COVID-19: did the masks work?

During the early stages of the COVID-19 pandemic, we called for mandatory public masking to 'flatten the curve'. We helped formulate a national standard (SWiFT 19) for barrier facemasks, and, using a novel laser-based approach, we determined that mask efficacy is dependent on both fabric and fit; with both variables being inversely related. Herein, we take a retrospective view of the role of masks during the pandemic and surmise that, on the balance of evidence to date, masks were effective at stemming the spread of SARS-CoV-2 and may well be an effective early control strategy for potential future respiratory pandemics.

Face coverings, which cover the nose and mouth, are a means of preventing infections that travel in the air. These include viruses such as SARS-CoV-2, which causes COVID-19. Face coverings, or masks, played a key role during the COVID-19 pandemic by reducing person-to-person spread of the virus. The key features of a mask that make it effective are the material from which it is made and how closely the mask fits the face. A loosely fitting mask, for example, will lead to gaps around the nose and cheeks through which droplets can escape. A better fitting mask will have less leakage. Masks made from light single-layer material is less able to prevent droplet penetration than thicker, multi-layered fabric. Properly fashioned and fitted face masks are an effective means of slowing the spread of infections that travel in the air.

Program Evaluation of Pharmacist-Performed Medication Adherence Assessments in Candidates for Living Donor Kidney Transplant.

Introduction: Medication education and adherence assessments are integral to kidney transplant success. This program evaluation aimed to describe candidate-reported findings using a standardized medication adherence assessment in candidates undergoing living-donor kidney transplantation. Design: This was a single-center retrospective description of medication adherence on adult HIV-negative living-donor candidates from July 1, 2018 to December 1, 2018 who had ≥6 months post-operative follow-up. Medication adherence assessments were performed by a pharmacist at the pre-operative visit within 2 weeks prior to transplant. Candidates were considered to (a) have adherence concerns if they reported missed/late medications within 2 weeks of assessment or ever stopped a medication without medical advice and (b) considered using adherence strategies if they reported active use of pill box, method to keep track of refills/auto-refill use, medication list, or medication reminder(s). Missed medication data were collected at 3- and 6-months posttransplant. Results: Among 181 candidates included, 81 (45%) had adherence concerns and 169 (93%) reported using adherence strategies. There were no significant differences with adherence concerns by age ≤ 29 years, sex, race, prior transplant/dialysis, or less than a high school education. More candidates with greater than a high school education used adherence strategies (96% vs 86%, P = .002). Too few candidates had documentation on missing medications at 3 and 6 months. Conclusions: Over 40% of candidates reported characteristics concerning medication nonadherence despite over 90% reporting adherence strategies used. Medication adherence assessments can assist with identification of medication nonadherence and education individualization.

From Species to Genes: A New Diagnostic Paradigm.

Molecular diagnostics has the potential to revolutionise the field of clinical microbiology. Microbial identification and nomenclature have, for too long, been restricted to phenotypic characterisation. However, this species-level view fails to wholly account for genetic heterogeneity, a result of lateral gene transfer, mediated primarily by mobile genetic elements. This genetic promiscuity has helped to drive virulence development, stress adaptation, and antimicrobial resistance in several important bacterial pathogens, complicating their detection and frustrating our ability to control them. We argue that, as clinical microbiologists at the front line, we must embrace the molecular technologies that allow us to focus specifically on the genetic elements that cause disease rather than the bacterial species that express them. This review focuses on the evolution of microbial taxonomy since the introduction of molecular sequencing, the role of mobile genetic elements in antimicrobial resistance, the current and emerging assays in clinical laboratories, and the comparison of phenotypic versus genotypic analyses. In essence, it is time now to refocus from species to genes as part of a new diagnostic paradigm.

Roles of collagen cross-links and osteon collagen/lamellar morphotypes in equine third metacarpals in tension and compression tests.

