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Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.
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Voo Espacial , Humanos , Voo Espacial/ética , AstronautasRESUMO
Human space exploration poses inherent risks to astronauts' health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA's GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.
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Envelhecimento , Biomarcadores , Fragilidade , Voo Espacial , Envelhecimento/genética , Animais , Camundongos , Humanos , Astronautas , Masculino , Ausência de Peso/efeitos adversos , Sarcopenia/metabolismoRESUMO
BACKGROUND: Breast cancer screening and surgical interventions are often underutilized in the Chinese community. For both Chinese American (CA) and native Chinese (NC) patients, screening rates are well below medical recommendations, which places these patients at risk for late diagnoses and larger tumors. There is also a notable reluctance to breast reconstruction after mastectomy. We investigated the role of sociodemographic and cultural barriers in breast treatment trends among Chinese breast cancer survivors. METHODS: A literature search for full-text articles published between 2011 and 2021 was performed using PubMed, The Web of Science, and Embase. The articles that were selected contained information regarding Chinese individuals in the United States or China who had undergone breast cancer screening or diagnosis of breast cancer and received treatment with or without reconstructive surgery. RESULTS: Both patient populations exhibited screening rates that were significantly lower than national recommendations. Of the CA patients, 25% reported never receiving a mammogram, whereas 450 million NCs have been left unscreened despite efforts made by the Chinese government. Misinformation, cultural beliefs, and fear significantly contributed to diminished breast health care among CA and NC women. Fear of recurrence, breast value, community influence, and limited health care resources were found to be the primary drivers of low breast reconstruction uptake. CONCLUSIONS: In both NC and CA women, there is a critical need for improved breast health information dissemination and overall quality of care. The findings summarized in this review can guide such efforts.
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Neoplasias da Mama , Mamoplastia , Feminino , Humanos , Asiático , Neoplasias da Mama/cirurgia , Neoplasias da Mama/prevenção & controle , Comunicação , Mastectomia , Estados Unidos , ChinaRESUMO
IMPORTANCE: Our study provides insights into the evolution of the coronavirus disease 2019 (COVID-19) pandemic in Malta, a highly connected and understudied country. We combined epidemiological and phylodynamic analyses to analyze trends in the number of new cases, deaths, tests, positivity rates, and evolutionary and dispersal patterns from August 2020 to January 2022. Our reconstructions inferred 173 independent severe acute respiratory syndrome coronavirus 2 introductions into Malta from various global regions. Our study demonstrates that characterizing epidemiological trends coupled with phylodynamic modeling can inform the implementation of public health interventions to help control COVID-19 transmission in the community.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Malta , Saúde Pública , Análise Espaço-Temporal , FilogeniaRESUMO
Across scar studies, there is a lack of dark-skinned individuals, who have a predisposition for keloid formation, altered pigmentation and poorer quality of life (QOL). There is a need for patients of colour to be included in scar scale development and validation. In this study, we evaluate the racial diversity of patients included in the validation of scar assessment scales. A systematic review was conducted for articles reporting on the validation of a scar assessment tool. Racial, ethnic and Fitzpatrick skin type (FST) data were extracted. Fifteen scar scale validation studies were included. Nine of the studies did not mention FST, race or ethnicity of the patients. Two of the studies that reported FST or race information only included White patients or included no FST V/VI patients: mapping assessment of scars (MAPS) and University of North Carolina '4P'. Only four studies included non-White patients or dark-skinned patients in the validation of their scar scale: the modified Vancouver Scar Scale (VSS), modified Patient and Observer Scar Assessment Scale (POSAS), acne QOL and SCAR-Q scales. The patients included in the modified VSS validation were 7% and 13% FST V/VI, 14% African in the modified POSAS and 4.5% FST V/VI in the SCAR-Q. We highlight the severe lack of diversity in scar scale validation, with only 4 out of 15 studies including dark-skinned patients. Given the susceptibility of darker-skinned individuals to have poorer scarring outcomes, it is critical to include patients of colour in the very assessment tools that determine their scar prognosis. Inclusion of patients of colour in scar scale development will improve scar assessment and clinical decision-making.
