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Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.
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Biodiversidade , Ecossistema , Humanos , Animais , Agricultura , Animais Selvagens , Mudança ClimáticaRESUMO
The corpora allata and the prothoracic glands control moulting and metamorphosis in insects. These endocrine glands are specified in the maxillary and labial segments at positions homologous to those forming the trachea in more posterior segments. Glands and trachea can be homeotically transformed into each other suggesting that all three evolved from a metamerically repeated organ that diverged to form glands in the head and respiratory organs in the trunk. While much is known about tracheal specification, there is limited information about corpora allata and prothorathic gland specification. Here we show that the expression of a key regulator of early gland development, the snail gene, is controlled by the Dfd and Scr Hox genes and by the Hedgehog and Wnt signalling pathways that induce localised transcription of upd, the ligand of the JAK/STAT signalling pathway, which lies at the heart of gland specification. Our results show that the same upstream regulators are required for the early gland and tracheal primordia specification, reinforcing the hypothesis that they originated from a segmentally repeated organ present in an ancient arthropod.
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Metamorfose Biológica , Muda , Animais , Genes Homeobox , Insetos/genética , Ligantes , Metamorfose Biológica/genéticaRESUMO
BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was non-inferior to caspofungin for Day 30 all-cause mortality (ACM) and Day 14 global cure in the Phase 3 ReSTORE trial (NCT03667690). We conducted pre-planned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization, or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included Day 30 ACM, Day 14 global cure rate, and Day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively: Day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval] 4.6% [-13.7, 23.5]); Day 14 global response was 55.3% and 50.0% (between-group difference 5.3% [-16.1, 26.0]); and Day 5 mycological eradication was 71.1% and 50.0% (between-group difference 21.1% [-0.2, 40.2]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.
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BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.
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Candidíase Invasiva , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Caspofungina/uso terapêutico , Administração Intravenosa , Candidíase Invasiva/tratamento farmacológico , Método Duplo-Cego , Resultado do TratamentoRESUMO
Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.
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Infecções Comunitárias Adquiridas , Pneumonia , Guias de Prática Clínica como Assunto , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Estados Unidos , Pneumonia/diagnóstico , Pneumonia/terapia , Pneumonia/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: The sphenomandibular ligament (SML) is considered to originate from Meckel's cartilage (MC). However, no study has examined how the os goniale contributes to SML development. METHODS: Semiserial histological sections of heads from 18 near-term fetuses at 27-40 weeks of gestation were examined. OBSERVATIONS: The os goniale and the anterior process of the malleus (AP) provided a long, bar-like membranous bone complex that passed through the petrotympanic and tympanosquamosal fissures. Notably, the AP-goniale complex is sometimes elongated inferiorly to join the SML (n = 4 specimens). Along the complex in the bone fissures, a degenerating MC was often present (n = 12). With (n = 6) or without (n = 3) the MC remnant, the tympanic bone (TYB) protruded inferomedially near the tympanosquamosal fissure, and it sometimes continued to a cartilaginous SML (n = 3). The temporal bone squamosa or petrosa provided a similar bony process approaching the SML. The middle meningeal artery often ran between the sphenoid and petrosa. CONCLUSIONS: Most of the specimens (n = 15) exhibited a sequential change from a cartilaginous SML as a continuation of the MC remnant to the ligament after the disappearance of the cartilage. The degenerating MC appeared to cause transformation from the AP-goniale complex and/or TYB to "another ligament" that replaced the usual SML at the upper part. Near the MC remnant, a similar transformation was also suggested on the squamosa or petrosa. The sphenoid spine appeared to originate often from the sphenoid ala major but sometimes from the TYB.
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Ligamentos Articulares , Articulação Temporomandibular , Humanos , Cartilagem , Feto , Osso Temporal , MandíbulaRESUMO
At the angle of the mouth, spoke-like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near-term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near-term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM-PM, LAOM-DAOM, zygomaticus major (ZMM)-orbicularis oris (OOM), buccinator (BM)-LAOM, and BM-PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site.
