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1.
Methods Mol Biol ; 2852: 171-179, 2025.
Artigo em Inglês | MEDLINE | ID: mdl-39235744

RESUMO

Studying host-pathogen interactions is essential for understanding infectious diseases and developing possible treatments, especially for priority pathogens with increased virulence and antibiotic resistance, such as Klebsiella pneumoniae. Over time, this subject has been approached from different perspectives, often using mammal host models and invasive endpoint measurements (e.g., sacrifice and organ extraction). However, taking advantage of technological advances, it is now possible to follow the infective process by noninvasive visualization in real time, using optically amenable surrogate hosts. In this line, this chapter describes a live-cell imaging approach to monitor the interaction of K. pneumoniae and potentially other bacterial pathogens with zebrafish larvae in vivo. This methodology is based on the microinjection of fluorescent bacteria into the otic vesicle, followed by time-lapse observation by automated fluorescence microscopy with environmental control, monitoring the dynamics of immune cell recruitment, bacterial load, and larvae survival.


Assuntos
Interações Hospedeiro-Patógeno , Infecções por Klebsiella , Klebsiella pneumoniae , Larva , Microinjeções , Microscopia de Fluorescência , Peixe-Zebra , Animais , Peixe-Zebra/microbiologia , Klebsiella pneumoniae/imunologia , Microinjeções/métodos , Larva/microbiologia , Larva/imunologia , Microscopia de Fluorescência/métodos , Interações Hospedeiro-Patógeno/imunologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/imunologia , Modelos Animais de Doenças
2.
Acta Med Philipp ; 58(16): 133-140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39399364

RESUMO

Background: The Philippine Primary Care Studies (PPCS) is a network of pilot studies that developed, implemented, and tested strategies to strengthen primary care in the country. These pilot studies were implemented in an urban, rural, and remote setting. The aim is to use the findings to guide the policies of the national health insurance program (PhilHealth), the main payor for individualized healthcare services in the country. Objective: The objective of this report is to compare baseline outpatient benefit utilization, hospitalization, and health spending, including out-of-pocket (OOP) expenses, in three health settings (urban, rural, and remote). These findings were used to contextualize strategies to strengthen primary care in these three settings. Methods: Cross-sectional surveys were carried out using an interviewer-assisted questionnaire on a random sample of families in the urban site, and a stratified random sample of households in the rural and remote sites. The questionnaire asked for out-patient and hospitalization utilization and spending, including the OOP expenses. Results: A total of 787 families/households were sampled across the three sites. For outpatient benefits, utilization was low in all sites. The remote site had the lowest utilization at only 15%. Unexpectedly, the average annual OOP expenses for outpatient consults in the remote site was PhP 571.92/per capita. This is 40% higher than expenses shouldered by families in the rural area, but similar with the urban site.For hospital benefits, utilization was lowest in the remote site (55.7%) compared to 75.0% and 78.1% for the urban and rural sites, respectively. OOP expenses per year were highest in the remote site at PhP 2204.44 per capita, probably because of delay in access to healthcare and consequently more severe conditions. Surprisingly, annual expenses per year for families in the rural sites (PhP 672.03 per capita) were less than half of what families in the urban sites spent (PhP 1783.38 per capita). Conclusions: Compared to families in the urban site and households in the rural sites, households in remote areas have higher disease rates and consequently, increased need for outpatient and inpatient health services. When they do get sick, access to care is more difficult. This leads to lower rates of benefit utilization and higher out-of-pocket expenses. Thus, provision of "equal" benefits can inadvertently lead to "inequitable" healthcare, pushing disadvantaged populations into a greater disadvantage. These results imply that health benefits need to be allocated according to need. Families in poorer and more remote areas may require greater subsidies.