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Cicatriz , Qualidade de Vida , Humanos , Cicatriz/patologia , Pigmentação da Pele , Cicatrização , Pele/patologiaRESUMO
Background: Spinal cord stimulation (SCS) involves the utilization of an implantable neurostimulation device, stereotypically used in the treatment of patients with chronic neuropathic pain. While these devices have been shown to have significant clinical benefits, there have also been documented potential complications, including the risk of infection, fractured electrodes, electrode migration, and lack of symptom improvement. In addition, there has been minimal documentation on gastrointestinal (GI) side effects after SCS implantation. Case Description: A 42-year-old patient with chronic axial and radicular neuropathic pain in her back and left leg status post multiple lumbar surgeries underwent implantation of an open paddle lead in the T8-T9 region. After the procedure, the patient endorsed a 50% decrease in pain at the 6-week follow-up with no further concerns. However, at the 18 months follow-up, the patient endorsed severe constipation when the SCS was turned on, leading to subsequent evaluation by gastroenterology, motility studies, and a thorough bowel regimen. Symptoms persisted, and the patient ultimately opted for the removal of the SCS implant at 21 months after the initial surgery. Conclusion: While the exact mechanism behind the GI side effects endorsed in this patient is unknown, current literature postulates a variety of theories, including a SCS-induced parasympathetic blockade of the GI tract. Further, investigation is needed to determine the exact effects of SCS on the GI tract.
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Background: Spinal cord stimulation (SCS) consists of the implantation of neuromodulatory devices in the spinal cord to treat refractory neuropathic pain. Although SCS technology has been proven of immense clinical benefit, complications remain including refractory pain, infection risk, and electrode migration or displacement. Till date, there are minimal reports of allergic side effects following SCS implantation. Case Description: In the first case, a 36-year-old male with chronic axial and radicular neuropathic pain in underwent implantation of an open paddle lead and generator. Within 1-3 h of activating the SCS, he developed diffuse raised erythematous hives. Over time, the SCS had immense clinical benefit for his pain reduction; however, he continued to experience recurrent hives and various other allergic reactions including facial flushing and photosensitivity. Four years later, he ultimately opted to retain the device for its clinical pain benefits. In the second case, a 35-year-old female with acute, intractable bilateral occipital neuralgia and a past medical history of Type 1 Chiari Malformation status-post-posterior fossa decompression underwent implantation of an occipital nerve stimulator (ONS). At 1-month follow-up, she began to experience pruritus across the back of her head and along the subcutaneous course of the lead. At 8 months, she continued to experience persistent symptoms, ultimately opting for device removal. Conclusion: Although allergic reactions to implanted neurostimulation systems are rare, and mechanisms not completely understood, existing studies posit multiple theories surrounding the pathophysiology of allergic reactions to these devices, such as delayed hypersensitivity reactions or contact dermatitis. Further research is needed to elucidate the cutaneous and immunologic side effects of SCS and ONS devices.
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Capacitive micromachined ultrasonic transducers (CMUT) are MEMS-based transducers with advantages over conventional ultrasonic transducers, such as their small size, the ease of integration with semiconductor electronics, and batch fabrication. In this study, the effect of different membrane topologies on the displacement, resonant frequency, and output pressure of the CMUT membrane is investigated in the transmission mode in an air environment. A novel structural-support feature, the rocker stem, is introduced, where the membrane is weakly held to the substrate in order to minimize mechanical constraints. Four different CMUT topologies are designed and assessed to analyze the impacts of topological variations. A new CMUT array configuration is also designed to provide an approach for maximizing CMUT density. This study aims to contribute to efficient CMUT design and the determination of optimum structural parameters for portable applications in air.
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The coronavirus disease 2019 (COVID-19) Exposure Assessment Tool (CEAT) allows users to compare respiratory relative risk to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for various scenarios, providing understanding of how combinations of protective measures affect risk. CEAT incorporates mechanistic, stochastic, and epidemiological factors including the (i) emission rate of virus, (ii) viral aerosol degradation and removal, (iii) duration of activity/exposure, (iv) inhalation rates, (v) ventilation rates (indoors/outdoors), (vi) volume of indoor space, (vii) filtration, (viii) mask use and effectiveness, (ix) distance between people (taking into account both near-field and far-field effects of proximity), (x) group size, (xi) current infection rates by variant, (xii) prevalence of infection and immunity in the community, (xiii) vaccination rates, and (xiv) implementation of COVID-19 testing procedures. CEAT applied to published studies of COVID-19 transmission events demonstrates the model's accuracy. We also show how health and safety professionals at NASA Ames Research Center used CEAT to manage potential risks posed by SARS-CoV-2 exposures.