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The human calcaneus is robust and provides a prominent heel for effective bipedal locomotion, although the adjacent talus has no muscle attachments. However, there is incomplete information about the morphological changes in these prominent bones during embryo development. We examined serial histological sections of 23 human embryos and early-term fetuses (approximately 5-10 weeks' gestational age [GA]). At a GA of 5 weeks, the precartilage talus was parallel to and on the medial side of the calcaneus, which had a prolate spheroid shape and consisted of three masses. At a GA of 6 weeks, the cartilaginous talus extended along the proximodistal axis, and the tuber calcanei became long and bulky, with a small sustentaculum talus at the "distal" side. At a GA of 6 to 8 weeks, the sustentaculum had a medial extension below the talus so that the talus "rode over" the calcaneus. In contrast, the talus had a more complex shape, depending on the growth of adjacent bones. At a GA of 9 to 10 weeks, the talus was above the calcaneus, but the medial part still faced the plantar subcutaneous tissue because of the relatively small sustentaculum. Therefore, the final morphology appeared after an additional several weeks. Muscle activity seemed to facilitate growth of the tuber calcanei, but growth of the other parts of calcaneus, including the sustentaculum, seemed to depend on active proliferation at the different sites of cartilage. Multiple tendons and ligaments seemed to fix the talus so that it remained close to the calcaneus.
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Calcâneo , Tálus , Humanos , Calcâneo/embriologia , Calcâneo/anatomia & histologia , Tálus/embriologia , Tálus/anatomia & histologia , Feto/anatomia & histologia , Feminino , Idade Gestacional , Tornozelo/anatomia & histologia , Tornozelo/embriologiaRESUMO
Wolves, akin to their fellow canids, extensively employ chemical signals for various aspects of communication, including territory maintenance, reproductive synchronisation and social hierarchy signalling. Pheromone-mediated chemical communication operates unconsciously among individuals, serving as an innate sensory modality that regulates both their physiology and behaviour. Despite its crucial role in the life of the wolf, there is a lacuna in comprehensive research on the neuroanatomical and physiological underpinnings of chemical communication within this species. This study investigates the vomeronasal system (VNS) of the Iberian wolf, simultaneously probing potential alterations brought about by dog domestication. Our findings demonstrate the presence of a fully functional VNS, vital for pheromone-mediated communication, in the Iberian wolf. While macroscopic similarities between the VNS of the wolf and the domestic dog are discernible, notable microscopic differences emerge. These distinctions include the presence of neuronal clusters associated with the sensory epithelium of the vomeronasal organ (VNO) and a heightened degree of differentiation of the accessory olfactory bulb (AOB). Immunohistochemical analyses reveal the expression of the two primary families of vomeronasal receptors (V1R and V2R) within the VNO. However, only the V1R family is expressed in the AOB. These findings not only yield profound insights into the VNS of the wolf but also hint at how domestication might have altered neural configurations that underpin species-specific behaviours. This understanding holds implications for the development of innovative strategies, such as the application of semiochemicals for wolf population management, aligning with contemporary conservation goals.
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Órgão Vomeronasal , Lobos , Animais , Órgão Vomeronasal/fisiologia , Lobos/fisiologia , Masculino , Feromônios/metabolismo , Feminino , Bulbo Olfatório/fisiologia , Bulbo Olfatório/anatomia & histologia , Cães , Imuno-HistoquímicaRESUMO
Topological corner states have been used to develop topologically robust Fano-resonant systems immune to structural perturbations while preserving the ultra-sensitive profiles under external factors. In this work, we have extended the possibility of obtaining Fano-resonant systems by introducing type-II and type-III corner states with a large modal surface to this class of resonance. Through photonic lattices with low symmetry, such as C2, it is easy to obtain type-II and type-III corner states due to the tailoring of long-range interactions. Subsequently, one can combine topological cavities of type-II and type-III corner modes with topological waveguides obtained from a first-order topological insulating phase. Our results may pave the way to generate devices suitable for creating non-classical light applicable in quantum computing and ultra-sensitive sensors employing large-area topological states.
