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1.
Cell Rep ; 43(4): 114066, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38578823

RESUMO

In human cells and yeast, an intact "hydrophobic patch" substrate docking site is needed for mitotic cyclin centrosomal localization. A hydrophobic patch mutant (HPM) of the fission yeast mitotic cyclin Cdc13 cannot enter mitosis, but whether this is due to defective centrosomal localization or defective cyclin-substrate docking more widely is unknown. Here, we show that artificially restoring Cdc13-HPM centrosomal localization promotes mitotic entry and increases CDK (cyclin-dependent kinase) substrate phosphorylation at the centrosome and in the cytoplasm. We also show that the S-phase B-cyclin hydrophobic patch is required for centrosomal localization but not for S phase. We propose that the hydrophobic patch is essential for mitosis due to its requirement for the local concentration of cyclin-CDK with CDK substrates and regulators at the centrosome. Our findings emphasize the central importance of the centrosome as a hub coordinating cell-cycle control and explain why the cyclin hydrophobic patch is essential for mitosis.


Assuntos
Ciclo Celular , Centrossomo , Ciclina B , Quinases Ciclina-Dependentes , Mitose , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Centrossomo/metabolismo , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Fosforilação , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Interações Hidrofóbicas e Hidrofílicas , Humanos
2.
BMJ Case Rep ; 17(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594194

RESUMO

We present the first published case of simultaneous pneumonitis and immune thrombocytopenic purpura secondary to primary cytomegalovirus (CMV) infection in an immunocompetent patient. Treatment with oral valganciclovir for 2 weeks successfully led to complete clinical recovery. CMV is traditionally associated with infection in immunocompromised patients and neonates; however, evidence of severe CMV infections in immunocompetent hosts is emerging. It is important to highlight the broad range of clinical presentations of CMV infections to prevent diagnostic delay and associated morbidity and expense.


Assuntos
Infecções por Citomegalovirus , Pneumonia , Púrpura Trombocitopênica Idiopática , Feminino , Recém-Nascido , Humanos , Citomegalovirus , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Ganciclovir/uso terapêutico , Diagnóstico Tardio , Queensland , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Pneumonia/complicações , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Antivirais/uso terapêutico
3.
J Invest Dermatol ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38513819

RESUMO

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.

4.
JAMA Netw Open ; 7(1): e2352387, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38241046

RESUMO

Importance: COVID-19 vaccine-derived antibodies in pregnant people may protect infants from severe infection in the first 6 months of life via transplacental antibody transfer. Few data exist on maternally derived SARS-CoV-2 antibodies in preterm compared with full-term infants in association with vaccination timing. Objective: To compare SARS-CoV-2 anti-Spike (anti-S) antibody levels in preterm and full-term infants in the context of vaccine dose timing before delivery. Design, Setting, and Participants: This prospective cohort study enrolled pregnant individuals and collected paired maternal and cord blood samples at delivery at the University of Washington between February 1, 2021, and January 31, 2023. Participants who had received at least 2 doses of a messenger RNA COVID-19 vaccine before delivery and did not have a history of prior COVID-19 infection or detectable anti-SARS-CoV-2 nucleocapsid antibodies were included. Exposures: Timing of the last vaccine dose and preterm or full-term gestational age at delivery. Main Outcomes and Measures: Paired maternal and cord samples were tested for anti-S antibody, and linear regression was used to evaluate associations between preterm delivery and anti-S antibody levels. Covariates included timing of last dose, number of doses, insurance status, and immunosuppressing medications. Results: A total of 220 participants (median [IQR] age, 34 [32-37] years; 212 [96.4%] female) with 36 preterm and 184 full-term deliveries were studied. Before delivery, 121 persons received 2 vaccine doses and 99 persons received 3 or more vaccine doses. The geometric mean concentration of maternal anti-S antibodies was 674 (95% CI, 577-787) after 2 doses and 8159 (95% CI, 6636-10 032) after 3 or more doses (P < .001). The cord anti-S antibody geometric mean concentration was 1000 (95% CI, 874-1144) after 2 doses and 9992 (95% CI, 8381-11 914) after 3 or more doses (P < .001). After adjustment for vaccine timing and number of doses before delivery, no association was found between preterm delivery and cord anti-S antibody levels (ß = 0.44; 95% CI, -0.06 to 0.94). Conclusions and Relevance: In this prospective cohort study of pregnant individuals with preterm and full-term deliveries, receipt of 3 or more compared with 2 doses of COVID-19 vaccine before delivery resulted in 10-fold higher cord anti-S antibody levels. Maternal antibody concentration appeared more important than delivery gestational age in determining cord anti-S antibody levels. The number of doses and timing considerations for COVID-19 vaccine in pregnancy should include individuals at risk for preterm delivery.


