A bacterial strain 2H isolated from soil and identified as Thermoactinomyces vulgaris produce a potent Type II restriction endonuclease activity that has been extracted by a PEG/dextran aqueous two-phase system. Optimal temperature for the restriction endonuclease activity was 55-65°C. Specific DNA cleavage was obtained at pH range 7-10 and 10-20mM MgCl2. Restriction cleavage analysis followed by sequencing confirms GG^CC as the recognition sequence. This enzyme, named Tvu2HI, is a thermostable isoschizomer of the mesophilic prototype restriction endonuclease HaeIII. Sequencing of the complete Thermoactinomyces vulgaris 2H genome revealed the presence of two adjacent ORFs coding for the restriction endonuclease Tvu2HI and the corresponding methyltransferase; an ORF coding for a putative Vsr nicking enzyme was found close to those coding for the Tvu2HI restriction-modification system. Phylogenetic analysis based on sequence alignment suggests a common origin of Tvu2HI R-M system with HaeIII-like R-M systems. This is the first investigation dealing with a Type II restriction endonuclease identified in a natural isolate of the genus Thermoactinomyces.An effective antibacterial nanofiber film was prepared through the incorporation of ε-polylysine (ε-PL) into gelatin/chitosan-based polymers. All nanofiber films had uniformly disordered fibrous structure with good diameter distribution. The weight ratio of the gelatin/chitosan/ε-PL (G/C/P) influenced the solution property and nanofiber morphology. The addition of ε-PL can decrease the viscosity and increase the conductivity of solutions, which lead to a decrease in the diameter of nanofibers. The three polymers of gelatin, chitosan, and ε-PL were interacted by hydrogen bonding, and the crystallinity of nanofiber films was decreased by the electrospinning process. The addition of ε-PL can enhance the thermal stability, and decrease the water vapor permeability and oxygen permeability of the films, and ε-PL did not easily release from the nanofiber films. The G/C/P (610.125) nanofiber film was more effective to control six foodborne pathogens than the G/C nanofiber films by destroying the bacterial cell membranes. The result indicated that the gelatin/chitosan/ε-PL nanofiber films can be used as a food-packaging material to reduce the risk of foodborne pathogens.Sulfated polysaccharides from sea cucumber possess unique chemical structure and various biological activities. In this study, four sulfated polysaccharides were purified from the body wall of Holothuria fuscopunctata by anion exchange chromatography and chemical depolymerization. They were identified as sulfated fucan (SFI, SFII), fucosylated chondroitin sulfate (FCS) and sulfated aminoglycan (AG) by physicochemical and structural analyses. The Mw of SFI, SFII, FCS and AG were 470.6, 36.8, 42.6, 39.6 kDa and the sulfate content was 21.40%, 35.86%, 33.70%, 35.70%, respectively. Their primary structures were clarified both by monosaccharide composition and 1D/2D NMR spectroscopy analysis. As a result, the repeating sequences of FCS and SFII were →4)-[L-Fuc3S4S-(α1 → 3)]-D-GlcA-(β1 → 3)-D-GalNAc4S6S-(β1 → and →4-L-Fuc-(3SO3-)-α1→, respectively. The primary structure of SFI was →3)-L-Fuc2S4S-(α1 → 4)-L-Fuc-(α1 → 3)-L-Fuc2S-(α1 → 4)-L-Fuc-(α1→. The sulfated AG was composed of four types of monosaccharides. Their anticoagulant activities were further evaluated in vitro. FCS and AG showed potent anticoagulant activity and intrinsic factor Xase inhibition activity. These results expand the knowledge on the structure types of sulfated polysaccharides from sea cucumber and further illustration of their functionality.In the present study, to verify the effect of polysaccharides derived from persimmon leaves (PLE) at epithelial-to-mesenchymal transition (EMT), A549 cells were treated with TGF-β1 alone or co-treated with TGF-β1 and PLE (50 and 75 μg/mL). PLE-treated cells showed higher expression of E-cadherin and lower expression of N-cadherin and vimentin compared to TGF-β1-treated cells by inhibiting the levels of transcription factors, including Snail, Slug, and ZEB1, all associated with EMT. PLE also significantly decreased migration, invasion, and anoikis resistance through TGF-β1 mediated EMT suppression, whereby PLE inhibited the levels of MMP-2 and MMP-9 while cleaving PARP. These inhibitory effects of PLE against EMT, migration, invasion, and anoikis resistance were determined by activating the canonical SMAD2/3 and non-canonical ERK/p38 signaling pathways. Therefore, these results suggest that PLE could be used as a potential chemical therapeutic agent for early metastasis of lung cancer in vitro.Development of biologics and biosimilars involves extensive physical and structural characterization, which underlines the further course of its implementation. These characterization techniques require considerable standardization and are labor intensive. It is therefore, important to have an immediate, independent and affordable characterization strategy that may meet the regulatory guidelines. In this study, we have compared the standard biophysical characterization of an anti-CD 20 antibody with characterization by small angle x ray scattering (SAXS). Aggregation of this mAb was analyzed using standard techniques like size exclusion HPLC, dynamic light scattering and sedimentation velocity – analytical ultracentrifugation, whereas structure analysis was conducted using mass spectrometry, circular dichroism spectroscopy and fluorescence spectroscopy. Our results demonstrated that the inferences about the state of mAb aggregation and its structure deduced using the standard approaches were comparable to the data interpreted using SAXS. The radius of gyration and the P(r) distribution plot obtained using the SAXS scattering data allowed analysis of aggregation and conformation of mAb via a single experiment. Thus, SAXS can be used as an independent technique to complement orthogonal analysis for determining the aggregation profile and structure of mAbs.Recently discovered Lytic Polysaccharide Mono-Oxygenase (LPMO) enhances the enzymatic deconstruction of complex polysaccharide by oxidation. The present study demonstrates the agricultural waste hydrolyzing capabilities of Paenibacillus dendritiformis CRN18, which exhibits the enzyme activity of exo-glucanase, β-glucosidase, β-glucuronidase, endo-1, 4 β-xylanases, arabinosidase, and α-galactosidase as 0.1U/ml, 0.3U/ml, 0.09U/ml, 0.1U/ml, 0.05U/ml, and 0.41U/ml, respectively. The genome analysis of strain reveals the presence of four LPMO genes, along with lignocellulolytic genes. The gene structure of LPMO and its phylogenetic analysis shows the evolutionary relatedness with the Bacillus LPMO gene. Gene position of LPMOs in the genome of strains shows the close association of two LPMOs with chitin active enzyme GH18, and the other two are associated with hemicellulases (GH39, GH23). Protein-protein interaction and gene networking of LPMO sheds light on the co-occurrence, neighborhood, and interaction of LPMOs with chitinase and xylanase enzymes. Structural prediction of LPMOs unravels the information of the LPMO’s binding site. Although the LPMO has been explored for its oxidative mechanism, a little light has been shed on its gene structure. This study provides insights into the LPMO gene structure in P. dendritiformis CRN18 and its potential in lignocellulose hydrolysis.

The existing literature on the microbiota of the ileum is inconsistent. To further characterize the microbiota, we analysed samples obtained directly from resected ileums used for urinary diversion after radical cystectomy.

We included 150 patients with bladder cancer operated on from March 2016 to March 2019. Samples obtained by rubbing a swab against the ileal mucosa 25 cm from the ileocecal valve were cultivated at the local laboratory. Microbial colonies were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF).

The microbial density of the distal ileum was low. Among our samples, 79% (95% confidence interval (CI) 71%, 84%) harboured less than 1.6×10

cfu/mL, whereas 36% (95% CI 28%, 44%) harboured less than 1.6cfu/mL. The flora was dominated by viridans streptococci, Candida, Actinomyces, Rothia and Lactobacillus species. Colon-related bacteria i.e. strict anaerobic bacteria, Enterobacteriales and enterococci, were recovered from 14% of the samples. Constipation was associated with increased recovery of colon-related bacteria. Antibiotic treatment prior to surgical procedures did not affect culture results. Increased age was significantly associated with more substantial fungal growth and use of proton pump inhibitors seemed to increase both bacterial and fungal growth.

The microbiota of the human distal ileum is sparse and differs significantly from the colonic microbiota both quantitatively and by composition. These findings contradict recent metagenomics studies based on samples collected by retrograde colonoscopy and emphasize the crucial importance of adequate sampling techniques.

The microbiota of the human distal ileum is sparse and differs significantly from the colonic microbiota both quantitatively and by composition. These findings contradict recent metagenomics studies based on samples collected by retrograde colonoscopy and emphasize the crucial importance of adequate sampling techniques.

The present study aimed to evaluate the performance of the 'TBDetect’ kit-based bio-safe fluorescent microscopy filter (BioFM-Filter) microscopy in comparison with direct smear microscopy and culture for the detection of pulmonary tuberculosis (TB) in a multi-centric setting in India.

The TBDetect kit enables sputum concentration through filtration using the BioFM-Filter for improved and bio-safe smear microscopy. We evaluated the performance of the TBDetect kit in a six-site multi-centric validation study on sputum collected from 2086 presumptive TB patients.

The combined positivity of TBDetect microscopy performed on these sputum samples was 20% (n=417/2086) vs 16.1% of light-emitting diode fluorescence microscopy (LED-FM, n=337/2086) and 16% of Ziehl Neelsen (ZN) smear microscopy (n=333/2086). The increment in positivity of TBDetect over both LED-FM and ZN smears was significant (p<0.001). The overall sensitivity of TBDetect for six sites was ~55% (202/367, 95% confidence interval (CI) 50, 60%) vspment-free TBDetect technology has the potential to improve TB diagnosis in basic laboratory settings by leveraging on the existing nationwide network of designated microscopy centres and primary healthcare centres.

To evaluate ocular symptoms in European non-hospitalized patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and to investigate associations with the demographic data as well as nasal and general physical symptoms.

In this prospective, observational study, 108 non-hospitalized patients with PCR-confirmed SARS-CoV-2 infection not requiring intensive care were asked about disease-associated ocular symptoms, demographic data, as well as general physical and nasal symptoms using a standardized questionnaire. Total ocular symptom score (TOSS) was evaluated during and, retrospectively, before development of coronavirus disease 2019 (COVID-19). Associations between TOSS and demographic data as well as general and nasal symptoms were evaluated.

Seventy-five of the 108 COVID-19 patients (69.4%) had at least one ocular symptom during COVID-19. The most common symptoms included burning sensations in 39 (36.1%), epiphora in 37 (34.3%) and redness in 28 (25.9%), compatible with conjuncatment.

Both EUCAST and CLSI recommend broth microdilution for antimicrobial susceptibility testing of colistin, but this method is cumbersome and takes 16-24h to give results. Our objective was to evaluate a rapid quantitative colistin MIC susceptibility assay based on flow cytometry analysis (FASTcolistin MIC) in comparison with standard broth microdilution assay.

One hundred and sixteen Gram-negative bacilli (78 Enterobacterales, 28 Pseudomonas aeruginosa and 10 Acinetobacter baumannii) were studied in parallel using standard broth microdilution following EUCAST recommendations and FASTcolistin MIC kit. In the last one, a bacteria suspension (0.5 MacFarland) was prepared, diluted in Muller-Hinton broth, incubated in the susceptibility panel containing different colistin concentrations (range 0.125-64 mg/L) with a fluorescent probe and incubated 1h at 35ºC. After that, a flow cytometry analysis using CytoFLEX (Beckmam) was performed. Using a dedicated software (BioFAST) an automated MIC result was obtained after 1.5h. Performance evaluation was performed according to the ISO standard 20776-2. Reproducibility and repeatability, categorical (CA) and essential agreement (EA), and lot-to-lot variation and operator-to-operator variability, as well as time to results were determined.

Overall, 100% CA (CI 97-100%) and 95.7% EA (CI 90-98%) was obtained with high repeatability (100%; CI 80-100%)and reproducibility (97%; (CI 83-99%)). Absence of lot-to-lot variations or differences in the operators’ performance was observed.

FASTcolistin MIC is an accurate, reliable and ultra-rapid method (1h incubation versus 24h) for susceptibility testing of colistin of common Gram-negative bacilli recovered in clinical laboratories.

FASTcolistin MIC is an accurate, reliable and ultra-rapid method (1 h incubation versus 24 h) for susceptibility testing of colistin of common Gram-negative bacilli recovered in clinical laboratories.Pulmonary surfactant protein-A (SP-A) is expressed by lung alveolar and bronchiolar epithelial cells and plays a critical role in innate immunity of the lung. Exposure of the lung to various environmental insults alters SP-A homeostasis. To investigate the cellular mechanisms involved in these alterations, we added the FLAG octapeptide (DYKDDDDK) to the carboxy-terminus (SP-A/C-FLAG) or near the amino-terminus (SP-A/N-FLAG) of mouse SP-A (WT-SP-A) to tag specific pools of protein. We hypothesized that addition of FLAG would have negligible effects on SP-A expression, oligomerization and secretion. Analysis of Chinese hamster ovary cells expressing these proteins indicated that tagged SP-A mRNA could be distinguished from WT-SP-A by northern analysis and RT-PCR using sequence-specific oligonucleotides. Tagged SP-A protein could be differentiated from WT-SP-A by western analysis using antibodies specific for the FLAG epitope. Subcellular fractionation and immunocytochemistry indicated the majority of each protein was present in punctuate (presumably endocytic) vesicles, and all forms of SP-A protein were secreted. These results suggest that a FLAG epitope added to the carboxy-terminus or inserted into the amino-terminus of the mature SP-A protein has little effect on its expression and cellular processing. However, disruptions of the amino-terminal end of SP-A prevents proper oligomerization, suggesting that this region of mature SP-A is critical in proper oligomeric assembly and is not useful for studies intended to define mechanisms underlying SP-A homeostasis.

Foot complications in patients with diabetes or peripheral artery disease (PAD) are serious events in the life of these patients that often lead to amputations and mortality. No evidence synthesis has been reported on the mortality rates after minor lower extremity amputation; thus, a quantitative evidence synthesis was needed.

A systematic literature search was performed to identify studies that had reported the survival or mortality rates after a minor LEA. The studies were required to include one or more of the following primary outcomes mortality rate at 30days, 1year, 3years, 5years, 6 to 7years, or 8 to 9years. The secondary outcomes were the mortality rates according to the anatomic location of the amputation in the foot and the independent risk factors for mortality.

A total of 28 studies with 17,325 subjects fulfilled the inclusion criteria. The meta-analytical results of the mortality rates were as follows 3.5% at 1month, 20% at 1year, 28% at 3years, 44.1% at 5years, 51.3% at 6 to 7years, and should be considered a pivotal event in the life of these patients.

Informed consent is an essential principle of high-quality health care. A core component of surgical informed consent is patient comprehension of basic information such as the diagnosis, risks, benefits, and alternatives of the proposed surgery. We sought to assess informed consent among vascular surgery patients and the association between frailty, education, decisional conflict, and patient comprehension.

We tested patient comprehension of basic information required for informed consent with a procedure-specific questionnaire in 102 consecutive patients undergoing selected vascular surgery procedures. Two patients who underwent open aortic aneurysm repair were excluded because of small sample size. All patients underwent assessment using the decisional conflict scale and the Frail/Nondisabled questionnaire. Analyses were performed to determine relationships between being informed and frailty, education level, and decisional conflict score. Patients included in this cohort had a median age of 71years, and to best determine causes of poor comprehension and strategies to mitigate the same.

As a group, patients have a poor comprehension of basic information related to surgical informed consent. These findings have potential ethical and clinical implications, and additional work is required to best determine causes of poor comprehension and strategies to mitigate the same.

The human population is aging at an astonishing rate. The aim of this study is to capture a situation snapshot revealing the proportion of individuals aged 65 years and over among inpatients in healthcare institutions in Turkey and the prevalence and type of infections in this patient group in order to draw a road map.

Hospitalized patients over 65 years at any of the 62 hospitals in 29 cities across Turkey on February 9, 2017 were included in the study. Web-based SurveyMonkey was used for data recording and evaluation system.

Of 17,351 patients 5871 (33.8%) were ≥65 years old. The mean age was 75.1±7.2 years; 3075 (52.4%) patients were male. Infection was reason for admission for 1556 (26.5%) patients. Pneumonia was the most common infection. The median length of hospital stay was 5 days (IQR 2-11 days). The Antibiotic therapy was initiated for 2917 (49.7%) patients at the time of admission, and 23% of the antibiotics prescribed were inappropriate. Healthcare-associated infections developed in 1059 (18%) patients. Urinary catheters were placed in 2388 (40.7%) patients with 7.5% invalid indication.

This study used real data to reveal the proportion of elderly patients in hospital admissions. The interventions done, infections developed during hospitalization, length of hospital stay, and excessive drug load emphasize the significant impact on health costs and illustrate the importance of preventive medicine in this group of patients.

This study used real data to reveal the proportion of elderly patients in hospital admissions. The interventions done, infections developed during hospitalization, length of hospital stay, and excessive drug load emphasize the significant impact on health costs and illustrate the importance of preventive medicine in this group of patients.

To determine the diagnostic yield of repeat testing for SARS-CoV-2.

A retrospective analysis was performed of all SARS-CoV-2 test results within the UCLA Health System between March 9th and April 29th, 2020. All patients with repeat test results were identified and those with discordant results were reviewed.

Between March 9th and April 29th there were 10,165 SARS-CoV-2 test results, of which 630 (6.2%) were positive. Among the 904 patients with repeat test results, 808 (89.4%) were initially negative and 96 (10.6%) were initially positive. Among the 808 patients with an initial negative test, 15 (1.9%) subsequently tested positive. Eleven cases with an initial negative SARS-CoV-2 test and without a known prior positive SARS-CoV-2 test were reviewed; 6 were employed as healthcare workers and 10 were positive on the second test.

We found a low diagnostic yield of repeat testing for SARS-CoV-2 in our health system. Repeat testing might prove useful in certain clinical scenarios, such as in healthcare workers, when symptoms develop after a negative test, and in hospitalized patients with a high clinical suspicion for COVID-19.

We found a low diagnostic yield of repeat testing for SARS-CoV-2 in our health system. Repeat testing might prove useful in certain clinical scenarios, such as in healthcare workers, when symptoms develop after a negative test, and in hospitalized patients with a high clinical suspicion for COVID-19.Valence-specific effects of oxytocin have been revealed in a selection of preceding studies, while others report that oxytocin could improve facial recognition, regardless of emotion valence. The reported effect was mediated by increased eye gaze during face processing, and attachment style proved to moderate the effect of oxytocin administration on social behavior and cognition. In this study, we used eye tracking to test whether attachment style moderates the effect of oxytocin on negative emotion recognition, which is crucial for social cognition. We employed a placebo-controlled, double-blind, within-participants design. The participants were 73 healthy individuals (41 men) who received a single dose of intranasal oxytocin (24 IU) on one occasion and a placebo dose on another occasion. Visual attention to the eye region was assessed on both occasions, through the completion of an emotion recognition task. Our results showed that oxytocin increased participants’ eye gaze towards facial expressions. Among participants who received oxytocin, as opposed to a placebo, only individuals with high attachment anxiety displayed more eye gaze and less mouth gaze towards facial expression, regardless of emotion valence. Our findings confirmed that oxytocin increases gaze to the eye region, thus improving facial recognition, regardless of emotion valence, this relationship was moderated by attachment anxiety. Further, our results highlighted the importance of considering individual differences when evaluating the effects of oxytocin on emotion recognition.In this review, I summarize historical and recent features of the classical pathways activated by growth hormone (GH) through the cell surface GH receptor (GHR). GHR is a cytokine receptor superfamily member that signals by activating the non-receptor tyrosine kinase, JAK2, and members of the Src family kinases. Activation of the GHR engages STATs, PI3K, and ERK pathways, among others, and details of these now-classical pathways are presented. Modulating elements, including the SOCS proteins, phosphatases, and regulated GHR metalloproteolysis, are discussed. In addition, a novel physical and functional interaction of GHR with IGF-1R is summarized and discussed in terms of its mechanisms, consequences, and physiological and therapeutic implications.The growth hormone (Gh)/insulin-like growth-factor (Igf)/Igf binding protein (Igfbp) system regulates growth and osmoregulation in salmonid fishes, but how this system interacts with other endocrine systems is largely unknown. Given the well-documented consequences of mounting a glucocorticoid stress response on growth, we hypothesized that cortisol inhibits anabolic processes by modulating the expression of hepatic igfbp mRNAs. Atlantic salmon (Salmo salar) parr were implanted intraperitoneally with cortisol implants (0, 10, and 40 μg g-1 body weight) and sampled after 3 or 14 days. Cortisol elicited a dose-dependent reduction in specific growth rate (SGR) after 14 days. While plasma Gh and Igf1 levels were unchanged, hepatic igf1 mRNA was diminished and hepatic igfbp1b1 and -1b2 were stimulated by the high cortisol dose. Plasma Igf1 was positively correlated with SGR at 14 days. Hepatic gh receptor (ghr), igfbp1a, -2a, -2b1, and -2b2 levels were not impacted by cortisol. Muscle igf2, but not igf1 or ghr, levels were stimulated at 3 days by the high cortisol dose. As both cortisol and the Gh/Igf axis promote seawater (SW) tolerance, and particular igfbps respond to SW exposure, we also assessed whether cortisol coordinates the expression of branchial igfbps and genes associated with ion transport. Cortisol stimulated branchial igfbp5b2 levels in parallel with Na+/K+-ATPase (NKA) activity and nka-α1b, Na+/K+/2Cl–cotransporter 1 (nkcc1), and cystic fibrosis transmembrane regulator 1 (cftr1) mRNA levels. The collective results indicate that cortisol modulates the growth of juvenile salmon via the regulation of hepatic igfbp1s whereas no clear links between cortisol and branchial igfbps previously shown to be salinity-responsive could be established.Thermoregulation is critical for survival and animals therefore employ strategies to keep their body temperature within a physiological range. As ectotherms, fish exclusively rely on behavioral strategies for thermoregulation. Different species of fish seek out their specific optimal temperatures through thermal navigation by biasing behavioral output based on experienced environmental temperatures. Like other vertebrates, fish sense water temperature using thermoreceptors in trigeminal and dorsal root ganglia neurons that innervate the skin. Recent research in larval zebrafish has revealed how neural circuits subsequently transform this sensation of temperature into thermoregulatory behaviors. Across fish species, thermoregulatory strategies rely on a modulation of swim vigor based on current temperature and a modulation of turning based on temperature change. Interestingly, temperature preferences are not fixed but depend on other environmental cues and internal states. The following review is intended as an overview on the current knowledge as well as open questions in fish thermoregulation.

Bone marrow derived mesenchymal stem cells (BMSCs) are an irresistible choice for use in stem cell therapy and regenerative medicine. BMSCs osteoblastic differentiation is also important in bone development, diseases, malignancies, and cancers studies. Wnt signaling pathway antagonists, Dickkopf-1 (Dkk 1), Secreted Frizzled-Related Proteins (sFRPs), and Wnt Inhibitory Factor 1 (Wif1) play important roles in inducing osteoblastic differentiation. This study is the first to investigate the association between DNA methylation and gene expression of Dkk1, sFRP2, sFRP4, and Wif1 during BMSCs osteoblastic differentiation.

Human BMSCs were isolated and characterized using flow cytometry. Then, cells were treated with osteo-differentiation medium for three weeks. Alizarin red S staining and polymerase chain reaction (PCR) (alkaline phosphatase/osteocalcin) were performed for confirmation. The expression of Dkk 1, sFRP2, sFRP4, and Wif1 genes was evaluated at days 7, 14, and 21 using real-time PCR. Methylation-spese that the Wnt antagonist gene promoters should remain un-methylated during osteoblastic differentiation of BMSCs and that the down-regulation of these genes may contribute to other epigenetic mechanisms, other than DNA methylation, which implicitly indicates the role of DNA methylation in osteogenic cancers.Fanconi anemia is the most common inherited bone marrow failure syndrome, and hematopoietic stem cell transplantation (HSCT) is the only curative option. Post-transplant cyclophosphamide (PTCy) is challenging in this group of children, given their increased sensitivity to chemotherapy. We performed a retrospective analysis of the data on children diagnosed with Fanconi anemia who underwent a haploidentical HSCT with PTCy from January 2014 to December 2019. Nineteen children (male/female, 0.751) underwent 21 haplo-HSCTs with PTCy. Fludarabine, low-dose cyclophosphamide, and 200 centi-gray total body irradiation were included in the conditioning regimen with 25 mg/kg PTCy on days +3 and +4. Haplo-graft was from a sibling in 38% and father in 57% of transplants. The source of stem cells was peripheral blood stem cells in 81% and bone marrow in 19% of transplants, with a median CD34 dose of 5.0 × 106/kg. We documented engraftment in 84% and primary graft failure in 10% of transplants. N-acetylcysteine (NAC) was inths versus 50 ± 6 months, respectively). The overall survival in our cohort was 68.4%, with a mean survival time of 41.5 months (95% confidence interval, 29.3 to 53.8 months), with a statistically significant correlation between inferior outcome and having received over 15 transfusions before HSCT (P = .01). PTCy can be considered a viable option in children with Fanconi anemia, particularly in resource-limited settings given the high costs of HSCTs. Focused interventions in this subset of children help improve survival outcomes. Early identification of cytokine release syndrome and risk-adapted steroid therapy during engraftment helps prevent mortality. The concomitant use of NAC during cyclophosphamide infusion helps reduce oxygen free radical related tissue damage and regimen-related toxicity.

Chronic constriction injury (CCI) is widely used as an animal neuropathic pain model. Neuropathic pain is considered to exist when withdrawal latency to thermal stimulation is decreased after inducing a CCI to the sciatic nerve. However, it is known that CCI leads to changes in skin temperature and that skin temperature can affect withdrawal latency. Aim of this study was to compare withdrawal latencies of constricted and contralateral hind limbs, to thermal stimulation, at the same artificially-induced skin temperatures.

Neuropathic pain was induced by four ligatures on the left sciatic nerve in adult male Wistar rats. Withdrawal latencies were measured from the 11th to 14th day after ligation, in different ambient temperatures, using the plantar test (Hargreaves method). By changing ambient we produced different hind limb skin temperatures.

Our results show that (1) CCI cause an increase in skin temperature; (2) the withdrawal latency was inversely related to ambient and skin temperature in the same manner for both the ligated and contralateral hind limbs; and (3) withdrawal latencies did not differ significantly for the ligated and contralateral hind limbs when the temperature of the hind limbs was artificially made the same (i.e., by changing the ambient temperature).

Withdrawal latencies to thermal stimulation did not differ on ligated and contralateral hind limb after CCI to the sciatic nerve if the temperature of the hind limbs was artificially or mathematically made the same. This finding may have significant impact on the interpretation results of neuropathic pain research.

Withdrawal latencies to thermal stimulation did not differ on ligated and contralateral hind limb after CCI to the sciatic nerve if the temperature of the hind limbs was artificially or mathematically made the same. This finding may have significant impact on the interpretation results of neuropathic pain research.The contribution of oxidative stress has been described in numerous studies as one of the main pathways involved in the pathophysiology of anxiety and its comorbidities, such as chronic pain. Therefore, in this study, we investigated the anxiolytic-like, antiallodynic, and anti-hyperalgesic effects of 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) in response to acute restraint stress (ARS) in mice through the modulation of oxidative stress and neuroendocrine responses. Mice were restrained for 2 h followed by SePy (1 or 10 mg/kg, intragastrically) treatment. Behavioral, and biochemical tests were performed after further 30 min. The treatment with SePy reversed (i) the decreased time spent and the number of entries in the open arms of the elevated plus-maze apparatus, (ii) the decreased time spent in the central zone of the open field test and the increased number of grooming, (iii) the increased number of marbles buried, (iv) the increased response frequency of Von Frey Hair stimulation, and (v) the decreased latency time to nociceptive response in the hot plate test stress induced by ARS. Biochemically, SePy reversed ARS-induced increased levels of plasma corticosterone, and reversed the ARS-induced alterations in the levels of reactive species, lipid peroxidation, and superoxide dismutase and catalase activities in the prefrontal cortices and hippocampi of mice. Moreover, a molecular docking approach suggested that SePy may interact with the active site of the glucocorticoid receptor. Altogether, these results indicate that SePy attenuated anxiolytic-like behavior, hyperalgesia, and mechanical allodynia while modulating oxidative stress and neuroendocrine responses in stressed mice.

Diarrhea is one of the five leading causes of mortality in children under the age of five, especially in developing countries. Nowadays, by increasing the resistance of pathogens to antibiotics, employment of probiotics as novel therapeutic method, could be considered as a necessity.The aim of this study was to examine the features and antagonistic action of Lactobacillus strains, against the growth and adhesion of Enterotoxigenic Escherichia coli (ETEC) and Enteroaggregative Escherichia coli (EAEC) strains creating diarrhea in children. Then, we introduced new strains of Lactobacillus as probiotic candidates, to prevent diarrheal infections in children.

Stool samples were collected from healthy individuals, and Lactobacillus strains were isolated. The antimicrobial effect of the isolates against ETEC and EAEC strains investigated by agar well diffusion method and their resistance to acidic and bile conditions. The potency of selected isolates in adhesion to HT-29 epithelial cells and their ability to inhnd are likely to be effective in preventing or treating diarrheal infections, especially in children.UTI has been reported as the most prevalent infectious complication after-kidney transplantation. This study aimed to evaluate the bacterial urinary tract infection among renal transplant recipients, and causative microorganisms from the Middle East. We searched literatures reporting the prevalence of UTI, bacterial pathogens, and antibiotic resistance pattern from January 1, 2010-May 10, 2020 for patients with renal transplant recipients from the Middle East in international databases. Terms used were; „Urinary tract infection”, „UTI”, „bacterial pathogens”, „bacterial infection”, „renal transplant”, „kidney transplant”, post – renal transplant, „antibiotic resistance”, „Middle East”, Turkey, Iran, Jordan, Kuwait, Bahrain, Lebanon, United Arab Emirates, Qatar, Cyprus, Yemen, Iraq, Egypt, Palestine, and Syria. Data analyzed using CMA software. The prevalence of UTI among renal transplant recipients from the Middle East varied between 4.5 and 85%. The combined prevalence of UTI was reported by 37.9% (95% Cl 28.3-48.5). The most prevalent organisms recovered from urine samples of patients with UTI were E. coli and Klebsiella with prevalence rate of 57.5%, and 15%, respectively. Also, Coagulase negative Staphylococcus (15%), and Enterococci (11.2%) were the most predominant among Gram positive microorganisms. The most resistance among Gram negative microorganisms belonged to Ceftazidime with frequency of 90% followed by Carbenicillin and Cephalexin with prevalence of 87.3%, and 84%, respectively. The effective antibiotic was Imipenem (15.2%). Regarding the high UTI rate in renal transplant recipients from the Middle East, and the significant presence of both Gram negative and Gram positive microorganisms as the most prevalent uropathogens after renal transplantation should be considered when selecting empirical antibacterial therapy.Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus that it disease spreads in over the world. Coronaviruses are single-stranded, positive-sense RNA viruses with a genome of approximately 30 KD, the largest genome among RNA viruses. Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment. Older people and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness. At this time, there are no specific vaccines or treatments for COVID-19. So, there is an emergency need for vaccines and antiviral strategies. The spike protein is the major surface protein that it uses to bind to a receptor of another protein that acts as a doorway into a human cell. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of COV19 infection. A combination of available bioinformatics tools are used to synthesis of such peptides that are important for the development of a vaccine. In conclusion, amino acids 250-800 were selected as effective B cell epitopes, T cell epitopes, and functional exposed amino acids in order to a recombinant vaccine against coronavirus.Plant fungal diseases generate serious losses in the agriculture. The bacteria producing biologically active substances that inhibit the growth of fungal pathogens can be an alternative to the chemicals. The chitinolytic bacteria were isolated from the rhizosphere of wheat (Triticum aestivum L.) and their physiological properties which may be useful in the promotion of plant growth have been investigated. Their chitinases and antifungal activity were studied. The isolates were also tested for indirect growth-promoting traits such as ammonia production, siderophore production, hydrogen cyanide production, and salicylic acid production. Two chitinolytic strains B3 and B5 were identified as Bacillus subtilis and Bacillus sp., respectively. They produced active chitinases on a medium containing shrimp shell powder. The purified chitinases having the molecular weight of 35-45 kDa inhibited the growth of important plant pathogens such as Alternaria alternata, and Fusarium oxysporum. Additionally, the isolates showed the ability to produce a broad range of biological substances promoting the growth of plants.Candida haemulonii species complex (Can. haemulonii sensu stricto, Can. duobushaemulonii and Can. haemulonii var. vulnera) and related species (Can. auris and Can. pseudohaemulonii) have attracted attention due to reduced susceptibility to azoles and amphotericin B. Furthermore, attributes of potential virulence have been recognized in Can. haemulonii species complex and Can. auris, like the capability to form biofilm, which represent the most important risk factors for persistent candidemia. However, the relationship between biofilm production and impact on host mortality is still unclear. To evaluate the potential virulence of Can. haemulonii species complex and Can. auris isolates by correlating biofilm production and capacity to kill Caenorhabditis elegans as an in vivo model. In this study, virulence factors were characterized among a total of sixty-six Can. haemulonii species complex and Can. auris isolates to gain insight about virulence traits of these pathogenic yeasts by evaluating the in vitro biofilm production and potential pathogenicity for Cae. elegans, as an in vivo infection model. All clinical isolates tested were biofilm producer, inter- and intra-specific differences on the biofilm forming capacity by the strains were observed. Can. auris and Can. haemuolonii var. vulnera showed similar biofilm production, both higher than Can. haemulonii sensu stricto and Can. duobushaemulonii. Regarding the virulence of the Cae. elegans model, Can. haemulonii species complex and Can. auris isolates were capable of causing infection in Cae. elegans, and our data suggest that the high biofilm production by Can. haemulonii var. vulnera and Can. duobushaemulonii isolates may impact in the pathogenicity caused on Cae. elegans.Mutations affecting SQSTM1 coding for p62 and TANK-Binding Kinase 1 (TBK1) have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TBK1 is a serine-threonine kinase that regulates p62’s activity as an autophagy receptor via phosphorylation and also has roles in neuroinflammatory signalling pathways. The mechanisms underlying ALS and FTLD pathogenesis as a result of TBK1 mutations are incompletely understood, however, loss of TBK1 function can lead to dysregulated autophagy and mitophagy. Here, we report that an ALS-associated TBK1 variant affecting the kinase domain, p.G175S, is defective in phosphorylation of p62 at Ser-403, a modification critical for regulating its ubiquitin-binding function, as well as downstream phosphorylation at Ser-349. Consistent with these findings, expression of p.G175S TBK1 was associated with decreased induction of autophagy compared to wild type and reduced degradation of the ALS-linked protein TDP-43. Expression of wild type TBK1 increased NF-κB signalling ~300 fold in comparison to empty vector cells, whereas p.G175S TBK1 was unable to promote NF-κB signalling above levels observed in empty vector transfected cells. We also noted a hitherto unknown role for TBK1 as a suppressor of oxidative stress (Nrf2) signalling and show that p.G175S TBK1 expressing cells lose this inhibitory function. Our data suggest that TBK1 ALS mutations may broadly impair p62-mediated cell signalling, which ultimately may reduce neuronal survival, in addition TDP-43 was not efficiently degraded, together these effects may contribute to TBK1 mutation associated ALS and FTLD pathogenesis.

The purpose of this study was to characterize health behavior profiles among active duty service members and associate these profiles with body-building and weight-loss dietary supplement (DS) use.

Based on U.S. active duty service members who completed the 2011 Health-Related Behavior Survey (n=39,877), we used latent class analysis to place respondents into latent classes (using healthy/unhealthy food consumption, aerobic activity, strength training, and sleep) and examined associations between latent class and DS use.

We identified seven health behavior classes that could be classified by physical activity and diet. Three classes with high activity were further characterized by healthy diet (24%); few unhealthy foods (18%); and unrestricted diet (9%). Three classes with low activity were further characterized by restricted diet (15%), healthy diet (15%), and unhealthy diet (6%). The last class (13%) reported moderate levels of all behaviors. The classes did not vary by sleep. Participant characteristics across most classes were relatively homogenous along demographics and military branch. The active classes had relatively higher usage of body-building and weight-loss DSs.

Latent classes from health behavior indicators might be considered „market segments”, which can be targeted with distinct messaging. Service members appear to consume DSs as part of an otherwise healthy lifestyle.

Latent classes from health behavior indicators might be considered „market segments”, which can be targeted with distinct messaging. Service members appear to consume DSs as part of an otherwise healthy lifestyle.

The purpose of this study was to evaluate the association between psychotropic medication use during pregnancy and gestational age at delivery, after adjusting for depressive symptom and perceived stress severity.

We analyzed data on singleton live births from 2914 female Pregnancy Study Online participants, aged 21 to 45, with a reported conception from 6/2013 to 6/2018. Women reported psychotropic medication use at 8 to 12weeks’ and ~32weeks’ gestation. We measured depressive symptoms using the Major Depressive Inventory and perceived stress using the 10-item Perceived Stress Scale. Data on gestational age at delivery were based on self-reports and/or birth certificates. We used restricted mean survival time models, stratifying by severity of depressive symptoms (Major Depression Inventory <25 vs. ≥25) and perceived stress (Perceived Stress Scale <20 vs. ≥20).

Two hundred and ten (7.2%) participants reported using psychotropic medications during pregnancy. Mean gestational age at delivery among women who never used psychotropic medications was 38.2weeks (95% confidence interval 37.7, 38.7), whereas it was 37.3weeks (95% confidence interval 36.7, 37.9) among women who used psychotropic medications during pregnancy. Results were similar across strata of depressive symptoms and perceived stress.

Our data indicate that the association between psychotropic medication use and gestational age at delivery is not confounded by indication.

Our data indicate that the association between psychotropic medication use and gestational age at delivery is not confounded by indication.

The purpose of the study was to convert waist circumference (WC) measurements obtained by the World Health Organization (WHO-WC) method to the National Heart, Lung, and Blood Institute (NHLBI-WC) method.

During 2016, the National Health and Nutrition Examination Survey participants aged 20 years and older had two different WC measurements taken (n= 2405). The mean differences in the WC between the NHLBI-WC and WHO-WC measurements were calculated. Multivariable prediction models were developed to predict the NHLBI-WC from the measured WHO-WC. Sensitivity and specificity of the abdominal obesity classification (AOC) were calculated for the measured WHO-WC and the predicted NHLBI-WC. Kappa coefficients were calculated to evaluate the agreements between the AOC derived from the NHLBI-WC and from the WHO-WC and the predicted NHLBI-WC.

The mean differences between the NHLBI-WC and WHO-WC were 0.8cm for males and 3.2cm for females (P≤.05). Sensitivity of the AOC for the measured WHO-WC was 93% for males and 87% for females, and the specificity of the AOC was 97% or greater for both genders. Sensitivity and specificity of the AOC for the predicted NHLBI-WC were 95% or greater for both genders. The AOC derived from the predicted NHLBI-WC had higher agreements for both genders.

The prediction equations provided may be used to predict the NHLBI-WC from the WHO-WC for comparability in WC estimates across studies.

The prediction equations provided may be used to predict the NHLBI-WC from the WHO-WC for comparability in WC estimates across studies.

We examine whether the race and armed status interact to modify the risk of being fatally shot by police within categories of civilian age and mental illness status, and U.S. region.

Data are from The Washington Post online public-use database of all U.S. police-involved shooting deaths. The sample includes black and white males with known armed status who were killed from 1/1/2015 through 12/31/2019 (n=3090). A case-only design is used to assess multiplicative interaction using adjusted logistic regression.

The fully adjusted interaction estimate is null (S

=0.75; 95% confidence interval [CI]=0.55-1.04). However, adjusted estimates within strata show that the risk of being armed versus unarmed when fatally shot is smaller for black than white males older than 54 years (S

=0.18; 95% CI=0.06-0.65), those showing mental illness signs (S

=0.50; 95% CI=0.26-0.98), and those killed in the South (S

=0.52; 95% CI=0.33-0.83), and that the risk is greater in the Midwest (S

=2.42; 95% CI=1.11-5.26). Notably, there is no black-white difference in armed status among younger age groups (S

≈0.89).

The race and armed status may interact leaving black males at a higher risk of being unarmed than white males when fatally shot by police among those older than 54 years, mentally impaired, and residing in the South. Causal interaction suggests a lower risk for unarmed blacks in the Midwest. Researchers should further explore the utility of the case-only design to study social-environmental interaction.

The race and armed status may interact leaving black males at a higher risk of being unarmed than white males when fatally shot by police among those older than 54 years, mentally impaired, and residing in the South. Causal interaction suggests a lower risk for unarmed blacks in the Midwest. Researchers should further explore the utility of the case-only design to study social-environmental interaction.Nuclear protein 1 (NUPR1) also known as p8 and candidate of metastasis 1 (COM1) functions as a transcriptional regulator, and plays a role in cell cycle, DNA damage response, apoptosis, autophagy, and chromatin remodeling in response to various cellular stressors. Since it was first suggested to contribute to cancer development and progression in 1999, a number of studies have sought to reveal its function. However, NUPR1 and its biological relevance in cancer have proven difficult to pinpoint. Based on evidence of NUPR1 expression in cancers, its function extends from carcinogenesis and tumorigenesis to metastasis and chemotherapeutic resistance. A tumor suppressive function of NUPR1 has also been documented in multiple cancers. By and large, literature involving NUPR1 and cancer is confined to pancreatic and breast cancers, yet significant progress has been made with respect to NUPR1 expression and its function in lung, colorectal, blood, and prostate cancers, among others. Recent evidence strongly supports the notion that NUPR1 is key in chemotherapeutic resistance by mediating both anti-apoptotic activity and autophagy when challenged with anti-cancer compounds. Therefore, it is of significant importance to understand the broad range of molecular functions directed by NUPR1. In this review, NUPR1 expression and its role in breast, lung, and colorectal cancer development and progression will be addressed.Recent research on cancer metabolism has revealed that individual tumors have highly heterogeneous metabolic profiles that contribute to the connective metabolic networks within the tumor and its environment. Indeed, tumor-associated cells types, including tumor cells, cancer-associated fibroblasts (CAFs) and immune cells, reprogram their metabolism in many different ways due to diverse genetic backgrounds and complex environmental stimuli. This intratumoral metabolic heterogeneity and the derived metabolic interactions play an instrumental role in cancer progression. Understanding how this heterogeneity occurs may provide promising therapeutic strategies. Here, we review the diverse metabolic profiles of several important cell subpopulations in tumors and their impact on tumor progression and discuss the consequent metabolic interactions as well as the related therapeutic concerns.The amygdala is a key component of the neural circuits mediating the processing and response to emotionally salient stimuli. Amygdala lesions dysregulate social interactions, responses to fearful stimuli, and autonomic functions. In rodents, the basolateral and central nuclei of the amygdala have divergent roles in behavioral control. However, few studies have selectively examined these nuclei in the primate brain. Moreover, the majority of non-human primate studies have employed lesions, which only allow for unidirectional manipulation of amygdala activity. Thus, the effects of amygdala disinhibition on behavior in the primate are unknown. To address this gap, we pharmacologically inhibited by muscimol or disinhibited by bicuculline methiodide the basolateral complex of the amygdala (BLA; lateral, basal, and accessory basal) in nine awake, behaving male rhesus macaques (Macaca mulatta). We examined the effects of amygdala manipulation on (1) behavioral responses to taxidermy snakes and social stimuli, (2) food competition and social interaction in dyads, (3) autonomic arousal as measured by cardiovascular response, and (4) prepulse inhibition of the acoustic startle (PPI) response.