Ralstondunlap1178
Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells. In conclusion, our study showed that puerarin mitigated skeletal muscle wasting in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition. Whether this effect in murine applies to humans remains to be determined.Retinal ischemia, one of the most common cause of visual loss, is associated with blood flow inadequacy and subsequent tissue injury. In this setting, some treatments that can counteract glutamate increase, arouse interest in ischemic pathogenesis. Ketamine, a potent N-methyl-d-aspartate (NMDA) receptor antagonist, provides a neuroprotective pathway via decreasing the excitotoxicity triggered by excess glutamatergic. Thus, the goal of this study was to evaluate the safety of intravitreal use of ketamine and their potential protective effects on retinal cells in retinal ischemia/reperfusion model. Initially, ketamine toxicity was evaluated by cytotoxicity assay and Hen's egg chorioallantoic membrane (HET-CAM) method. Afterward, some ketamine concentrations were tested in rat's eyes to verify the safety of the intravitreal use. To investigate the neuroprotective effect on retinal, a single intravitreal injection of ketamine in concentrations of 0.059 mmol.L-1 and 0.118 mmol.L-1 was performed one day before the ntravitreal ketamine showed a number of retinal cells significantly higher than the vehicle group. In TUNEL assay a reduction on TUNEL-positive cells was observed in all the layers for both concentrations which allow to affirm that ketamine contributes to reducing cell death in the retina. Transmission electron microscopy (TEM) reaffirms this finding. Ketamine intravitreal pretreatment showed reduced ultrastructural changes. Our findings demonstrate that ketamine is safe for intravitreal use in doses up to 0.118 mmol.L-1. They seem to be particularly efficient to protect the retina from ischemic injury.Tramadol, a weak agonist of mu-opioid receptors, causes seizure via several mechanisms. Preconditioning has been purposed to reduce the epileptic seizures in animal models of epilepsy. The preconditioning effect of tramadol on seizure is not studied yet. This study was designed to evaluate the preconditioning effect of ultra-low dose of tramadol on the seizures induced by tramadol at high dose. Furthermore, regarding the critical role of glutamate signaling in the pathogenesis of epilepsy, the effect of preconditioning on some glutamate signaling elements was also examined. Male Wistar rats received tramadol (2 mg/kg, i.p) or normal saline (1 mL/kg, i.p) in preconditioning and control groups, respectively. After 4 days, the challenging tramadol dose (150 mg/kg) was injected to all rats. Epileptic behaviors were recorded during 50 min. The expression of Norbin (as a regulator of metabotropic glutamate receptor 5), Calponin3 (as a regulator of excitatory synaptic markers), NR1 (NMDA receptor subunit 1) and GluR1 (AMPA receptor subunit 1) was measured in hippocampus, prefrontal cortex (PFC) and amygdala. Preconditioning decreased the number and duration of tremors and tonic-clonic seizures. Norbin, Calponin3, NR1 and GluR1 expression were decreased in hippocampus, and preconditioning had no effect on them. In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose. These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.
The railway industry in Indonesia has grown substantially in the past five years, with greater network and tracks length that will double in 2030. There has been a growing concern, however, that fatigue among front-line personnel have not been addressed satisfactorily. This study aimed at evaluating the degree of fatigue among passenger train drivers and suggested practical recommendations to the Indonesian Railway Company.
A total of 32 train drivers (driving for about 4h during the morning or afternoon shifts) agreed to participate in the study. Subjective and objective measures of fatigue (and sleepiness) were obtained prior to, during, and immediately following the end of a duty. Fatigue and driving performance were also determined based on (off-line) analysis of continuous video recordings of the drivers performing the duty.
Fatigue generally increased as a function of time and, for some, 2h of driving was sufficient in inducing substantial level of fatigue increase. Unlike the morning shift, the ain this study that the company pay a much closer attention to the work-sleep schedules, and to improve sleep quality by redesigning better sleeping arrangements.Chronotype refers to individual differences in the timing of circadian sleep-wake cycles and subjective alertness throughout the day. It is a potential factor influencing people's driving behaviour, but no research has explored the mechanisms underlying this topic. The current study aimed to explore the relationship between morningness-eveningness preferences and driving behaviour and the mediating effect of visual search between them. Thirty-eight drivers were selected to participate in this study based on their chronotype. They were divided into morning-type and evening-type groups by their score on the reduced Morningness-Eveningness Questionnaire (rMEQ). Both groups completed a visual search task and a simulated driving task in a morning session and an evening session. The results showed that morningness-eveningness preferences had synchronous effects on basic driving performance; specifically, morning-type drivers showed better driving behaviour in the morning than in the evening, and evening-type drivers showed the opposite trend. Furthermore, visual search abilities showed a mediating effect between morningness-eveningness preference and driving performance. The mechanisms underlying these results are discussed. Related results and data could aid with schedule arrangements for professional drivers.TK1646 is a highly thermostable single strand specific 3'-5' exonuclease. Exonucleases play important role in maintaining the genome integrity at elevated temperatures. Therefore, it is important to examine the factors contributing to thermostability of these exonucleases. In this study we report on production, purification and characterization of S187G and Y50H mutants of TK1646, focusing on the factors leading to thermostability of TK1646. Characterization of the recombinant proteins indicated that these substitutions did not drastically affect the catalysis of single stranded DNA. However, both of these substitutions reduced the thermostability of the recombinant proteins. Half-lives of Y50H and S187G mutants were 95 and 155 min, respectively, at 100 °C in comparison to 180 min of the wild type. Bioinformatics analysis indicated an increase in solvent accessibility of the mutated residues and disruption of hydrogens bonds. Molecular modelling and superimposition of the 3D structures of the mutants and the wild type demonstrated that one of the active site residues, Glu145, was shifted away from the metal ion in both the mutants which may be responsible for the decrease in catalytic activity. Compact secondary structure, hydrophobicity and hydrogen bonding might be the major factors contributing to the thermostability of TK1646.