Assuntos
COVID-19 , Distrofias de Cones e Bastonetes , Nascimento Prematuro , Lactente , Gravidez , Recém-Nascido , Feminino , Humanos , Adulto , Masculino , Vacinas contra COVID-19 , Estudos Prospectivos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Antivirais
5.
Vet Rec ; 193(7): 287, 2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37800497
6.
Emerg Infect Dis ; 29(8): 1566-1579, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37486179

RESUMO

More than 60 zoonoses are linked to small mammals, including some of the most devastating pathogens in human history. Millions of museum-archived tissues are available to understand natural history of those pathogens. Our goal was to maximize the value of museum collections for pathogen-based research by using targeted sequence capture. We generated a probe panel that includes 39,916 80-bp RNA probes targeting 32 pathogen groups, including bacteria, helminths, fungi, and protozoans. Laboratory-generated, mock-control samples showed that we are capable of enriching targeted loci from pathogen DNA 2,882‒6,746-fold. We identified bacterial species in museum-archived samples, including Bartonella, a known human zoonosis. These results showed that probe-based enrichment of pathogens is a highly customizable and efficient method for identifying pathogens from museum-archived tissues.


Assuntos
DNA , Zoonoses , Animais , Humanos , DNA/genética , Zoonoses/microbiologia , Fungos , Bactérias/genética , Mamíferos
7.
J Neurosurg Pediatr ; 32(3): 358-365, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37310054

RESUMO

OBJECTIVE: Epilepsy surgery remains one of the most underutilized procedures in epilepsy despite its proven superiority to other available therapies. This underutilization is greater in patients in whom initial surgery fails. This case series examined the clinical characteristics, reasons for initial surgery failure, and outcomes in a cohort of patients who underwent hemispherectomy following unsuccessful smaller resections for intractable epilepsy (subhemispheric group [SHG]) and compared them to those of a cohort of patients who underwent hemispherectomy as the first surgery (hemispheric group [HG]). The objective of this paper was to determine the clinical characteristics of patients in whom a small, subhemispheric resection failed, who went on to become seizure free after undergoing a hemispherectomy. METHODS: Patients who underwent hemispherectomy at Seattle Children's Hospital between 1996 and 2020 were identified. Inclusion criteria for SHG were as follows: 1) patients ≤ 18 years of age at the time of hemispheric surgery; 2) initial subhemispheric epilepsy surgery that did not produce seizure freedom; 3) hemispherectomy or hemispherotomy after the subhemispheric surgery; and 4) follow-up for at least 12 months after hemispheric surgery. Data collected included the following: patient demographics; seizure etiology; comorbidities; prior neurosurgeries; neurophysiological studies; imaging studies; and surgical details-plus surgical, seizure, and functional outcomes. Seizure etiology was classified as follows: 1) developmental, 2) acquired, or 3) progressive. The authors compared SHG to HG in terms of demographics, seizure etiology, and seizure and neuropsychological outcomes. RESULTS: There were 14 patients in the SHG and 51 patients in the HG. All patients in the SHG had Engel class IV scores after their initial resective surgery. Overall, 86% (n = 12) of the patients in the SHG had good posthemispherectomy seizure outcomes (Engel class I or II). All patients in the SHG who had progressive etiology (n = 3) had favorable seizure outcomes, with eventual hemispherectomy (1 each with Engel classes I, II, and III). Engel classifications posthemispherectomy between the groups were similar. There were no statistical differences in postsurgical Vineland Adaptive Behavior Scales Adaptive Behavior Composite scores or postsurgical full-scale IQ scores between groups when accounting for presurgical scores. CONCLUSIONS: Hemispherectomy as a repeat surgery after unsuccessful subhemispheric epilepsy surgery has a favorable seizure outcome, with stable or improved intelligence and adaptive functioning. Findings in these patients are similar to those in patients who had hemispherectomy as their first surgery. This can be explained by the relatively small number of patients in the SHG and the higher likelihood of hemispheric surgeries to resect or disconnect the entire epileptogenic lesion compared to smaller resections.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Hemisferectomia , Criança , Humanos , Epilepsia Resistente a Medicamentos/cirurgia , Hemisferectomia/métodos , Resultado do Tratamento , Convulsões/etiologia , Convulsões/cirurgia , Epilepsia/cirurgia , Eletroencefalografia , Estudos Retrospectivos
8.
Pragmat Obs Res ; 14: 39-49, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138785

