Features and frequency of use of electronic health records in primary care across 20 countries: a cross-sectional study.

OBJECTIVES: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability. STUDY DESIGN: Cross-sectional study. METHODS: PCPs from 20 countries completed cross-sectional online survey between June and September 2020. Responses which reported frequency of EHRs use were retained. Associations between everyday EHRs use and PCP and practice factors (country, urbanicity, and digital maturity) were explored using multivariable logistic regression analyses. The effect of practice factors on the variation in availability of ten EHRs features was estimated using Cramer's V. RESULTS: Responses from 1520 out of 1605 PCPs surveyed (94·7%) were retained. Everyday EHRs use was reported by 91·2% of PCPs. Everyday EHRs use was associated with PCPs working >28 h per week, having more years of experience using EHRs, country of employment, and higher digital maturity. EHRs features concerning entering, and retrieving data were available to most PCPs. Few PCPs reported having access to tools for 'interactive patient education' (37·3%) or 'home monitoring and self-testing of chronic conditions' (34·3%). Country of practice was associated with availability of all EHRs features (Cramer's V range: 0·2-0·6), particularly with availability of tools enabling patient EHRs access (Cramer's V: 0·6, P < 0.0001). Greater feature availability of EHRs features was observed with greater digital maturity. CONCLUSIONS: EHRs features intended for patient use were uncommon across countries and levels of digital maturity. Systems-level research is necessary to identify the country-specific barriers impeding the implementation of EHRs features in primary care, particularly of EHRs features enabling patient interaction with EHRs, to develop strategies to improve systems-wide EHRs use.

What role do endogenous retroviruses play in domestic cats infected with feline leukaemia virus?

Feline leukaemia virus (FeLV) is a retrovirus that infects domestic and wild cats around the world. FeLV infection is associated with the development of neoplasms, bone marrow disorders and immunosuppression. Viral subgroups arise from mutations in the FeLV genome or from recombination of FeLV with ancestral endogenous retroviruses in the cat genome. The retroviral endogenisation process has allowed generation of a diversity of endogenous viruses, both functional and defective. These elements may be part of the normal functioning of the feline genome and may also interact with FeLV to form recombinant FeLV subgroups, enhance pathogenicity of viral subgroups, or inhibit and/or regulate other retroviral infections. Recombination of the env gene occurs most frequently and appears to be the most significant in terms of both the quantity and diversification of pathogenic effects in the viral population, as well as affecting cell tropism and types of disease that occur in infected cats. This review focuses on available information regarding genetic diversity, pathogenesis and diagnosis of FeLV as a result of the interaction between endogenous and exogenous viruses.

Optimum timing for assessing phenotypic resistance against gastrointestinal nematodes in Pelibuey ewes.

The objective was to identify the optimal stage of production to evaluate the resistance of Pelibuey ewes against gastrointestinal nematodes (GIN). Faecal egg count (FEC) was used to classify the ewes as resistant, sensible or intermediate against GIN. Forty-seven ewes were mating during 30 d. The gestation was verified by ultrasonography, and the breeding date was used to calculate the productive stages. Faeces were taken weekly to determine the FEC. Blood samples were taken to determine the packed cell volume (PCV), the peripheral eosinophils count (PEC), plasma protein concentration (PP), and Immunoglobulin A (IgA) against Haemonchus contortus. The body condition score (BCS) was recorded at each visit. Six moments during the study (early, mid and late gestation; early, mid and late lactation) were considered. The ewes were classified according to FEC (mean FEC ± three standard errors). The higher FEC occurred during all lactation stages than during early and mid-gestation stages (P<0.05). PCV, PP, and BCS during early gestation stage were higher than shown during the lactation stages (P<0.01). The PEC and IgA were higher during all lactation stages than early and mid-gestation stages (P<0.05). Concerning the type of birth, double births showed higher FEC than single birth (P<0.01). The highest values of accuracy (100 %) and concordance (Youden's J = 1.0) were found during early lactation. Therefore, it is concluded that the optimal stage of production to evaluate phenotypic resistance against GIN infections in Pelibuey ewes was during the early lactation.

