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1.
Braz. j. biol ; 83: e246803, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1339417

ABSTRACT

Abstract Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitant's age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.


Resumo A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados ​​por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das plantas da área para suas necessidades de saúde e outros usos como vegetal, lenha, forragem etc. O resultado atual de RFC, UV, ICF, FL e JI mostra que a flora medicinal precisa ser investigada farmacológica e fitoquimicamente para comprovar sua eficácia. A documentação do conhecimento medicinal é importante para preservar esse precioso conhecimento antigo antes que se perca para sempre, devido às mudanças tecnológicas e ambientais do mundo.


Subject(s)
Humans , Middle Aged , Aged , Aged, 80 and over , Young Adult , Plants, Medicinal , Pakistan , Surveys and Questionnaires , Plant Leaves , Ethnobotany , Phytotherapy , Medicine, Traditional
2.
Braz. j. biol ; 83: e249911, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1339366

ABSTRACT

Abstract Hematological and hematopoietic cells malignancies of the genes and hematopoietic cells are associated with the genetic mutation, often at the chromosomal level. The standard cytogenetic study is widely accepted as one of the main diagnostics and prognostic determinants in patients. Therefore, the current descriptive and cross-sectional study sought to determine the cytogenetic analysis of frequent hematological malignancies in Pakistan. A total of 202 peripheral bone marrow or blood samples from patients with benign and malignant hematological malignancy were taken using a conventional G-banding technique. Among enrolled patients, the mean age was 21.5 years ± 23.4, and gender-wise distribution showed a marked predominance of the male 147 (73%) population compared to the female 55 (27%). Patients in the age group (2-10 years) had the highest frequency, 48 (24%), of hematological neoplasms, followed by age (11-20 years) with 40 (20%). Normal karyotypes (46, XX/46, XY) was found in 51% (n=103) patients. Furthermore, the frequency of complex karyotype was 30 (15%), while normal was seen in 171 (85%) patients. Pre-B Acute Lymphoblastic Leukemia (Pre-B ALL) was the most prevalent malignancy of 66 (33%), followed by Chronic Myelogenous Leukemia (CML) of 41 (20%) and Acute Lymphocytic Leukemia of 29 (14%). Translocation was the most prevalent 50 (25%), followed by hypotriploidy 14 (7%) and monosomy 8 (4%) on chromosome aberration analysis. In addition, t(9:22) translocation was found to be 20 (10%) in CML, with the majority in the age group (31-40 years). This study recommends that karyotyping should be tested frequently in hematological conditions because it may provide insight into the relative chromosomal changes associated with particular malignancies.


Resumo As neoplasias hematológicas e de células hematopoiéticas dos genes e as células hematopoiéticas estão associadas à mutação genética, geralmente em nível cromossômico. O estudo citogenético padrão é amplamente aceito como um dos principais determinantes diagnósticos e prognósticos em pacientes. Portanto, o presente estudo descritivo e transversal buscou determinar a análise citogenética de neoplasias hematológicas frequentes no Paquistão. Um total de 202 amostras de medula óssea periférica ou sangue de pacientes com malignidade hematológica benigna e maligna foi coletado usando uma técnica convencional de banda G. Entre os pacientes inscritos, a média de idade foi de 21,5 anos ± 23,4, e a distribuição por gênero mostrou uma marcada predominância da população masculina de 147 (73%) em comparação com a feminina de 55 (27%). Pacientes na faixa etária (2-10 anos) tiveram a maior frequência, 48 (24%), de neoplasias hematológicas, seguida da idade (11-20 anos) com 40 (20%). Cariótipos normais (46, XX / 46, XY) foram encontrados em 51% (n = 103) dos pacientes. Além disso, a frequência de cariótipo complexo foi de 30 (15%), enquanto normal foi observada em 171 (85%) pacientes. Leucemia linfoblástica aguda pré-B (LLA Pré-B) foi a doença maligna mais prevalente de 66 (33%), seguida por leucemia mieloide crônica (LMC) de 41 (20%) e leucemia linfocítica aguda de 29 (14%). A translocação foi o 50 mais prevalente (25%), seguido por hipotriploidia 14 (7%) e monossomia 8 (4%) na análise de aberração cromossômica. Além disso, a translocação t (9:22) encontrada foi de 20 (10%) na LMC, com a maioria na faixa etária (31-40 anos). Este estudo recomenda que o cariótipo deve ser testado com frequência em condições hematológicas porque pode fornecer informações sobre as alterações cromossômicas relativas associadas a doenças malignas específicas.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Young Adult , Chromosome Aberrations , Hematologic Neoplasms/genetics , Hematologic Neoplasms/epidemiology , Pakistan/epidemiology , Cross-Sectional Studies , Karyotyping
3.
Clin Pharmacol Drug Dev ; 11(2): 165-172, 2022 02.
Article in English | MEDLINE | ID: mdl-34453416

