, ≥23 vs <23) and lung function (forced expiratory volume in 1 second [FEV1], ≥70% vs <70%).

Of the total participants, 89 (44.1%) indicated cognitive impairment, of whom 23.1% were aged less than 65 years and 72.9% were aged 65 years or older. MoCA scores were significantly different according to age (24.91 ± 3.89 for ages <65 years vs 19.11 ± 5.11 for ages ≥65 years, P < .001) and lung function (23.29 ± 5.17 for FEV1 ≥70% vs 21.23 ± 5.21 for FEV1 <70%, P= .006), but not according to asthma control (22.35 ± 5.38 for nonsevere asthma vs 22.88 ± 4.91 for severe asthma, P= .55). Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.014-1.13; P= .01), educational status (OR, 6.068; CI, 2.175-16.927; P= .001), and asthma duration (OR, 1.007; CI, 1.001-1.013; P= .02) were significantly associated with cognitive impairment.

Cognitive impairment was largely observed in adults (44.1%) with asthma and was more prevalent in older adults than in younger adults. Longer asthma duration and lower lung function were more associated with cognitive dysfunction.
Cognitive impairment was largely observed in adults (44.1%) with asthma and was more prevalent in older adults than in younger adults. Longer asthma duration and lower lung function were more associated with cognitive dysfunction.Statistical methods are essential in medical research. They are used for data analysis and drawing appropriate conclusions. Clarity and accuracy of statistical reporting in medical journals can enhance readers' understanding of the research conducted and the results obtained. In this manuscript, we provide guidelines for statistical reporting in medical journals for authors to consider, with a focus on the Journal of Thoracic Oncology.
Interstitial pneumonia (IP) is one of the most common and poor prognostic comorbidities in patients with NSCLC and a known risk factor for pneumonitis. Atezolizumab monotherapy is an established treatment for recurrent NSCLC and reported to have a lower risk of pneumonitis than programmed cell death protein 1 inhibitors. This study aimed to assess the safety and efficacy of atezolizumab monotherapy in patients with pretreated advanced or recurrent NSCLC with idiopathic IP.

Patients with advanced or recurrent NSCLC with comorbid idiopathic, chronic fibrotic IP with % forced vital capacity of greater than 70% and no history of immune checkpoint inhibitors were enrolled. The patients received atezolizumab (1200 mg) every 3 weeks until the discontinuation criteria were met. The primary end point of this study was the 1-year survival rate. A sample size of 38 patients was set.

This study was terminated early owing to high incidence of pneumonitis. A total of 17 patients were enrolled, with a median age of 70 years. The median % forced vital capacity and % diffusing capacity for carbon monoxide at baseline were 85.4% and 54.4%, respectively. The incidence of pneumonitis was 29.4% (5 of 17) for all grades, 23.5% (4 of 17) for grade greater than or equal to 3, and 5.9% (1 of 17) for grade 5. A total of 57.1% patients (4 of 7) with honeycomb lung developed pneumonitis with a grade greater than or equal to 3, whereas only one patient (10%) without honeycomb lung (n= 10) with grade 1 pneumonitis was found.

Patients with NSCLC with comorbid IP as defined by the selection criteria for this study might have an increased risk of immune checkpoint inhibitor-induced pneumonitis.
Patients with NSCLC with comorbid IP as defined by the selection criteria for this study might have an increased risk of immune checkpoint inhibitor-induced pneumonitis.
To describe associations between symptoms and signs of dry eye disease (DED) and meibomian gland (MG) morphology.

Cross-sectional study utilizing data from the Dry Eye Assessment and Management (DREAM) Study. Readers graded MG features in the middle third of upper and lower lids on infrared meibography images. Associations with signs and symptoms of DED were evaluated with adjustment for age and sex.

