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Osseous involvement by diffuse large B-cell lymphoma (DLBCL-bone) is a heterogeneous disease. There is limited data regarding response assessment by positron emission tomography with fluorodeoxyglucose, which may demonstrate residual avidity despite a complete response. We analyzed clinical data of patients with newly diagnosed DLBCL and identified all cases with DLBCL-bone. End of treatment scans were reviewed by two independent experts classifying osseous lesions into Deauville (DV) ≤3; DV ≥4, or reactive uptake in the bone marrow (M), site of fracture (F) or surgery (S). We compared outcomes of DLBCL-bone to other extranodal sites (EN) matched on International Prognotic Index features and regimen. Of 1,860 patients with DLBCL (bone 16%; EN 45%; nodal 39%), 41% had localized disease and 59% advanced. Only 9% (n=27) of patients with initial bone involvement had residual fluorodeoxyglucose avidity at the osseous site. In half of these cases, the uptake was attributed to F/S/M, and of the remaining 13, only two were truly refractory (both with persistent disease at other sites). Overall survival and progression-free survival (PFS) were found to be similar for early- stage nodal DLBCL and DLBCL-bone, but inferior in EN-DLBCL. Advanced-stage disease involving the bone had a similar 5-year PFS to nodal disease and EN-DLBCL. After matching for International Prognotic Index and treatment regiments, PFS between bone and other EN sites was similar. Osseous involvement in DLBCL does not portend a worse prognosis. End of treatment DV ≥4 can be expected in 5-10% of cases, but in the absence of other signs of refractory disease, may be followed expectantly.
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Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Fluordesoxiglucose F18/uso terapêutico , Tomografia por Emissão de Pósitrons , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia , Estudos RetrospectivosRESUMO
Viral promoters can be used to drive heterologous gene expression in transgenic plants. As part of our quest to look for new promoters, we have explored, for the first time, the promoters of okra enation leaf curl virus (OELCuV), a begomovirus infecting okra (Abelmoschus esculentus). The Rep and CP promoters of OELCuV fused with the gfp reporter gene, were expressed transiently in the natural host okra and the laboratory host cotton and Nicotiana benthamiana. The expression levels of the promoters were quantified through confocal laser scanning microscopy and GFP assay in N. benthamiana and okra. The results indicated that the Rep promoter was more active than the CP promoter, whose activity was similar to that of CaMV 35S promoter. Additionally, the Rep and CP promoters showed increase of expression, probably due to transactivation, when assayed following inoculation of OELCuV and betasatellite DNAs in cotton plants. A moderate increase in promoter activity in N. benthamiana was also seen, when assayed following the inoculation of the heterologous begomovirus Sri Lankan cassava mosaic virus.
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Abelmoschus , Begomovirus , Gossypium , Nicotiana , Regiões Promotoras Genéticas , Nicotiana/virologia , Nicotiana/genética , Begomovirus/genética , Abelmoschus/virologia , Abelmoschus/genética , Gossypium/virologia , Gossypium/genética , Plantas Geneticamente Modificadas/virologia , Doenças das Plantas/virologia , Proteínas de Fluorescência Verde/genética , Genes Reporter , Expressão GênicaRESUMO
BACKGROUND: African American men are much more likely than Caucasian men to be diagnosed with and to die of prostate cancer. Genetic differences likely play a role. The cBioPortal database reveals that African American men with prostate cancer have higher rates of CDK12 somatic mutations compared to Caucasian men. However, this does not account for prior prostate cancer treatments, which are particularly important in the castrate-resistant setting. We aimed to compare somatic mutations based on circulating tumor DNA (ctDNA) in metastatic castration-resistant prostate cancer (mCRPC) between African American and Caucasian men after exposure to abiraterone and/or enzalutamide. METHODS: This single-institution retrospective study characterizes the somatic mutations detected on ctDNA for African American and Caucasian men with mCRPC who had progressed after abiraterone and/or enzalutamide from 2015 through 2022. We evaluated the gene mutations and types of mutations in this mCRPC cohort. RESULTS: There were 50 African American and 200 Caucasian men with CRPC with available ctDNA data. African American men were younger at the time of diagnosis (p = 0.008) and development of castration resistance (p = 0.006). African American men were more likely than Caucasian men to have pathogenic/likely pathogenic (P/LP) mutations in CDK12 (12% vs. 1.5%; p = 0.003) and copy number amplifications and P/LP mutations in KIT (8.0% vs. 1.5%; p = 0.031). African American men were also significantly more likely to have frameshift mutations (28% vs. 14%; p = 0.035). CONCLUSIONS: Compared to Caucasian men, African American men with mCRPC after exposure to abiraterone and/or enzalutamide had a higher incidence of somatic CDK12 P/LP mutations and KIT amplifications and P/LP mutations based on ctDNA. African American men also had more frameshift mutations. We hypothesize that these findings have potential implications for tumor immunogenicity.