Many bones experience bending, placing one side in net compression and the other in net tension. Because bone mechanical properties are relatively reduced in tension compared with compression, adaptations are needed to reduce fracture risk. Several toughening mechanisms exist in bone, yet little is known of the influences of secondary osteon collagen/lamellar 'morphotypes' and potential interplay with intermolecular collagen cross-links (CCLs) in prevalent/predominant tension- and compression-loaded regions. Paired third metacarpals (MC3s) from 10 adult horses were prepared for mechanical testing. From one MC3/pair, 5 mm cubes were tested in compression at several mid-shaft locations. From contralateral bones, dumbbell-shaped specimens were tested in tension. Hence, habitual/natural tension- and compression-loaded regions were tested in both modes. Data included: elastic modulus, yield and ultimate strength, and energy absorption (toughness). Fragments of tested specimens were examined for predominant collagen fiber orientation (CFO; representing osteonal and non-osteonal bone), osteon morphotype score (MTS, representing osteonal CFO), mineralization, porosity and other histological characteristics. As a consequence of insufficient material from tension-tested specimens, CCLs were only examined in compression-tested specimens (HP, hydroxylysylpyridinoline; LP, lysylpyridinoline; PE, pentosidine). Among CCLs, only LP and HP/LP correlated significantly with mechanical parameters: LP with energy absorption, HP/LP with elastic modulus (both r=0.4). HP/LP showed a trend with energy absorption (r=-0.3, P=0.08). HP/LP more strongly correlated with osteon density and mineralization than CFO or MTS. Predominant CFO more strongly correlated with energy absorption than MTS in both testing modes. In general, CFO was found to be relatively prominent in affecting regional toughness in these equine MC3s in compression and tension.

An exploratory in silico analysis of bacteriocin gene clusters in the urobiome.

Background: The role of the urobiome in health and disease remains an understudied area compared to the rest of the human microbiome. Enhanced culturing techniques and next-generation sequencing technologies have identified the urobiome as an untapped source of potentially novel antimicrobials. The aim of this study was to screen the urobiome for genes encoding bacteriocin production. Methods: The genomes of 181 bacterial urobiome isolates were screened in silico for the presence of bacteriocin gene clusters using the bacteriocin mining tool BAGEL4 and secondary metabolite screening tool antiSMASH7. Results: From these isolates, an initial 263 areas of interest were identified, manually annotated, and evaluated for potential bacteriocin gene clusters. This resulted in 32 isolates containing 80 potential bacteriocin gene clusters, of which 72% were identified as class II, 13.75% as class III, 8.75% as class I, and 5% as unclassified bacteriocins. Conclusion: Overall, 53 novel variants were discovered, including nisin, gassericin, ubericin, and colicins.

Rhizospheric Bacteria of Cover Legumes from Acidic Soils Are Capable of Solubilizing Different Inorganic Phosphates.

Due to its adsorption with aluminum and iron hydroxides, phosphorus viability is low in acidic soils; thus, the aim of this study was to isolate and identify bacteria from the rhizosphere of four legumes growing in acidic soils of the Cumbaza Sub-basin, San Martín, Peru, as well as to characterize their ability to solubilize aluminum phosphate and iron phosphate. The isolation process was conducted on TSA medium and the isolates were classified based on their origin and morphocolonial characteristics, with the bacillary shape being the most frequent, followed by cocci. To assess the solubilization of aluminum and iron phosphates, the liquid medium GELP was employed. Sixteen strains were selected, among which three stood out for their effectiveness in solubilizing AlPO4 (Sfcv-098-02, 22.65 mg L-1; Sfc-093-04, 26.50 mg L-1; and Sfcv-041-01-2, 55.98 mg L-1) and one for its ability to solubilize FePO4 (Sfcr-043-02, 32.61 mg L-1). These four strains were molecularly characterized, being identified as Enterobacter sp., Pseudomonas sp., and Staphylococcus sp. Additionally, a decrease in pH was observed in the reactions, with values ranging from 5.23 to 3.29, which enhanced the phosphate of solubilization. This suggests that the selected bacteria could be used to improve phosphorus availability in agricultural soils.

Approach to non-compressive myeloneuropathy through a rendezvous of 11 cases from an Indian backdrop.