Among 268 patients, no MG features were associated with symptom scores (p>0.08). Among 394 upper eyelids, better tear break-up times (<2, >2- <3.2and≥3.2s) were associated with more tortuous glands (mean (SD) 0.58(0.95), 0.83(1.2) and 1.14 (1.4), p=0.01) and with higher scores on a composite score of MG features (21.90 (9.76), 23.29 (9.50), 26.26 (10.27); p=0.02). Longer Schirmer test wetting lengths (0-5, >5-10, and >10mm) were associated with increasing composite scores (22.02 (9.29), 23.80 (10.34), 24.96 (9.96), p=0.03). Patients with Sjogren syndrome compared to other patients had fewer distorted MGs (mean 3.4 (2.3) vs 4.3 (2.3), p=0.03) and fewer ghost glands (mean 0.33 (0.88) vs 0.89 (1.8), p=0.006) in the upper lid.

In the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.
In the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.The COVID-19 pandemic highlighted healthcare disparities in multiple countries. As such morbidity and mortality vary significantly around the globe between populations and ethnic groups. Underlying medical conditions and environmental factors contribute higher incidence in some populations and a genetic predisposition may play a role for severe cases with respiratory failure. Here we investigated whether genetic variation in the key genes for viral entry to host cells-ACE2 and TMPRSS2-and sensing of viral genomic RNAs (i.e., TLR3/7/8) could explain the variation in incidence across diverse ethnic groups. Overall, these genes are under strong selection pressure and have very few nonsynonymous variants in all populations. Genetic determinant for the binding affinity between SARS-CoV-2 and ACE2 does not show significant difference between populations. Non-genetic factors are likely to contribute differential population characteristics affected by COVID-19. Nonetheless, a systematic mutagenesis study on the receptor binding domain of ACE2 is required to understand the difference in host-viral interaction across populations.Emerging results indicate that an uncontrolled host immune response, leading to a life-threatening condition called cytokine release syndrome (also termed "cytokine storm"), is the major driver of pathology in severe COVID-19. In this pandemic, considerable effort is being focused on identifying host genomic factors that increase susceptibility or resistance to the complications of COVID-19 and translating these findings to improved patient care. In this regard, the chemokine receptor-ligand nexus has been reported as potentially important in severe COVID-19 disease pathogenesis and its treatment. Valuable genomic insights into the chemokine receptor-ligand nexus have been gained from HIV infection and disease progression studies. Applying that knowledge, together with newly discovered potential host genomic factors associated with COVID-19, may lead to a more comprehensive understanding of the pathogenesis and treatment outcomes in COVID-19 patients.Background A variety of inflammatory and non-inflammatory indicators were increased in severe and critical Coronavirus disease-19 (COVID-19) and some of them were used to evaluate the severity and predict prognosis of community-acquired pneumonia. The aim of this study was to investigate the association of these indicators in COVID-19 with different severity. Methods Clinical data of 46 patients with severe COVID-19 and 31 patients with critical COVID-19 were collected. The general characteristics and comorbidities of the patients were retrospectively analyzed. The initial and peak concentrations of serum troponin I (cTnI), D-dimer (D-D), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), initial and peak neutrophil counts and initial and trough lymphocyte counts were compared between two groups. The correlation between the variation of cTnI, D-D, CRP, IL-6, PCT, neutrophils, lymphocytes and the severity of the disease was analyzed. The efficacy of the initial concentrations of cTnI, D-D, CRConclusions The severe and critical COVID-19 patients had significant differences in concentrations of serum cTnI, D-D, CRP, IL-6, PCT, neutrophil and lymphocyte counts. The increase of cTnI, CRP, IL-6, PCT, neutrophils and decrease of lymphocytes indicated severe condition. The initial IL-6 might be a good indicator of COVID-19 severity.The global burden of breast cancer (BC) is increasing significantly. This trend is caused by several factors such as late diagnosis, limited treatment options for certain BC subtypes, drug resistance which all lead to poor clinical outcomes. Recent research has reported the role of epigenetic alterations in the mechanism of BC pathogenesis and its hallmarks include drug resistance and stemness features. The understanding of these modifications and their significance in the management of BC carcinogenesis is challenging and requires further attention. Nevertheless, it promises to provide novel insight needed for utilizing these alterations as potential diagnostic, prognostic markers, predict treatment efficacy, as well as therapeutic agents. This highlights the importance of continuing research development to further advance the existing knowledge on epigenetics and BC carcinogenesis to overcome the current challenges. Hence, this review aims to shed light and discuss the current state of epigenetics research in the diagnosis and management of BC.
Gait and cognitive impairments are common in individuals with Multiple Sclerosis (MS) and can interfere with everyday function. Those with MS have difficulties executing cognitive tasks and walking simultaneously, a reflection of dual-task interference. Therefore, dual-task training may improve functional ambulation. Additionally, using technology such as virtual reality can provide personalized rehabilitation while mimicking real-world environments. The purpose of this randomized controlled trial is to establish the benefits of a combined cognitive-motor virtual reality training on MS symptoms compared to conventional treadmill training.