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Antineoplásicos , Negro ou Afro-Americano , DNA Tumoral Circulante , Neoplasias de Próstata Resistentes à Castração , Brancos , Humanos , Masculino , Antineoplásicos/uso terapêutico , Negro ou Afro-Americano/genética , DNA Tumoral Circulante/genética , Mutação/genética , Nitrilas , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/etnologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/secundário , Estudos Retrospectivos , Resultado do Tratamento , Brancos/genéticaRESUMO
The emergence of Plasmodium falciparum resistance raises an urgent need to find new antimalarial drugs. Here, we report the rational repurposing of the anti-hepatitis C virus drug, alisporivir, a nonimmunosuppressive analog of cyclosporin A, against artemisinin-resistant strains of P. falciparum. In silico docking studies and molecular dynamic simulation predicted strong interaction of alisporivir with PfCyclophilin 19B, confirmed through biophysical assays with a Kd value of 354.3 nM. Alisporivir showed potent antimalarial activity against chloroquine-resistant (PfRKL-9 with resistance index [Ri] 2.14 ± 0.23) and artemisinin-resistant (PfKelch13R539T with Ri 1.15 ± 0.04) parasites. The Ri is defined as the ratio between the IC50 values of the resistant line to that of the sensitive line. To further investigate the mechanism involved, we analyzed the expression level of PfCyclophilin 19B in artemisinin-resistant P. falciparum (PfKelch13R539T). Semiquantitative real-time transcript, Western blot, and immunofluorescence analyses confirmed the overexpression of PfCyclophilin 19B in PfKelch13R539T. A 50% inhibitory concentration in the nanomolar range, together with the targeting of PfCyclophilin 19B, suggests that alisporivir can be used in combination with artemisinin. Since artemisinin resistance slows the clearance of ring-stage parasites, we performed a ring survival assay on artemisinin-resistant strain PfKelch13R539T and found significant decrease in parasite survival with alisporivir. Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity in vivo. Altogether, with the rational target-based Repurposing of alisporivir against malaria, our results support the hypothesis that targeting resistance mechanisms is a viable approach toward dealing with drug-resistant parasite.
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Antimaláricos , Artemisininas , Malária Falciparum , Malária , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Reposicionamento de Medicamentos , Resistência a Medicamentos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparumRESUMO
Viruses belonging to the family Geminiviridae infect plants and are responsible for a number of diseases of crops in the tropical and sub-tropical regions of the World. The innate immune response of the plant assists in its defense against such viral pathogens by the recognition of pathogen/microbe-associated molecular patterns through pattern-recognition receptors. Phytohormone signalling pathways play a vital role in plant defense responses against these devastating viruses. Geminiviruses, however, have developed counter-defense strategies that prevail over the above defense pathways. The proteins encoded by geminiviruses act as suppressors of plant immunity by interacting with the signalling components of several hormones. In this review we focus on the molecular interplay of phytohormone pathways and geminiviral infection and try to find interesting parallels with similar mechanisms known in other plant-infecting viruses and strengthen the argument that this interplay is necessary for disease development.