Introduction: Myeloneuropathy is a diagnosis ascribed to disorders that concomitantly affect the spinal cord and peripheral nerves. Recognizing this syndrome may sometimes be arduous, even for the most consummate clinicians, because symptomatology can mimic either spinal cord or peripheral nerve disease. Besides, examination findings suggest a predominantly myelopathic or neuropathic picture. This article reports a rendezvous of rare cases of clinically diagnosed myeloneuropathy with different etiological backgrounds and therapeutic responses. Methods: Eleven cases of non-compressive myeloneuropathy were admitted to the Department of General Medicine of Burdwan Medical College and Hospital, Burdwan, West Bengal, India, between May 2018 and May 2022. Results: We report the cases of 11 patients (6 men and 5 women) who presented with myeloneuropathy of different etiologies (vitamin B12, copper, and vitamin E deficiencies, organophosphate poisoning, chronic alcohol abuse, illicit substances abuse, anti-thyroid peroxidase/anti-thyroglobulin antibody-related neurologic disorder responsive to steroids, Sjögren syndrome, chikungunya infection, paraneoplastic, and hereditary). Conclusion: Meticulous historical analysis, careful clinical examination, and apposite utilization and interpretation of biochemical, electrophysiological, and neuroimaging findings are sine-qua-non for an accurate and consistent approach to evaluating a suspected case of myeloneuropathy, facilitating early treatment and recovery. Differential identification of these disorders needs an in-depth perception of the mode of onset of symptoms, the course of progression of the disease, the pattern of myelopathic/neuropathic findings, and recognition of other neurological or systemic manifestations. For untroubled understanding, etiologies of myeloneuropathies should be subdivided into a few broad categories, e.g., metabolic (nutritional), toxic (toxin-induced), infectious, inflammatory (immune-mediated), paraneoplastic, and hereditary disorders.

Introducción: La mieloneuropatía es un síndrome que afecta concomitantemente la médula espinal y los nervios periféricos. Reconocerlo a veces puede ser arduo, incluso para los médicos más experimentados, porque la sintomatología puede simular una enfermedad de la médula espinal o de los nervios periféricos. Además, los hallazgos del examen sugieren un cuadro predominantemente mielopático o neuropático. Este artículo describe una serie de casos raros de mieloneuropatía de distintas causas y con respuestas terapéuticas distintas. Métodos: Once casos de mieloneuropatía no compresiva fueron ingresados en el Departamento de Medicina General del Burdwan Medical College, and Hospital, Burdwan, Bengala Occidental, India, entre mayo de 2018 y mayo de 2022. Resultados: Presentamos 11 pacientes (seis hombres y cinco mujeres) con mieloneuropatía de diferentes etiologías (deficiencias de vitamina B12, cobre y vitamina E, intoxicación por organofosforados, abuso crónico de alcohol, abuso de sustancias ilícitas, trastorno neurológico relacionado con anticuerpos anti-tiroglobulina / antiperoxidasa tiroidea que responde a esteroides, síndrome de Sjögren, infección por chikungunya, paraneoplásico y hereditario). Conclusión: El análisis meticuloso de la historia y del examen clínico, así como la utilización e interpretación adecuadas de los hallazgos bioquímicos, electrofisiológicos y de neuroimagen son condiciones sine qua non para un enfoque preciso y consistente para evaluar un caso sospechoso de mieloneuropatía, lo que facilita el tratamiento temprano y su recuperación. El diagnóstico diferencial de esta patología requiere un conocimiento del modo de inicio de los síntomas, su progresión, el patrón de hallazgos mielopáticos/neuropáticos y el reconocimiento de otras manifestaciones neurológicas o sistémicas. Las etiologías de las mieloneuropatías deben subdividirse en trastornos metabólicos (nutricionales), tóxicos (inducidos por toxinas), infecciosos, inflamatorios (mediados por mecanismos inmunitarios), paraneoplásicos y hereditarias.

Towards a standardized framework for AI-assisted, image-based monitoring of nocturnal insects.

Automated sensors have potential to standardize and expand the monitoring of insects across the globe. As one of the most scalable and fastest developing sensor technologies, we describe a framework for automated, image-based monitoring of nocturnal insects-from sensor development and field deployment to workflows for data processing and publishing. Sensors comprise a light to attract insects, a camera for collecting images and a computer for scheduling, data storage and processing. Metadata is important to describe sampling schedules that balance the capture of relevant ecological information against power and data storage limitations. Large data volumes of images from automated systems necessitate scalable and effective data processing. We describe computer vision approaches for the detection, tracking and classification of insects, including models built from existing aggregations of labelled insect images. Data from automated camera systems necessitate approaches that account for inherent biases. We advocate models that explicitly correct for bias in species occurrence or abundance estimates resulting from the imperfect detection of species or individuals present during sampling occasions. We propose ten priorities towards a step-change in automated monitoring of nocturnal insects, a vital task in the face of rapid biodiversity loss from global threats. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Turbidimetric bioassays: A solution to antimicrobial activity detection in asymptomatic bacteriuria isolates against uropathogenic Escherichia coli.

