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1.
Nat Commun ; 15(1): 2962, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580642

RESUMO

The projected trajectory of multidrug resistant tuberculosis (MDR-TB) epidemics depends on the reproductive fitness of circulating strains of MDR M. tuberculosis (Mtb). Previous efforts to characterize the fitness of MDR Mtb have found that Mtb strains of the Beijing sublineage (Lineage 2.2.1) may be more prone to develop resistance and retain fitness in the presence of resistance-conferring mutations than other lineages. Using Mtb genome sequences from all culture-positive cases collected over two years in Moldova, we estimate the fitness of Ural (Lineage 4.2) and Beijing strains, the two lineages in which MDR is concentrated in the country. We estimate that the fitness of MDR Ural strains substantially exceeds that of other susceptible and MDR strains, and we identify several mutations specific to these MDR Ural strains. Our findings suggest that MDR Ural Mtb has been transmitting efficiently in Moldova and poses a substantial risk of spreading further in the region.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Moldávia/epidemiologia , Genótipo , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Farmacorresistência Bacteriana Múltipla/genética
2.
Comp Biochem Physiol C Toxicol Pharmacol ; 281: 109922, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615807

RESUMO

While wastewater and paint particles discharged from the in-water cleaning process of ship hulls are consistently released into benthic ecosystems, their hazardous effects on non-target animals remain largely unclear. In this study, we provide evidence on acute harmful effects of hull cleaning wastewater in marine polychaete Perinereis aibuhitensis by analyzing physiological and biochemical parameters such as survival, burrowing activity, and oxidative status. Raw wastewater samples were collected during ship hull cleaning processes in the field. Two wastewater samples for the exposure experiment were prepared in the laboratory: 1) mechanically filtered in the in-water cleaning system (MF) and 2) additionally filtered with a 0.45 µm filter in the laboratory (LF). These wastewater samples contained high concentrations of metals (zinc and copper) and metal-based booster biocides (copper pyrithione and zinc pyrithione) compared to those analyzed in seawater. Polycheates were exposed to different concentrations of the two wastewater samples for 96 h. Higher mortality was observed in response to MF compared to LF-exposed polychaetes. Both wastewater samples dose-dependently decreased burrowing activity and AChE activity. Drastic oxidative stress was observed in response to the two wastewater samples. MDA levels were significantly increased by MF and LF samples. Significant GSH depletion was observed with MF exposure, while increased and decreased GSH contents were observed in LF-exposed polychaetes. Enzymatic activities of antioxidant components, catalase, superoxide dismutase, and glutathione S-transferase were significantly modulated by both wastewater samples. These results indicate that even filtered hull cleaning wastewater can have deleterious effects on the health status of polychaetes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38469999

RESUMO

The combined cilostazol and rosuvastatin therapy is frequently used for coronary artery disease treatment. This open-label, 3 × 3 crossover clinical trial evaluated the pharmacokinetics and safety of a fixed-dose combination (FDC) of cilostazol/rosuvastatin (200 + 20 mg) versus a concurrent administration of the separate components (SCs) under both fasted and fed conditions. Among 48 enrolled healthy adults, 38 completed the study. Participants were administered a single oral dose of cilostazol/rosuvastatin (200 + 20 mg), either as an FDC or SCs in a fasted state, or FDC in a fed state, in each period of the trial. Blood samples were taken up to 48 hours after dosing, and plasma concentrations were analyzed using validated liquid chromatography-tandem mass spectrometry. The geometric mean ratios of FDC to SCs for area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast ) and maximum plasma concentration (Cmax ) were 0.94/1.05 and 1.06/1.15 for cilostazol and rosuvastatin, respectively (AUClast /Cmax ). Compared with that during fasting, fed-state administration increased the AUClast and Cmax for cilostazol by approximately 72% and 160% and decreased these parameters for rosuvastatin by approximately 39% and 43%, respectively. To conclude, the FDC is bioequivalent to the SCs, with notable differences in pharmacokinetics when administered in a fed state. No significant safety differences were observed between the treatments.