3.
Acta Med Philipp ; 58(15): 24-31, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308883

RESUMO

Background: Peritoneal tuberculosis comprises 5% of all forms of tuberculosis in children. There are limited reports of peritoneal TB in children. Objective: To determine the clinical, biochemical, radiologic, histologic, and microbiologic features and outcome of pediatric patients diagnosed with peritoneal tuberculosis. Methods: Review of medical records from 2011-2020 of patients fulfilling diagnostic criteria of peritoneal TB. Patient was considered as bacteriologically-confirmed if with positive AFB smear, culture, or PCR on peritoneal or omental tissue; and clinically-diagnosed if with clinical findings AND presence of histologic and/or radiologic evidence of extra-pulmonary TB. Data was presented as mean (SD) or n (%), as appropriate. Results: Eighteen patients [Mean (SD) age: 14.27 (± 4.1) years old, 56% males] were included. All had disseminated TB with peritoneal involvement. One case was bacteriologically-confirmed (TB PCR positive omental tissue); 17 were clinically-diagnosed. Most common presentation was abdominal distention (83%) and abdominal pain (61%). Most common physical finding was abdominal distention (83%) and abdominal tenderness (44%). Seven patients (39%) had anemia, 11 (61%) had leukocytosis, and three (17%) had thrombocytosis. Thirteen (72%) had hypoalbuminemia. Ten (56%) were positive on AFB smear, TB culture, and PCR of various specimens. Fourteen of sixteen (88%) with abdominal CT scan had ascites and intrabdominal lymphadenopathy. Nine of 12 tissue samples from seven patients demonstrated chronic granulomatous inflammation. Seventeen were given quadruple anti-TB. Six also had surgery. Overall, 15 were discharge improved after mean of 4.2 weeks of hospital stay, while three died of sepsis. Eleven of the 15 were well one month after discharge. Conclusion: Peritoneal TB presents with non-specific clinical and laboratory features. Radiologic and histologic findings increase the likelihood of diagnosis. The prognosis is favorable for patients who are diagnosed and treated with anti-TB drugs.

4.
Acta Med Philipp ; 58(14): 99-104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39238556

RESUMO

Jaundice in older children can occur when any obstruction is found within the bile ducts, either from bile stones, parasites, choledochal cysts and rarely, secondary to tumors. We present a previously well, 10-year-old Filipino boy with three-week history of progressive jaundice and tea-colored urine, and was initially assessed to have biliary ascariasis. Ultrasound showed a heterogeneous focus spanning the gallbladder neck and confirmed on endoscopic retrograde cholangiopancreatography as an exophytic mass at the ampulla of Vater. Tumor biopsy and immunohistochemical staining confirmed the diagnosis of Embryonal Rhabdomyosarcoma of the Bile Ducts. Chemotherapy was initiated to reduce the size of the tumor before any surgical intervention could be attempted. Despite chemotherapy, the tumor progressively grew. He acquired a respiratory infection which led to sepsis and his eventual demise. The disease should be considered in the differential diagnosis of a child with obstructive jaundice after exclusion of other more common causes.

5.
Appl Radiat Isot ; 214: 111516, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39276635

RESUMO

Thermoluminescence (TL) and Radioluminescence (RL) are widely used in dosimetry applications. We present a custom-built integrated system, designated LUMI22, for measuring TL, TL spectroscopy, RL, and RL as a function of temperature. LUMI22 includes a heating system based on Kanthal® A1 alloy (FeCrAl), a microcontroller to regulate the temperature ramps (e.g. 1-5 °C/s). To irradiate samples an X-ray tube (Moxtek 50 kV, 50 µA) is powered, controlled, and monitored by an FTC-200 standard controller. The dose rate at the sample position is 0.43 Gy/min. Light collection includes a Photomultiplier Tube (PMT, Hamamatsu H10493-012:HA, 185-850 nm). Additionally, a miniature fiber optic spectrometer (Ocean Optics, QE65000, range 200-1100 nm) coupled with a 1000 µm diameter fiber optic (QP1000- 2-UV-VIS) was employed for TL and RL spectroscopy measurements. To assess the functionality of the system, it was used to measure TL and RL from Al2O3:C,Mg, Al2O3:C and TLD-100 phosphors which have been previously well investigated. The measured TL and RL data were well compared to the published ones, confirming the functionality of the system.