Traditional bacteriocin screening methods often face limitations due to diffusion-related challenges in agar matrices, which can prevent the peptides from reaching their target organism. Turbidimetric techniques offer a solution to these issues, eliminating diffusion-related problems and providing an initial quantification of bacteriocin efficacy in producer organisms. This study involved screening the cell-free supernatant (CFS) from eight uncharacterized asymptomatic bacteriuria (ABU) isolates and Escherichia coli 83972 for antimicrobial activity against clinical uropathogenic E. coli (UPEC) strains using turbidimetric growth methods. ABU isolates exhibiting activity against five or more UPEC strains were further characterized (PUTS 37, PUTS 58, PUTS 59, S-07-4, and SK-106-1). The inhibition of the CFS by proteinase K suggested that the antimicrobial activity was proteinaceous in nature, potentially bacteriocins. The activity of E. coli PUTS 58 and SK-106-1 was enhanced in an artificial urine medium, with both inhibiting all eight UPECs. A putative microcin H47 operon was identified in E. coli SK-106-1, along with a previously identified microcin V and colicin E7 in E. coli PUTS 37 and PUTS 58, respectively. These findings indicate that ABU bacteriocin-producers could serve as viable prophylactics and therapeutics in the face of increasing antibiotic resistance among uropathogens.

Monocyte to macrophage differentiation and changes in cellular redox homeostasis promote cell type-specific HIV latency reactivation.

HIV latency regulation in monocytes and macrophages can vary according to signals directing differentiation, polarization, and function. To investigate these processes, we generated an HIV latency model in THP-1 monocytes and showed differential levels of HIV reactivation among clonal populations. Monocyte-to-macrophage differentiation of HIV-infected primary human CD14+ and THP-1 cells induced HIV reactivation and showed that virus production increased concomitant with macrophage differentiation. We applied the HIV-infected THP-1 monocyte-to-macrophage (MLat) model to assess the biological mechanisms regulating HIV latency dynamics during monocyte-to-macrophage differentiation. We pinpointed protein kinase C signaling pathway activation and Cyclin T1 upregulation as inherent differentiation mechanisms that regulate HIV latency reactivation. Macrophage polarization regulated latency, revealing proinflammatory M1 macrophages suppressed HIV reactivation while anti-inflammatory M2 macrophages promoted HIV reactivation. Because macrophages rely on reactive-oxygen species (ROS) to exert numerous cellular functions, we disrupted redox pathways and found that inhibitors of the thioredoxin (Trx) system acted as latency-promoting agents in T-cells and monocytes, but opposingly acted as latency-reversing agents in macrophages. We explored this mechanism with Auranofin, a clinical candidate for reducing HIV reservoirs, and demonstrated Trx reductase inhibition led to ROS induced NF-κB activity, which promoted HIV reactivation in macrophages, but not in T-cells and monocytes. Collectively, cell type-specific differences in HIV latency regulation could pose a barrier to HIV eradication strategies.

Investigations into Increased Incidence of Severe Gizzard Erosions and Ulcerations in U.S. Commercial Broilers.