ABSTRACT

Tadalafil is an effective, reversible, and competitive phosphodiesterase 5 inhibitor mainly used to treat erectile dysfunction. This study investigated the bioequivalence of generic and marketed formulations of 10-mg tadalafil tablets under fasted and fed conditions. This open-label, randomized, single-dose, 2-period crossover study included 53 healthy Chinese men (aged 20-43 years). Plasma samples were collected from 0.5 hours before treatment to 72 hours after each dose and analyzed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety assessments were performed throughout the study. For the fasted state, the 90% confidence intervals of the geometric mean ratios between the generic and marketed formulations were 86.1% to 99.1% for the maximum plasma concentration and 88.4% to 100.3% for the area under the plasma concentration-time curve from time 0 to infinity, and the corresponding values under the fed state were and 99.9% to 108.4% and 95.7% to 104.3%, respectively. All data were within the accepted bioequivalence range of 80% to 125%. After consuming high-fat, high-calorie meals in the fed condition, the time to the maximum plasma concentration was similar between the formulations, and area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 10.2% and 6.55% higher, respectively, for the marketed formulation. Thus, food had no clinically relevant effect on tadalafil exposure following a single oral dose in healthy Chinese men. No serious adverse reactions were reported. These results indicated that the analyzed generic and marketed tadalafil tablets were bioequivalent with similar safety profiles.


Subject(s)
Fasting , Adult , China , Cross-Over Studies , Humans , Male , Tablets , Tadalafil/adverse effects , Therapeutic Equivalency , Young Adult
4.
Gigascience ; 112022 03 07.
Article in English | MEDLINE | ID: mdl-35254424

ABSTRACT

BACKGROUND: One of the goals of neuropsychology is to understand the brain mechanisms underlying aspects of attention and cognitive control. Several tasks have been developed as a part of this body of research, however their results are not always consistent. A reliable comparison of the data and a synthesis of study conclusions has been precluded by multiple methodological differences. Here, we describe a publicly available, high-density electroencephalography (EEG) dataset obtained from 42 healthy young adults while they performed 3 cognitive tasks: (i) an extended multi-source interference task; (ii) a 3-stimuli oddball task; (iii) a control, simple reaction task; and (iv) a resting-state protocol. Demographic and psychometric information are included within the dataset. DATASET VALIDATION: First, data validation confirmed acceptable quality of the obtained EEG signals. Typical event-related potential (ERP) waveforms were obtained, as expected for attention and cognitive control tasks (i.e., N200, P300, N450). Behavioral results showed the expected progression of reaction times and error rates, which confirmed the effectiveness of the applied paradigms. CONCLUSIONS: This dataset is well suited for neuropsychological research regarding common and distinct mechanisms involved in different cognitive tasks. Using this dataset, researchers can compare a wide range of classical EEG/ERP features across tasks for any selected subset of electrodes. At the same time, 128-channel EEG recording allows for source localization and detailed connectivity studies. Neurophysiological measures can be correlated with additional psychometric data obtained from the same participants. This dataset can also be used to develop and verify novel analytical and classification approaches that can advance the field of deep/machine learning algorithms, recognition of single-trial ERP responses to different task conditions, and detection of EEG/ERP features for use in brain-computer interface applications.


Subject(s)
Brain-Computer Interfaces , Electroencephalography , Brain/physiology , Cognition/physiology , Electroencephalography/methods , Evoked Potentials/physiology , Humans , Young Adult
5.
J Clin Pharmacol ; 62(2): 206-219, 2022 02.
Article in English | MEDLINE | ID: mdl-34435684

ABSTRACT

Population pharmacokinetic (PK) and exposure-safety analyses of alisertib were performed in children enrolled in 2 clinical trials: NCT02444884 and NCT01154816. NCT02444884 was a dose-finding study in children with relapsed/refractory solid malignancies (phase 1) or neuroblastomas (phase 2). Patients received oral alisertib 45 to 100 mg/m2 as powder-in-capsule once daily or twice daily for 7 days in 21-day cycles. Serial blood samples were collected up to 24 hours after dosing on cycle 1, day 1. NCT01154816 was a phase 2 single-arm study evaluating efficacy in children with relapsed/refractory solid malignancies or acute leukemias. Patients received alisertib 80 mg/m2 as enteric-coated tablets once daily for 7 days in 21-day cycles. Sparse PK samples were collected up to 8 hours after dosing on cycle 1, day 1. Sources of alisertib PK variability were characterized and quantified using nonlinear mixed-effects modeling to support dosing recommendations in children and adolescents. A 2-compartment model with oral absorption described by 3 transit compartments was developed using data from 146 patients. Apparent oral clearance and central distribution volume were correlated with body surface area across the age range of 2 to 21 years, supporting the use of body surface area-based alisertib dosing in the pediatric population. The recommended dose of 80 mg/m2 once daily enteric-coated tablets provided similar alisertib exposures across pediatric age groups and comparable exposure to that in adults receiving 50 mg twice daily (recommended adult dose). Statistically significant relationships (P < .01) were observed between alisertib exposures and incidence of grade ≥2 stomatitis and febrile neutropenia, consistent with antiproliferative mechanism-related toxicities.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Azepines/pharmacokinetics , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacokinetics , Pyrimidines/pharmacokinetics , Adolescent , Antineoplastic Agents/adverse effects , Azepines/adverse effects , Body Surface Area , Child , Child, Preschool , Drug Administration Schedule , Female , Humans , Male , Maximum Tolerated Dose , Models, Biological , Neoplasm Staging , Neoplasms/pathology , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Young Adult
6.
Dermatol Ther ; 35(2): e15229, 2022 02.
Article in English | MEDLINE | ID: mdl-34820974