7.
J Chem Phys ; 161(5)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39092947

RESUMO

The elongation of metallic nanoparticles (NPs) embedded in a dielectric matrix after irradiation with swift heavy ions is a phenomenon that has been known for several years. However, the precise mechanism behind this deformation process is still not fully understood, primarily due to the dearth of information during intermediate stages of deformation. In this study, we report the continuation of our previous work [Peña-Rodríguez et al., Sci. Rep. 7(1), 922 (2017)], exploiting the strong dependence of the localized surface plasmon resonance on the aspect ratio of elongated metal NPs to study the elongation kinetics in situ. In situ optical absorption spectra were measured using a polarizing beam splitter to separate the longitudinal and transverse plasmon modes of the anisotropic NPs. Then, the detailed geometrical and compositional parameters were determined from a fit of these spectra. The use of linearly polarized light allowed for a more accurate analysis of the elongation kinetics, particularly useful in the first stages, where longitudinal and transverse modes overlap.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39002069

RESUMO

PURPOSE: To establish a reliable machine learning model to predict malignancy in breast lesions identified by ultrasound (US) and optimize the negative predictive value to minimize unnecessary biopsies. METHODS: We included clinical and ultrasonographic attributes from 1526 breast lesions classified as BI-RADS 3, 4a, 4b, 4c, 5, and 6 that underwent US-guided breast biopsy in four institutions. We selected the most informative attributes to train nine machine learning models, ensemble models and models with tuned threshold to make inferences about the diagnosis of BI-RADS 4a and 4b lesions (validation dataset). We tested the performance of the final model with 403 new suspicious lesions. RESULTS: The most informative attributes were shape, margin, orientation and size of the lesions, the resistance index of the internal vessel, the age of the patient and the presence of a palpable lump. The highest mean negative predictive value (NPV) was achieved with the K-Nearest Neighbors algorithm (97.9%). Making ensembles did not improve the performance. Tuning the threshold did improve the performance of the models and we chose the algorithm XGBoost with the tuned threshold as the final one. The tested performance of the final model was: NPV 98.1%, false negative 1.9%, positive predictive value 77.1%, false positive 22.9%. Applying this final model, we would have missed 2 of the 231 malignant lesions of the test dataset (0.8%). CONCLUSION: Machine learning can help physicians predict malignancy in suspicious breast lesions identified by the US. Our final model would be able to avoid 60.4% of the biopsies in benign lesions missing less than 1% of the cancer cases.

9.
JAMA ; 332(2): 133-140, 2024 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-38837131

RESUMO

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.


Assuntos
Causas de Morte , Países em Desenvolvimento , Cardiopatia Reumática , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Endocardite/mortalidade , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/complicações , Hospitalização/estatística & dados numéricos , Morbidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Febre Reumática/complicações , Febre Reumática/mortalidade , Cardiopatia Reumática/complicações , Cardiopatia Reumática/economia , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/mortalidade , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/epidemiologia
10.
BMC Genomics ; 25(1): 614, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890559

RESUMO

BACKGROUND: To unravel the evolutionary history of a complex group, a comprehensive reconstruction of its phylogenetic relationships is crucial. This requires meticulous taxon sampling and careful consideration of multiple characters to ensure a complete and accurate reconstruction. The phylogenetic position of the Orestias genus has been estimated partly on unavailable or incomplete information. As a consequence, it was assigned to the family Cyprindontidae, relating this Andean fish to other geographically distant genera distributed in the Mediterranean, Middle East and North and Central America. In this study, using complete genome sequencing, we aim to clarify the phylogenetic position of Orestias within the Cyprinodontiformes order. RESULTS: We sequenced the genome of three Orestias species from the Andean Altiplano. Our analysis revealed that the small genome size in this genus (~ 0.7 Gb) was caused by a contraction in transposable element (TE) content, particularly in DNA elements and short interspersed nuclear elements (SINEs). Using predicted gene sequences, we generated a phylogenetic tree of Cyprinodontiformes using 902 orthologs extracted from all 32 available genomes as well as three outgroup species. We complemented this analysis with a phylogenetic reconstruction and time calibration considering 12 molecular markers (eight nuclear and four mitochondrial genes) and a stratified taxon sampling to consider 198 species of nearly all families and genera of this order. Overall, our results show that phylogenetic closeness is directly related to geographical distance. Importantly, we found that Orestias is not part of the Cyprinodontidae family, and that it is more closely related to the South American fish fauna, being the Fluviphylacidae the closest sister group. CONCLUSIONS: The evolutionary history of the Orestias genus is linked to the South American ichthyofauna and it should no longer be considered a member of the Cyprinodontidae family. Instead, we submit that Orestias belongs to the Orestiidae family, as suggested by Freyhof et al. (2017), and that it is the sister group of the Fluviphylacidae family, distributed in the Amazonian and Orinoco basins. These two groups likely diverged during the Late Eocene concomitant with hydrogeological changes in the South American landscape.


