Clinical outcomes following switching antipsychotic treatment due to market withdrawal: a retrospective naturalistic cohort study of pipotiazine palmitate injection (Piportil Depot) discontinuation, subsequent acute care use and effectiveness of medication to which patients switched

Introduction: Pipotiazine palmitate depot injection (Piportil) was withdrawn from the UK marketplace in 2015. Few studies exist on the clinical impact of such market withdrawal. Purpose: We aimed to identify a cohort of patients switching from pipotiazine following this withdrawal and explore factors associated with effectiveness of the medication switched to and subsequent acute service use. Methods: A naturalistic retrospective cohort study was conducted in Sussex, United Kingdom. Those discontinuing pipotiazine solely due to market withdrawal were identified from electronic patient database and manual searching. Multivariate logistic regression analyses and survival analyses were performed to explore associations between available baseline variables and dichotomous all-cause discontinuation of the next prescribed medication and admission to acute mental health services over the subsequent year. Results: Of 205 patients identified as receiving pipotiazine in October 2014, 137 switched from this due to market withdrawal. Over the subsequent year, 31.5% discontinued the medication to which they were switched and 19% required acute care. Drug class switched to (typical depot vs atypical long acting injection (LAI) vs atypical oral) had no significant association with discontinuation. Switch to atypical LAI was significantly associated with acute care in comparison to typical depot. Those with a schizophrenia diagnosis were significantly less likely to discontinue switched medication or to receive acute care in comparison to those with schizoaffective disorder. Women were significantly more likely to discontinue switched medication than men. Of those requiring acute care, only 38% had required this in the previous 2 years. Conclusions: Antipsychotic market withdrawal has demonstrable negative clinical implications and requires careful clinical management. Increased acute care rates in those receiving an atypical LAI versus a typical depot following pipotiazine suggests lower effectiveness or possible withdrawal effects. No significant difference between depots, LAIs and oral medications on discontinuation supports the importance of a collaborative, fully informed approach when deciding next treatment options

Phylogenetic Position of a Copper Age Sheep (Ovis aries) Mitochondrial DNA

BACKGROUND: Sheep (Ovis aries) were domesticated in the Fertile Crescent region about 9,000-8,000 years ago. Currently, few mitochondrial (mt) DNA studies are available on archaeological sheep. In particular, no data on archaeological European sheep are available. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the first portion of mtDNA sequence of a Copper Age European sheep. DNA was extracted from hair shafts which were part of the clothes of the so-called Tyrolean Iceman or Ötzi (5,350-5,100 years before present). Mitochondrial DNA (a total of 2,429 base pairs, encompassing a portion of the control region, tRNA(Phe), a portion of the 12S rRNA gene, and the whole cytochrome B gene) was sequenced using a mixed sequencing procedure based on PCR amplification and 454 sequencing of pooled amplification products. We have compared the sequence with the corresponding sequence of 334 extant lineages. CONCLUSIONS/SIGNIFICANCE: A phylogenetic network based on a new cladistic notation for the mitochondrial diversity of domestic sheep shows that the Ötzi's sheep falls within haplogroup B, thus demonstrating that sheep belonging to this haplogroup were already present in the Alps more than 5,000 years ago. On the other hand, the lineage of the Ötzi's sheep is defined by two transitions (16147, and 16440) which, assembled together, define a motif that has not yet been identified in modern sheep populations

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Relating mechanical properties of vertebral trabecular bones to osteoporosis

Osteoporosis is an osteometabolic disease, which promotes structural degradation of bone tissue and reduction of mineral density. We reported here a mechanical resistance assay from normal, osteopenic and osteoporotic trabecular vertebral bones of human cadavers. We performed a compressed test on ninety samples, evaluating Young's modulus and X-ray microtomography to measure bone volume fraction and trabecular thickness. This experimental data are employed for computing the orthotropic macroscopic behavior of vertebral trabecular bones using known analytical formulae that were obtained by Galka et al. (Arch Mech 51: 335-355, 1999) via an asymptotic homogenization model. A geometrical model with a periodic orthogonal plate-like structure is applied. The properties of the bone-trabecular mass are considered linear, homogeneous and orthotropic. Average values for all technical or engineering elastic properties are computed for three important regions of the trabecular bones corresponding to thirty individuals classified as normal, osteopenic or osteoporotic by calcaneus ultrassometry. This study could be useful for a better understanding of the elastic behavior of trabecular bones in human vertebral bodies, allowing an estimation of bone answer under stress in different directions and the risk of fracture associated with osteoporosis2325468CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES149100/2010-8sem informação2010/51698-0; 2014/02163-7; 2017/011958-

Probiotic actions of Bacillus cereus var. toyoi and Saccharomyces boulardii in silver catfish (Rhamdia quelen) larvae culture

The objective of this study was to evaluate the use of Bacillus cereus var. toyoi and Saccharomyces boulardii as probiotics to improve Rhamdia quelen culture. Six hundred larvaes (0.16±0.07 g) were divided in three replicate tanks (25-L recirculation, 20 ºC, photoperiod of 12 h light/12 h darkness) per treatment and were randomly assigned to the following treatments: Bacillus cereus var. toyoi; Saccharomyces boulardii; B. toyoi and S. boulardii; and control (without probiotic addition) for a period of 30 days. The fish were fed five times daily (56% crude protein - Supra alevino inicial®) and the probiotics were applied in water once a day. The doses of probiotics were <img src="/img/revistas/rbz/v41n3/aproximadamente.jpg">5 × 10(8) and <img src="/img/revistas/rbz/v41n3/aproximadamente.jpg">2 × 10(9) CFU (colony forming unit)/mL for B. cereus var. toyoi and S. boulardii, respectively. Both probiotics have an inhibitory effect in vitro against Vibrio carchariae and are able to grow in media prepared with fishery water; however, no effect was observed on growth parameters when they were administered to Rhamdia quelen larvae