This study will be a single-blinded, two arm RCT with a six-week intervention period. 144 people with MS will be randomized into a treadmill training alone group or treadmill training with virtual reality group. Both groups will receive 18 sessions of training while walking on a treadmill, with the virtual reality group receiving feedback from the virtual system. PrimaryMS symptoms and increase functional ambulation. We anticipate that those in the virtual reality group will have a significantly greater increase in dual-task gait speed and information processing speed than those achieved via treadmill training alone.DO-HEALTH is a multi-center clinical trial among 2157 community-dwelling European men and women age 70 and older. The 2x2x2 randomized-control factorial design trial tested the individual and additive benefit, as well as the cost-effectiveness, of 3 interventions vitamin D 2000 IU/day, omega-3 fatty acids 1000 mg/day (EPA + DHA, ratio 12), and a 30-minute 3 times/week home exercise (strength versus flexibility). Each treatment tested has shown considerable prior promise from mechanistic studies, small clinical trials, or large cohort studies, in the prevention of common age-related chronic diseases, but definitive data are missing. DO-HEALTH will test these interventions in relation to 6 primary endpoints (systolic and diastolic blood pressure, non-vertebral fractures, Short Physical Performance Battery score, the Montreal Cognitive Assessment, and risk of infections), plus several secondary endpoints explored in ancillary studies (i.e. rate of any falls and injurious falls, joint pain, oral health, quality of life, and incident frailty). As the 3 interventions have distinct mechanisms of action for each of the 6 primary endpoints, a maximum benefit is expected for their additive benefit as a "multi-modal" intervention. The trial duration is 3 years with in-person contacts with all participants at 4 clinical visits and by quarterly phone calls. Baseline and follow-up blood samples were collected in all participants to measure changes in 25-hydroxyvitamin D and poly-unsaturated fatty acid concentrations. Our objective was to test interventions that are expected to promote healthy aging and longer life expectancy and that can be easily and safely implemented by older community-dwelling adults.
Older adults (age 65 and older) use the emergency department (ED) at a rate of nearly 50 ED visits per 100 older adults, accounting for over 23 million ED visits in the US annually, up to 20% of all ED visits. These ED visits are sentinel health events as discharged patients often return to the ED, experience declines in health-related quality of life (HRQoL) and disability, or are later hospitalized. Those who are admitted incur increased costs and greater risk for poor outcomes including infections, delirium, and falls. The objective of this randomized controlled trial (RCT) is to evaluate the efficacy of the Geriatric Emergency Department Innovations (GEDI) program, an ED nurse-led geriatric assessment and care coordination program, in decreasing unnecessary health services use and improving Health-Related Quality-of-Life (HRQoL) for older adults in the ED.

Community dwelling older adults aged 65 and older who are vulnerable or frail according to the Clinical Frailty Scale (CFS) during an ED visit will be randomized to either GEDI (n=420) or to usual ED care (n=420). Outcome variables will be assessed during the ED visit and at 7-11days and 28-32days post ED visit.

The primary outcome is hospitalization or death within 30days of the ED visit. Secondary outcomes include health service use outcomes (ED visits and hospitalizations), healthcare costs, and HRQoL outcomes [Patient-Reported Outcomes Measurement Information System (PROMIS) scores PROMIS-Preference, Physical Function, Ability to Participate in Social Roles and Activities, Anxiety, and Depression].