4.
Mar Pollut Bull ; 200: 116121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354590

RESUMO

While wastewater discharged from in-water cleaning process of ship hulls on rotifer consistently released into aquatic ecosystem, its detrimental effects on non-target animals are largely unclear. In this study, we provide evidence on detrimental effects of hull cleaning wastewater in the monogonont rotifer Brachionus manjavacas by analyzing biochemical and physiological parameters in its oxidative status, survival, lifespan, growth, fecundity, and population. The wastewater contained high concentrations of metals (Zn and Cu) and metal-based antifoulants (CuPT and ZnPT). Significant oxidative stress was observed in response to two wastewater samples [1) raw wastewater (RW) and 2) mechanical filtrated in the cleaning system (MF)]. Higher detrimental effects in survival, lifespan, fecundity, and population growth for 10 days were measured in the RW-exposed rotifers than those results analyzed in the MF-exposed rotifers. Two growth parameters, lorica length and width were also significantly modulated by both wastewater samples. These results indicate that even filtered hull cleaning wastewater would have deleterious effects on the maintenance of the rotifer population when they exposed constantly.


Assuntos
Rotíferos , Poluentes Químicos da Água , Animais , Águas Residuárias , Crescimento Demográfico , Ecossistema , Estágios do Ciclo de Vida , Estresse Oxidativo , Poluentes Químicos da Água/toxicidade
5.
Exp Mol Med ; 56(2): 453-460, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38413820

RESUMO

The major drawbacks of RNA sequencing (RNA-seq), a remarkably accurate transcriptome profiling method, is its high cost and poor scalability. Here, we report a highly scalable and cost-effective method for transcriptomics profiling called Bulk transcriptOme profiling of cell Lysate in a single poT (BOLT-seq), which is performed using unpurified bulk 3'-end mRNA in crude cell lysates. During BOLT-seq, RNA/DNA hybrids are directly subjected to tagmentation, and second-strand cDNA synthesis and RNA purification are omitted, allowing libraries to be constructed in 2 h of hands-on time. BOLT-seq was successfully used to cluster small molecule drugs based on their mechanisms of action and intended targets. BOLT-seq competes effectively with alternative library construction and transcriptome profiling methods.


Assuntos
Perfilação da Expressão Gênica , RNA , RNA/genética , RNA Mensageiro/genética , Biblioteca Gênica , DNA Complementar/genética , Perfilação da Expressão Gênica/métodos
6.
J Pers Med ; 14(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38392618

RESUMO

This study aimed to investigate whether targeted temperature management (TTM) could enhance outcomes in patients with out-of-hospital cardiac arrest (OHCA) treated with extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest. Using a nationwide OHCA registry, adult patients with witnessed OHCA of presumed cardiac origin who underwent ECPR at the emergency department between 2008 and 2021 were included. We examined the effect of ECPR with TTM on survival and neurological outcomes at hospital discharge using propensity score matching and multivariable logistic regression compared with patients treated with ECPR without TTM. Odds ratios and 95% confidence intervals were determined. A total of 399 ECPR cases were analyzed among 380,239 patients with OHCA. Of these, 330 underwent ECPR without TTM and 69 with TTM. After propensity score matching, 69 matched pairs of patients were included in the analysis. No significant differences in survival and good neurological outcomes between the two groups were observed. In the multivariable logistic regression, no significant differences were observed in survival and neurological outcomes between ECPR with and without TTM. Among the patients who underwent ECPR after OHCA, ECPR with TTM did not improve outcomes compared with ECPR without TTM.