RESUMO

Introduction: Electronic medical records (EMRs) maintained in primary care in the UK and collected and stored in EMR databases offer a world-leading resource for observational clinical research. We aimed to profile one such database: the Optimum Patient Care Research Database (OPCRD). Methods and Participants: The OPCRD, incepted in 2010, is a growing primary care EMR database collecting data from 992 general practices within the UK. It covers over 16.6 million patients across all four countries within the UK, and is broadly representative of the UK population in terms of age, sex, ethnicity and socio-economic status. Patients have a mean duration of 11.7 years' follow-up (SD 17.50), with a majority having key summary data from birth to last data entry. Data for the OPCRD are collected incrementally monthly and extracted from all of the major clinical software systems used within the UK and across all four coding systems (Read version 2, Read CTV3, SNOMED DM+D and SNOMED CT codes). Via quality-improvement programmes provided to GP surgeries, the OPCRD also includes patient-reported outcomes from a range of disease-specific validated questionnaires, with over 66,000 patient responses on asthma, COPD, and COVID-19. Further, bespoke data collection is possible by working with GPs to collect new research via patient-reported questionnaires. Findings to Date: The OPCRD has contributed to over 96 peer-reviewed research publications since its inception encompassing a broad range of medical conditions, including COVID-19. Conclusion: The OPCRD represents a unique resource with great potential to support epidemiological research, from retrospective observational studies through to embedded cluster-randomised trials. Advantages of the OPCRD over other EMR databases are its large size, UK-wide geographical coverage, the availability of up-to-date patient data from all major GP software systems, and the unique collection of patient-reported information on respiratory health.

9.
Front Psychiatry ; 14: 1154557, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139317

RESUMO

Postpartum psychosis is defined as a psychotic episode occurring within 4 to 6 weeks of childbirth. While there is robust evidence that adverse life events are associated with the onset and relapse of psychosis outside the postpartum period, the extent to which these contribute to postpartum psychosis is less clear. This systematic review examined whether adverse life events are associated with an increased likelihood of developing postpartum psychosis or subsequent relapse in women diagnosed with postpartum psychosis. The following databases were searched from inception to June 2021: MEDLINE, EMBASE, PsycInfo. Study level data were extracted including setting, number of participants, type of adverse event, and differences between groups. A modified version of the Newcastle-Ottawa Quality Assessments Scale was used to assess risk of bias. In total, 1933 records were identified, of which 17 met the inclusion criteria, comprising nine case-control studies and eight cohort studies. Most studies (16/17) examined the association between adverse life events and the onset of postpartum psychosis, with only in which the outcome was relapse of psychosis. Overall, there were 63 different measures of adversity examined (most of which were examined in a single study only) and 87 associations between these measures and postpartum psychosis tested across the studies. In terms of statistically significant associations with onset/relapse of postpartum psychosis, 15 (17%) were positive (i.e., the adverse event increased the risk of onset/relapse), 4 (5%) were negative, and 68 (78%) were not statistically significant. Our review highlights the diversity of risk factors examined in this field, with few attempts at replication, hence limiting the ability to conclude that any single risk factor is robustly associated with the onset of postpartum psychosis. Further large-scale studies, that attempt to replicate earlier studies, are urgently needed to determine whether adverse life events play a role in the onset and exacerbation of postpartum psychosis. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260592], identifier [CRD42021260592].