Uteroplacental vascular dysfunction, characterized by diminished uterine artery (UtA) blood flow in the second trimester is a clinically useful predictor of the further development of preeclampsia, fetal growth restriction and stillbirth. Efforts to develop effective treatments to protect pregnancies with abnormal UtA Dopplers would be of significant clinical benefit for mothers and their fetuses.
The aim of this pilot non randomized control study was to use pravastatin +L-arginine to improve uteroplacental haemodynamics and prevent adverse maternal and neonatal outcomes in women with abnormal Dopplers and high risk for developing adverse pregnancy outcomes.
This study was performed between 2015 and 2018. All women received primary care at OB/GYN Polyclinic Jurisic and Narodni Front University Hospital, University of Belgrade Medical School, Serbia. Approval for investigational drug use was obtained and all women gave informed consent. 10 pregnant women with a poor obstetric history that developed uteroh restricted and spent several months at NICU. Two neonates died due to prematurity-associated complications. PRAV+L-arginine treatment prolonged pregnancies for 4.1months, compared to 26days in the untreated group, preventing neonatal complications associated with prematurity. The infants are now 1-3years old and show normal growth and development.
This study describes the successful management with pravastatin+L-arginine of 10 pregnant patients with uteroplacental vascular dysfunction and high risk of adverse maternal and fetal outcomes. A larger study is being organized to confirm these observations.
This study describes the successful management with pravastatin+L-arginine of 10 pregnant patients with uteroplacental vascular dysfunction and high risk of adverse maternal and fetal outcomes. A larger study is being organized to confirm these observations.Though therapist-guided Internet-based cognitive behavior therapy (ICBT) appears to be efficacious for depression, social anxiety disorder, and panic disorder, relatively little is known about real-world settings and predictors of treatment effects derived from cognitive-behavioral theory. We examined treatment effectiveness and predictors of improvement in a prospective cohort study where patients took part in 10 weeks of ICBT for depression (n = 114), social anxiety disorder (n = 150), or panic disorder (n = 106) at a teaching clinic. Patients self-reported symptoms before, during, and after treatment. Effect sizes were large for improvement in the primary symptom domain of each treatment group depression (d = 1.48), social anxiety disorder (d = 1.01), and panic disorder (d = 1.15). In ICBT for depression, having no previous experience of psychological treatment (r = 0.21), and more frequent baseline negative automatic thoughts (r = 0.20) predicted larger improvement. In ICBT for panic disorder, having more baseline safety behaviors (r = 0.25) predicted larger improvement. Predictors remained significant when baseline symptoms were included in the statistical models. We conclude that ICBT can be effective in a real-world teaching clinic, and that patients with greater deficits at baseline benefit the most.
Cervical insufficiency is a defect of the cervix that leads to failure to preserve a full-term intrauterine pregnancy. Laparoscopic cerclage and open transabdominal cerclage (TAC) are effective ways to manage patients with cervical insufficiency. We performed this systematic review and meta-analysis to investigate the complications of laparoscopic cerclage and open TAC in the management of cervical insufficiency.
We searched PubMed, Cochrane, Scopus, and Web of Science using our search strategy and screened the results for our criteria. We extracted the results reported and analyzed them using Open Meta-Analyst (OpenMeta[Analyst], Brown School of Public Health, Providence, RI) and Review Manager (Cochrane Collaboration, London, United Kingdom) software.
We included all randomized controlled and observational trials performed on patients with cervical insufficiency undergoing open TAC or laparoscopic cerclage that matched our search strategy. We excluded letters to the editor, reviews, meetings/conferencly significant lower incidence of fetal loss, blood loss, and rate of hemorrhage in the laparoscopic cerclage group. Clinically, this evidence may help support favoring a laparoscopic approach over an open one in appropriate patients, although it is unclear whether this benefit is limited to cerclages placed either before pregnancy or placed in the first-trimester or both.
Laparoscopic cerclage may be safer than open TAC in the management of cervical insufficiency because we found a statistically significant lower incidence of fetal loss, blood loss, and rate of hemorrhage in the laparoscopic cerclage group. Clinically, this evidence may help support favoring a laparoscopic approach over an open one in appropriate patients, although it is unclear whether this benefit is limited to cerclages placed either before pregnancy or placed in the first-trimester or both.
To demonstrate stepwise techniques for the successful use of the laparoscopic single-site technique for safely performing transvaginal sacrocolpopexy for pelvic organ prolapse.
Stepwise demonstration with narrated video footage (Canadian Task Force classification III).
Academic tertiary care hospital. The patient, aged 69 years gravida 2 para 2-0-0-2 with a history of SVD × 2, presented with symptomatic stage II anterior vaginal prolapse (Aa +1) and stage II posterior vaginal prolapse (Ap -1). The preoperative vaginal length was measured at 9 cm.