7.
Laryngoscope ; 134(1): 315-317, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37530589

RESUMO

OBJECTIVE: Muscle tension in the head and neck may co-occur with temporomandibular dysfunction (TMD) possibly leading to voice change. Several studies have reported a correlation between TMD and dysphonia. However, literature on TMD and voice-related quality of life (QOL) is scant. This study aimed to investigate the relationship between TMD and self-perceived voice-related QOL impairment. METHODS: Patients from TMD clinic were prospectively surveyed on voice-related quality of life using the Voice Handicap Index (VHI) questionnaire. Patients were queried using paper and pen upon initial evaluation in dentistry clinic for temporomandibular disorders by a single dentist or dental assistant in the otolaryngology department. RESULTS: A total of 53 patients completed the VHI. 80% of patients presenting to TMD clinic had VHI scores above zero, but most had minimal to mild impairment. Forty-two patients had scores between 1 and 86, (average 10.98); 11 patients had a score of zero (20.75%). Total average score: 8.70, range: 0-86, median: 4. Functional average score: 3.13, range: 0-29, median: 1. Physical average score: 3.58. range: 0-25, median: 2. Emotional average score: 1.98, range: 0-32, median: 0; these averages did not differ from historical controls. CONCLUSION: The majority of patients presenting to TMD clinic also presented with some level of voice-related QOL impairment, although minimal and consistent with historical VHI controls. Data indicates that TMD disease may be primarily defined as functionally and physically uncomfortable. Incorporation of interdisciplinary care, with laryngology, speech pathology, physical therapy, counseling, and pain management may be warranted. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:315-317, 2024.


Assuntos
Disfonia , Transtornos da Articulação Temporomandibular , Voz , Humanos , Qualidade de Vida/psicologia , Qualidade da Voz , Inquéritos e Questionários , Índice de Gravidade de Doença , Transtornos da Articulação Temporomandibular/complicações , Avaliação da Deficiência
8.
Artigo em Inglês | MEDLINE | ID: mdl-38061617

RESUMO

Triclosan, a chlorinated biphenyl ether is widely used in industrial products and cosmetics due to its antibiotic activity. Although relatively levels of triclosan have been detected in aquatic ecosystems, limited information is available regarding the acute and chronic impacts of triclosan on aquatic invertebrates, especially planktonic crustaceans. In this study, we analyzed the acute (24 h) and chronic (14 days exposure across three generations) effects of different concentrations of triclosan [1/10 of the no observed effect concentration (NOEC), the NOEC, and 1/10 of the LC50] calculated from the 24 h acute toxicity value, on the water flea Moina macrocopa. In the acute exposure experiment, the 1/10 LC50 value of triclosan significantly reduced survival, feeding rate, thoracic limb activity, heart activity, and acetylcholinesterase activity. In response to the 1/10 LC50 value, intracellular reactive oxygen species increased along with elevated levels of malondialdehyde and glutathione. Enzymatic activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly increased by the 1/10 LC50 value, suggesting active protection of the antioxidant defense system against oxidative stress. Chronic exposure to the 1/10 NOEC and NOEC values revealed multigenerational adverse impacts of triclosan. The second generation was found to be the most sensitive to triclosan, as the NOEC value significantly reduced the survival rate, body length, and the number of neonates per brood, along with a delayed hatching period. Taken together, these results indicate that even sublethal levels of triclosan can have detrimental effects on the water flea population's maintenance through intergenerational toxicity.


Assuntos
Cladóceros , Triclosan , Poluentes Químicos da Água , Animais , Humanos , Recém-Nascido , Triclosan/toxicidade , Acetilcolinesterase , Ecossistema , Poluentes Químicos da Água/toxicidade
9.
Otolaryngol Head Neck Surg ; 170(3): 708-723, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38108590

RESUMO

OBJECTIVE: The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax. REVIEW METHODS: Outcome data for the meta-analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta-analysis was performed using the DerSimonian-Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta-analysis. RESULTS: Thirty-six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta-analysis of the various outcome variables. Our pooled meta-analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17-1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36). CONCLUSION: Our pooled Meta-analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.


Assuntos
60523 , Sinusite , Humanos , Sobrepeso/epidemiologia , Leptina , Obesidade/complicações , Obesidade/epidemiologia , Sinusite/complicações , Sinusite/epidemiologia , Doença Crônica
10.
Ecol Lett ; 26 Suppl 1: S62-S80, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37840022

RESUMO

Gene drive technology, in which fast-spreading engineered drive alleles are introduced into wild populations, represents a promising new tool in the fight against vector-borne diseases, agricultural pests and invasive species. Due to the risks involved, gene drives have so far only been tested in laboratory settings while their population-level behaviour is mainly studied using mathematical and computational models. The spread of a gene drive is a rapid evolutionary process that occurs over timescales similar to many ecological processes. This can potentially generate strong eco-evolutionary feedback that could profoundly affect the dynamics and outcome of a gene drive release. We, therefore, argue for the importance of incorporating ecological features into gene drive models. We describe the key ecological features that could affect gene drive behaviour, such as population structure, life-history, environmental variation and mode of selection. We review previous gene drive modelling efforts and identify areas where further research is needed. As gene drive technology approaches the level of field experimentation, it is crucial to evaluate gene drive dynamics, potential outcomes, and risks realistically by including ecological processes.


