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CONTEXT: The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms. This study provides a significant contribution to understanding bilastine's polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products. METHODS: The molecular conformation of two bilastine forms was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311 + + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

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A proper balance of metabolic pathways is crucial for engineering microbial strains that can efficiently produce biochemicals on an industrial scale while maintaining cell fitness. High production loads can negatively impact cell fitness and hinder industrial-scale production. To address this, fine-tuning gene expression using engineered promoters and genetic circuits can promote control over multiple targets in pathways and reduce the burden. We took advantage of the robust carbon catabolite repression system of Bacillus subtilis to engineer a glucose-inducible genetic circuit that supports growth and production. The circuit is resilient, enabling a quick switch in the production status when exposed to the correct carbon source. By performing serial cultivations for 61 generations under repressive conditions, we preserved the production capacity of the cells, which could be fully accessed by switching to glucose in the next cultivation step. Switching to glucose after 61 generations resulted in 34-fold activation and generated 70% higher production in comparison to standard cultivation in glucose. Conversely, serial cultivation under permanent induction resulted in 62% production loss after 67 generations alongside an increase in the culture growth rate. As a pathway-independent circuit activated by the preferred carbon source, our engineered glucose-inducible genetic circuit is broadly useful and imposes no additional cost to traditional production processes.

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CONTEXT: The number of pediatric anterior cruciate ligament reconstructions (ACLRs) occurring yearly increased almost 6-fold from 2004-2014. We find it interesting that limited recent data exist on rates of ACL injury and reconstruction in children and adolescents, especially in the context of COVID-19. OBJECTIVE: Given the effect of the COVID-19 pandemic on youth sports seasons and the postponement of many elective surgeries, we sought to examine the changes in rates of ACLR during this period. DESIGN: Retrospective cohort study. SETTING: This study used the Pediatric Health Information System (PHIS) database to identify eligible patients at PHIS-participating hospitals nationwide from January 2016-June 2021, with March 1, 2020, considered the start of the COVID-19 pandemic. PATIENTS OR OTHER PARTICIPANTS: Using Current Procedural Terminology codes, patients 18 years old and younger who underwent ACLR surgery were identified. MAIN OUTCOME MEASURE(S): Patient demographics and overall rates of surgery prepandemic and intrapandemic were compared. Data were analyzed using bivariate, mixed-model, and time series analyses. RESULTS: A total of 24 843 ACLRs were identified during this time period. In total, 1853 fewer surgeries than expected were performed after March 2020 given prepandemic trends. Intrapandemic demographics revealed an increase in the proportion of patients who identified as White and with private insurance and a decrease in the proportion who identified as Black and with public insurance. Also, the proportion of ACLRs by region shifted, with more surgeries performed in the Midwest and fewer in the Northeast. In the model adjusted for hospital-level variability, only race and insurance status remained significant. CONCLUSIONS: Based on prepandemic trends, fewer patients than projected underwent ACLR once the pandemic began, likely due to a combination of decreased rates of injury and delayed surgery.

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Many taxonomic groups successfully exploit groundwater environments and have adapted to a subterranean (stygobiotic) existence. Among these groups are freshwater gastropods (stygosnails), which represent a widespread and taxonomically diverse component of groundwater ecosystems in North America. However, owing to sampling difficulty and lack of targeted study, stygosnails remain among the most understudied of all subterranean groups. We conducted a literature review to assess the biodiversity and geographic associations of stygosnails, along with the threats, management activities, and policy considerations related to the groundwater systems they inhabit. We identified 39 stygosnail species known to occur in a range of groundwater habitats from karst regions in the United States and Mexico. Most stygosnails exhibit extreme narrow-range endemism, resulting in a high risk of extinction from a single catastrophic event. We found that anthropogenically driven changes to surface environments have led to changes in local hydrology and degradation of groundwater systems inhabited by stygosnails such as increased sedimentation, introduction of invasive species, groundwater extraction, or physical collapse of water-bearing passages. Consequently, 32 of the 39 described stygosnail species in the United States and Mexico have been assessed as imperiled under NatureServe criteria, and 10 species have been assessed as threatened under International Union for Conservation of Nature criteria. Compared with surface species of freshwater snails, stygosnail conservation is uniquely hindered by difficulties associated with accessing subterranean habitats for monitoring and management. Furthermore, only three species were found to have federal protection in either the United States or Mexico, and current laws regulating wildlife and water pollution at the state and federal level may be inadequate for protecting stygosnail habitats. As groundwater systems continue to be manipulated and relied on by humans, groundwater-restricted fauna such as stygosnails should be studied so unique biodiversity can be protected.