During a series of pathology surveys in four production complexes of a U.S. broiler integrator, the technical services veterinarians of an animal health company noted a high incidence of severe gizzard erosions and ulcerations (GEU), prompting further clinical investigation and a battery trial. No growth-promoting antibiotics or ionophore coccidiostats were used during the period of these surveys. All used tribasic copper chloride (TBCC) at ≤120 ppm added copper in broiler rations. Clostridium perfringens was isolated from 83% and 67% of gizzard lesions cultured in two complexes, and cecal C. perfringens most probable number determinations were higher in severely affected than in mildly affected or unaffected birds. Histopathology revealed both acellular koilin fusion defects characteristic of copper toxicity, as well as inflammatory cell infiltrates. Intralesional bacilli suggestive of C. perfringens were noted in 78% of affected flocks examined. Species E Aviadenovirus was isolated from one bird in one complex, and that bird had a single intranuclear inclusion body; no other flocks had Adenoviruses isolated or detected on PCR, nor any inclusion bodies. Other viruses detected were thought to be incidental. A pilot study using feed with supplemental copper from TBCC or copper sulfate and challenge with one of the isolated C. perfringens strains reproduced the lesions. A battery study was conducted with an unchallenged negative control group fed a diet with 16 ppm added copper, a group fed the control diet and orally challenged with 108 organisms of a field strain of C. perfringens at 21 and 22 days, and a group treated with the same diet containing 250 ppm added copper from TBCC and orally challenged with C. perfringens. Birds were necropsied at 23 and 28 days. All challenged groups developed lesions, with those receiving both TBCC and C. perfringens having significantly higher gross and histopathological lesion scores than the unchallenged negative controls. Lesions were qualitatively similar to those in the field and contained suspected C. perfringens bacilli. Because the levels of TBCC used in the commercial birds and in the battery trial generally have been considered safe, and because C. perfringens is usually regarded as a pathogen of the lower GI tract, the possible association of these two agents with GEU is a novel observation and warrants further investigation.

Investigaciones sobre el aumento de la incidencia de erosiones y ulceraciones severas en la molleja en pollos de engorde comerciales en los Estados Unidos. Durante una serie de estudios de patología en cuatro complejos de producción de un integrador de pollos de engorde de los Estados Unidos, veterinarios de servicio técnico de una empresa de salud animal observaron una alta incidencia de erosiones y ulceraciones severas de la molleja (GEU), lo que motivó una mayor investigación clínica y un estudio en batería. Durante el período de estas encuestas no se utilizaron antibióticos promotores del crecimiento ni coccidiostáticos ionóforos. Todos utilizaron cloruro de cobre tribásico (TBCC) con un nivel de ≤120 ppm de cobre agregado en raciones para pollos de engorde. Se aisló Clostridium perfringens del 83% y el 67% de las lesiones de molleja cultivadas en dos complejos, y las determinaciones del número más probable de C. perfringens en los sacos ciegos fueron mayores en aves severamente afectadas que en aves levemente afectadas o no afectadas. La histopatología reveló defectos de fusión de la capa córnea acelular característicos de la toxicidad por cobre, así como infiltrados de células inflamatorias. Se observaron bacilos intralesionales sugestivos de C. perfringens en el 78% de las parvadas afectadas examinadas. La especie Aviadenovirus E se aisló de un ave en un complejo, y esa ave tenía un único cuerpo de inclusión intranuclear; en ninguna otra parvada se aislaron o detectaron adenovirus mediante PCR, ni se observaron cuerpos de inclusión. Se pensó que otros virus detectados fueron incidentales. Un estudio piloto que utilizó alimento con cobre suplementario de cloruro de cobre tribásico o sulfato de cobre y con desafío con una de las cepas aisladas de C. perfringens reprodujo las lesiones. Se realizó un estudio de batería con un grupo de control negativo no desafiado alimentado con una dieta con 16 ppm de cobre agregado, un grupo alimentado con la dieta de control y desafiado por vía oral con 108 organismos de una cepa de campo de C. perfringens a los 21 y 22 días, y un grupo tratado con la misma dieta que contenía 250 ppm de cobre agregado de cloruro de cobre tribásico y desafiados por vía oral con C. perfringens. A las aves se les realizó la necropsia a los 23 y 28 días. Todos los grupos desafiados desarrollaron lesiones, y aquellos que recibieron cloruro de cobre tribásico y C. perfringens tuvieron puntuaciones de lesiones macroscópicas e histopatológicas significativamente más altas que los controles negativos no desafiados. Las lesiones eran cualitativamente similares a las del campo y contenían bacilos sospechosos de C. perfringens. Debido a que los niveles de cloruro de cobre tribásico utilizados en las aves comerciales y en el ensayo en batería generalmente se han considerado seguros, y debido a que C. perfringens generalmente se considera un patógeno del tracto gastrointestinal inferior, la posible asociación de estos dos agentes con erosiones y ulceraciones severas de la molleja es una observación reciente y justifica una mayor investigación.

The Management of Persistent Distal Occlusions after Mechanical Thrombectomy and Thrombolysis: An Inter- and Intrarater Agreement Study.