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BACKGROUND: KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions. METHODS: Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines. Colony formation assays and Western blot analysis were also performed. RNA isolation from tumors of KRAS-mutant NSCLC patients was performed and KRAS and MET mRNA expression was determined by real-time RT-qPCR. In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model. RESULTS: Our research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Moreover, in a xenograft mouse model, combination of omeprazole plus tepotinib caused tumor growth regression. We observed that the combination of these two drugs downregulates phosphorylation of the glycolytic enzyme enolase 1 (ENO1) and the low-density lipoprotein receptor-related protein (LRP) 5/6 in the H358 KRAS G12C cell line, but not in the H358 sotorasib resistant, indicating that the effect of the combination could be independent of ENO1. In addition, we examined the probability of recurrence-free survival and overall survival in 40 early lung adenocarcinoma patients with KRAS G12C mutation stratified by KRAS and MET mRNA levels. Significant differences were observed in recurrence-free survival according to high levels of KRAS mRNA expression. Hazard ratio (HR) of recurrence-free survival was 7.291 (p = 0.014) for high levels of KRAS mRNA expression and 3.742 (p = 0.052) for high MET mRNA expression. CONCLUSIONS: We posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mutação , Omeprazol , Proteínas Proto-Oncogênicas c-met , Proteínas Proto-Oncogênicas p21(ras) , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Linhagem Celular Tumoral , Animais , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Camundongos , Piridinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Pirimidinonas/farmacologia , Pirimidinonas/uso terapêutico , Feminino , Triazinas/farmacologia , Triazinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Piperazinas , Piperidinas , Piridazinas , PiridonasRESUMO
The aim of the study was to analyze the differences in suffering stressful life events (SLE) among women experiencing homelessness who had or had not been in prostitution. Data were collected from a sample of 135 women experiencing homelessness in Madrid. A total of 81% of the women interviewed had never been in prostitution, while 19% had been in prostitution at some point in their lives. Participants were recruited from shelters, drop-in centers, and public spaces. The information was collected using a structured interview. The results showed that women experiencing homelessness who had been in prostitution suffered a greater number of SLE, both in childhood and adolescence and throughout life. The interviewed who had been in prostitution were between two and nine times more likely to have experienced during their childhood and adolescence violence in their family, as well as to have run away from home, experienced abuse, attempted suicide, and used drugs excessively. Furthermore, during their lifetime, the interviewed who had been in prostitution were between two and four times more likely to suffer from serious physical and mental health issues, excessive alcohol consumption, intimate partner violence, physical violence from others, suicide attempts, police reporting, and unwanted pregnancies. Additionally, they were four to six times more likely to have been sexually assaulted or convicted/imprisoned for a crime, seven times more likely to have been arrested, and a striking 32 times more likely to have used drugs excessively.
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Candida species are now considered global threats by the CDC and WHO. Candida auris specifically is on the critical pathogen threat list along with Candida albicans. In addition, it is not uncommon to find Candida spp. in a mixed culture with bacterial organisms, especially Staphylococcus aureus producing polymicrobial infections. To eradicate these organisms from the environment and from patient surfaces, surface agents such as chlorhexidine (CHD) and Puracyn are used. Biofilm disrupters (BDs) are novel agents with a broad spectrum of antimicrobial activity and have been used in the management of chronic wounds and to sterilise environmental surfaces for the past several years. The goal of this study was to evaluate BDs (BlastX, Torrent, NSSD) and CHD against Candida spp. and S. aureus using zone of inhibition assays, biofilm and time-kill assays. All BDs and CHD inhibited C. auris growth effectively in a concentration-dependent manner. Additionally, CHD and the BDs showed excellent antimicrobial activity within polymicrobial biofilms. A comparative analysis of the BDs and CHD against C. auris and C. albicans using biofilm kill-curves showed at least 99.999% killing. All three BDs and CHD have excellent activity against different Candida species, including C. auris. However, one isolate of C. auris in a polymicrobial biofilm assay showed resistance/tolerance to CHD, but not to the BDs. The fungicidal activity of these novel agents will be valuable in eradicating surface colonisation of Candida spp, especially C. auris from colonised environmental surfaces and from wounds in colonised patients.
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Anti-Infecciosos , Candida auris , Humanos , Staphylococcus aureus , Candida , Candida albicans , Biofilmes , Clorexidina/farmacologia , Antifúngicos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Testicular torsion is a medical emergency that requires an immediate and multidisciplinary approach from emergency, surgical, and radiological services. In this article, we discuss the current knowledge and growing value of ultrasound (US) for intravaginal testicular torsion diagnosis and our experience with manual testicular detorsion with US assistance. Testicular torsion requires prompt and accurate diagnosis and quick therapeutic action. Technological advances in US equipment and knowledge of this pathology place the radiologist in an excellent position for its diagnosis and management. During the same medical procedure, the radiologist can both confirm the intravaginal testicular torsion and attempt manual testicular detorsion. US-assisted manual testicular detorsion is a non-invasive, simple, quick, safe, and effective manoeuvre that can rapidly restore testicular blood flow, maximising testicular salvage, relieving the patient's symptoms, and facilitating surgery.