Assuntos
Ciprinodontiformes , Evolução Molecular , Genoma , Filogenia , Animais , Ciprinodontiformes/genética , Ciprinodontiformes/classificação , Elementos de DNA Transponíveis/genética , Tamanho do Genoma
11.
Cancer Discov ; 14(9): 1717-1731, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-38722595

RESUMO

Clonal hematopoiesis (CH) is a phenomenon of clonal expansion of hematopoietic stem cells driven by somatic mutations affecting certain genes. Recently, CH has been linked to the development of hematologic malignancies, cardiovascular diseases, and other conditions. Although the most frequently mutated CH driver genes have been identified, a systematic landscape of the mutations capable of initiating this phenomenon is still lacking. In this study, we trained machine learning models for 12 of the most recurrent CH genes to identify their driver mutations. These models outperform expert-curated rules based on prior knowledge of the function of these genes. Moreover, their application to identify CH driver mutations across almost half a million donors of the UK Biobank reproduces known associations between CH driver mutations and age, and the prevalence of several diseases and conditions. We thus propose that these models support the accurate identification of CH across healthy individuals. Significance: We developed and validated gene-specific machine learning models to identify CH driver mutations, showing their advantage with respect to expert-curated rules. These models can support the identification and clinical interpretation of CH mutations in newly sequenced individuals. See related commentary by Arends and Jaiswal, p. 1581.


Assuntos
Hematopoiese Clonal , Aprendizado de Máquina , Mutagênese , Mutação , Humanos , Hematopoiese Clonal/genética , Simulação por Computador , Neoplasias Hematológicas/genética
12.
J Wildl Dis ; 60(3): 561-571, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38777337

RESUMO

Freshwater fish species are experiencing the highest decline among vertebrates in this century. Although a great effort has been made to identify and tackle threats to the conservation of this taxa, several knowledge gaps still exist particularly for noncommercial endangered species, including considerations regarding fish health status. These species face deteriorating environmental conditions in their natural habitats that may lead to stress and increased risk for infectious disease outbreaks. Establishing health surveillance is crucial to identify and predict physiologic disruption in fish populations. Additionally, information retrieved may be used to direct targeted efforts to contribute to improving the conservation status of these species. We used threatened Iberian leuciscids as a case study to discuss the current knowledge regarding their health surveillance and to suggest recommendations for the establishment of practical health assessments that can benefit conservation plans for these species and be implemented in threatened or endangered freshwater fish species plans globally.


Assuntos
Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Peixes , Animais , Água Doce , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/prevenção & controle
13.
Adv Mater ; 36(31): e2401809, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38717569

RESUMO

Realizing topological superconductivity by integrating high-transition-temperature (TC) superconductors with topological insulators can open new paths for quantum computing applications. Here, a new approach is reported for increasing the superconducting transition temperature ( T C onset ) $( {T_{\mathrm{C}}^{{\mathrm{onset}}}} )$ by interfacing the unconventional superconductor Fe(Te,Se) with the topological insulator Bi-Te system in the low-Se doping regime, near where superconductivity vanishes in the bulk. The critical finding is that the T C onset $T_{\mathrm{C}}^{{\mathrm{onset}}}$ of Fe(Te,Se) increases from nominally non-superconducting to as high as 12.5 K when Bi2Te3 is replaced with the topological phase Bi4Te3. Interfacing Fe(Te,Se) with Bi4Te3 is also found to be critical for stabilizing superconductivity in monolayer films where T C onset $T_{\mathrm{C}}^{{\mathrm{onset}}}$ can be as high as 6 K. Measurements of the electronic and crystalline structure of the Bi4Te3 layer reveal that a large electron transfer, epitaxial strain, and novel chemical reduction processes are critical factors for the enhancement of superconductivity. This novel route for enhancing TC in an important epitaxial system provides new insight on the nature of interfacial superconductivity and a platform to identify and utilize new electronic phases.