10.
Aorta (Stamford) ; 11(2): 63-70, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37055016

RESUMO

BACKGROUND: Pregnant patients with Marfan's syndrome (MFS) are at an increased risk for adverse aortic outcomes. While beta-blockers are used to slow aortic root dilatation in nonpregnant MFS patients, the benefit of such therapy in pregnant MFS patients remains controversial. The purpose of this study was to investigate the effect of beta-blockers on aortic root dilatation during pregnancy in MFS patients. METHODS: This was a longitudinal single-center retrospective cohort study of females with MFS who completed a pregnancy between 2004 and 2020. Clinical, fetal, and echocardiographic data were compared in patients on- versus off-beta-blockers during pregnancy. RESULTS: A total of 20 pregnancies completed by 19 patients were evaluated. Beta-blocker therapy was initiated or continued in 13 (65%) of the 20 pregnancies. Pregnancies on-beta-blocker therapy experienced less aortic growth compared with those off-beta-blockers (0.10 [interquartile range, IQR: 0.10-0.20] vs. 0.30 cm [IQR: 0.25-0.35]; p = 0.03). Using univariate linear regression, maximum systolic blood pressures (SBP), increase in SBP, and absence of beta-blocker use in pregnancy were found to be significantly associated with greater increase in aortic diameter during pregnancy. There were no differences in rates of fetal growth restriction between pregnancies on- versus off-beta-blockers. CONCLUSION: This is the first study that we are aware of to evaluate changes in aortic dimensions in MFS pregnancies stratified by beta-blocker use. Beta-blocker therapy was found to be associated with less aortic root growth during pregnancy in MFS patients.

11.
J Vet Intern Med ; 37(2): 670-675, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36799664

RESUMO

A 3-month-old female entire Beagle presented with a progressive history of caudotentorial encephalopathy. Reactive encephalopathies were ruled out and tests for the most common infectious diseases agents were negative. Magnetic resonance imaging of the brain using a 1.5 Tesla scanner showed diffuse, bilateral, T2-weighted and T2-weighted-FLAIR hyperintense, T1-weighted hypointense, noncontrast-enhancing lesions involving the white matter of the cerebellum, brainstem, spinal cord, and forebrain to a lesser extent. There was cerebellar enlargement. Abnormalities were not detected on cerebrospinal fluid examination. Given the progressive nature of the disease and suspected poor prognosis the dog was euthanized. Histopathological analysis of the brain was consistent with fibrinoid leukodystrophy, also known as Alexander disease. Based on the classification used in humans, this is a description of MRI of a case of type II Alexander disease in veterinary medicine, with characteristics different to other described leukoencephalopathies in dogs.


Assuntos
Doença de Alexander , Doenças do Cão , Substância Branca , Humanos , Cães , Animais , Feminino , Doença de Alexander/diagnóstico por imagem , Doença de Alexander/veterinária , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Imageamento por Ressonância Magnética/veterinária , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia
13.
Ann Surg Oncol ; 30(3): 1312-1326, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36335273

RESUMO

BACKGROUND: The National Comprehensive Cancer Network recommends genetic testing in patients with potentially hereditary breast, ovarian, pancreatic, and prostate cancers (HBOPP). Knowledge of genetic mutations impacts decisions about screening and treatment. METHODS: A retrospective cohort study of 28,586 HBOPP patients diagnosed from 2013 to 2019 was conducted using a linked administrative-cancer database in the Seattle-Puget Sound SEER area. Guideline-concordant testing (GCT) was assessed annually according to guideline updates. Frequency of testing according to patient/cancer characteristics was evaluated using chi-squared tests, and factors associated with receipt of genetic testing were identified using multivariable logistic regression. RESULTS: Testing occurred in 17% of HBOPP patients, increasing from 9% in 2013 to 21% in 2019 (p < 0.001). Ovarian cancer had the highest testing (40%) and prostate cancer the lowest (4%). Age < 50, female sex, non-Hispanic White race, commercial insurance, urban location, family history of HBOPP, and triple negative breast cancer (TNBC) were associated with increased testing (all p < 0.05). GCT increased from 38% in 2013 to 44% in 2019, and was highest for early age at breast cancer diagnosis, TNBC, male breast cancer, and breast cancer with family history of HBOPP (all > 70% in 2019), and lowest for metastatic prostate cancer (6%). CONCLUSIONS: The frequency of genetic testing for HBOPP cancer has increased over time. Though GCT is high for breast cancer, there are gaps in concordance among patients with other cancers. Increasing provider and patient education, genetic counseling, and insurance coverage for testing among HBOPP patients may improve guideline adherence.