Diversidad y Conservación de Gasterópodos Subterráneos de Agua Dulce en los Estados Unidos y en México Resumen Muchos grupos taxonómicos aprovechan exitosamente los ambientes de aguas subterráneas y se han adaptado eficazmente a una existencia subterránea (estigobiótica). Entre estos grupos están los gasterópodos (estigocaracoles), los cuales representan un componente taxonómicamente diverso y de amplia distribución en los ecosistemas de aguas subterráneas en América del Norte. Sin embargo, debido a la dificultad del muestreo y a la falta de estudios enfocados, los estigocaracoles todavía son de los grupos menos estudiados de los taxones subterráneos. Realizamos una revisión de la literatura para evaluar las asociaciones geográficas y la biodiversidad de los estigocaracoles, junto con las amenazas, actividades de manejo y consideraciones políticas relacionadas con los sistemas de aguas subterráneas que habitan. Identificamos a 39 especies de estigocaracoles que se sabe se encuentran en una gama de hábitats de aguas subterráneas de las regiones kársticas en los Estados Unidos y en México. La mayoría de los estigocaracoles exhiben un endemismo extremo de extensión limitada, lo que resulta en un riesgo elevado de extinción a partir de un evento catastrófico único. Descubrimos que los cambios causados por el hombre en los ambientes superficiales han resultado en cambios en la hidrología local y en la degradación de los sistemas de aguas subterráneas habitadas por los estigocaracoles. Dichos cambios incluyen incremento de la sedimentación, la introducción de especies invasoras, la extracción de aguas subterráneas y el colapso físico de los pasos de agua. Como consecuencia, 32 de las 39 especies descritas de estigocaracoles en los Estados Unidos y en México han sido valoradas como en peligro bajo los criterios de NatureServe, y diez especies han sido valoradas como amenazadas bajo los criterios de la Unión Internacional para la Conservación de la Naturaleza. Comparada con las especies superficiales de caracoles de agua dulce, la conservación de los estigocaracoles está singularmente obstaculizada por las dificultades asociadas con el acceso a los hábitats subterráneos para su monitoreo y manejo. Además, se encontró que sólo tres especies cuentan con protección federal ya sea en Estados Unidos o en México, y puede que las leyes actuales que regulan la vida silvestre y la contaminación del agua a nivel estatal y federal sean inadecuadas para la protección de los hábitats de los estigocaracoles. Mientras los sistemas de aguas subterráneas sigan siendo manipulados y los humanos sigan dependiendo de ellos, la fauna restringida a las aguas subterráneas, como los estigocaracoles, debería ser estudiada para proteger a la biodiversidad tan única.

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Two new genera and species of freshwater turtle blood flukes (TBFs) are described herein based on specimens infecting the nephritic and mesenteric blood vessels of "matamatas" (a side-necked turtle, Chelus fimbriata [Schneider, 1783] [Pleurodira: Chelidae]) from the Amazon River Basin, Peru. These taxa comprise the first-named species and the first-proposed genera of freshwater TBFs from the continent of South America. A new comparison of all TBF genera produced 6 morphologically diagnosed groups that are discussed in light of previous TBF classification schemes and a novel phylogenetic hypothesis based on the nuclear large subunit ribosomal DNA (28S). Considering external and internal anatomical features, species of the new genera (Atamatam Bullard and Roberts n. gen., Paratamatam Bullard and Roberts n. gen.) are most similar to each other and are together most similar to those of several marine TBF genera. The 28S phylogenetic analysis supported the monophyly of all 6 morphologically diagnosed groups of genera. Most notably, the freshwater TBFs of South America comprise a derived group nested within the clade that includes the paraphyletic marine TBFs. Not surprisingly in light of morphology, another marine TBF lineage (Neospirorchis Price, 1934) clustered with the freshwater TBFs of Baracktrema Roberts, Platt, and Bullard, 2016 and Unicaecum Stunkard, 1925. Our results, including an ancestral state reconstruction, indicated that (1) freshwater TBFs have colonized marine turtles twice independently and that (2) the South American freshwater TBFs comprise a marine-derived lineage. This is the first evidence that TBFs have twice independently transitioned from a marine to freshwater definitive host. Marine incursion is considered as a possible mechanism affecting the natural history of marine-derived freshwater TBFs in South America. A dichotomous key to accepted TBF genera is provided.