14.
Braz J Biol ; 84: e279979, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38747860

RESUMO

Papaya is a climacteric fruit, rapidly ripening after harvesting due to ethylene production and increased respiratory rate. This swift ripening results in softening of fruit tissues, shortening the fruit shelf life. Pre-cooling serves as an alternative to minimize fruit ripening and post-harvest losses by reducing metabolism. This study aimed to evaluate the effect of pre-cooling on the quality and conservation of Formosa 'Tainung I' papaya. Papayas at maturation stage II were obtained from a commercial orchard with conventional production. The experimental design was a completely randomized 4×6 split-plot scheme, with pre-cooling treatments (Control, without pre-cooling treatment; pre-cooling at 15 °C in a cold chamber; pre-cooling at 7 °C in a cold chamber; and forced-air cooling at 7 °C) in the plot, and days of storage (0, 7, 14, 21, 28, and 35 days) in the subplot. Pre-cooling effectively delayed the ripening and senescence of Formosa papaya, reducing the loss of green color and firmness. Regardless of the treatment used, chilling injury and incidence of fungi from the genus Fusarium and Alternaria limited the shelf life of Formosa 'Tainung I' papaya up to 21 days of storage. Additionally, the appearance of hardened regions in the pulp compromised the sensory quality of the fruits, necessitating further investigation into the causes of this disorder.


Assuntos
Carica , Temperatura Baixa , Armazenamento de Alimentos , Frutas , Carica/fisiologia , Carica/microbiologia , Fatores de Tempo , Frutas/microbiologia , Conservação de Alimentos/métodos
15.
Sci Total Environ ; 932: 172976, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38705304

RESUMO

Drylands impacted by energy development often require costly reclamation activities to reconstruct damaged soils and vegetation, yet little is known about the effectiveness of reclamation practices in promoting recovery of soil quality due to a lack of long-term and cross-site studies. Here, we examined paired on-pad and adjacent undisturbed off-pad soil properties over a 22-year chronosequence of 91 reclaimed oil or gas well pads across soil and climate gradients of the Colorado Plateau in the southwestern United States. Our goals were to estimate the time required for soil properties to reach undisturbed conditions, examine the multivariate nature of soil quality following reclamation, and identify environmental factors that affect reclamation outcomes. Soil samples, collected in 2020 and 2021, were analyzed for biogeochemical pools (total nitrogen, and total organic and inorganic carbon), chemical characteristics (salinity, sodicity, pH), and texture. Predicted time to recovery across all sites was 29 years for biogeochemical soil properties, 31 years for soil chemical properties, and 6 years for soil texture. Ordination of soil properties revealed differences between on- and off-pad soils, while site aridity explained variability in on-pad recovery. The predicted time to total soil recovery (distance between on- and off-pad in ordination space) was 96 years, which was longer than any individual soil property. No site reached total recovery, indicating that individual soil properties alone may not fully indicate recovery in soil quality as soil recovery does not equal the sum of its parts. Site aridity was the largest predictor of reclamation outcomes, but the effects differed depending on soil type. Taken together, results suggest the recovery of soil quality - which reflects soil fertility, carbon sequestration potential, and other ecosystem functions - was influenced primarily by site setting, with soil type and aridity major mediators of on-pad carbon, salinity, and total soil recovery following reclamation.