Assuntos
Tecnologia de Impulso Genético , Evolução Biológica , Alelos , Retroalimentação , Dinâmica Populacional
11.
Healthcare (Basel) ; 11(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37570421

RESUMO

This study aimed to evaluate the effects of an 8-week self-administered moxibustion program on blood pressure, stress, sleep quality, and quality of life in hypertensive patients. We compared its effects with those of self-acupressure to assess the feasibility of using moxibustion as a self-management method for hypertension. Forty-six subjects were recruited and randomly assigned to a moxibustion group and an acupressure group. The moxibustion group applied moxa sticks to seven acupoints by themselves five times a week for 8 weeks, while the acupressure group placed acupressure patches on the same acupoints by themselves. Systolic and diastolic blood pressures were measured. Stress was assessed with plasma epinephrine, plasma norepinephrine, and the Perceived Stress Scale (PSS). Sleep quality and quality of life were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF), respectively. Systolic and diastolic blood pressures decreased in the moxibustion and acupressure groups to a similar extent after the 8-week intervention. Plasma epinephrine and norepinephrine levels and PSQI variables were not changed in both groups. PSS decreased only in the moxibustion group. Quality of life related to physical health and environmental health, as assessed by the WHOQOL-BREF, significantly improved to a similar degree in both groups. Both self-administered moxibustion and acupressure therapies were effective in reducing blood pressure in hypertensive patients.

12.
BMC Womens Health ; 23(1): 456, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37641079

RESUMO

BACKGROUND: Sleep deprivation is known to be a risk factor for premenstrual syndrome and primary dysmenorrhea in adults. However, it has rarely been investigated in adolescents. The aim of this study was to investigate whether sleep pattern, duration, and quality independently affect premenstrual syndrome and primary dysmenorrhea in adolescent girls. An additional purpose was to investigate the sleep status in Korean adolescent girls during the COVID-19 pandemic. METHODS: A cross-sectional survey study was conducted in 519 high school girls aged 15 to 18 years in Gyeonggido, South Korea, in 2021 during the COVID-19 lockdown. Menstrual pain intensity and menstrual symptoms were assessed using the visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS), respectively. Premenstrual syndrome was assessed by the premenstrual symptoms screening tool (PSST). Sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). The known risk factors of dysmenorrhea, including menstrual and lifestyle characteristics and stress, were assessed as covariates. RESULTS: During the pandemic, approximately 68% of girls slept 7 h or less, while about 60% reported poor sleep quality. Additionally, 64% of participants had a bedtime later after 1AM, and 34% woke up later after 8AM. Late bedtime significantly affected VAS (P = 0.05), CMSS severity and frequency (both P < 0.01), and PSST symptom (P < 0.01). Waking up late affected CMSS severity (P < 0.05), PSST symptom (P = 0.05), and PSST function (P < 0.05). However, the significance of these effects disappeared after controlling for covariates. Sleeping less than 5 h affected CMSS frequency (P < 0.05) and PSST symptoms (P < 0.001). After controlling for covariates, the significance of the effect on PSST symptom remained (P < 0.05). General sleep quality and PSQI components, including subjective sleep quality, sleep latency, sleep disturbance, use of sleeping medication, and daytime dysfunction, significantly affected CMSS frequency and severity and PSST symptom after controlling for covariates (P < 0.05, P < 0.01, or P < 0.001). The multiple regression analysis revealed that among sleep characteristics, sleep quality was the most important risk factor of premenstrual syndrome and dysmenorrhea. CONCLUSION: Our study result heightens the importance of healthy sleep hygiene, especially sleep quality in the management of premenstrual syndrome and dysmenorrhea in adolescent girls.


Assuntos
COVID-19 , Síndrome Pré-Menstrual , Feminino , Adolescente , Adulto , Humanos , Dismenorreia/epidemiologia , Estudos Transversais , Pandemias , Controle de Doenças Transmissíveis , Síndrome Pré-Menstrual/epidemiologia , Sono , República da Coreia/epidemiologia
13.
Eur J Hum Genet ; 31(11): 1283-1290, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37567955

RESUMO

In many forensic settings, identity of a DNA sample is sought from poor-quality DNA, for which the typical STR loci tabulated in forensic databases are not possible to reliably genotype. Genome-wide SNPs, however, can potentially be genotyped from such samples via next-generation sequencing, so that queries can in principle compare SNP genotypes from DNA samples of interest to STR genotype profiles that represent proposed matches. We use genetic record-matching to evaluate the possibility of testing SNP profiles obtained from poor-quality DNA samples to identify exact and relatedness matches to STR profiles. Using simulations based on whole-genome sequences, we show that in some settings, similar match accuracies to those seen with full coverage of the genome are obtained by genetic record-matching for SNP data that represent 5-10% genomic coverage. Thus, if even a fraction of random genomic SNPs can be genotyped by next-generation sequencing, then the potential may exist to test the resulting genotype profiles for matches to profiles consisting exclusively of nonoverlapping STR loci. The result has implications in relation to criminal justice, mass disasters, missing-person cases, studies of ancient DNA, and genomic privacy.


Assuntos
Impressões Digitais de DNA , Polimorfismo de Nucleotídeo Único , Humanos , Impressões Digitais de DNA/métodos , Repetições de Microssatélites , Genótipo , Genômica , DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos
14.
Sensors (Basel) ; 23(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37447799

RESUMO

Wireless sensor networks (WSNs) have been utilized as communication infrastructure for smart grid applications. The primary requirement of WSNs for smart grid applications is to transmit delay-critical data from smart grid assets ether at the maximum rate or by reducing collision rates. Additionally, WSNs should utilize the limited resources of the network to provide the required long-term QoS. The achievement of these objectives requires a remarkable design of WSN protocols to satisfy the requirements of smart grid applications. In this study, a multi-channel cluster tree protocol is proposed to prevent collisions and increase network performance. In the proposed scheme, the cluster head serves to broadcast a beacon frame containing information on the allocated channels and time slots. This enables the new node to determine its channel and timeslot. A performance analysis reveals that the proposed scheme can achieve a low end-to-end delay and low collision rates compared with the well-known IEEE 802.15.4 MAC protocols widely used in the literature to provide QoS to smart-grid applications.


Assuntos
Redes de Comunicação de Computadores , Tecnologia sem Fio
15.
Transl Clin Pharmacol ; 31(2): 95-104, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37440778

RESUMO

This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a non-compartmental method with Phoenix WinNonlin®. A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (Cmax) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795-0.9614) and 0.8630 (0.8472-0.8791) in the fasting study and 1.0926 (1.0102-1.1818) and 0.9998 (0.9675-1.0332) in the fed study, respectively. The time to reach Cmax of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow. Trial Registration: Clinical Research Information Service Identifier: KCT0007177, KCT0003304.

16.
Healthcare (Basel) ; 11(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37510517

RESUMO

The effect of Pilates on dysmenorrhea has been little studied. The purpose of this study was to evaluate the effect of Pilates on menstrual pain and symptoms, premenstrual syndrome, and risk factors of dysmenorrhea. Thirty young women with primary dysmenorrhea were randomly assigned into a Pilates group (PG; n = 15) and a waitlist control group (CG; n = 15). The Pilates was performed twice a week for 12 weeks. Menstrual pain and symptoms were measured by visual analogue scale (VAS) and the Cox menstrual symptom scale (CMSS), respectively. Premenstrual syndrome was assessed using the premenstrual symptoms screening tool (PSST). Additionally, back flexibility, hip muscle strength, sleep duration and quality, perceived stress, state-trait anxiety, and depression were evaluated. The VAS, CMSS severity and frequency, and PSST symptoms and functional impairments decreased in the PG compared to the CG (p < 0.001 or p < 0.01) with large effect sizes. Back flexibility and the strength of hip flexors, hip extensors, and hip abductors significantly increased in the PG compared to the CG (all p < 0.01) with large effect sizes. Sleep quality (p < 0.01) and stress (p < 0.05) improved in the PG. Sleep duration, anxiety, and depression did not change in either group. In conclusion, the 12-week Pilates intervention ameliorates dysmenorrhea, partly mediated by improved physical function and sleep quality.

17.
J Funct Biomater ; 14(4)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37103282

RESUMO

Cyclooxygenase-2 (COX-2) is a biomolecule known to be overexpressed in inflammation. Therefore, it has been considered a diagnostically useful marker in numerous studies. In this study, we attempted to assess the correlation between COX-2 expression and the severity of intervertebral disc (IVD) degeneration using a COX-2-targeting fluorescent molecular compound that had not been extensively studied. This compound, indomethacin-adopted benzothiazole-pyranocarbazole (IBPC1), was synthesized by introducing indomethacin-a compound with known selectivity for COX-2-into a phosphor with a benzothiazole-pyranocarbazole structure. IBPC1 exhibited relatively high fluorescence intensity in cells pretreated with lipopolysaccharide, which induces inflammation. Furthermore, we observed significantly higher fluorescence in tissues with artificially damaged discs (modeling IVD degeneration) compared to normal disc tissues. These findings indicate that IBPC1 can meaningfully contribute to the study of the mechanism of IVD degeneration in living cells and tissues and to the development of therapeutic agents.

18.
PLoS Comput Biol ; 19(3): e1010897, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36940209

RESUMO

The coalescent is a powerful statistical framework that allows us to infer past population dynamics leveraging the ancestral relationships reconstructed from sampled molecular sequence data. In many biomedical applications, such as in the study of infectious diseases, cell development, and tumorgenesis, several distinct populations share evolutionary history and therefore become dependent. The inference of such dependence is a highly important, yet a challenging problem. With advances in sequencing technologies, we are well positioned to exploit the wealth of high-resolution biological data for tackling this problem. Here, we present adaPop, a probabilistic model to estimate past population dynamics of dependent populations and to quantify their degree of dependence. An essential feature of our approach is the ability to track the time-varying association between the populations while making minimal assumptions on their functional shapes via Markov random field priors. We provide nonparametric estimators, extensions of our base model that integrate multiple data sources, and fast scalable inference algorithms. We test our method using simulated data under various dependent population histories and demonstrate the utility of our model in shedding light on evolutionary histories of different variants of SARS-CoV-2.


Assuntos
COVID-19 , Humanos , Teorema de Bayes , COVID-19/epidemiologia , SARS-CoV-2/genética , Dinâmica Populacional , Modelos Estatísticos , Algoritmos , Modelos Genéticos , Genética Populacional
19.
Nat Genet ; 55(4): 607-618, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36928603

RESUMO

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma Maligno/genética , Mesotelioma Maligno/complicações , Mesotelioma/genética , Mesotelioma/patologia , Multiômica , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/genética
20.
Am J Otolaryngol ; 44(4): 103862, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37001394

RESUMO

Soft-tissue calcifications in the head and neck are relatively common and are the result of a wide variety of benign and malignant pathologies. They can present a diagnostic challenge given the broad range of underlying etiologies. Uremic tumoral calcinosis (UTC) is a rare complication of end-stage renal disease (ESRD) resulting from metastatic soft tissue calcification. Common sites include periarticular soft tissues of the shoulders, elbows, and hands (Pan and Chen, 2016). UTC can also affect the cervical spine and mimic osteosarcomas (Zhou et al., 2018). We present the case of a 71-year-old female with hypertension, left carotid artery stenosis, mitral valve prolapse, and ESRD secondary to diabetes mellitus type II (DMII) on peritoneal dialysis who was found to have large, heterogeneous, bilateral calcified neck masses. Given her clinical history, laboratory results, and imaging findings, she was diagnosed with UTC. In addition to this case, we provide an overview of tumoral calcinosis (TC) and a differential diagnosis for calcified lesions of the head and neck.


Assuntos
Calcinose , Falência Renal Crônica , Humanos , Feminino , Idoso , Calcinose/complicações , Calcinose/diagnóstico por imagem , Pescoço , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Vértebras Cervicais , Cabeça
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