BACKGROUND AND PURPOSE: The best management of patients with persistent distal occlusion after mechanical thrombectomy with or without IV thrombolysis remains unknown. We sought to evaluate the variability and agreement in decision-making for persistent distal occlusions. MATERIALS AND METHODS: A portfolio of 60 cases was sent to clinicians with varying backgrounds and experience. Responders were asked whether they considered conservative management or rescue therapy (stent retriever, aspiration, or intra-arterial thrombolytics) a treatment option as well as their willingness to enroll patients in a randomized trial. Agreement was assessed using κ statistics. RESULTS: The electronic survey was answered by 31 physicians (8 vascular neurologists and 23 interventional neuroradiologists). Decisions for rescue therapies were more frequent (n = 1116/1860, 60%) than for conservative management (n = 744/1860, 40%; P < .001). Interrater agreement regarding the final management decision was "slight" (κ = 0.12; 95% CI, 0.09-0.14) and did not improve when subgroups of clinicians were studied according to background, experience, and specialty or when cases were grouped according to the level of occlusion. On delayed re-questioning, 23 of 29 respondents (79.3%) disagreed with themselves on at least 20% of cases. Respondents were willing to offer trial participation in 1295 of 1860 (69.6%) cases. CONCLUSIONS: Individuals did not agree regarding the best management of patients with persistent distal occlusion after mechanical thrombectomy and IV thrombolysis. There is sufficient uncertainty to justify a dedicated randomized trial.

Unravelling the genetic basis of Schizophrenia.

Neuronal development is a highly regulated mechanism that is central to organismal function in animals. In humans, disruptions to this process can lead to a range of neurodevelopmental phenotypes, including Schizophrenia (SCZ). SCZ has a significant genetic component, whereby an individual with an SCZ affected family member is eight times more likely to develop the disease than someone with no family history of SCZ. By examining a combination of genomic, transcriptomic and epigenomic datasets, large-scale 'omics' studies aim to delineate the relationship between genetic variation and abnormal cellular activity in the SCZ brain. Herein, we provide a brief overview of some of the key omics methods currently being used in SCZ research, including RNA-seq, the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and high-throughput chromosome conformation capture (3C) approaches (e.g., Hi-C), as well as single-cell/nuclei iterations of these methods. We also discuss how these techniques are being employed to further our understanding of the genetic basis of SCZ, and to identify associated molecular pathways, biomarkers, and candidate drug targets.

Antimicrobial Metaphylaxis and its Impact on Health, Performance, Antimicrobial Resistance, and Contextual Antimicrobial Use in High-Risk Beef Stocker Calves.

The objective of this blinded, cluster-randomized, complete block trial was to evaluate the impact of metaphylaxis on health, performance, antimicrobial resistance, and contextual antimicrobial use (AMU) in high-risk beef stocker calves. Calves (n = 155) were randomly assigned to receive either saline or tulathromycin at the time of arrival processing. Deep nasopharyngeal swabs were collected from each calf at arrival and 14 d later. Calves were monitored for bovine respiratory disease (BRD) for 42 d. Body weights were obtained at arrival, days 14, 28, and 42. Contextual antimicrobial use (AMU) was calculated using dose and mass-based metrics. Calves given tulathromycin had a greater average daily gain (0.96 ±â€…0.07 kg vs. 0.82 ±â€…0.07 kg; P = 0.034) and lower prevalence of BRD than controls (17% vs. 40%; P = 0.008). Proportions of calves with BRD pathogens identified at arrival were similar between treatment groups [17%; P = 0.94]. Proportions of calves with BRD pathogens identified at day 14 were lower for calves receiving tulathromycin compared to controls (15% vs. 60%, P < 0.001). Overall, 81% of Pastuerella multocida isolates and 47% of Mannheimia haemolytica isolates were pansusceptible. When measured as regimens per head in, AMU in calves receiving tulathromycin was higher than calves receiving saline (P = 0.01). Under the conditions of this study, metaphylaxis had positive impacts on the health and performance of high-risk beef stocker calves, did not contribute to the selection of resistant bacterial isolates in the nasopharynx of treated cattle, and increased AMU.

In this study, we investigated the impact of metaphyactic antimicrobial administration on health, performance, and antimicrobial use in high-risk beef stocker calves. Our findings demonstrated that metaphylaxis improves performance and has positive effects on animal health and well-being but increases total antimicrobial use. Additionally, our study revealed that metaphylaxis alone does not contribute to the selection of antimicrobial-resistant pathogens in the upper airway of treated cattle.