16.
Front Cell Neurosci ; 18: 1384085, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38644973

RESUMO

Amyotrophic lateral sclerosis (ALS) corresponds to a neurodegenerative disorder marked by the progressive degeneration of both upper and lower motor neurons located in the brain, brainstem, and spinal cord. ALS can be broadly categorized into two main types: sporadic ALS (sALS), which constitutes approximately 90% of all cases, and familial ALS (fALS), which represents the remaining 10% of cases. Transforming growth factor type-ß (TGF-ß) is a cytokine involved in various cellular processes and pathological contexts, including inflammation and fibrosis. Elevated levels of TGF-ß have been observed in the plasma and cerebrospinal fluid (CSF) of both ALS patients and mouse models. In this perspective, we explore the impact of the TGF-ß signaling pathway using a transient zebrafish model for ALS. Our findings reveal that the knockdown of tgfb1a lead to a partial prevention of motor axon abnormalities and locomotor deficits in a transient ALS zebrafish model at 48 h post-fertilization (hpf). In this context, we delve into the proposed distinct roles of TGF-ß in the progression of ALS. Indeed, some evidence suggests a dual role for TGF-ß in ALS progression. Initially, it seems to exert a neuroprotective effect in the early stages, but paradoxically, it may contribute to disease progression in later stages. Consequently, we suggest that the TGF-ß signaling pathway emerges as an attractive therapeutic target for treating ALS. Nevertheless, further research is crucial to comprehensively understand the nuanced role of TGF-ß in the pathological context.

17.
Mol Psychiatry ; 29(9): 2701-2713, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38548982

RESUMO

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk.


Assuntos
Bancos de Espécimes Biológicos , Transtorno Bipolar , Comorbidade , Registros Eletrônicos de Saúde , Herança Multifatorial , Fenótipo , Humanos , Transtorno Bipolar/genética , Transtorno Bipolar/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Herança Multifatorial/genética , Estudo de Associação Genômica Ampla/métodos , Predisposição Genética para Doença/genética , Adulto , Idoso de 80 Anos ou mais , Fatores de Risco , Fenômica/métodos
18.
Artigo em Inglês | MEDLINE | ID: mdl-38492558

RESUMO

OBJECTIVES: Bar dislocation is one of the most feared complications of the minimally invasive repair of pectus excavatum. METHODS: Prospective randomized parallel-group clinical trial intending to assess whether oblique stabilizers can reduce bar displacement in comparison with regular stabilizers used in minimally invasive repair of pectus excavatum. Additionally, we evaluated pain, quality of life and other postoperative complications. Participants were randomly assigned to surgery with perpendicular (n = 16) or oblique stabilizers (n = 14) between October 2017 and September 2018 and followed for 3 years. Bar displacements were evaluated with the bar displacement index. Pain scores were evaluated through visual analogue scale and quality of life through the Pectus Excavatum Evaluation Questionnaire. RESULTS: Control group average displacement index was 17.7 (±26.7) and intervention group average displacement index was 8.2 (±10.9). There was 1 reoperation in each group that required correction with 2 bars. Bar displacement was similar among groups (P = 0.12). No other complications were recorded. There was no statistically significant difference on pain score. There was a significant difference between pre- and postoperative composite scores of the participants' body image domain and psycho-social aspects in both groups. The difference between the pre- and postoperative participants' perception of physical difficulties was greater and statistically significant in the intervention group. CONCLUSIONS: There was no statistical difference in the use of perpendicular or oblique stabilizers, but the availability of different models of stabilizers during the study suggested that this can be advantageous. The trial is registered at ClinicalTrials.gov, number NCT03087734.

19.
Cureus ; 16(1): e53302, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38435902

RESUMO

The Epstein-Barr virus (EBV) is a DNA virus that has been infecting humans since ancient times, capable of causing a wide range of pathologies and affecting approximately 90% of the population. A 61-year-old male with no significant medical history presented with a 5-day history of imbalance and difficulty walking. Neurological examination revealed specific findings, including absent reflexes, bilateral asynergy, and gait abnormalities. Contrasting with Guillain-Barré Syndrome, lumbar puncture suggested a central nervous system infection. Serological testing confirmed Epstein-Barr virus (EBV) positivity, and intravenous immunoglobulin led to significant improvement. Electromyogram results suggested inflammatory/ipnfectious polyradiculopathy. Repeat EBV serology, showing strongly positive IgG and negative IgM, confirmed the diagnosis of Polyradiculoneuropathy secondary to EBV. This case underscores the rare neurological complications of EBV and the importance of considering viral infections in such presentations.

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