Laparoscopic transvaginal single-site sacrocolpopexy has been demonstrated to be feasible and safe in the surgical management of pelvic organ prolapse. However, the retroperitoneal dissection or suturing/knot tying can be technically challenging to perform, especially in the event of an anatomic variation of a deeply angled S1 vertebra. Wristed robotic instrumentation may overcome some of these obstacles and result in easier suturing and knot tying. Integratieasured postoperative vaginal length of 7 cm. The patient's postoperative pelvic organ prolapse quantification was stage 0.
Robot-assisted transvaginal single-site sacrocolpopexy for pelvic organ prolapse is feasible, effective, and safe in patients with pelvic organ prolapse. Patients experience improved cosmesis, decreased postoperative pain, and faster recovery compared with abdominal sacrocolpopexy.
Robot-assisted transvaginal single-site sacrocolpopexy for pelvic organ prolapse is feasible, effective, and safe in patients with pelvic organ prolapse. Patients experience improved cosmesis, decreased postoperative pain, and faster recovery compared with abdominal sacrocolpopexy.
Risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations. The aim of this meta-analysis is to evaluate the risk of endometrial cancer (EC) in BRCA1 or BRCA2 germline mutation carriers and to examine the justifiability of prophylactic hysterectomy at the time of RRSO.
PubMed, Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched. Eleven articles were selected and analyzed using the OpenMetaAnalyst 2012 software.
Randomized controlled studies, cohort studies, and case-control studies evaluating the risk of EC and specifically uterine papillary serous carcinoma (UPSC) in germline BRCA1/2 mutation carriers were included. Articles were excluded if they did not meet the inclusion criteria, or if data were not reported and the authors did not respond to inquiries. We assessed the methodological quality of the included studies on the basis of the Newcastle-Ottawa scale. Dichotomous resuterectomy should be tailored individually to each patient on the basis of the patient's age, type of mutation, future need for hormone replacement treatment, history of breast cancer, tamoxifen use, and personal operative risks.
Most studies in this meta-analysis suggest a slightly increased risk of EC in BRCA mutation carriers, mainly for BRCA1. The decision regarding concurrent hysterectomy should be tailored individually to each patient on the basis of the patient's age, type of mutation, future need for hormone replacement treatment, history of breast cancer, tamoxifen use, and personal operative risks.
To evaluate the efficacy of flushing the uterine cavity with lidocaine before hysterosalpingo-foam sonography (HyFoSy) to reduce procedure-related pain.
A double-blind randomized controlled trial was conducted at the Department of Obstetrics and Gynecology, Shamir Medical Center, Israel between June 2020 and September 2020 involving 80 women undergoing a HyFoSy procedure.
University-affiliated medical center.
A total of 40 women were assigned randomly to the lidocaine group and 40 to the saline (placebo) group using a predetermined randomization code. Intrauterine instillation before the procedure consisting of either lidocaine 2% or normal saline alone was conducted, respectively.
The primary outcome measure was the visual analog scale (VAS) pain score during the phase of intrauterine foam instillation reported by the women after the procedure. The VAS consisted of a 10-cm line ranging from 0 to 10 (anchored by 0 = no pain and 10 = very severe pain). On the basis of the VAS scores, the pain level ry affect compliance with this procedure.
To establish an endometrioma treatment paradigm (decision tree) in the treatment of an ovarian endometrioma through the review of current literature.
A thorough literature search, including PubMed, Google Scholar, and the Cochrane Library, was performed from April 2020 to July 2020. The review was completed by using the following keywords METHODS OF STUDY SELECTION Articles published in English that addressed the endometrioma in regard to the following were included (1) diagnosis, (2) treatment of pain on the basis of size and/or surgical intervention, (3) treatment of fertility on the basis of size and/or surgical intervention, (4) surgical technique, (5) in vitro fertilization success on the basis of size and/or surgical intervention, (6) risk of rupture at the time of egg retrieval, (7) impact on the antimüllerian hormone and antral follicle count postsurgery, and (8) impact on implantation.
Fifty-six articles were included in this systematic review. While conducting this literature review, several te literature review, an easy-to-use algorithm for the diagnosis, evaluation, and treatment of endometriomas was developed to help clinicians in their treatment of patients with endometriosis in the short and long terms.Evidence for the effectiveness of population health screenings to reduce the burden of non-communicable diseases in low-income countries remains very limited. We investigate the sustained effects of a health screening in Malawi where individuals received a referral letter if they had elevated blood pressure. Using a regression discontinuity design and a matching estimator, we find that receiving a referral letter reduced blood pressure and the probability of being hypertensive by about 22 percentage points four years later. These lasting effects are explained by a 20 percentage points increase in the probability of being diagnosed with hypertension. There is also evidence of an increase in the uptake of medication, while we do not identify improvements in hypertension-related knowledge or risk behaviors. On the contrary, we find an increase in sugar intake and a decrease in physical activity both of which are considered risky behaviors in Western contexts. The health screening had some positive effects on mental health. Overall, this study suggests that population-based hypertension screening interventions are an effective tool to improve health in low-income contexts.Understanding the effects of oil exposure on early life stage fish species is critical to fully assessing the environmental impacts of oil spills. Oil released from the 2010 Deepwater Horizon spill reached habitats where estuarine fish routinely spawn. In addition, estuaries are highly dynamic environments, therefore, fish in these areas are routinely exposed to varying salinity and dissolved oxygen (DO) levels, each of which are known to modulate transcriptional responses. Fish exposed to oil often display altered immune competence, and several studies have shown that Deepwater Horizon oil in particular causes modulation of various immune functions. However, few studies have directly examined how environmental parameters may affect oil-induced immunomodulation, particularly in early life stage fishes when the immune system is still developing. To this end, we examined transcriptional patterns of immune genes and pathways in Fundulus grandis larvae to various oil (0, 15 μg/L), salinity (3, 30 ppt), and DO (2.5, 6 mg/L) regimes in a fully factorial design. Our results suggest that immune pathways are generally activated in all treatment groups with the exception of the Low Salinity/No Oil/Hypoxia treatment where immune pathways are largely suppressed, and the High Salinity/No Oil/Hypoxia treatment where pathways are unchanged. The High Salinity/Oil/Hypoxia treatment had the largest number of enriched immune pathways (44 as defined by IPA and 43 as defined by ConsensusPathDB), indicating that oil under certain environmental conditions has the potential to further modulate immune-related genes, pathways, and responses in fish.The current global health problem caused by SARS-CoV-2 has challenged the scientific community in various ways. Therefore, worldwide several scientific groups are exploring SARS-CoV-2 from different aspects including its origin, spread, severe infectivity, and also to find a cure. It is now well known that spike glycoprotein helps SARS-CoV-2 to enter inside the human host through a cellular receptor ACE2. However, the role of coevolutionary forces that makes SARS-CoV-2 spike glycoprotein more fit towards its human host remains unexplored. Therefore, in present bioinformatics study we identify coevolving amino acids in spike glycoprotein. Additionally, the effects of coevolution on the stability of the spike glycoprotein as well as its binding with receptor ACE2 were predicted. The results clearly indicate that coevolutionary forces play a pivotal role in increasing the fitness of spike glycoprotein against ACE2.Porcine reproductive and respiratory syndrome virus (PRRSV) is a causative pathogen of PRRS, one of the most economically disastrous swine diseases. Non-structural protein 1 (NSP1) of PRRSV consists of NSP1α and NSP1β which exhibit papain like cysteine protease activity. Recent evidence demonstrates that PRRSV NSP1 may be participated in modulating host immunity, but very few host proteins were discovered as targets for NSP1. In this study, we used RNA-seq to investigate the functional role of PRRSV NSP1 in porcine alveolar macrophages, 3D4/31 cells. Compared to empty vector (mock) transfectant, NSP1, NSP1α, and NSP1β expressing 3D4/31 cells displayed a total of 60 genes, 63 genes, and 80 genes as differentially expressed genes (DEGs), respectively. Most of DEGs are involved in early inflammatory responses including interleukin (IL)-17 signaling pathway, chemokine signaling pathway, tumor necrosis factor (TNF)-α signaling pathway, and cell adhesion molecules. Interestingly, PRRSV NSP1 expression in 3D4/31 cells decreased mRNA transcripts of Fosb and Gdf15 known to be involved in host cell signaling or host cell protection during inflammation. Therefore, PRRSV NSP1 might block the signaling involved in host immune surveillance. Further study is required to define the mechanism on how PRRSV NSP1 protein represses mRNA transcripts of specific host genes.Chronic neuropathic pain affects 7-10 % of the population and is often accompanied by comorbid emotional disorders, which greatly reduce the quality of life of the patients, impairing physical, cognitive, emotional, and social functioning. Despite the higher prevalence and severity of chronic pain in women, the number of publications using female animals remains scarce. While in the chronic constriction injury (CCI) model the development of mechanical/thermal hyperalgesia, allodynia and spontaneous pain has been shown in both sexes, little is known on CCI-induced emotional impairments and sciatic nerve histopathology in female rats, as well as on the contributions of ovarian hormones to peripheral nerve injury. In this work, young adult rats (Wistar Han) were assigned to one of five groups gonadally intact females (SHAM/SHAM), ovariectomized females (SHAM/OVX), gonadally intact females with CCI (CCI/SHAM); ovariectomized females with CCI (CCI/OVX) and males with CCI (CCIM). In the postoperative period, CCI an males, and that ovariectomy aggravates females' responses to peripheral nerve injury.3,4-Dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) is a selective μ-opioid receptor agonist originally synthesized as a prospective analgesic drug. Several times more potent than morphine, U-47700 has high abuse potential and may cause clinical neurotoxicity, euphoria, respiratory depression and occasional mortality. U-47700 also evokes analgesia, sedation and euphoria-like states in both humans and rodents. Despite the growing use and abuse of U-47700, its psychopharmacological and toxicological profiles in vivo remain poorly understood. The zebrafish (Danio rerio) is rapidly becoming a popular aquatic model organism for central nervous system (CNS) disease modeling and drug discovery. Here, we examine acute (1, 5, 10, 25 and 50 mg/L for 20-min) and chronic (0.1, 0.5 and 1 mg/L for 14 days) effects of U-47700 in adult zebrafish. Overall, we found overt sedation evoked in fish by acute, and hyperlocomotion with an anxiolytic-like action by chronic, drug treatments. Acute treatment with 1 and 10 mg/L U-47700 also resulted in detectable amounts of this drug in the brain samples, supporting its permeability through the blood-brain barrier. Collectively, these findings emphasize complex dose- and treatment-dependent CNS effects of U-47700 following its acute and chronic administration. Our study also supports high sensitivity of zebrafish to U-47700, and suggests these aquatic models as promising in-vivo screens for probing potential CNS effects evoked by novel synthetic opioid drugs.Citric acid (CA) has been widely used in different industrial sectors, being produced through fermentation of low-cost feedstock. The development of downstream processes, easier to operate, environmentally friendly, and more economic than precipitation, is certainly a challenge in CA bioproduction. Large volumes of by-products generated in precipitation require treatment before disposal. Adsorption, extraction, and membrane separation have been shown to have a lower environmental impact than precipitation, but the technological maturity of these methods is still limited. However, reactive extraction and adsorption have great potential for industrial applications. This review shows that there is still much to be explored, both about the factors that are intrinsic to the techniques, but also in their combination for new processes' development. This review reports the most recent advances on CA bioproduction, with significant information about recovery and purification methods involving this highly industrially demanded organic acid.The most prominent aromatic feedstock on Earth is lignin, however, lignin valorization is still an underrated subject. The principal preparatory strategies for lignin valorization are fragmentation and depolymerization which help in the production of fuels and chemicals. Owing to lignin's structural heterogeneity, these strategies result in product generation which requires tedious separation and purification to extract target products. The bacterial genus Pseudomonas has been dominant for its lignin valorization potency, owing to a robust enzymatic machinery that is used to funnel variable lignin derivatives into certain target products such as polyhydroxyalkanotes (PHAs) and cis, cis-muconic acid (MA). In this review, the potential of genus Pseudomonas in lignin valorization is critically reviewed along with the advanced genetic techniques and tools to ease the use of lignin/lignin-model compounds for the synthesis of bioproducts. This review also highlights the research gaps in lignin biovalorization and discuss the challenges and possibilities for future research.Dengue virus (DENV) infection elevates intracellular Ca2+ concentration ([Ca2+]i), but it is unknown whether Ca2+ and calmodulin (CaM) are involved in DENV infection. We conducted immunofluorescence and western blot experiments and measured [Ca2+]i examining the effects of DENV infection and drugs that alter Ca2+/CaM functions on CaM translocation, DENV2 infection, protein expression, virus-inducible STAT2 protein abundance, and CREB phosphorylation in H9c2 cells. DENV infection increased CaM expression, its nuclear translocation and NS3 and E viral proteins expression and colocalization in a manner that could be blocked by the ryanodine receptor antagonist dantrolene. DENV infection also increased CREB phosphorylation, an effect inhibited by either dantrolene or the CaM inhibitor W7. Dantrolene substantially hindered infection as assessed by focus assays in Vero cells. These results suggest that Ca2+ and CaM play an important role in DENV infection of cardiac cells and that dantrolene may protect against severe DENV cardiac morbidity.
To determine which factors are associated with plans for in-person school attendance during the 2020-2021 school year and with support for 15 school-based COVID-19 risk mitigation measures among parents and guardians.
In June 2020, we conducted an online survey of parents and guardians of public school children in Illinois, Michigan, and Ohio. In a child-level analysis, we used linear regression to assess which demographic factors, health-related concerns, and parent/guardian views were associated with plans for in-person school attendance. In a respondent-level analysis, we used linear regression to assess factors associated with the number of risk mitigation measures supported.
Among 2202 children in the child-level analysis, in-person school attendance was planned for 71.0%. Such plans were less likely among children of Black respondents (-14.1 percentage points, 95% confidence interval [CI] -25.7, -2.6) and Asian respondents (-16.8, 95% CI -31.3, -2.2), and among children with perceived high-risk heparents and guardians to implement substantial numbers of risk mitigation measures.Human pasteurellosis with a gynecologic tropism is rare. A 54 year-old woman presented with sepsis due to a uterine abscess from pasteurella multocida (PM) secondarily complicated by gluteal abscess. She had a history of adenomyosis and had previously undergone hysteroscopic sterilization with micro-inserts. Treatment consisted in antibiotherapy, laparoscopic hysterectomy with salpingectomy and abscess drainage, which resulted in complete recovery. This is the first case of uterine abscess from PM with a second septic location.This study was conducted to evaluate the antimicrobial potential of the antimicrobial peptides (AMP) LL-37 and human Lactoferricin (LfcinH) on the planktonic growth and biofilm formation of oral pathogenic anaerobes related to caries and periodontitis. Multi-species bacterial suspensions of either facultative anaerobic bacteria (FAB Streptococcus mutans, Streptococcus sanguinis, Actinomyces naeslundii) or obligate anaerobic bacteria (OAB Veillonella parvula, Parvimonas micra, Fusobacterium nucleatum) were incubated with different concentrations of AMP solutions for 8 h. Planktonic growth was registered with an ATP-based cell viability assay for FAB and via plate counting for OAB. Biofilms were grown on ZrO2 discs for 4 days in a mixture of the multi-species bacterial suspensions and AMP solutions. Biofilm mass was quantified using a microtiter plate biofilm assay with crystal violet staining. An overall planktonic growth inhibition and biofilm mass reduction of FAB and OAB was registered for LL-37 and LfcinH. Significant inhibitory threshold concentrations of LL-37 were observed in all experiments (p less then 0.0001). No significant threshold was observed for LfcinH. Biofilm mass of OAB was barely reduced by LfcinH. The complete mechanisms of the AMPs are not fully understood yet. While LL-37 shows promising features as potential therapeutic for biofilm-associated oral diseases, LfcinH seems unsuitable for this particular indication. For clinical AMP use, further investigations will be necessary.
A sufficient supply of oxygen is crucial to avoid hypoxic cardiac arrest and brain damage within 30 min in completely-buried avalanche victims. Snow density influences levels of hypoxia and hypercapnia. The goal of this study was to investigate the effects of hypoxia and hypercapnia on cerebral oxygenation (ScO
) in humans breathing into an artificial air pocket.
Each subject breathed into a closed system (air-tight face mask - plastic tube - snow air-pocket of 4 L) up to 30 min. Each subject performed three tests in different snow densities. ScO
was measured by a near-infrared spectroscopy (NIRS) device. Measurements included peripheral oxygen saturation (SpO
), end-tidal carbon dioxide (ETCO
), air pocket gases and blood gases. Snow density was assessed via standard methods and micro-computed tomography. Based on predetermined criteria, tests were classified based on whether they were terminated before 30 min and the reason for termination. The categories were completed tests (30 min), tests terminficant decrease caused by a critical decrease in oxygen supply. This could lead to a higher risk of hypoxic cardiac arrest and brain damage.
Our data show that ScO2 determined by NIRS was not always impaired in humans breathing into an artificial air pocket despite decreased oxygen supply and decreased carbon dioxide removal. This may indicate that in medium to low snow densities brain oxygenation can be sufficient, which may reflect the initial stage of the triple H (hypothermia, hypoxia, and hypercapnia) syndrome. In high snow densities, ScO2 showed a significant decrease caused by a critical decrease in oxygen supply. This could lead to a higher risk of hypoxic cardiac arrest and brain damage.
To develop an effective enrichment method for tet(X) detection, we performed PCR and Sanger sequencing to screen and confirm the presence of tet(X) gene.
Species were identified by MALDI-TOF MS analysis. The minimum inhibitory concentrations (MICs) of common antibiotics were determined by broth microdilution and interpreted according to the CLSI guidelines and EUCAST breakpoints.
We obtained 29 (2.26%, 29/1284) tet(X4)-positive Escherichia coli, and 96.6% of those (28 isolates) exhibited resistance to tigecycline.
This specific screening strategy for functional tet(X) mediating tigecycline resistance will be useful to facilitate development and advancement of our knowledge of tet(X).
This specific screening strategy for functional tet(X) mediating tigecycline resistance will be useful to facilitate development and advancement of our knowledge of tet(X).
Huntington's disease (HD) is characterized by psychiatric, cognitive, and motor disturbances. The study aimed to determine electroencephalography (EEG) global state and microstate changes in HD and their relationship with cognitive and behavioral impairments.
EEGs from 20 unmedicated HD patients and 20 controls were compared using global state properties (connectivity and dimensionality) and microstate properties (EEG microstate analysis). For four microstate classes (A, B, C, D), three parameters were computed duration, occurrence, coverage. Global- and microstate properties were compared between groups and correlated with cognitive test scores for patients.
Global state analysis showed reduced connectivity in HD and an increasing dimensionality with increasing HD severity. Microstate analysis revealed parameter increases for classes A and B (coverage), decreases for C (occurrence) and D (coverage and occurrence). Disease severity and poorer test performances correlated with parameter increases for class A (coverage and occurrence), decreases for C (coverage and duration) and a dimensionality increase.
Global state changes may reflect higher functional dissociation between brain areas and the complex microstate changes possibly the widespread neuronal death and corresponding functional deficits in brain regions associated with HD symptomatology.
Combining global- and microstate analyses can be useful for a better understanding of progressive brain deterioration in HD.
Combining global- and microstate analyses can be useful for a better understanding of progressive brain deterioration in HD.Oral delivery of macromolecular drugs is the most patient-preferred route of administration because it is painless and convenient. Over the past 30 years, significant attention has been paid to oral protein delivery in adults. Unfortunately, there is an outstanding need for similar efforts in infants, a patient population with distinct intestinal physiology and treatment needs. Here, we assess the intestinal permeability of neonatal and infant mice to determine the feasibility of orally delivering peptide and protein drugs without permeation enhancers or other assistance. Using the non-everted gut sac model, we found that macromolecular permeability depended on molecular size, mouse age, and intestinal tissue type using model dextrans. For example, the apparent permeability of 70 kDa FITC-Dextran (FD70) in infant small intestinal tissue was 2-5-fold higher than in adult tissue. As mice aged, the expression of barrier-forming and pore-forming tight junction proteins increased and decreased, respectively. The in vivo oral absorption of 4 kDa FITC-Dextran (FD4) and FD70 was significantly higher in younger mice, and there was a fourfold increase in oral absorption of the 80 kDa protein lactoferrin compared to adults. Oral gavage of insulin (5 IU/kg) reduced blood glucose levels in infants by >20% at 2 and 3 h but had no effect in adults. Oral insulin had 35% and less then 1% of the pharmacodynamic effect of a 1 IU/kg subcutaneous dose in infants and adults, as measured by area above the curve. These data indicate that the uniquely leaky nature of the infantile intestine may support the oral delivery of biologics without the need for traditional oral delivery technology.To date there is no clinically approved adjuvant to drive a protective T-helper cell 17 (Th17) immune response against Mycobacterium tuberculosis (Mtb). Trehalose Dimycolate (TDM) is a glycolipid molecule found in the cell wall of Mtb and similar species. Our team has discovered novel synthetic TDM derivatives that target Mincle receptors and when presented on the surface of amine functionalized silica nanoparticles (A-SNPs) adopt the requisite supramolecular structure for Mincle receptor agonism. Here we describe the preparation and characterization methods for these critical silica nanoparticles (SNPs) co-loaded with Mincle agonists (MAs) and a model antigen. In this work, A-SNPs with a particle diameter of 246 ± 11 nm were prepared and examined for co-adsorption of two synthetic MAs along with ovalbumin (OVA). Due to the insolubility of the studied MAs in aqueous environment, aggregation of the MAs made separation of the adjuvant-loaded A-SNPs from the free-form MAs via centrifugation very challenging. To structural features and biophysical properties.
According to the theory of traditional Chinese medicine (TCM), Alzheimer's disease (AD) is identified as "forgetfulness" or "dementia", and it can be caused by spleen deficiency. Longan Aril (the aril of Dimocarpus longan Lour., LA) is a kind of Chinese medicine, and it can improve intelligence attributed to entering the spleen-meridian. This study aimed to explore the therapeutic effects of LA on AD mice with spleen deficiency, and to understand anti-AD mechanism of LA.
A mouse model of AD with spleen deficiency was established by D-gal (140mg/kg, intraperitoneal injection) and AlCl
(20mg/kg, intragastrical administration) in combination with an irregular diet for 60 days, in which mice in LA group were daily given LA (0.5, 1.0 or 2.0g/kg). The anti-AD effects of LA were evaluated by the Morris water maze, enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E), Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The anti-AD mechanism of LA was stuia inhibition of RAS/MEK/ERK singling pathway.
To report on our institution's first year of experience with a preferred vendor program for implants and disposables for sports medicine surgery.
Cost and utilization data for implants and disposables were analyzed for knee and shoulder sports medicine surgeries performed during the 2-year period including the 12 months preceding the start of the contract (contract year 0 [CY0] and the first 12 months of the contract period (CY1). The costs of grafts and biological therapies were excluded. Utilization of the preferred vendor's products, operative time, and per-case costs were compared between the 2 time periods and adjusted for patient factors and case mix.
Utilization of the preferred vendor's shavers (0% to 94%, P < .001) and radiofrequency ablation wands (0% to 91%, P < .001) increased significantly in CY1 (n= 5,068 cases) compared with CY0 (n= 5,409 cases), with a small but significant increase in use of the preferred vendor's implants (64% to 67%, P= .023). There was no significant difference in mean operative time between CY0 and CY1 (P= .485). Mean total per-case implant and disposable costs decreased by 12% (P < .001) in CY1 versus CY0.
Our institution was able to reduce the costs of sports medicine surgery with the implementation of a preferred single-vendor program for implants and disposables. This program had widespread surgeon adoption and did not have any detrimental effect on operating room efficiency.
III, retrospective comparative study.
III, retrospective comparative study.
To determine whether curettage of the cartilage on the glenoid edge in arthroscopic Bankart repair reduces the postoperative recurrence rate compared with noncuretted glenoid.
Between January 2010 and December 2013, 134 patients underwent arthroscopy and stabilization for recurrent anterior dislocation of shoulder; 42 patients were excluded. Alternate glenoid edge was curetted in 92 patients undergoing arthroscopic Bankart repair. Twelve patients were lost to follow-up. The remaining 80 patients were divided into 2 groups of 40 patients each, curettage and noncurettage. In both groups, the Bankart lesion was repaired using ≥3 bioanchors loaded with nonabsorbable braided sutures. Postoperative rehabilitation was the same for the 2 groups. We recorded recurrence of instability, pain, and Constant and Rowe shoulder scores. Statistical analysis of data was performed using unpaired t test (significance level P<.05).
The 2 groups were comparable in terms of age, number of dislocations, and bone loss. The average follow-up was 7 years and 9 months (range 6 to 10 years). Of the total 40 patients in the curettage group, 6 (15%) had recurrence of dislocation and none had subluxations, whereas in the noncurettage group, 13 (32.5%) had recurrence of dislocation and 3 (7.5%) had subluxations. The difference in postoperative recurrence of instability was statistically significant (P= .012). The average (standard deviation) Rowe score was 83.75 (23.28) in the curettage group and 70.13 (31.29) in the noncurettage group (P= .030).
During arthroscopic Bankart repair, curettage of the cartilage on the anterior glenoid edge reduces the incidence of postoperative recurrence of instability.
II, therapeutic; prospective, randomized, controlled study.
II, therapeutic; prospective, randomized, controlled study.Lornoxicam is a nonsteroidal anti-inflammatory drug extensively used in human medicine, which is not approved for canine use. Lornoxicam intoxication has been rarely reported in dogs. Four dogs of various breeds, aged 7 months to 10 years, were admitted with a recent history of melena, anorexia and depression, occurring 1-4 days after the ingestion of lornoxicam (dose range 0.53-2.7 [median 1.17] mg/kg). No clinically relevant comorbidities were documented, but low doses of prednisolone had been given in 3 of the dogs, in close temporal association with lornoxicam. Major clinical and clinicopathologic findings on admission included mucosal pallor, melena, depression, severe anemia, neutrophilic leucocytosis, and panhypoproteinemia. Perforated pyloric and duodenal ulcers were documented in 3 dogs by exploratory celiotomy or postmortem. Prolonged hospitalization (5-20 days) with extensive supportive care and multiple blood transfusions was required in 3 of the 4 dogs who survived to discharge. Lornoxicam ingestion may cause protracted and severe gastrointestinal tract injury and bleeding, blood loss anemia, panhypoproteinemia, and perforated gastrointestinal ulcers, associated with significant morbidity and mortality in dogs.Ultrasonography is one of the most common methods for the diagnosis of prostate disorders, such as benign prostatic hyperplasia (BPH), in dogs. Changes in the echotexture are one of the indicators used to diagnose prostate disorders. The purpose of this study was to investigate the changes occurred in the dogs' prostate echotexture during the induction of BPH using image analysis. Twenty sexually mature male intact mixed-breed dogs were selected and divided randomly into control and BPH-induced groups. BPH was induced using testosterone and estrogen injections for 63 days. The ultrasound imaging of the dogs' prostate was performed during the induction of BPH on days 0, 21, 42, and 63. The echotexture of the prostate parenchyma was analyzed using the Image J software. Then, the changes in the echotexture and its correlation and linear regression with the prostate volume and canine prostate specific esterase (CPSE) concentration were evaluated by statistical tests. The prostate parenchyma echotexture did not show any significant changes during the induction of BPH and in comparison with that of the control group. While prostate volume and CPSE concentration increased significantly, indicating that BPH was induced in the dogs. There was no significant correlation and linear regression between the prostate echotexture and prostate volume or between the CPSE concentration and prostate echotexture. According to the results, the alteration in the prostate parenchymal echotexture did not occur in the early stages of induced BPH, but significant changes occurred in the prostate volume and CPSE concentration during those early stages.Muscular dystrophies in dogs and cats represent a heterogeneous group of inherited, sometimes congenital, but infrequently diagnosed, progressive neuromuscular disorders. A correct identification and characterization of canine and feline muscular dystrophies could increase diagnostic and treatment strategies for veterinary neurologists and could identify useful animal models for the study of human dystrophies. However, in dogs and cats, diagnosis of muscular dystrophies is challenging due to a nonspecific clinical phenotype and pathological lesions, thus is most likely underestimated. We performed immunofluorescence and Western blot techniques using a wide panel of antibodies against proteins involved in human dystrophies (dystrophin mid-rod and carboxyterminal domain, α, β, γ, and δ-sarcoglycan, α-dystroglycan, caveolin-3, emerin, merosin, dysferlin, calpain-3, spectrin epitopes), on 9 canine and 3 feline muscle biopsies characterized by myopathic changes. Dystrophin deficiency was detected in 3 dogs and 2 novel canine muscular dystrophies have been identified, characterized by deficiency of caveolin-3 and calpain-3, respectively. In 2 cats, deficiency of β-SG and carboxyterminal domain of dystrophin in all muscle fibers has been detected. Performing immunofluorescence and Western blot analyses with a wider panel of antibodies allowed a correct identification of muscular dystrophies in dogs and cats and provides a direction for subsequent targeted genetic testing.The aim of this paper was to determine whether digital imagery can be employed in veterinary medicine to measure and analyze wound healing dynamics. A smartphone application (ImitoMeasure) was used to capture, measure, and analyze the metatarsal wound images in a cat patient. The smartphone app was used to evaluate the wound area, width, length, and circumference at the time of topical treatments. Further analysis of the measurements taken by the ImitoMeasure app revealed significant correlations among all analyzed parameters. The day of treatment was inversely correlated with all the parameters of the wound, showing the healing progress over time. Also, the width was the most influential parameter (P ≤ .05) when assessing wound area. Thus, the app provided a noncontact, easy to use, and accurate smart wound measurement solution. Additionally, this case report describes the treatment of a cat with a severe chronic metatarsal wound and extensive soft tissue loss using a commercially available silver calcium alginate dressing (Askina Calgitrol Ag, B. Braun). The dressing was changed every 2 days, in the first week of treatment, and then every 3 days until the cat was discharged, 21 days later. Granulation tissue formed rapidly, from the fourth day of treatment and continued to expand in the entire wound bed; epithelization process started since the 16th day of treatment and mature scar tissue could be observed 21 days postinjury.Pyometra management in the high quality, high volume spay-neuter (HQHVSN) environment is not well documented. The goal of this study was to identify pyometra management practices and patient outcomes in the HQHVSN environment. An electronic survey was piloted and distributed to HQHVSN clinics using Survey Monkey via email lists and social media. A total of 118 responses were received from June to July 2020. Respondents were distributed across the United States with the majority of clinics associated with a shelter (75%). Clinics performed a median of 25 spays and neuters per day and 5000 per year. Most clinics (86%) were willing to treat nonincidental pyometras at least sometimes, and nearly all of these clinics (97%) were willing to accept pyometra referrals. Of these clinics, nearly all (95%) felt they had the necessary resources to treat most pyometras that presented and that a pyometra case was only modestly disruptive to their surgery flow. Most clinics (70%) charged a fee for treatment, charging a median of $200 for dogs and $125 for cats. This is much lower as compared to the estimated ranges for private practice ($600-$2500) and emergency hospitals ($1500-$3579). The majority of patients that HQHVSN clinics accepted for treatment were seen the same day (50%) or next day (42%). These clinics estimated that of the animals who presented, 76% were BAR or QAR, 20% were depressed or nonambulatory, and 4% were obtunded and lateral. Estimated survival for these treated groups were 98%, 80%, and 38%, respectively. HQHVSN clinics may represent a resource for treating pyometras when treatment is disruptive to the schedule of a private practice or clients present with financial limitations. There is an opportunity for HQHVSN and private practice to form a partnership to leverage the strengths of both models and improve access to care for pets.