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Thermal simulations have become increasingly popular in assessing energy efficiency and predicting thermal behaviors in various structures. Calibration of these simulations is essential for accurate predictions. A crucial aspect of this calibration involves investigating the influence of meteorological variables. This study aims to explore the impact of meteorological variables on thermal simulations, particularly focusing on ships. Using TRNSYS (TRaNsient System Simulation) software (v17), renowned for its capability to model complex energy systems within buildings, the significance of incorporating meteorological data into thermal simulations was analyzed. The investigation centered on a patrol vessel stationed in a port in Galicia, northwest Spain. To ensure accuracy, we not only utilized the vessel's dimensions but also conducted in situ temperature measurements onboard. Furthermore, a dedicated weather station was installed to capture real-time meteorological data. Data from multiple sources, including Meteonorm and MeteoGalicia, were collected for comparative analysis. By juxtaposing simulations based on meteorological variables against those relying solely on in situ measurements, we sought to discern the relative merits of each approach in enhancing the fidelity of thermal simulations.
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Barathronus is a genus of blind cusk eels comprising 11 valid species. In this paper, we report the second specimen ever documented of Barathronus roulei (Bythitidae) obtained from the Porcupine Bank by R.V. Vizconde de Eza using a bottom trawl at a depth of 1349 m. Morphological description and illustrations, including a radiograph, are provided. In addition, three new sequences corresponding to three different genes, cytochrome c oxidase subunit I (COI)-DNA barcoding, 16S ribosomal RNA (16S), and recombination activating protein 1 (RAG1), have been added to the molecular repositories, representing the first sequences for the species.
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BACKGROUND: There is no information about muscle growth in eyelids with infrequent blinking in fetuses. METHODS: To examine the muscle and nerve morphology, we morphometrically and immunohistochemically examined sagittal sections of unilateral upper eyelids obtained from 21 term fetuses (approximately 30-42 weeks of gestation) and, for the comparison, those from 10 midterm fetuses (12-15 weeks). RESULTS: The approximation margin of the upper eyelid always corresponded to the entire free margin in midterm fetuses, whereas it was often (18/21) restricted in the posterior part in term fetuses. Thus, in the latter, the thickness at the approximation site to the lower lid often ranged from 0.8 to 1.6 mm and corresponded to 18-56% of the nearly maximum thickness of the lid. In the lower part of the upper eyelid, a layer of the orbicularis oculi muscles often (14/21) provided posterior flexion at 90-120° to extend posteriorly. Nerve fibers running along the mediolateral axis were rich along the approximation surface at term, but they might not be reported in the upper eyelid of adults. CONCLUSION: Being different from adult morphologies, the term eyelid was much thicker than the approximation surface and it carried a flexed muscle layer and transversely-running nerve. The infrequent blinking in fetuses seemed to provide a specific condition for the muscle-nerve growth. Plastic and pediatric surgeons should pay attention to a fact that infants' upper eyelid was unlikely to be a mini-version of the adult morphology.
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Pálpebras , Corrida , Adulto , Criança , Humanos , Pálpebras/anatomia & histologia , Piscadela , Músculos Faciais/inervação , Feto , Músculos OculomotoresRESUMO
BACKGROUND: There is currently no information on positional changes in the brachial nerve plexus during prenatal growth. The subclavian-axillary artery passing through the medianus nerve ansa is considered a good landmark for evaluating the height of the plexus. MATERIALS AND METHODS: We used histologic sections from 9 embryos and 17 fetuses (approximately 6-15 weeks of gestational age) to identify the height of the ansa by referring to the level of the rib and the glenohumeral joint. RESULTS: The nerve ansa was usually (23 plexuses) observed at the level of the first and/or second ribs. However, it was sometimes observed above the first rib, at a distance equal to or more than an intercostal width (7 plexuses). In the latter group, the ansa was usually located below the glenohumeral joint. Thus, the joint was located higher than the first rib, although the upper extremities were in the anatomic position for all specimens. The left-right difference in the height of the plexus corresponded to or was less than the width of the first intercostal space. Despite the synchronized growth between the thorax and shoulder girdle, the brachial plexus showed a considerable variation in comparative height; the range corresponded to twice of an intercostal width. Whether the nerve plexus is located high or low is determined at an early developmental stage and is maintained during the later growth stages. CONCLUSION: The high-positioned plexus might cause nerve injury at delivery, followed by a glenohumeral joint deformity because of the fragility without fixation in the thorax.