Mechanobiology as a tool for addressing the genotype-to-phenotype problem in microbiology.

The central hypothesis of the genotype-phenotype relationship is that the phenotype of a developing organism (i.e., its set of observable attributes) depends on its genome and the environment. However, as we learn more about the genetics and biochemistry of living systems, our understanding does not fully extend to the complex multiscale nature of how cells move, interact, and organize; this gap in understanding is referred to as the genotype-to-phenotype problem. The physics of soft matter sets the background on which living organisms evolved, and the cell environment is a strong determinant of cell phenotype. This inevitably leads to challenges as the full function of many genes, and the diversity of cellular behaviors cannot be assessed without wide screens of environmental conditions. Cellular mechanobiology is an emerging field that provides methodologies to understand how cells integrate chemical and physical environmental stress and signals, and how they are transduced to control cell function. Biofilm forming bacteria represent an attractive model because they are fast growing, genetically malleable and can display sophisticated self-organizing developmental behaviors similar to those found in higher organisms. Here, we propose mechanobiology as a new area of study in prokaryotic systems and describe its potential for unveiling new links between an organism's genome and phenome.

Colchicine twice a day for hand osteoarthritis (COLOR): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Colchicine has been suggested for osteoarthritis treatment, but evidence is contradictory. We aimed to investigate colchicine's efficacy and safety compared with placebo in people with hand osteoarthritis. METHODS: In this single-centre, double-blind, randomised, placebo-controlled trial we recruited adults with symptomatic hand osteoarthritis and finger pain of at least 40 mm on a 100 mm visual analogue scale from an outpatient clinic in Denmark. The hand with the most severe finger pain at inclusion was the target hand. Participants were randomly assigned (1:1) to 0·5 mg colchicine or placebo taken orally twice a day for 12 weeks, stratified by BMI (≥30 kg/m2), sex, and age (≥75 years). Participants, outcome assessors, and data analysts were masked to treatment allocation. The primary endpoint was change from baseline to week 12 in target hand finger pain, assessed on a 100 mm visual analogue scale with a pre-specified minimal clinically important difference of 15 mm, in the intention-to-treat population. Safety was assessed at week 12 in the intention-to-treat population. The study was registered with ClinicalTrials.gov, NCT04601883, and with EudraCT, 2020-002803-20. FINDINGS: Between Jan 15, 2021, and March 3, 2022, 186 people were screened for eligibility, and 100 were randomly assigned to receive colchicine (n=50) or placebo (n=50). Participants had a mean age of 70·9 (SD 7·5) years, 69 (69%) of 100 were women and 31 (31%) were men. All participants completed the study. The mean change from baseline to week 12 in finger pain were -13·9 mm (SE 2·8) in the colchicine group and -13·5 mm (2·8) in the placebo group, with a between-group difference (colchicine vs placebo) of -0·4 mm (95% CI -7·6 to 6·7; p=0·90). In the colchicine group, there were 76 adverse events in 36 (72%) of 50 participants and one serious adverse advent (migraine attack leading to hospital admission). In the placebo group, there were 42 adverse events in 22 (44%) of 50 participants and two serious adverse events (cholecystitis and elevated alanine aminotransferase concentrations, in the same patient). INTERPRETATION: In people with painful hand osteoarthritis, treatment with 0·5 mg of colchicine twice day for 12 weeks did not effectively relieve pain, and treatment with colchicine was associated with more adverse events. FUNDING: The Oak Foundation, IMK Almene Fond, Minister Erna Hamilton's Scholarship for Science and Art, AP Moller and Wife Chastine McKinney Moller's Foundation for Medical Science Advancement, The Danish Medical Association, the Velux Foundation, Aase and Ejnar Danielsen's Foundation, and Director Emil C Hertz and Wife Inger Hertz's foundation.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee

To develop an evidence- based guideline for the comprehensive management of osteoarthritis (OA) as a collabora-tion between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommenda-tions for the management of hand, hip, and knee OA.Methods. We identied clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benets and harms of available educational, behavioral, psychosocial, physical, mind- body, and pharmacologic therapies for OA. Grading of Recommen-dations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, includ-ing rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.Results. Based on the available evidence, either strong or conditional recommendations were made for or against the ap-proaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self- efcacy and self- management programs, tai chi, cane use, hand orthoses for rst carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exer-cises, yoga, cognitive behavioral therapy, kinesiotaping for rst CMC OA, orthoses for hand joints other than the rst CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, du-loxetine, and tramadol.Conclusion. This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision- making that accounts for patients' values, preferences, and comor-bidities. These recommendations should not be used to limit or deny access to therapies

Diagnóstico de hepatozoon spp. en perros (Canis familiaris) y sus vectores en áreas rurales de los Estados Lara y Yaracuy-Venezuela / Diagnosis of hepatozoon spp. in dogs (Canis familiaris) and its vectors from rural areas of Lara and Yaracuy States, Venezuela

El objetivo de este trabajo fue diagnosticar Hepatozoon spp. en perros de áreas rurales en algunos municipios de los estados Lara y Yaracuy, así como su relación con los potenciales artrópodos vectores involucrados en su transmisión. Babesia canis vogeli, Ehrlichia canis y en menor frecuencia Hepatozoon canis son los agentes parasitarios más importantes en caninos teniendo todos ellos como vector a Rhipicephalus sanguineus. Estos hemotrópicos infectan frecuentemente a los animales sin causarles sintomatología clínica y en otros casos les causan enfermedad de gravedad variable. La asociación de estos agentes es muy común, lo que favorece la gravedad de los síntomas clínicos. Además de R. sanguineus, otros géneros de garrapatas pueden ser encontradas parasitando perros, como Amblyomma e Ixodes. Durante el estudio se realizaron frotis sanguíneos de sangre periférica de la oreja de 300 perros y se colectaron 604 garrapatas por medio de extracción manual. Estos ixódidos fueron identificados taxonómicamente en el Laboratorio de Parasitología con la ayuda de claves dicotómicas y luego fueron sometidas a disección en busca de fases evolutivas de Hepatozoon spp. Los resultados fueron analizados a través de estadísticas no paramétricas indicando la presencia o ausencia de Hepatozoon spp. y la identificación de los vectores involucrados. Se observó Hepatozoon spp. en las muestras de sangre periférica de 11 de los perros estudiados, correspondiendo a tres perros del estado Lara y ocho al estado Yaracuy. En relación a los vectores, se identificaron en el estado Lara, 557 Rhipicephalus sanguineus, 11 Amblyomma ovale y 10 Ixodes spp. y en el estado Yaracuy solamente se diagnosticaron 26 especímenes de Amblyomma ovale. Es importante destacar la presencia de Hepatozoon spp. en áreas rurales donde no se identificó R. sanguineus.

The purpose of this research was to diagnose Hepatozoon spp. in dogs from rural areas in some municipalities of the States of Lara and Yaracuy, Venezuela, and its relationship with potential arthropods vectors involved in its transmission. Babesia canis vogeli, Ehrlichia canis, and less frequently, Hepatozoon canis, are the most important hemoparasites of dogs, all having as a common vector Rhipicephalus sanguineus. These hemoparasites frequently infest both domestic and rural animals without overt clinical symptoms; in other cases, they cause diseases of varied severity. Coinfections by hemoparasites are very common, which favors the severity of clinical symptoms. Besides R. sanguineus, other tick genera like Amblyomma and Ixodes, can be found infesting dogs. To carry out this study, thin blood smears from peripheral ear veins of 300 dogs were performed; and 604 ticks were collected by manual extraction. These ixodids were taxonomically identified at the Parasitology Laboratory, with the help of dichotomous taxonomic keys. Then, they were subjected to dissections looking for evolutionary stages of Hepatozoon spp. Results obtained were analyzed through non-parametric statistics, showing the presence or absence of Hepatozoon spp. and the identification of the involved vectors. Hepatozoon spp. was found in samples of peripheral blood in 11 of the dogs studied, three from the State of Lara and eight from the State of Yaracuy. Regarding vectors, 557 Rhipicephalus sanguineus, 11 Amblyomma ovale and 10 Ixodes spp. were identified in Lara, whereas only 26 specimens of Amblyomma ovale were identified in Yaracuy. It is important to underscore the presence of Hepatozoon spp. in rural areas where R. sanguineus was not identified.