Assuntos
Neoplasias da Mama , Testes Genéticos , Neoplasias Ovarianas , Neoplasias Pancreáticas , Neoplasias da Próstata , Feminino , Humanos , Masculino , Neoplasias da Mama/genética , Aconselhamento Genético , Neoplasias Ovarianas/genética , Hormônios Pancreáticos , Neoplasias da Próstata/genética , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias Pancreáticas/genética
14.
J Am Coll Health ; 71(4): 1143-1151, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34242549

RESUMO

Purpose: College students with chronic illnesses are vulnerable to poor adjustment, but it remains unclear how these students differ from healthy peers. This study compares psychosocial adjustment and risky behavior between students with and without chronic illnesses. Participants: Participants (N = 629, 78% Caucasian, 77% Female) were recruited from universities. Methods: Participants completed measures of illness history, anxiety, depression, stressful life events, social support, and risky behavior. Results: College students with chronic illnesses demonstrated significantly greater symptoms of anxiety F(1,620) = 8.742, p < .003, depression F(1,614) = 26.947, p < .001, more stressful life events F(1,476) = 23.671, p < .001, and lower social support F(1,613) = 15.645, p < .001. No differences in risky behaviors between groups emerged F(1,601) = 3.432, p = .064. An indirect effect of health status on risk-taking behavior was observed [b = .677, 95% CI (.351, 1.072)] partially mediated by depression. Conclusion: College students with chronic illnesses demonstrated worse psychosocial outcomes than healthy students, warranting programs to support these students. Depressive symptoms partially mediated risky behavior.


Assuntos
Funcionamento Psicossocial , Estudantes , Humanos , Feminino , Masculino , Universidades , Estudantes/psicologia , Doença Crônica , Nível de Saúde
15.
JFMS Open Rep ; 8(2): 20551169221125207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36226303

RESUMO

Case summary: A 6-year-old male neutered domestic longhair cat was referred for investigation of weight loss, hyporexia, vomiting and diarrhoea. The cat was diagnosed with primary hypoadrenocorticism, exocrine pancreatic insufficiency, cobalamin deficiency and a chronic enteropathy, and started on therapeutic treatment. Diabetes mellitus developed 4.5 months later, and the cat was started on insulin therapy. The cat was euthanased 10 months following the diagnosis of hypoadrenocorticism due to the development of status epilepticus, which was not associated with glucose or electrolyte abnormalities. Histopathological assessment of the adrenal glands at post-mortem examination documented lymphoplasmacytic adrenalitis, with the lymphocytic population being predominant. Immunohistochemical staining classified the lymphocytic infiltrate as T-cell rich, supportive of the cat's hypoadrenocorticism being due to autoimmune disease. Relevance and novel information: This case documents the novel use of immunohistochemical staining in combination with histopathology to further assess the adrenal glands in non-neoplastic-associated primary hypoadrenocorticism in a cat. This identified similar pathological changes to those previously described in dogs with autoimmune primary hypoadrenocorticism. Additionally, this is the first report of a cat with multiple endocrine disease that included primary hypoadrenocorticism and highlights that monitoring for the development of additional endocrine disease should be advised in these cases.