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The COVID-19 Exposure Assessment Tool (CEAT) allows users to compare respiratory relative risk to SARS-CoV-2 for various scenarios, providing understanding of how combinations of protective measures affect exposure, dose, and risk. CEAT incorporates mechanistic, stochastic and epidemiological factors including the: 1) emission rate of virus, 2) viral aerosol degradation and removal, 3) duration of activity/exposure, 4) inhalation rates, 5) ventilation rates (indoors/outdoors), 6) volume of indoor space, 7) filtration, 8) mask use and effectiveness, 9) distance between people, 10) group size, 11) current infection rates by variant, 12) prevalence of infection and immunity in the community, 13) vaccination rates of the community, and 14) implementation of COVID-19 testing procedures. Demonstration of CEAT, from published studies of COVID-19 transmission events, shows the model accurately predicts transmission. We also show how health and safety professionals at NASA Ames Research Center used CEAT to manage potential risks posed by SARS-CoV-2 exposures. Given its accuracy and flexibility, the wide use of CEAT will have a long lasting beneficial impact in managing both the current COVID-19 pandemic as well as a variety of other scenarios.
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Tumor invasion and metastasis remain the leading causes of mortality for patients with cancer despite current treatment strategies. In some cancer types, recurrence is considered inevitable due to the lack of effective anti-metastatic therapies. Recent studies across many cancer types demonstrate a close relationship between cancer-initiating cells (CICs) and metastasis, as well as general cancer progression. First, this review describes CICs' contribution to cancer progression. Then we discuss our recent understanding of mechanisms through which CICs promote tumor invasion and metastasis by examining the role of CICs in each stage. Finally, we examine the current understanding of CICs' contribution to therapeutic resistance and recent developments in CIC-targeting drugs. We believe this understanding is key to advancing anti-CIC clinical therapeutics.
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Neoplasias , Células-Tronco Neoplásicas , Linhagem Celular Tumoral , Humanos , Neoplasias/patologia , Células-Tronco Neoplásicas/patologiaRESUMO
BACKGROUND: Routine outcome-based monitoring is required to assess the status of consumption of iodized salt as USI strategy. OBJECTIVE: To assess the extent of recent iodine intake among children from 6 to 15 years of age in the hilly terrain of northern states of India. METHODS: A school-based cross-sectional observational study among 227 children attending school was done for assessment of socio-demographic, dietary, salt consumption and urinary iodine concentration (UIC). RESULTS: Mean age of children was about 6 years and 87.7% were consuming salt of >30 and none with <15 ppm iodine content. Median UIC was 138.0 µg/L. Among those assessed, 37.9% had adequate level of UIC, whereas about 20% and 40% participants had less (<99.0 µg/L) and more than adequate to excessive (≥200 µg/L) levels of UIC. Insignificant difference (p = 0.07) was observed for mean log UIC between cabbage eaters (2.3) and non-eaters (1.9) consuming salt >5 grams/day. CONCLUSION: Recent iodine intake among children observed to be inadequate and effect of cruciferous food items on UIC needs to be studied despite high coverage of iodized salt among children.
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Carbon capture and storage has been recognized as the most promising method for CO2 control. Among the many sorbents, char derived from pyrolysis and hydrothermal carbonization (HTC) of biomass have demonstrated excellent CO2 adsorption capability. This paper reviews the different parameters to produce a higher yield of biochar and hydrochar suitable for carbon sequestration. The mechanism of physisorption and chemisorption is briefly presented. The different kinetic models, diffusion models to describe adsorption mechanism, and adsorption isotherms for CO2 uptake from biomass-derived hydrochar are reviewed. The different factors that affect the CO2 uptake are the type of activation, surface area and porosity, the ratio of activation agent to char, activation temperature, adsorption pressure and temperature, additives, and other physicochemical properties. The optimal conditions for CO2 uptake with chemical activation of KOH is a KOH/char ratio of 2-3, activation temperature of 700 °C, and an adsorption temperature below 50 °C.