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Geminiviridae , Doenças das Plantas , Geminiviridae/genética , Imunidade Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas , Receptores de Reconhecimento de PadrãoRESUMO
OBJECTIVE: Congenital pulmonary airway malformation (CPAM) is a rare developmental lung disease. The aim of this study is to analyze the histomorphological spectrum of CPAM in a series of 15 cases. MATERIALS AND METHODS: A retrospective descriptive study of 15 cases of CPAM was carried out from 2013 to 2018 in our hospital, and cases were classified based on the Stocker's classification. RESULTS: The age ranged from 4 days to 9 years (66.6% were infants). The left lung was most commonly involved (66.6%). The most common lobe was the left upper lobe (60%), followed by right lower lobe (20%). Grossly, cysts measured 0.2-5 cm, filled with mainly serous fluid with few having hemorrhagic and brownish mucoid secretions. On microscopy, single to multiple noncommunicating cysts of size 0.2-5 cm were seen, lined by ciliated columnar epithelium (60%), pseudostratified ciliated columnar epithelium (26.7%), mucin-secreting columnar epithelium (6.7%), and flattened epithelium (6.7%). Few cases showed smooth muscle (20%) and cartilage (13.3%) in the cyst wall. Chronic inflammation (73.3%) with dense histiocytic infiltrate (13.3%) was also seen. Emphysematous changes were also observed (13.3%). Cytomegalovirus inclusions (6.7%), zygomycete fungus (6.7%), and red hepatization (6.7%) were observed. The most common type was type II (60%), followed by type I (33.3%) and type IV (6.7%). CONCLUSION: Type II was the most common variant in this study. A careful observation should be done to look for fungal hyphae or viral inclusions.
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Stress is known to cause contrasting patterns of morphological and physiological plasticity in the hippocampus and amygdala. An obligatory cellular process underlying such neural changes is de novo translation and alterations in protein expression. Yet the nature of the translational response to stress in neurons remains largely unexplored. Even less is known about how glia are affected. Using a click-chemistry-based method to label the de novo proteome in live brain slices, we monitored translation in neurons and astrocytes of the basolateral amygdala (BLA) and dorsal hippocampal area CA3 (dCA3) in rats at different time-points after a single 2-hr exposure to immobilization stress. We observed enhancements in neuronal translation in both brain regions 1 hour after stress. This initial increase persisted in the BLA up to 10 days afterwards. In contrast, dCA3 neuronal translation gradually decreased to below control levels 10 days later. Translation profiles of dCA3 astrocytes followed timelines similar to neurons, but in BLA astrocytes translation peaked 1 day later and remained elevated 10 days later. Together our results demonstrate that stress causes an immediate upregulation of protein synthesis in both amygdalar and hippocampal neurons and astrocytes. However, these two areas eventually exhibit opposite temporal profiles of protein expression well after the end of stress. These findings identify new metrics of stress-induced plasticity at the level of cell-type specific proteomic landscape that may provide important insights into the molecular basis of the divergent temporal effects of stress across brain regions and biological scales.
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Complexo Nuclear Basolateral da Amígdala/fisiologia , Região CA3 Hipocampal/fisiologia , Plasticidade Neuronal/fisiologia , Estresse Psicológico/metabolismo , Animais , Astrócitos/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiopatologia , Região CA3 Hipocampal/fisiopatologia , Masculino , Neurônios/fisiologia , Biossíntese de Proteínas/fisiologia , Ratos , Ratos Wistar , Restrição Física , Estresse Psicológico/fisiopatologiaRESUMO
Sickle cell disease (SCD) is a genetic disorder associated with hemolytic anemia, end-organ damage, reduced survival, and pain. One of the unique features of SCD is recurrent and unpredictable episodes of acute pain due to vasoocclusive crisis requiring hospitalization. Additionally, patients with SCD often develop chronic persistent pain. Currently, sickle cell pain is treated with opioids, an approach limited by adverse effects. Because pain can start at infancy and continue throughout life, preventing the genesis of pain may be relatively better than treating the pain once it has been evoked. Therefore, we provide insights into the cellular and molecular mechanisms of sickle cell pain that contribute to the activation of the somatosensory system in the peripheral and central nervous systems. These mechanisms include mast cell activation and neurogenic inflammation, peripheral nociceptor sensitization, maladaptation of spinal signals, central sensitization, and modulation of neural circuits in the brain. In this review, we describe potential preventive/therapeutic targets and their targeting with novel pharmacologic and/or integrative approaches to ameliorate sickle cell pain.