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Gymnurahemecus bulbosus gen. et sp. nov. infects the heart of smooth butterfly rays, Gymnura micrura in the Gulf of Mexico. Gymnurahemecus differs from all other accepted aporocotylid genera by having one column of C-shaped lateral tegumental spines, a medial oesophageal bulb anterior to a diverticulate region of the oesophagus, inverse U-shaped intestinal caeca, a non-looped testis, an oviducal ampulla, a Laurer's canal, and a post-caecal common genital pore. The new species, the shark blood flukes (Selachohemecus spp. and Hyperandrotrema spp.), and the chimaera blood fluke Chimaerohemecus trondheimensis are unique by having C-shaped lateral tegumental spines. Selachohemecus spp. and the new species have a single column of lateral tegumental spines, whereas Hyperandrotrema spp. and C. trondheimensis have 2-7 columns of lateral tegumental spines. The new species differs from Selachohemecus spp. most notably by having an inverse U-shaped intestine. The other ray blood flukes (Orchispirium heterovitellatum, Myliobaticola richardheardi, and Ogawaia glaucostegi) differ from the new species by lacking lateral tegumental spines, a medial oesophageal bulb, and a Laurer's canal and by having a looped testis. Phylogenetic analysis using large subunit ribosomal DNA (28S) indicated that the new species is sister to the clade that includes the other sequenced adult blood fluke (O. glaucostegi), which infects a ray in Australia. These results agree with and extend previous morphology- and nucleotide-based phylogenetic assertions that the blood flukes of early-branching jawed craniates (Chondrichthyes) are monophyletic and phylogenetically separated from the blood flukes of later-branching ray-finned fishes (Actinopterygii: Euteleostei).

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BACKGROUND: Orthopaedic interest groups (OIGs) are student-run organizations that can provide medical students with early exposure to orthopaedic surgery. OIGs can serve as venues for musculoskeletal education, clinical experiences, and mentorship to students with otherwise limited access to orthopaedics. The purpose of this study was to evaluate the prevalence and opportunities offered by OIGs. METHODS: The websites of all allopathic medical schools in the United States were evaluated. Each website was examined for an established OIG and any pertinent information regarding shadowing, research opportunities, lectures, workshops, or opportunities to interact with residents. OIGs were categorized based on the number and type of offerings provided to their members. RESULTS: Of the 141 allopathic medical school websites evaluated, 108 (108/141, 76%) had evidence of an orthopaedic interest group. Sixty-nine (69/108, 64%) of these schools described the opportunities provided. The most common opportunities were clinical skills workshops (41/69, 59%), lectures (32/69, 46%), and opportunities to interact with current residents (30/69, 43%). The majority of OIGs (39/69, 57%) offered fewer than half of the possible opportunities and only 6 groups (9%) offered all five opportunities. CONCLUSION: The majority of allopathic medical schools in the United States have an OIG; however, the opportunities provided to orthopaedic interest group members vary widely from institution to institution.

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BACKGROUND: Despite extensive study on hemoglobins and hemocyanins, little is known about hemerythrin (Hr) evolutionary history. Four subgroups of Hrs have been documented, including: circulating Hr (cHr), myohemerythrin (myoHr), ovohemerythrin (ovoHr), and neurohemerythrin (nHr). Annelids have the greatest diversity of oxygen carrying proteins among animals and are the only phylum in which all Hr subgroups have been documented. To examine Hr diversity in annelids and to further understand evolution of Hrs, we employed approaches to survey annelid transcriptomes in silico. RESULTS: Sequences of 214 putative Hr genes were identified from 44 annelid species in 40 different families and Bayesian inference revealed two major clades with strong statistical support. Notably, the topology of the Hr gene tree did not mirror the phylogeny of Annelida as presently understood, and we found evidence of extensive Hr gene duplication and loss in annelids. Gene tree topology supported monophyly of cHrs and a myoHr clade that included nHrs sequences, indicating these designations are functional rather than evolutionary. CONCLUSIONS: The presence of several cHrs in early branching taxa suggests that a variety of Hrs were present in the common ancestor of extant annelids. Although our analysis was limited to expressed-coding regions, our findings demonstrate a greater diversity of Hrs among annelids than previously reported.

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Two cases of neonatal varicella in Jamaica are reported. This condition is reported for the first time in the Caribbean. Though the condition is rare, it is important to be aware of life-saving measures to be adopted in severe neonatal varicella.

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Two cases of neonatal varicella in Jamaica are reported. This condition is reported for the first time in the Caribbean. Though the condition is rare, it is important to be aware of life-saving measures to be adopted in severe neonatal varicella.(AU)

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Hypohidrotic ectodermal dysplasia (Christ-Siemans-Touraine Syndrome) is reported in three male siblings. The patients gave a history of repeated hospital admissions from the age of 4 months for hyperpyrexia and seizures. They were being followed up for "febrile convulsions". Since the condition is familial, each member of the family should be carefully investigated for hair, teeth and sweating abnormalities in order to detect both homozygous and heterozygous forms of the condition (AU)

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A case of craniofacial dysostosis (Crouzon's disease) is reported in a 6-year-old negro girl. The condition is very rare, and is inherited as an autosomal dominant trait. Early diagnosis and surgical correction of the deformities are essential in order to enhance intellectual development, limit social rejection, and minimize complications. Periodic psychological assessment is necessary for evaluating the effectiveness of surgical correction of the skull deformities (AU)

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