Isolation and molecular identification of native As-resistant bacteria: As(III) and As(V) removal capacity and possible mechanism of detoxification.

The study of arsenic (As)-resistant microorganisms with high As removal capacity is fundamental for the development of economically sustainable technologies used for the treatment of water contaminated with metalloid. In the current study, four bacterial strains were isolated from As-contaminated water samples of the Xichu region, Mexico. Based on 16S rRNA gene sequencing and phylogenetic analysis of the isolated strains, Rhodococcus gordoniae, Microbacterium hydrocarbonoxydans, Exiguobacterium indicum, and Pseudomonas kribbensis were identified as potential As removal strains. R. gordoniae shows the highest growth capacity in both As(III) and As(V). R. gordoniae, M. hydrocarbonoxydans, and E. indicum removed approximately 81.6, 79.9, and 61.7% of As(III), as well as 77.2, 68.9, and 74.8% of As(V), respectively. P. kribbensis removed only about 80.2% of As(V). This study contributes to the possible detoxification mechanisms employed by these bacteria. Such insight could be crucial in the successful implementation of in situ bioremediation programs using these little-known bacteria.

Identification of Somatic Proteins in Haemonchus Contortus Infective Larvae (L3) and Adults.

Haemonchus contortus is considered the most pathogenic nematode in sheep production systems based on grazing. Comparing infective larvae (L3) with adult parasites can lead to the identification of proteins that play an important role in parasite-host interactions. In this study, we report a list of H. contortus somatic proteins and made a comparative analysis of somatic proteins of L3 and adult worms. L3 and adult parasites were subjected to protein extraction and subsequently to peptide fractionation. Peptides were analysed by mass spectrometry and LC-MS/MS data analysis. Data analysis and search on SEQUEST and MASCOT against H. contortus from the WormBase ParaSite database resulted in the identification of 775 unique peptide sequences corresponding to 227 proteins at 1 % FDR. From these, 18 proteins were specific to L3 and 63 to adult parasites. The gene ontology (GO) enrichment analysis of the proteins specific to L3 and adult worms to gain insight into cellular components, molecular functions and biological processes that affect the parasite-host interaction showed some differences between the two parasite stages. The list of proteins found provides a database to identify target proteins that could be useful as biomarkers of the infection or in the generation of anthelmintic drugs that inhibit proteins essential for the establishment of the infection and the survival of adult parasites. They can also serve as new candidates for vaccine research.

Roles of the multiplex real-time PCR assay and ß-D-glucan in a high-risk population for intra-abdominal candidiasis (IAC).

Multiplex quantitative real-time PCR (MRT-PCR) using blood can improve the diagnosis of intra-abdominal candidiasis (IAC). We prospectively studied 39 patients with suspected IAC in the absence of previous antifungal therapy. Blood cultures, MRT-PCR, and ß-D-glucan (BDG) in serum were performed in all patients. IAC was defined according to the 2013 European Consensus criteria. For MRT-PCR, the probes targeted the ITS1 or ITS2 regions of ribosomal DNA. Candidaemia was confirmed only in four patients (10%), and IAC criteria were present in 17 patients (43.6%). The sensitivity of MRT-PCR was 25% but increased to 63.6% (P = .06) in plasma obtained prior to volume overload and transfusion; specificity was above 85% in all cases. BDG performance was improved using a cutoff > 260 pg/ml, and improvement was not observed in samples obtained before transfusion. In this cohort of high risk of IAC and low rate of bloodstream infection, the performance of non-culture-based methods (MRT-PCR or BDG) was moderate but may be a complementary tool given the limitations of diagnostic methods available in clinical practice. Volume overload requirements, in combination with other factors, decrease the accuracy of MRT-PCR in patients with IAC.