Clinicaltrials.Gov identifier NCT04115371.
Clinicaltrials.Gov identifier NCT04115371.Clinical manifestations of SARS-CoV-2 infection include more frequently fever and cough, but complications (such as pneumonia, respiratory distress syndrome, and multiorgan failure) can occur in persons with additional comorbidities. Liver dysfunction is one of the most striking affections among patients suggesting that SARS-CoV-2 may represent a new king of liver aggressor. However, the molecular process underlying this phenomenon is still unclear. In this work, we overview the most recent findings between the molecular biology of the virus, pathogenic mechanisms, and its relationship to liver disease observed in patients.
Typically, the clinical presentation of a spinal dural arteriovenous fistula (SDAVF) will be insidious, with patients' symptoms regularly attributed to other conditions. Although previous studies have characterized the neurologic outcomes after treatment for SDAVFs, little is known about the pretreatment patient characteristics associated with poor and/or positive patient outcomes. We sought to characterize the pretreatment patient demographics, diagnostic history, and neurologic outcomes of patients treated for SDAVFs and to identify the patient factors predictive of these outcomes.

The medical records of patients who had been treated for SDAVFs from 2006 to 2018 across 1 healthcare system were retrospectively analyzed. Neurologic status was assessed both before and after intervention using the Aminoff-Logue scales for gait and micturition disturbances.

Of 46 total patients, 16 (35%) had a documented misdiagnosis. Patients with a history of misdiagnosis had had a significantly longer symptom duration before treatment compared with those without a misdiagnosis (median, 2.3 vs. 0.9 years; P= 0.018). A shorter symptom duration before intervention was significantly associated with both improved motor function (median, 0.8 vs. 3.1 years; P= 0.001) and improved urinary function (median, 0.8 vs. 2.2 years; P= 0.040) after intervention.

Misdiagnosis has been relatively common in patients with SDAVFs and contributes to delays in treatment. Delays in diagnosis and treatment of SDAVFs appear to be associated with worse clinical outcomes for patients who, ultimately, receive treatment.
Misdiagnosis has been relatively common in patients with SDAVFs and contributes to delays in treatment. Delays in diagnosis and treatment of SDAVFs appear to be associated with worse clinical outcomes for patients who, ultimately, receive treatment.
Although distal dorsal scapular nerve (DSN) anatomy has been well characterized, a paucity of literature exists detailing its proximal origin. To our knowledge, this is the first study examining DSN origin and its anatomy relative to the C5 nerve root, which may help localize pathology and provide insight into timing of DSN or C5 nerve root clinical and electrophysiological recovery.

Eighteen cadaveric dissections were performed using a posterior-midline approach. Calipers were used for DSN branching and course characterization with statistical analysis completed for the following measurements DSN diameter, C5 nerve root diameter, distance of DSN branch-point from the C5 ganglion, dural edge, and posterior foraminal tubercle (intra-vs. extraforaminal origin), as well as C5 root-SC branch-point distance.

Average/mean measurements (standard error) were as follows DSN diameter 3.7 mm (0.3 mm), C5 nerve root diameter 6.2 mm (0.5 mm), DSN origin to C5 DRG 12.4 mm (1.9 mm) distal, DSN origin to dural edge 19. 6mm (1.8 mm), DSN origin to C5 root origin 23.3 mm (2.2 mm), DSN origin to the posterior foraminal tubercle 2.3 mm (2.5 mm) proximal/intraforaminal (first branch from C5 in all cases, and the majority [12 of 18, 67%] of DSNs originating from the C5 spinal nerve root within the foramen).