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Dióxido de Carbono , Carvão Vegetal , Adsorção , Biomassa , Carbono , Pirólise , TemperaturaRESUMO
BACKGROUND: A novel subjective Motivational Value toward Child Gender (MVCG) tool was developed using the theoretical construct of 10 motivational domains described by Shalom H Schwartz. OBJECTIVE: The study aimed to summarize the pattern of correlations of (MVCG) in women of reproductive age in Himachal Pradesh, India. METHODS: A cross-sectional study was conducted from October 2018 to November 2019 among a sample of 355 women. Required data were collected through an interviewer-administered questionnaire. Maximum likelihood exploratory factor analysis (EFA) with oblique rotation was done with Bartlett's test sphericity and Kaiser-Meyer-Olkin test. RESULTS: A total of 28 (53.8%) questions loaded on eight factors explaining maximum variance (68.7%). Reliability analysis of these questions, with high loadings on extracted factors, of the questionnaire, observed with poor Cronbach's alpha of 0.61 and intraclass cluster coefficient (ICC) 0.49. However, selected domains such as tradition, power, achievement, self-direction, and benevolence were observed with a good Cronbach's alpha and ICC. CONCLUSION: MCVG is novel tool in its kind with well scalable properties in measuring subjective motivational values towards child gender. After EFA, total questions across 10 domains reduced from 52 to 28, across 8 domains, loaded on 8 factors with good reliability and agreement.
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Hospitais , Criança , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Índia , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Glioblastoma (GBM) is the most common primary brain malignancy in adults, with a 100% recurrence rate and 21-month median survival. Our lab and others have shown that GBM contains a subpopulation of glioma stem cells (GSCs) that expand during chemotherapy and may contribute to therapeutic resistance and recurrence in GBM. To investigate the mechanism behind this expansion, we applied gene set expression analysis (GSEA) to patient-derived xenograft (PDX) cells in response to temozolomide (TMZ), the most commonly used chemotherapy against GBM. Results showed significant enrichment of cancer stem cell and cell cycle pathways (False Discovery Rate (FDR) < 0.25). The ligand of numb protein 1 (LNX1), a known regulator of Notch signaling by targeting negative regulator Numb, is strongly upregulated after TMZ therapy (p < 0.0001) and is negatively correlated with survival of GBM patients. LNX1 is also upregulated after TMZ therapy in multiple PDX lines with concomitant downregulations in Numb and upregulations in intracellular Notch1 (NICD). Overexpression of LNX1 results in Notch1 signaling activation and increased GSC populations. In contrast, knocking down LNX1 reverses these changes, causing a significant downregulation of NICD, reduction in stemness after TMZ therapy, and resulting in more prolonged median survival in a mouse model. Based on this, we propose that during anti-GBM chemotherapy, LNX1-regulated Notch1 signaling promotes stemness and contributes to therapeutic resistance.
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The Snowtrout, Schizothorax richardsonii, is a vulnerable fish species found in different rivers and rivulets of the Himalayan region. The species is also a suitable poikilotherm to study the low-temperature tolerance as it dwells well at a temperature range of 5-20 °C. The solute carrier (SLC) group of membrane transport proteins play an integral role in cellular acclimation response. The present RNA sequencing was done to identify solute carrier transporter which are the major gene cascades responsible for transport of sugars, amino acids, oligonucleotides, ions, drugs, etc. to and from the cell organelles. A reference transcriptome database was created from liver tissue of Schizothorax richardsonii through RNA sequencing on Illumina HiSeq 2000 platform. The sequences were annotated and characterized under various solute carrier families in the species. So far, 113 transcripts were identified as solute carrier transporter genes categorized under 13 different families. This data will be useful for many researchers working on gene cloning and differential expression of solute carriers.
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BACKGROUND: Tuberculosis (TB) recurrence observed to be an important event in its treatment and has future implications under national TB control efforts. The present study was carried out to assess the recurrence rate along with its risk factors among patients undergoing treatment for TB under Revised National TB Control Program (RNTCP). MATERIAL AND METHODS: Total 204 patients in health block of district Una, Himachal Pradesh were studied using pretested structured interviewer-administered questionnaire. Along with univariate a non-hierarchal multi-way frequency analysis (MFA) was done to study the one and multi-way effects between the discrete variables included in a hypothesized model. The variables were under-nutrition, pulmonary TB, injecting drug use (IDU), multi-drug resistant (MDR) TB, and past TB (recurrent cases). RESULTS: Total 29 cases (14.2%) had recurrence (17.7/100,000 population) with significantly high fraction for alternate residence (Recurrent: 50.0%, Non-recurrent: 47.4%; p = 0.001), Multi-drug resistance (MDR) TB (Recurrent: 13.8%, Non-recurrent: 2.3%; p = 0.003), and sputum negative patients (Recurrent: 51.7%, Non-recurrent: 14.5%; p = 0.000). Non-recurrent cases had significantly high fraction for sputum positive cases (Recurrent: 48.3%, Non-recurrent: 72.1%; p = 0.011), and extra-pulmonary TB (Recurrent: 00.0%, Non-recurrent: 13.4%; p = 0.036). MFA observed all significant one-way effects. Significant two-way effects were IDU and pulmonary TB (p = 0.001), MDR and past TB (p = 0.004), IDU and past TB (p = 0.019), and IDU and MDR-TB (p = 0.039). CONCLUSION: Proportion of TB recurrence was expected with a significant difference between the history of change of residence, MDR-TB, pulmonary and extra-pulmonary nature of the disease. Hypothesized model observed with a significant association of IDU, pulmonary TB, MDR-TB and past TB.
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Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Índia/epidemiologia , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Serviços Preventivos de Saúde/organização & administração , Recidiva , Fatores de Risco , População Rural , Inquéritos e Questionários , Tuberculose Resistente a Múltiplos Medicamentos/etiologia , Tuberculose Pulmonar/etiologia , Adulto JovemRESUMO
The snow trout (Schizothorax richardsonii) belonging to family Cyprinidae, is an endemic fish of the Himalayan region. The species is tagged as vulnerable species in the IUCN red list of threatened species. The fish thrives well in snowmelt water of several streams and rivers in the region but are occasionally exposed to more than 20 °C during the summer season. Therefore, we have used deep RNA sequencing to decipher the transcriptome of snow trout and characterize the genes and molecular pathways involved in heat shock response. In this study 72,601,298 and 65,428,283 raw reads for heat-shocked and control, respectively, were obtained by Illumina paired-end sequencing technology. The de novo assembled transcriptome was tested for differential gene expression across the treatment groups. The quality of assembly was high with N75 and N50 lengths of 461 and 1274 bases, respectively. A total of 65 unique transcripts were differentially expressed in liver under heat shock and control. Annotated blast matches reveal that differentially expressed transcripts correspond to critical chaperones and molecular pathways, previously shown to be important for thermal stress in other fish species. Eight randomly selected heat-stressed responsive transcripts were also observed to be upregulated during qRT-PCR analysis. This study is the preliminary step to understanding the responses during sudden environmental changes like heat shock. The reference transcriptome database would also aid further studies on biological and physiological aspects of the snow trout under abiotic stresses.
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Proteínas de Peixes/genética , Proteínas de Choque Térmico/genética , Resposta ao Choque Térmico/genética , Transcriptoma , Truta/genética , Altitude , Animais , Perfilação da Expressão Gênica , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Temperatura Alta , Índia , Anotação de Sequência MolecularRESUMO
The complete mitochondrial genome of Tor tor, a threatened "Mahseer" was sequenced for the first time. The mitochondrial genome size determined to be 16,554 bp in length and consisted of 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNA genes and a control region or displacement loop (D-Loop) region, resembling the typical organizational pattern of most of the teleost. The overall base composition found was A: 31.8%, T: 25%, G: 15.7% and C: 27.4%; A + T: 56.9% and G + C: 43.1%. The phylogenetic tree constructed using 11 other cyprinids' total mtDNA datasets confirmed the location of present species among mahseers. The total sequence data could support further study in molecular systematics, species identification, evolutionary and conservation genetics.
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Cyprinidae/genética , Genoma Mitocondrial/genética , Animais , Composição de Bases/genética , Cyprinidae/classificação , DNA Mitocondrial/genética , Filogenia , RNA Ribossômico/genética , RNA de Transferência/genéticaRESUMO
The complete mitochondrial genome of Schizothorax plagiostomus, an endemic coldwater fish of Himalayas, was determined for the first time. The genome is 16,576 bp in length and consists of 13 protein coding genes, 22 tRNAs, 2rRNA genes and 1 putative control region. The gene organization and its order were similar to other vertebrates. The overall base composition was A 30%, G 17.4%, C 26.8%, T 25.8%, A + T content 55.8% and the G + C content 44.2%. The control region consists of a microsatellite locus (TA)12 between 16,460 and 16,483 bp. The present study will provide the rationale for the management and conservation of S. plagiostomus.