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Dor Aguda/prevenção & controle , Analgésicos/uso terapêutico , Anemia Falciforme/tratamento farmacológico , Dor Crônica/prevenção & controle , Manejo da Dor/métodos , Dor Aguda/etiologia , Dor Aguda/metabolismo , Dor Aguda/fisiopatologia , Analgésicos/efeitos adversos , Anemia Falciforme/complicações , Anemia Falciforme/metabolismo , Anemia Falciforme/fisiopatologia , Animais , Dor Crônica/etiologia , Dor Crônica/metabolismo , Dor Crônica/fisiopatologia , Modelos Animais de Doenças , Humanos , Terapia de Alvo Molecular , Manejo da Dor/efeitos adversos , Percepção da Dor , Limiar da Dor , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
Rotavirus G1 strains are the predominant cause of diarrhoea in children. Universally common rotavirus vaccines (Rotarix and RotaTeq) include G1 as the immunological component. India has recently introduced rotavirus vaccine in Universal Immunization Programme. Therefore, in the present study, VP7 gene of rotavirus G1 strains circulating in Himachal Pradesh, India is analysed to study their phylogenetic characteristics, and further comparative analysis was performed for assessment of their divergence from the vaccine strains. The rotavirus strains (JU-SOL-5, JU-SOL-58, JU-SOL-77, JU-SOL-173 and JU-SHI-14) analysed in the study were isolated from the faeces of diarrhoeic children during active surveillance for rotaviruses. The Himachal strains clustered together in G1-Lineage 1 in the phylogenetic analysis. All five isolates showed 96.4-98.8 % similarity with the other G1-Lineage 1 strains at amino acid level. However, none of them clustered in the pre-defined sublineages within lineage 1. Interestingly, all the strains were distantly related to the vaccine strains having 93.9-94.5 and 91.9-92.6 % similarities at amino acid level with Rotarix and RotaTeq strains, respectively. The comparative sequence and structural analysis of the Himachal strains with vaccine strains revealed differences in amino acids in epitope region of the protein especially at the antibody neutralization sites. The study highlights variations between the G1 strains from Himachal Pradesh, India and Rotarix and RotaTeq vaccine strains. These differences might have an impact on the neutralization efficiency of vaccine and subsequently on vaccine efficacy. This underscores further investigation to study intragenotype antigenic variability and also impact of viral evolution on vaccine effectiveness.
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Antígenos Virais/genética , Proteínas do Capsídeo/genética , Infecções por Rotavirus/virologia , Rotavirus/genética , Sequência de Aminoácidos , Antígenos Virais/química , Antígenos Virais/metabolismo , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Diarreia/epidemiologia , Diarreia/virologia , Humanos , Índia , Dados de Sequência Molecular , Filogenia , Rotavirus/classificação , Rotavirus/isolamento & purificação , Rotavirus/metabolismo , Infecções por Rotavirus/epidemiologia , Alinhamento de SequênciaRESUMO
Within afrotherians, sirenians are unusual due to their aquatic lifestyle, large body size and relatively large lissencephalic brain. However, little is known about the neuron type distributions of the cerebral cortex in sirenians within the context of other afrotherians and aquatic mammals. The present study investigated two cortical regions, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2), in the presumptive primary somatosensory cortex (S1) in Florida manatees (Trichechus manatus latirostris) to characterize cyto- and chemoarchitecture. The mean neuron density for both cortical regions was 35,617 neurons/mm(3) and fell within the 95% prediction intervals relative to brain mass based on a reference group of afrotherians and xenarthrans. Densities of inhibitory interneuron subtypes labeled against calcium-binding proteins and neuropeptide Y were relatively low compared to afrotherians and xenarthrans and also formed a small percentage of the overall population of inhibitory interneurons as revealed by GAD67 immunoreactivity. Nonphosphorylated neurofilament protein-immunoreactive (NPNFP-ir) neurons comprised a mean of 60% of neurons in layer V across DL1 and CL2. DL1 contained a higher percentage of NPNFP-ir neurons than CL2, although CL2 had a higher variety of morphological types. The mean percentage of NPNFP-ir neurons in the two regions of the presumptive S1 were low compared to other afrotherians and xenarthrans but were within the 95% prediction intervals relative to brain mass, and their morphologies were comparable to those found in other afrotherians and xenarthrans. Although this specific pattern of neuron types and densities sets the manatee apart from other afrotherians and xenarthrans, the manatee isocortex does not appear to be explicitly adapted for an aquatic habitat. Many of the features that are shared between manatees and cetaceans are also shared with a diverse array of terrestrial mammals and likely represent highly conserved neural features. A comparative study across manatees and dugongs is necessary to determine whether these traits are specific to one or more of the manatee species, or can be generalized to all sirenians.
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Neurônios/citologia , Córtex Somatossensorial/citologia , Trichechus manatus/anatomia & histologia , Animais , Contagem de Células , Elefantes/anatomia & histologia , Feminino , Imuno-Histoquímica , Especificidade da Espécie , Xenarthra/anatomia & histologiaRESUMO
INTRODUCTION: Twin pregnancy with hydatidiform mole and coexistent live fetus is a rare condition with severe maternal and fetal complications such as preeclampsia, vaginal bleeding, persistent gestational trophoblastic tumor, and fetal death. CASE PRESENTATION: We report a case of a twin pregnancy with histopathologically proven hydatidiform mole and a coexistent live fetus in a 30-year-old Indian woman diagnosed by first trimester ultrasound. DISCUSSION: Our case emphasizes the role of ultrasound in diagnosing this condition in early pregnancy. A succinct overview of etiological mechanisms, possible complications, and clinical management is provided. CONCLUSION: Ultrasound is an effective diagnostic tool to diagnose hydatidiform mole with coexistent live fetus. Early diagnosis of this condition is important for risk stratification and facilitates an informed decision by the patient whether to terminate the pregnancy or to continue until full term with close monitoring after delivery.
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Mola Hidatiforme/diagnóstico por imagem , Neoplasias Uterinas/diagnóstico por imagem , Aborto Induzido , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Gravidez , Gravidez Múltipla , UltrassonografiaRESUMO
A 17-year-old male presented with acute onset right-sided facial swelling, trismus, pharyngitis, and sepsis. An initial CT abdomen and pelvis revealed multifocal bilateral nodular cavitary lung lesions. CT soft tissue neck with contrast demonstrated a parapharyngeal abscess and thrombophlebitis of the right internal jugular vein. The patient was subsequently diagnosed with Lemierre's syndrome. On the following day, the patient's neurological status markedly declined. Brain MRI/MRA/MRV showed right internal carotid artery narrowing, multiple areas of acute and subacute infarctions secondary to vasculitis, meningitis, venous sinus thrombosis, and intracerebral abscesses. Workup for primary causes of intracranial vasculitis was negative. Although commonly presented as venous disease, this case highlights a rare presentation of Lemierre's syndrome with arterial involvement and significant intracranial complications. Clinicians should consider vasculitis and central nervous system involvement as potential complications of Lemierre's syndrome rather than searching for separate aetiologies.
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A new conductive and transparent organohydrogel is developed with high stretchability, excellent mechanical, self-healing, antifreezing, and adhesive properties. A simple one-pot polymerization method is used to create polyacrylamide cross-linked through N,N'-methylenebis(acrylamide) (MBAA) and divinylbenzene (DVB). The dual chemical cross-linked gel network is complemented by several physical cross-links via hydrogen bonding and π-π interaction. Multiple chemical and physical cross-links are used to construct the gel network that allows toughness (171 kPa), low modulus (≈45 kPa), excellent stretchability (>1100%), and self-healing ability. The use of appropriate proportions of the water/glycerol binary solvent system ensures efficient environment tolerance (-20 to 40 °C). Phytic acid is used as a conductive filler that provides excellent conductivity and contributes to the physical cross-linking. Dopamine is incorporated in the gel matrix, which endows excellent adhesive property of the gel. The organohydrogel-based strain sensors are developed with state-independent properties, highly linear dependence, and excellent antifatigue performance (>100 cycles). Moreover, during the practical wearable sensing tests, human motions can be detected, including speaking, smiling, and joint movement. Additionally, the sensor is biocompatible, indicating the potential applications for the next generation of epidermal sensors.
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Acrilamida , Dopamina , Humanos , Condutividade Elétrica , Epiderme , Excipientes , HidrogéisRESUMO
OBJECTIVES: Multicystic dysplastic kidney (MCDK) is defined as the presence of multiple noncommunicating cysts of various sizes, detected sonographically, without evidence of functioning renal parenchyma on dimercaptosuccinic acid renal scan. It has an incidence of 1:4000 live births. They are more commonly diagnosed in boys, usually on the left side, but may also be bilateral. There is the presence of primitive ducts surrounded by fibromuscular connective tissue. These are because of the disturbed connection of the ureteric bud with renal blastema and abnormal division at the stage of metanephros, resulting in an abnormal metanephros differentiation. MATERIALS AND METHODS: Thirty cases of MCDK were included to study their histomorphology along with their clinical features. Cases were retrieved from the last seven years (2015-2021) from the Department of Pathology, Maulana Azad Medical College. RESULT: Age ranged from 10 days to 18 years. The cases were between 1 years and 5 years of age. Six out of 30 cases (20%) were infants with three of them being neonates. Twenty-one cases were males. All the cases had unilateral kidney involvement with the left kidney being involved in 20 out of 30 cases. Twenty-eight cases underwent nephrectomy in view of small contracted nonfunctional kidneys with one of them being horseshoe shaped. Five cases had associated hydronephrosis (two ipsilateral and three bilateral). One case had Hirshprung's disease, four had anorectal malformation, two had posterior urethral valves with vesicourethral reflux, one had duplex moiety, and one had undescended testes. On histopathological examination, all of them showed the presence of immature disorganized tubules surrounded by a collarette of immature mesenchymal stroma. One of the cases showed osteoid formation and four had areas of immature cartilage. Normal kidney parenchyma was seen at the periphery in four cases. CONCLUSION: This series has been presented to highlight the various histomorphological features of MCDK. MCDK can be managed conservatively in most of cases due to autoinvolution and, hence, needs to be differentiated from other close differentials like polycystic kidney disease, cystic nephroma, and cystic partially differentiated nephroblastoma in order to avoid unnecessary surgical intervention.
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Rim , Rim Displásico Multicístico , Centros de Atenção Terciária , Humanos , Rim Displásico Multicístico/patologia , Masculino , Feminino , Criança , Lactente , Adolescente , Pré-Escolar , Recém-Nascido , Rim/patologia , Rim/anormalidades , NefrectomiaRESUMO
The evolutionary history of canids and felids is marked by a deep time separation that has uniquely shaped their behavior and phenotype toward refined predatory abilities. The caudate nucleus is a subcortical brain structure associated with both motor control and cognitive, emotional, and executive functions. We used a combination of three-dimensional imaging, allometric scaling, and structural analyses to compare the size and shape characteristics of the caudate nucleus. The sample consisted of MRI scan data obtained from six canid species (Canis lupus lupus, Canis latrans, Chrysocyon brachyurus, Lycaon pictus, Vulpes vulpes, Vulpes zerda), two canid subspecies (Canis lupus familiaris, Canis lupus dingo), as well as three felids (Panthera tigris, Panthera uncia, Felis silvestris catus). Results revealed marked conservation in the scaling and shape attributes of the caudate nucleus across species, with only slight deviations. We hypothesize that observed differences in caudate nucleus size and structure for the domestic canids are reflective of enhanced cognitive and emotional pathways that possibly emerged during domestication.