The C5 nerve root contributed to the DSN in all specimens that originated from the proximal, intraforaminal, C5 nerve root in the majority of specimens. As the first C5 nerve branch, surgeon knowledge of this proximal DSN pattern will help localize lesional pathology, as well as may help monitor clinical and electrophysiological recovery.
The C5 nerve root contributed to the DSN in all specimens that originated from the proximal, intraforaminal, C5 nerve root in the majority of specimens. As the first C5 nerve branch, surgeon knowledge of this proximal DSN pattern will help localize lesional pathology, as well as may help monitor clinical and electrophysiological recovery.Transcription factors (TFs) as key regulators play crucial roles in biological processes. The identification of TF-target regulatory relationships is a key step for revealing functions of TFs and their regulations on gene expression. The accumulated data of chromatin immunoprecipitation sequencing (ChIP-seq) provide great opportunities to discover the TF-target regulations across different conditions. In this study, we constructed a database named hTFtarget, which integrated huge human TF target resources (7190 ChIP-seq samples of 659 TFs and high-confidence binding sites of 699 TFs) and epigenetic modification information to predict accurate TF-target regulations. hTFtarget offers the following functions for users to explore TF-target regulations (1) browse or search general targets of a query TF across datasets; (2) browse TF-target regulations for a query TF in a specific dataset or tissue; (3) search potential TFs for a given target gene or non-coding RNA; (4) investigate co-association between TFs in cell lines; (5) explore potential co-regulations for given target genes or TFs; (6) predict candidate TF binding sites on given DNA sequences; (7) visualize ChIP-seq peaks for different TFs and conditions in a genome browser. hTFtarget provides a comprehensive, reliable and user-friendly resource for exploring human TF-target regulations, which will be very useful for a wide range of users in the TF and gene expression regulation community. hTFtarget is available at http//bioinfo.life.hust.edu.cn/hTFtarget.The utility of thoracoscopic lung surgery is well established, however, reoperation for pulmonary resections has not been thoroughly studied. We sought to evaluate patient perioperative outcomes following redo thoracoscopic pulmonary resections for malignancy by comparing first and second ipsilateral operations. We included patients undergoing redo thoracoscopic pulmonary resections for clinically recurrent disease following prior lung resection for malignancy from January 1, 2011 to May 31, 2019. Nonmalignant indications were excluded. We analyzed type of procedure, diagnosis, rate of conversion to open, estimated blood loss, operating time, margin status, length of stay and complications. Forty-one patients met our inclusion criteria. The median age was 68 years (range 13-84) and 20 were women. Redo operations had longer lengths of stay with a trend toward higher rate of conversion to thoracotomy, but other perioperative outcomes were similar. No difference in outcomes was seen when patients were grouped by indication for reoperation (recurrence, multiple primaries, and metastasis) or approach of first operation (VATS vs open). However, patients undergoing an anatomic resection after a prior anatomic resection had more complications, higher blood loss, higher rate of conversions to thoracotomy, significantly longer length of stay and longer operative times than nonanatomic resections. Thoracoscopic reoperation for recurrent, metachronous, or metastatic cancer to the lung is a reasonable approach. However, the surgeon must recognize and counsel patients that in patients undergoing a redo anatomic resection, thoracoscopic reoperations are more difficult with more adverse outcomes.Unroofing surgery for anomalous aortic origin of a coronary artery (AAOCA) alters coronary anatomy by opening the intramural segment so that the anomalous coronary orifice arises perpendicularly from appropriate aortic sinus. Computational fluid dynamics modeling (CFD) allows for quantification of hemodynamics linked to morbidity such as wall shear stress (WSS), relative to patient-specific features like the angle of origin (AO). We hypothesize that CFD will reveal abnormal WSS indices in unroofed arteries that are related to AO. Six AAOCA patients (3 left, 3 right) status post unroofing (median = 13.5 years, range 9-17) underwent cardiac magnetic resonance imaging. CFD models were created from pre (n = 2) and postunroofing (n = 6) cardiac magnetic resonance imaging data, for the anomalous and contralateral normally-arising arteries. Downstream vasculature was represented by lumped parameter networks. Time-averaged WSS (TAWSS) and oscillatory shear index (OSI) were quantified relative to AO and measured hemodynamics.
Here's my website: