c-Maf Transcription Factor Regulates ADAMTS-12 Expression in Human Chondrogenic Cells.

ObjectiveADAMTS (a disintegrin and metalloproteinase with thrombospondin type-1 motif) zinc metalloproteinases are important during the synthesis and breakdown of cartilage extracellular matrix. ADAMTS-12 is up-regulated during in vitro chondrogenesis and embryonic limb development; however, the regulation of ADAMTS-12 expression in cartilage remains unknown. The transcription factor c-Maf is a member of Maf family of basic ZIP (bZIP) transcription factors. Expression of c-Maf is highest in hypertrophic chondrocytes during embryonic development and postnatal growth. We hypothesize that c-Maf and ADAMTS-12 are co-expressed during chondrocyte differentiation and that c-Maf regulates ADAMTS-12 expression during chondrogenesis.DesignPromoter analysis and species alignments identified potential c-Maf binding sites in the ADAMTS-12 promoter. c-Maf and ADAMTS-12 co-expression was monitored during chondrogenesis of stem cell pellet cultures. Luciferase expression driven by ADAMTS-12 promoter segments was measured in the presence and absence of c-Maf, and synthetic oligonucleotides were used to confirm specific binding of c-Maf to ADAMTS-12 promoter sequences.ResultsIn vitro chondrogenesis from human mesenchymal stem cells revealed co-expression of ADAMTS-12 and c-Maf during differentiation. Truncation and point mutations of the ADAMTS-12 promoter evaluated in reporter assays localized the response to the proximal 315 bp of the ADAMTS-12 promoter, which contained a predicted c-Maf recognition element (MARE) at position -61. Electorphoretic mobility shift assay confirmed that c-Maf directly interacted with the MARE at position -61.ConclusionsThese data suggest that c-Maf is involved in chondrocyte differentiation and hypertrophy, at least in part, through the regulation of ADAMTS-12 expression at a newly identified MARE in its proximal promoter

Innovation in wastewater near-source tracking for rapid identification of COVID-19 in schools [Comment]

COVID-19 is one of the biggest global public health challenges of the century with almost 42 million cases and more than a million deaths to date. Until a COVID-19 vaccine or effective pharmaceutical intervention is developed, alternative tools for the rapid identification, containment, and mitigation of the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance for managing community transmission. Within this context, school closure has been one of the strategies implemented to reduce spread at local and national levels. [...

Prevalence of zoonotic helminths in italian house dogs

Introduction: Dogs may act as potential sources of zoonotic parasites, e.g. intestinal helminths like Toxocara spp., Ancylostoma spp., Echinococcus spp. In particular circumstances, the environment contaminated by parasitic elements represents a source of infection for people and animals. The present study has evaluated the presence of zoonotic helminths in house dogs from central and north-eastern Italy. Methodology: Stool samples from 493 dogs were examined by a qualitative copromicroscopic technique and differences in prevalence of zoonotic parasites were statistically examined in relation to canine individual data. Results: 48/493 (9.7%) were positive for at least one parasite. Helminths recovered were Trichuris vulpis (5.5%), Toxocara canis (4.3%), Ancylostoma spp. (0.6%) and Eucoleus aerophilus (0.4%), while no cestodes were detected. Age and living with other dogs resulted risk factors for T. canis infection. Conclusions: The health risk associated with the occurrence of parasitic nematodes in privately owned dogs, along with the current anthelmintic treatment plans, are discussed

Antioxidants in sport sarcopenia

The decline of skeletal muscle mass and strength that leads to sarcopenia is a pathology that might represent an emergency healthcare issue in future years. Decreased muscle mass is also a condition that mainly affects master athletes involved in endurance physical activities. Skeletal muscles respond to exercise by reshaping the biochemical, morphological, and physiological state of myofibrils. Adaptive responses involve the activation of intracellular signaling pathways and genetic reprogramming, causing alterations in contractile properties, metabolic status, and muscle mass. One of the mechanisms leading to sarcopenia is an increase in reactive oxygen and nitrogen species levels and a reduction in enzymatic antioxidant protection. The present review shows the recent experimental models of sarcopenia that explore molecular mechanisms. Furthermore, the clinical aspect of sport sarcopenia will be highlighted, and new strategies based on nutritional supplements, which may contribute to reducing indices of oxidative stress by reinforcing natural endogenous protection, will be suggested

Oral platelet gel supernatant plus supportive medical treatment versus supportive medical treatment in the management of radiation-induced oral mucositis: a matched explorative active control trial by propensity analysis

OBJECTIVES:: In this active control trial, the rate of radio-induced WHO grade 3/4 oral mucositis and the change in quality of life, assessed by OMWQ-HN, were measured in subjects with head and neck cancer treated by platelet gel supernatant (PGS) and supportive medical treatment versus subjects treated by supportive medical treatment alone. MATERIALS AND METHODS:: Eighty patients with nonmetastatic head and neck cancer underwent curative or adjuvant radiotherapy. All patients underwent supportive medical treatment and/or PGS at the beginning and during radiotherapy. Sixteen patients received PGS in association with supportive medical treatment. To obtain 2 groups virtually randomized for important clinical characteristics subjects were matched, by propensity analysis, with a group of subjects (64 patients) treated with supportive medical treatment alone. RESULTS:: Subjects treated with standard supportive treatment experienced significant higher WHO grade 3/4 toxicity (55%; 35/64) than subjects treated by PGS (13%; 3/16). The reduced toxicity found in PGS group paralleled with the evidence that they developed later symptoms with respect to controls. The Cox proportional hazard model indicated that patients treated with standard supportive medical treatment experienced 2.7-fold increase (hazard ratio=2.7; 95% confidence interval, 1.3-5.7) in the occurrence of WHO grade 3/4 toxicity. PGS group significantly experienced higher quality of life than control groups as measured by OMWQ-HN. A significant decrease in the opioid analgesics usage was found in the PGS group. CONCLUSIONS:: These preliminary data should be interpreted with caution and could serve as a framework around which to design future trials

Evaluating equality in prescribing Novel Oral Anticoagulants (NOACs) in England: the protocol of a Bayesian small area analysis

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 1.6% of the population in England. Novel oral anticoagulants (NOACs) are approved AF treatments that reduce stroke risk. In this study, we estimate the equality in individual NOAC prescriptions with high spatial resolution in Clinical Commissioning Groups (CCGs) across England from 2014 to 2019. Methods A Bayesian spatio-temporal model will be used to estimate and predict the individual NOAC prescription trend on ‘prescription data’ as an indicator of health services utilisation, using a small area analysis methodology. The main dataset in this study is the “Practice Level Prescribing in England,” which contains four individual NOACs prescribed by all registered GP practices in England. We will use the defined daily dose (DDD) equivalent methodology, as recommended by the World Health Organization (WHO), to compare across space and time. Four licensed NOACs datasets will be summed per 1,000 patients at the CCG-level over time. We will also adjust for CCG-level covariates, such as demographic data, Multiple Deprivation Index, and rural-urban classification. We aim to employ the extended BYM2 model (space-time model) using the RStan package. Discussion This study suggests a new statistical modelling approach to link prescription and socioeconomic data to model pharmacoepidemiologic data. Quantifying space and time differences will allow for the evaluation of inequalities in the prescription of NOACs. The methodology will help develop geographically targeted public health interventions, campaigns, audits, or guidelines to improve areas of low prescription. This approach can be used for other medications, especially those used for chronic diseases that must be monitored over time

Continuous rate infusion of dexmedetomidine vs subcutaneous administration in anaesthetized horses undergoing MRI examination

Up to 2005, dexmedetomidine use had not been reported in equine. Since then, several experimental and clinical studies have been published. The main reason for this increase relies on its beneficial pharmacological profile, including short half-life and rapid redistribution (1). The aim of the study is to compare the clinical effects and recovery quality after continuous rate infusion (CRI) or subcutaneous administration of dexmedetomidine in horses undergoing general anaesthesia. Fourteen horses scheduled for MRI examination were included. All horses were sedated with acepromazine 0.03 mg kg-1 intravenously (IV) and detomidine 10 \ub5g kg-1 (IV). Anaesthesia was induced with ketamine 3 mg kg-1 (IV) and diazepam 0.04 mg kg-1 (IV) and maintained with isofluorane in 60% oxygen; end-tidal isoflurane concentration was maintained between 1.3-1.4 %. Horses were randomly divided in two groups. Group \u201cDex CRI\u201d received dexmedetomidine intravenously at 1 \ub5g kg-1 hour-1, group \u201cDex SC\u201d received 2 \ub5g kg-1 of dexmedetomidine subcutaneously every 60 minutes. If nystagmus or incessant fighting against ventilator occurred, ketamine rescue at 0.1 mg kg-1 was given. In case of sudden movements, thiopental 0.5-1.0 mg kg-1 IV was given. Ringer\u2019s lactate was given at 3 mL kg-1 hour-1, dobutamine was administered IV and the rate adjusted to maintain MAP>70 mmHg. Controlled mechanical ventilation using intermittent positive pressure ventilation was adjusted to maintain arterial carbon dioxide partial pressure between 38-45 mmHg. Heart rate, invasive arterial blood pressure, arterial blood gases, total dose of dobutamine administered, ketamine rescue needed, urine production were recorded. Time required until extubation and time to attain sternal and standing position were noted. The main anaesthesiologist assessed recovery quality graded on a standard scoring 5-point scale with a score of 1 representing the best recovery (2). Mann-Whitney U test was applied for non-parametric data and T-test for parametric data (p 640.05). There was no statistically differences in physiological intra-anaesthetic parameters, in body weight (kg) (CRI 521\ub153; SC 506\ub176), age (years) (CRI 10.7\ub12.1; SC 10.8\ub14.1), anaesthesia duration (min) (CRI 139\ub19.,7; SC 144\ub116.2), number of ketamine rescue needed (CRI 1\ub11.15; SC 0.5\ub11.13), recovery score (CRI 1.8\ub11,2; SC 1.5\ub10,5). Also time until extubation (min) (CRI 11.5\ub15.0; SC 9.7\ub12.6), time to attain sternal (min) (CRI 41.5\ub112.2; SC 49.7\ub16.0) and standing position (min) (CRI 50.7\ub114.6; SC 57.2\ub16.,0) were not statistically different. There was statistical significance in urine production (L) (CRI 8.0\ub13.5; SC 11.1\ub14.4) and total dobutamine mcg/kg/min (CRI 0.89\ub10.35; SC 0.56\ub10.18). Subcutaneous administration of dexmedetomidine has product similar clinical effects to those achieved with CRI. It has permitted a significative reduction in dobutamine administration and a more stable depth of anaesthesia confirmed by the lower number of rescue ketamine boluses required even if not statistically different. Further studies are required to evaluate different dosages both in CRI and subcutaneous administration

Simultaneous exposure to angiostrongylus vasorum and vector-borne pathogens in dogs from italy

Several drivers have recently fostered the expansion of Angiostrongylus vasorum through-out Europe, where Vector-Borne Pathogens (VBPs) are also spreading. However, the level of simultaneous risk of infection is still unknown in canine populations. This study evaluated the simultaneous exposure to A. vasorum and major canine VBPs in dogs of Italy. Sera of 294 dogs were subjected to two ELISAs, detecting A. vasorum circulating antigens and antibodies against the parasite, and to the following assays: (i) SNAP® 4DX (IDEXX Laboratories Inc.) detecting Dirofilaria immitis antigens, and antibodies vs. Borrelia burgdorferi, Anaplasma spp. and Ehrlichia spp. and (ii) IFAT for the detection of antibodies vs. Leishmania infantum, Babesia canis and Rickettsia conorii. Twenty-two (7.5%, CI: 4.8–11.1%) and six (2%, CI: 0.7–4.4%) dogs scored positive for circulating A. vasorum antibodies and antigens, respectively. Seventeen dogs (5.8%, CI: 3.4–9.1%) were positive for A. vasorum antibodies + at least one VBP, three (1%, CI: 0.2–3%) for A. vasorum antigen + at least one VBP, while one dog (0.3%, CI: 0.01–1.88%) was positive for A. vasorum antigen + A. vasorum antibodies + B. canis antibodies. These results show that dogs living in different regions of Italy are at risk of simultaneous infections with both A. vasorum and VBPs. Despite the same scenario being likely in other countries of Europe, the current knowledge is scant. Therefore, further studies are warranted to amplify current epizootiological information and to understand whether control programs should be im-proved

Case Report: Altered NK Cell Compartment and Reduced CXCR4 Chemotactic Response of B Lymphocytes in an Immunodeficient Patient With HPV-Related Disease

the study of inborn errors of immunity (IEI) provides unique opportunities to elucidate the microbiome and pathogenic mechanisms related to severe viral infection. several immunological and genetic anomalies may contribute to the susceptibility to develop human papillomavirus (HPV) pathogenesis. they include different acquired immunodeficiencies, EVER1-2 or CIB1 mutations underlying epidermodysplasia verruciformis (EV) syndrome and multiple IEI. whereas EV syndrome patients are specifically unable to control infections with beta HPV, individuals with IEI show broader infectious and immune phenotypes. the WHIM (warts, hypogammaglobulinemia, infection, and myelokathexis) syndrome caused by gain-of-CXCR4-function mutation manifests by HPV-induced extensive cutaneous warts but also anogenital lesions that eventually progress to dysplasia. Here we report alterations of B and NK cells in a female patient suffering from cutaneous and mucosal HPV-induced lesions due to an as-yet unidentified genetic defect. despite no detected mutations in CXCR4, B but not NK cells displayed a defective CXCR4-dependent chemotactic response toward CXCL12. In addition, NK cells showed an abnormal distribution with an expanded CD56(bright) cell subset and defective cytotoxicity of CD56(dim) cells. our observations extend the clinical and immunological spectrum of IEI associated with selective susceptibility toward HPV pathogenesis, thus providing new insight on the immune control of HPV infection and potential host susceptibility factors