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Canidae , Núcleo Caudado , Felidae , Imageamento por Ressonância Magnética , Animais , Núcleo Caudado/anatomia & histologia , Núcleo Caudado/diagnóstico por imagem , Felidae/anatomia & histologia , Felidae/fisiologia , Canidae/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Masculino , Comportamento Animal/fisiologia , Feminino , Especificidade da Espécie , Encéfalo/anatomia & histologiaRESUMO
The persistence of drug resistance poses a significant obstacle to the advancement of efficacious malaria treatments. The remarkable efficacy displayed by 1,2,3-triazole-based compounds against Plasmodium falciparum highlights the potential of triazole conjugates, with diverse pharmacologically active structures, as potential antimalarial agents. We aimed to synthesize 7-dichloroquinoline-triazole conjugates and their structure-activity relationship (SAR) derivatives to investigate their anti-plasmodial activity. Among them, QP11, featuring a m-NO2 substitution, demonstrated efficacy against both chloroquine-sensitive and -resistant parasite strains. QP11 selectively inhibited FP2, a cysteine protease involved in hemoglobin degradation, and showed synergistic effects when combined with chloroquine. Additionally, QP11 hindered hemoglobin degradation and hemozoin formation within the parasite. Metabolic stability studies indicated high stability of QP11, making it a promising antimalarial candidate. In vivo evaluation using a murine malaria model demonstrated QP11's efficacy in eradicating parasite growth without neurotoxicity, presenting it as a promising compound for novel antimalarial development.
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Antimaláricos , Malária , Animais , Camundongos , Antimaláricos/química , Piperazina/farmacologia , Triazóis/química , Cloroquina/farmacologia , Malária/tratamento farmacológico , Plasmodium falciparum , Hemoglobinas/metabolismo , Hemoglobinas/farmacologia , Hemoglobinas/uso terapêuticoRESUMO
Recognizing and treating reversible causes of lethargy and altered mental status is crucial for emergency department physicians. One such tool that can quickly help guide resuscitation and a patient's workup is a point-of-care glucose reading. This simple test is performed routinely; however, how much thought is given to the accuracy of these tests? What factors can alter these results? Here, we present a patient who was reported to be hyperglycemic in the field by emergency medical services (EMS) but was profoundly hypoglycemic during his workup in the emergency department. This case report highlights factors that can cause false hyper- and hypoglycemic readings on point-of-care glucose meters.
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A broad spectrum of spinal pathologies can affect the pediatric population. Ultrasound (US) is the primary modality for pediatric spine assessment due to its widespread availability, non-requirement of sedation, and absence of ionizing radiation. Supplementing this, MRI offers an in-depth exploration of these conditions, aiding in preoperative strategizing. In this review, we examine the clinical indications, methodologies, and protocols for US and MRI scans of the pediatric spine. Additionally, we illustrate normal pediatric spinal anatomy, highlighting several examples of normal variants that are often misinterpreted. Through a series of case-based illustrations, we offer a comprehensive overview of various pathological conditions such as tethered cord, spinal dysraphism, spinal lipoma, diastematomyelia, and dermal sinus tract, among others. Furthermore, we explore the correlation between US and MRI findings for these lesions, employing real-world cases to enhance our understanding of this topic.
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Allotetraploid cotton plants Gossypium hirsutum and Gossypium barbadense have been widely cultivated for their natural, renewable textile fibres. Even though ncRNAs in domesticated cotton species have been extensively studied, systematic identification and annotation of lncRNAs and miRNAs expressed in various tissues and developmental stages under various biological contexts are limited. This influences the comprehension of their functions and future research on these cotton species. Here, we report high confidence lncRNAs and miRNA collection from G. hirsutum accession and G. barbadense accession using large-scale RNA-seq and small RNA-seq datasets incorporated into a user-friendly database, CoNCRAtlas. This database provides a wide range and depth of lncRNA and miRNA annotation based on the systematic integration of extensive annotations such as expression patterns derived from transcriptome data analysis in thousands of samples, as well as multi-omics annotations. We assume this comprehensive resource will accelerate evolutionary and functional studies in ncRNAs and inform future breeding programs for cotton improvement. CoNCRAtlas is accessible at http://www.nipgr.ac.in/CoNCRAtlas/.
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A rare consequence of hysterectomy is vaginal vault dehiscence, which commonly occurs five to seven weeks after the procedure. Its frequency ranges from 0% to 7.5%. The incidence of delayed dehiscence is rare. The small bowel is the organ that prolapses most frequently, but other organs and multi-organ prolapses have also been documented. Due to potential catastrophes such as intestinal ischemia, blockage, and perforation, transvaginal protrusion of abdominal viscera is an emergency. A laparoscopic approach facilitates a thorough evaluation of the abdominal contents and provides assistance in challenging circumstances where the contents are not reducible.