16.
Harm Reduct J ; 19(1): 100, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050735

RESUMO

BACKGROUND: Vaccine-hesitant persons who inject drugs are at increased risk for several vaccine-preventable diseases. However, vaccination rates among this population remain low. While syringe services programs (SSPs) are places where persons who inject drugs feel comfortable accessing services, few offer vaccination services. This study describes facilitators and barriers to vaccination at SSPs. METHODS: We used convenience sampling to conduct semi-structured, qualitative in-depth interviews with 21 SSPs in the USA from June to August 2021. Interview questions asked SSPs about their perceptions, priorities, barriers, facilitators, and the effects of partnerships and policies on vaccine administration. We used deductive thematic analysis to identify the main themes. RESULTS: Eight (n = 8) SSPs offered vaccinations, and thirteen (n = 13) did not offer vaccinations. Most SSPs believed offering vaccination services was important, although addressing SSP participants' immediate needs often took precedence. Staffing, physical space, and logistical issues were the most common barriers to vaccine administration reported by SSPs, followed by SSP participant-related barriers. Facilitators of vaccine administration included access to a tracking system, partnering with agencies or other organizations providing vaccines, and having a licensed vaccination provider on-site. Partnerships provided SSPs opportunities to expand capacity but could also restrict how SSPs operate. Recommended policy changes to facilitate vaccine administration included subsidizing the cost of vaccinations and addressing restrictions around who could administer vaccinations. CONCLUSIONS: Increasing the availability of vaccination services at SSPs requires addressing the varying capacity needs of SSPs, such as tracking systems, licensed vaccinators, and free or low-cost vaccination supplies. While these needs can be met through partnerships and supportive policies, both must consider and reflect cultural competence around the lived experiences of persons who inject drugs.


Assuntos
Usuários de Drogas , Abuso de Substâncias por Via Intravenosa , Vacinas , Humanos , Programas de Troca de Agulhas , Abuso de Substâncias por Via Intravenosa/epidemiologia , Seringas , Vacinação
17.
Vet Med Sci ; 8(6): 2273-2276, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36054812

RESUMO

A 10-year-old, entire male, English Springer Spaniel was referred for evaluation of weight loss, polyuria, polydipsia and gastrointestinal tract signs including melena/haematochezia for the previous six months. Results of serum protein electrophoresis, urine analysis, computed tomography of the thorax/abdomen, bone marrow aspiration and core biopsy, and splenic and mesenteric lymph node cytology were consistent with multiple myeloma. Endoscopically obtained gastrointestinal tract biopsies identified marked plasma cell infiltration within the duodenum, ileum and colon; immunohistochemistry showed positive labelling to MUM1 and Lambda confirming clonal plasma cell involvement. The dog entered complete clinical remission seven weeks after starting a melphalan/prednisolone protocol. The dog was euthanised 475 days after starting treatment due to cervical pain and collapse. At the time of euthanasia, blood work was not supportive of a relapse of multiple myeloma. To the authors' knowledge, this is the first report of multiple myeloma involving the gastrointestinal tract in a dog.


Assuntos
Doenças do Cão , Mieloma Múltiplo , Masculino , Cães , Animais , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/veterinária , Recidiva Local de Neoplasia/veterinária , Trato Gastrointestinal , Baço , Doenças do Cão/diagnóstico por imagem
18.
Genome Biol ; 23(1): 155, 2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35821049

RESUMO

BACKGROUND: Speciation genes contribute disproportionately to species divergence, but few examples exist, especially in vertebrates. Here we test whether Zan, which encodes the sperm acrosomal protein zonadhesin that mediates species-specific adhesion to the egg's zona pellucida, is a speciation gene in placental mammals. RESULTS: Genomic ontogeny reveals that Zan arose by repurposing of a stem vertebrate gene that was lost in multiple lineages but retained in Eutheria on acquiring a function in egg recognition. A 112-species Zan sequence phylogeny, representing 17 of 19 placental Orders, resolves all species into monophyletic groups corresponding to recognized Orders and Suborders, with <5% unsupported nodes. Three other rapidly evolving germ cell genes (Adam2, Zp2, and Prm1), a paralogous somatic cell gene (TectA), and a mitochondrial gene commonly used for phylogenetic analyses (Cytb) all yield trees with poorer resolution than the Zan tree and inferior topologies relative to a widely accepted mammalian supertree. Zan divergence by intense positive selection produces dramatic species differences in the protein's properties, with ordinal divergence rates generally reflecting species richness of placental Orders consistent with expectations for a speciation gene that acts across a wide range of taxa. Furthermore, Zan's combined phylogenetic utility and divergence exceeds those of all other genes known to have evolved in Eutheria by positive selection, including the only other mammalian speciation gene, Prdm9. CONCLUSIONS: Species-specific egg recognition conferred by Zan's functional divergence served as a mode of prezygotic reproductive isolation that promoted the extraordinary adaptive radiation and success of Eutheria.


Assuntos
Placenta , Sêmen , Animais , Eutérios , Feminino , Masculino , Filogenia , Gravidez , Espermatozoides/metabolismo
19.
Drug Alcohol Depend ; 237: 109540, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35753280

RESUMO

BACKGROUND: Syringe services programs (SSPs) are an important venue for reaching people who inject drugs (PWID) to offer preventive services; however, not all SSPs offer vaccinations. We aimed to describe barriers and opportunities for SSPs to offer vaccinations. METHODS: During June-August 2021, we conducted a descriptive, cross-sectional survey of SSP providers in the United States. SSPs were recruited from national listservs using purposive sampling to ensure geographic diversity. The survey included questions about SSP characteristics, client demographics, existing vaccination resources, resource needs, and staff perspectives on client vaccination barriers. Statistical comparisons were made using Pearson's chi-square test. RESULTS: In total, 105 SSPs from 34 states responded to the survey; 46 SSPs (43.8%) offered on-site vaccinations. SSPs without on-site vaccinations were more likely operated by community-based organizations (81.4% vs 30.4%, p < 0.001) in urban areas (71.4% vs 40.0%, p = 0.002) than SSPs offering on-site vaccinations. The most common staffing need was for personnel licensed to administer vaccines (74/98, 75.5%). Over half of SSPs reported vaccine supply, administration supplies, storage equipment, and systems to follow-up clients for multidose series as important resource needs. The most common resource need was for reminder/recall systems for vaccines with multidose series (75/92, 81.5%). Vaccine safety concerns (92/95, 96.8%) and competing priorities (92/96, 95.8%) were the most common staff-reported client barriers to vaccinations. CONCLUSIONS: Addressing missed opportunities for offering vaccinations to PWID who use SSPs will require increased numbers of on-site personnel licensed to administer vaccines and additional training, vaccination supplies, and storage and handling equipment.


Assuntos
Abuso de Substâncias por Via Intravenosa , Vacinas , Estudos Transversais , Humanos , Programas de Troca de Agulhas , Abuso de Substâncias por Via Intravenosa/epidemiologia , Seringas , Estados Unidos , Vacinação
20.
Ecol Evol ; 12(4): e8849, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35462978

RESUMO

Translocation records indicate aoudad (Ammotragus lervia) populations in the United States are a product of multiple human-mediated introductions. Two mitochondrial markers (cytochrome b, cytb; displacement loop, D loop) and one nuclear gene (prion protein gene exon 3, PRNP) were used to determine: (1) genetic variation, (2) if genetic units correspond to taxonomic designations, (3) the number and geographic origin of translocations, and (4) divergence times. Three phylogenetic analyses (Bayesian inference, maximum likelihood, and parsimony) produced similar topologies with two clades (I and II). Clade I contained progeny of individuals resulting from introductions to Texas and Spain, and individuals from Algeria. Individuals in Clade II were progeny of past introductions to the United States and Europe, and northern Algeria. Clade II was subdivided into two subclades (A and B) representing two haplogroups. No genetic variation was detected in the PRNP sequences. Three haplogroups appeared to correspond to the subspecies A. l. lervia and A. l. sahariensis whose native distribution includes northwestern Africa. Network analyses assigned haplogroups to two major groups similar to those depicted in the phylogenetic analyses. Genetic distances ranged from 0.80% to 5.17% and 2.99% to 15.42% for cytb and D loop, respectively; and were higher than normally recovered for caprids, warranting a reexamination of subspecific status. Divergence dates indicated a major split between A. l. lervia and A. l. sahariensis circa 2.38 mya. Together, the high level of genetic divergences among US populations and apparent presence of two subspecies of aoudad in the United States support the hypothesis of multiple introductions from multiple sources.

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