Analysis of the effectiveness of the prophylaxis of vestibular migraine depending on the diagnostic category and the prescribed drug.

INTRODUCTION: Vestibular migraine (VM) consists of recurrent episodes of vestibular symptoms that are accompanied by migraine in at least 50% of the episodes. The criteria of the Bárány Society include two diagnostic categories: "actual" vestibular migraine and probable vestibular migraine. There is a wide range of drugs that can be prescribed for the prophylactic treatment of VM, but recommendations for the selection of the most appropriate drug are currently lacking. OBJECTIVE: To measure the extent to which the prophylactic treatment of VM reduces vestibular symptoms, headache and the number of crises depending on the diagnostic category of the Bárány Society and the drug used for prophylaxis. MATERIAL AND METHODS: This is a multicenter prospective study. Patients with VM who presented to any of the participating centers and who subsequently met the VM criteria were prescribed one of the following types of prophylaxis: acetazolamide, amitriptyline, flunarizine, propranolol or topiramate. Patients were called back for a follow-up visit 5 weeks later. This allowed the intensity of vestibular symptoms, headache and the number of crises before and during treatment to be compared. RESULTS: 31 Patients met the inclusion criteria. During the treatment, all the measured variables decreased significantly. In a visual analogue scale, the intensity of vestibular symptoms decreased by 45.8 points, the intensity of headache decreased by 47.8 points and patients suffered from 15.6 less monthly crises compared to the period before the treatment. No significant between-group differences were found when patients were divided based on their diagnostic category or the choice of prophylaxis prescribed to them. CONCLUSION: The treatment of VM produces a reduction of symptoms and crises with no significant differences based on patients' diagnostic categories or the choice of prophylaxis prescribed to them.

Advances of hyaluronic acid in stem cell therapy and tissue engineering, including current clinical trials.

Hyaluronic acid (HA), as one of the main components of the extracellular matrix (ECM), plays a significant role in a multitude of biological processes involving cell migration, proliferation, differentiation, wound healing and inflammation. Thanks to its excellent biocompatibility, biodegradability and hygroscopic properties, HA has been used in its natural form for joint lubrication and ocular treatment. The chemical structure of HA can be easily modified by direct reaction with its carboxyl and hydroxyl groups. Recently, HA derivatives have been synthesised with the aim of developing HA-based materials with increased mechanical strength, improved cell interactions and reduced biodegradation and studied for regenerative medicine purposes, including cell therapy and tissue engineering. In this context, the present manuscript reviews HA applications from a basic point of view - including chemical modifications and cellular biology aspects related to clinical translation - and future perspectives of using biofabrication technologies for regenerative medicine. A detailed description of current clinical trials, testing advanced therapies based on combination of stem cells and HA formulations, is included. The final goal was to offer an integral portrait and a deeper comprehension of the current applications of HA from bench to bedside.

Healing criteria: How should an episode of benign paroxistic positional vertigo of posterior semicircular canal's resolution be defined? Prospective observational study.

OBJECTIVES: To compare the outcome of the Epley maneuver (EM) in benign paroxysmal positional vertigo of the posterior canal (CSP-BPPV) depending on the definition used for recovery. DESIGN: Multicenter observational prospective study. SETTING: Otoneurology Units of 5 tertiary reference hospitals. PARTICIPANTS: All patients presenting with unilateral CSP-BPPV assisted for 1-year period. EXCLUSION CRITERIA: Spontaneous nystagmus, positive McClure-Pagnini maneuver, positive bilateral Dix-Hallpike maneuver (DHM), positive DHM for vertigo but negative for nystagmus and atypical nystagmus. MAIN OUTCOME MEASURES: Response to EM was measured after 7 days in 3 different outcomes: disappearance of nystagmus during the DHM in the follow-up visit, disappearance of vertigo during the DHM and general status (GS) during daily life activities. RESULTS: 264 patients were recruited (68 male/166 female, mean age 62 years). After the EM, nystagmus disappeared in 67% of them, vertigo in 54% and 36% were asymptomatic in their daily life. These outcomes were strongly correlated, but they were not concordant in a clinically significant group of cases; only the 26% of patients met all of them. The healing process follows the next sequence: negativization of positional nystagmus, then disappearance of positional vertigo and, finally, the improvement of GS during daily life activities. CONCLUSION: Nowadays, healing criteria for the resolution of an PSC-BPPV episode have not been specifically defined yet. Provided that other otoneurological disorders have been ruled out, the next resolution criterion is proposed: absence of nystagmus and specifically during control DHM and disappearance of symptoms during daily life activities.

Impact of TGF-ß family-related growth factors on chondrogenic differentiation of adipose-derived stem cells isolated from lipoaspirates and infrapatellar fat pads of osteoarthritic patients.

The success of cell-based approaches for the treatment of cartilage defects requires an optimal autologous cell source with chondrogenic differentiation ability that maintains its differentiated properties and stability following implantation. The objective of this study was to compare the chondrogenic capacity of mesenchymal stem cells (MSCs) isolated from lipoaspirates (ASCs) and the infrapatellar fat pad (IFPSCs) of osteoarthritic patients and treated with transforming growth factor (TGF)-ß family-related growth factors. Cells were cultured for 6 weeks in a 3D pellet culture system with the chimeric activin A/bone morphogenic protein (BMP)-2 ligand (AB235), the chimeric nodal/BMP-2 ligand (NB260) or BMP-2. To investigate the stability of the new cartilage, ASCs-treated pellets were transplanted subcutaneously into severe combined immunodeficiency (SCID) mice. Histological and immunohistochemical assessment confirmed that the growth factors induced cartilage differentiation in both isolated cell types. However, reverse transcription-quantitative PCR results showed that ASCs presented a higher chondrogenic potential than IFPSCs. In vivo results revealed that AB235-treated ASCs pellets were larger in size and could form stable cartilage-like tissue as compared to NB260-treated pellets, while BMP-2-treated pellets underwent calcification. The chondrogenic induction of ASCs by AB235 treatment was mediated by SMAD2/3 activation, as proved by immunofluorescence analysis. The results of this study indicated that the combination of ASCs and AB235 might lead to a cell-based cartilage regeneration treatment.

Impact of specific modes of circumferential resection margin involvement in rectal cancer local recurrence: A retrospective study.

PURPOSE: To compare the local recurrence rate and overall survival between patients with circumferential resection margin (CRM) involvement by direct tumor spread and by a tumor within a lymph node. METHODS: A total of 776 patients diagnosed with rectal cancer underwent rectal resection. Patients with CRM involvement by direct tumor spread were named group A. CRM involvement by tumor within a lymph node formed group B. Patient data, including sex, age, pT, pN, stage I-III versus IV, neoadjuvant radiotherapy, adjuvant chemotherapy, carcinoembryonic antigen, primary tumor location, lymph node retrieval, and need for abdominoperineal resection, were compared between both groups. RESULTS: In total, 10.5% of the patients had CRM involvement. Of these, in 57 cases (7.3%), it was by direct tumor spread and in 19 cases (2.4%) by tumor within a lymph node. Other types of CRM involvement were found in six patients. With a mean follow-up of 32.9 months, 18 patients from group A (31.5%) and one patient from group B (5.2%) suffered a local recurrence. Local recurrence-free survival was significantly higher in patients from group B (P = 0.049). Patients in stage I-III (P = 0.037) and from group B ( P = 0.049) had better overall survival. CONCLUSION: Patients with CRM involvement by tumor within a lymph node have a low risk of local recurrence and better overall survival than patients with CRM involvement by direct tumor spread.

Clinical and therapeutic potential of protein kinase PKR in cancer and metabolism.

The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease. We emphasise the importance of PKR as a molecular target for both conventional chemotherapeutics and emerging treatments based on novel drugs, and its potential as a biomarker and therapeutic target for several pathologies. Finally, we discuss the impact that the recent knowledge regarding PKR involvement in metabolism has in our understanding of the complex processes of cancer and metabolism pathologies, highlighting the translational research establishing the clinical and therapeutic potential of this pleiotropic kinase.

Compound heterozygous mutations in the IFT140 gene cause Opitz trigonocephaly C syndrome in a patient with typical features of a ciliopathy.

〈 We report on an infant with Opitz trigonocephaly C syndrome (OTCS), who also had manifestations of ciliopathy, including short ribs (non-asphyxiating), trident acetabular roofs, postaxial polydactyly cone-shaped epiphyses, and dysplasia of the renal, hepatic and pancreatic tissues. To investigate the molecular cause, we used an exome sequencing strategy followed by Sanger sequencing. Two rare variants, both predicted to result in loss of functional protein, were identified in the IFT140 gene; a substitution at the splice donor site of exon 24 (c.723 + 1 G > T) and a 17 bp deletion, impacting the first coding exon (c.-11_6del). The variants were confirmed as being biallelic using Sanger sequencing, showing that the splice variant was inherited from the propositus mother and the deletion from the father. To date, Mainzer-Saldino syndrome, Jeune syndrome, and a form of nonsyndromic retinal dystrophy, have been identified as ciliopathies caused by IFT140 mutations. We provide the first description of an OTCS phenotype that appears to result from IFT140 mutations. The presentation of this patient is consistent with previous reports showing that OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy.

Biofunctional Ionic-Doped Calcium Phosphates: Silk Fibroin Composites for Bone Tissue Engineering Scaffolding.

The treatment and regeneration of bone defects caused by traumatism or diseases have not been completely addressed by current therapies. Lately, advanced tools and technologies have been successfully developed for bone tissue regeneration. Functional scaffolding materials such as biopolymers and bioresorbable fillers have gained particular attention, owing to their ability to promote cell adhesion, proliferation, and extracellular matrix production, which promote new bone growth. Here, we present novel biofunctional scaffolds for bone regeneration composed of silk fibroin (SF) and ß-tricalcium phosphate (ß-TCP) and incorporating Sr, Zn, and Mn, which were successfully developed using salt-leaching followed by a freeze-drying technique. The scaffolds presented a suitable pore size, porosity, and high interconnectivity, adequate for promoting cell attachment and proliferation. The degradation behavior and compressive mechanical strengths showed that SF/ionic-doped TCP scaffolds exhibit improved characteristics for bone tissue engineering when compared with SF scaffolds alone. The in vitro bioactivity assays using a simulated body fluid showed the growth of an apatite layer. Furthermore, in vitro assays using human adipose-derived stem cells presented different effects on cell proliferation/differentiation when varying the doping agents in the biofunctional scaffolds. The incorporation of Zn into the scaffolds led to improved proliferation, while the Sr- and Mn-doped scaffolds presented higher osteogenic potential as demonstrated by DNA quantification and alkaline phosphatase activity. The combination of Sr with Zn led to an influence on cell proliferation and osteogenesis when compared with single ions. Our results indicate that biofunctional ionic-doped composite scaffolds are good candidates for further in vivo studies on bone tissue regeneration.

Analysis of risk factors influencing the outcome of the Epley maneuver.

Benign paroxysmal positional vertigo (BPPV) is the most frequent type of vertigo. The treatment of canalithiasis of the posterior semicircular canal consists in performing a particle-repositioning maneuver, such as the Epley maneuver (EM). However, the EM is not effective in all cases. The objective of this study is to identify risk factors, which predict the EM failure, among the clinical variables recorded in anamnesis and patient examination. This is an observational prospective multicentric study. All patients presenting with BPPV were recruited and applied the EM and appointed for a follow-up visit 7 days later. The following variables were recorded: sex, age, arterial hypertension, diabetes, hyperlipidemia, smoking habit, alcohol consumption, migraine, osteoporosis, diseases of the inner ear, previous ipsilateral BPPV, previous traumatic brain injury, previous sudden head deceleration, time of evolution, sulpiride or betahistine treatment, experienced symptoms, outcome of the Halmagyi maneuver, laterality, cephalic hyperextension of the neck, intensity of nystagmus, intensity of vertigo, duration of nystagmus, occurrence of orthotropic nystagmus, symptoms immediately after the EM, postural restrictions, and symptoms 7 days after the EM. Significant differences in the rate of loss of nystagmus were found for six variables: hyperlipidemia, previous ipsilateral BPPV, intensity of nystagmus, duration of nystagmus, post-maneuver sweating, and subjective status. The most useful significant variables in the clinical practice to predict the success of the EM are previous BPPV and intensity of nystagmus. In the other significant variables, no physiopathological hypothesis can be formulated or differences between groups are too small.

[Treatment of postpartum hemorrhage with intrauterine hydrostatic condom]. / Tratamiento de la hemorragia posparto con condón hidrostático intrauterine.

OBJECTIVE: To report of experience of intrauterine hydrostatic condom to control obstetric hemorrhage. MATERIAL AND METHOD: Descriptive, retro-prospective study. The method was use in patients who had obstetric hemorrhage and do not responded to medical management during the period from March 1st to August27, 2015 in a rural facility. RESULTS: 955 patients that had a vaginal delivery were identified, 40 (4.1%) of which needed the application of the method. The method was unsuccessful in 2 of 40 patients (5%), one requiring emergency obstetric hysterectomy and other exploratory laparotomy with conservative measures. 11 of 40 patients (2 7.5%) required at least 1-3 globular packs transfusion. None of the 38 patients (95%) who responded to the method presented endometritis in the postpartum follow up or complications associated with the use of hydrostatic condom. CONCLUSION: The use of intrauterine hydrostatic condom is an effective method to control postpartum obstetric hemorrhage secondary to uterine atony unresponsive to medical management.

Esophageal motor disorders in subjects with incidentally discovered Chagas disease: a study using high-resolution manometry and the Chicago classification.

In patients with chronic indeterminate Chagas disease, conventional manometry has shown that 25-48% had esophageal motor disorders. Recently, esophageal high-resolution manometry (HRM) has revolutionized the assessment of esophageal motor function. In this study, we performed esophageal HRM in a group of subjects with incidentally positive serological findings for Trypanosoma cruzi. In this prospective observational study, we evaluated subjects who had positive serological tests for Chagas disease detected during a screening evaluation for blood donation. All subjects underwent symptomatic evaluation and esophageal HRM with a 36 solid-state catheter. Esophageal abnormalities were classified using the Chicago classification. Forty-two healthy subjects (38 males) aged 18-61 years (mean age, 40.7 years) were included. When specific symptoms questionnaire was applied, 14 (33%) subjects had esophageal symptoms. Esophageal high-resolution manometry revealed that 28 (66%) of the subjects had an esophageal motility disorder according to the Chicago classification. Most common findings were hypocontractile disorders in 18 subjects (43%) and esophagogastric junction (EGJ) outflow obstruction in 6 (15%). Esophageal high-resolution manometry reveals that up to two thirds of the subjects with an incidental diagnosis of Chagas disease have esophageal abnormalities. This technology increases the detection and allows a more complete assessment of esophageal motor function in subjects infected with T. cruzi even in the early stages of the disease.

[Anatomy and vascularization on the male urethra and penis]. / Anatomia y vascularizacion de la uretra y el pene.

In this review we present an update on the anatomy and vascularization of the male urethra. The real objective of this review is to make the following chapters more understandable, both to know the physio-pathological mechanisms of urethral pathology and also to help us in their surgical management.