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Neuropatias do Plexo Braquial , Plexo Braquial , Parede Torácica , Humanos , Ombro , Plexo Braquial/lesões , Extremidade Superior , FetoRESUMO
PURPOSE: Little information is known about the mentalis nerve course from the lower lip approximation margin (free margin) to the upper lip. Likewise, no difference in nerve distribution has been observed between the cutaneous and mucosal parts of the lip. Therefore, this study reexamined mentalis nerve morphology. METHODS: For macroscopic observations, three fresh cadavers were dissected (one male and two females; aged 78-93). We also evaluated histological sections obtained from five donated elderly cadavers (two males and three females, aged 82-96 years) and 15 human fetuses (11-40 weeks or crown-rump length 80-372 mm). Immunohistochemical analysis for S100 protein and tyrosine hydroxylase was performed. RESULTS: In both fetuses and adult cadavers, one to three nerve branches ran upward in the submucosal tissue from the mental foramen. Near the free margin of the lip, some branches passed through the orbicularis oris muscle layer toward the lip skin, whereas others followed a reversed J-shaped course along the free margin. Nerve twigs ran in parallel beneath the mucosa, whereas wavy nerve twigs attached to the basal lamina of the lip epidermis. The difference in nerve endings abruptly occurred at the skin-mucosal junction. Tyrosine hydroxylase-positive sympathetic nerve twigs surrounded arteries and formed a branch composed of S100-negative unmyelinated fibers. CONCLUSION: The lower lip skin was innervated by a perforating branch passing through the orbicularis oris muscle, that was different from the lip mucosa. A sudden change in the nerve ending configuration at the mucocutaneous junction seemed to develop postnatally.
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Cadáver , Feto , Lábio , Humanos , Feminino , Lábio/inervação , Masculino , Idoso de 80 Anos ou mais , Idoso , Proteínas S100/análise , Proteínas S100/metabolismo , Tirosina 3-Mono-Oxigenase/análise , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
BACKGROUND: The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essential for optimal productivity and sustainability. Recently, Council on Dairy Cattle Breeding (CDCB) and USDA have developed new evaluations of heifer health and fertility traits. However, the genetic basis of these traits has yet to be thoroughly studied. RESULTS: Leveraging the extensive U.S dairy genomic database maintained at CDCB, we conducted large-scale GWAS analyses of two heifer traits, livability and early first calving. Despite the large sample size, we found no major QTL for heifer livability. However, we identified a major QTL in the bovine MHC region associated with early first calving. Our GO analysis based on nearby genes detected 91 significant GO terms with a large proportion related to the immune system. This QTL in the MHC region was also confirmed in the analysis of 27 K bull with imputed sequence variants. Since these traits have few major QTL, we evaluated the genome-wide distribution of GWAS signals across different functional genomics categories. For heifer livability, we observed significant enrichment in promotor and enhancer-related regions. For early calving, we found more associations in active TSS, active Elements, and Insulator. We also identified significant enrichment of CDS and conserved variants in the GWAS results of both traits. By linking GWAS results and transcriptome data from the CattleGTEx project via TWAS, we detected four and 23 significant gene-trait association pairs for heifer livability and early calving, respectively. Interestingly, we discovered six genes for early calving in the Bovine MHC region, including two genes in lymph node tissue and one gene each in blood, adipose, hypothalamus, and leukocyte. CONCLUSION: Our large-scale GWAS analyses of two heifer traits identified a major QTL in the bovine MHC region for early first calving. Additional functional enrichment and TWAS analyses confirmed the MHC QTL with relevant biological evidence. Our results revealed the complex genetic basis of heifer health and fertility traits and indicated a potential connection between the immune system and reproduction in cattle.