ABSTRACT

Carboxytherapy has been used in the treatment of autoimmune skin diseases such as psoriasis and morphea. Carboxytherapy has antioxidant effects, and leads to better tissue oxygenation, and release of growth factors. In this article, we decided to evaluate efficacy of combined carboxytherapy and narrowband-ultraviolet B (NB-UVB) compared to NB-UVB alone in the treatment of vitiligo. This is a prospective, split-body double-blind comparative study performed in patients with generalized stable vitiligo in acral areas and extremities referred to dermatology clinic of Afzalipour hospital in Kerman University of Medical Sciences. NB-UVB was performed three times a week in non-consecutive days for 4 months. In each patient, one lesion was randomly treated with carboxytherapy (weekly sessions for total of 16 sessions). Efficacy of treatment was evaluated by percentage of repigmentation of the lesions. Chi-square test and analysis of variance test (ANOVA) were used to compare efficacy of treatment based on demographic features of the patients and clinical features of the lesions, respectively. Twenty-eight patients with mean age of 32.35 ± 7.37 years old completed the study. At the end of the treatment, 37% of the patients in combination therapy group demonstrated more than 75% improvement compared to 0% in the monotherapy group (p = 0.001). There was no significant difference between either demographic features of the patients (age, sex, and skin phototypes) or duration of disease with efficacy of the treatment in both groups. Combination of carboxytherapy with NB-UVB leads to higher percentage of repigmentation and patients' satisfaction compared to monotherapy with NB-UVB.


Subject(s)
Ultraviolet Therapy , Vitiligo , Adult , Combined Modality Therapy , Humans , Prospective Studies , Skin/pathology , Treatment Outcome , Ultraviolet Therapy/adverse effects , Vitiligo/diagnosis , Vitiligo/drug therapy , Vitiligo/radiotherapy , Young Adult
7.
Horm Metab Res ; 54(2): 67-75, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35130567

ABSTRACT

Resistance to thyroid hormone syndrome (RTHS) is defined as increased thyroxine and triiodothyronine associated with normal or increased thyrotropin. This is usually due to a pathogenic variant of the gene coding for thyroid hormone receptor B (THRB). THRB is a rare genetic disorder characterized by an altered response of target tissue to the thyroid hormone action. Retrospective cross-sectional observational study with diagnosis of RTHS evaluated in secondary and tertiary hospitals for 6 years, from 2014 to 2020, in order to describe variables including age, sex, anthropometric data, clinical and biochemical characteristics of patients, who were divided according to age, in a pediatric group from 0 to 14 years (index cases), and an adult group composed of adult relatives of index cases. A molecular analysis of the THRB gene was performed. The total retrospective cohort included 7 pediatric patients and 15 adults. We found 22 cases with a clear male predominance (14/22). Mean age is 24.8 years old (22 days-70 years). Patients were referred because of symptoms 18.2% (4/22), analysis results 22.7% (5/22), or familial study 59.1% (13/22). About 31.8% (7/22) cases show goiter, 31.8% (7/22) sympathetic symptoms and 13.6% (3/22) abnormalities in behavior. In most cases, 77.3%, (17/22) show familial background of thyroid abnormalities. It is important to remark that 18.2% (4/22) relatives received previous incorrect treatments such as thyroidectomy, because of wrong diagnosis. In conclusion, a better understanding of RTHS, its prompt molecular diagnosis and genetic counseling, could avoid unnecessary tests and inappropriate treatments.


Subject(s)
Thyroid Hormone Resistance Syndrome , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Infant, Newborn , Male , Mutation , Retrospective Studies , Thyroid Hormone Receptors beta/genetics , Thyroid Hormone Resistance Syndrome/diagnosis , Thyroid Hormone Resistance Syndrome/genetics , Thyrotropin , Thyroxine , Triiodothyronine , Young Adult
8.
Ann R Coll Surg Engl ; 104(4): 308-313, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34931547

ABSTRACT

INTRODUCTION: This study reviews our experience with the management a retained knife in the setting of thoracic stab wounds. METHODS: A retrospective study was conducted at a major trauma in South Africa over a 15-year period from January 2004 to December 2018. RESULTS: There were 40 patients, of whom 37 were males (93%). Median age was 24 years; 78% of cases (31 of 40) were a retained knife and 23% (9 of 40) were a retained blade. The locations of the stab wounds were 19 (48%) anterior and 21 (53%) posterior. Plain x-ray was performed in 85% (34) of patients and computed tomography angiography was performed in 85% (34). Six patients had haemodynamic instability and were expedited to the operating room without further imaging. Three of these had cardiac tamponade and three a massive haemothorax. Simple extraction and wound exploration were performed in 58% (23 of 40) of cases and the remaining 43% (17 of 40) required operative exploration and extraction. The operative approach was anterolateral thoracotomy in nine cases, posterolateral thoracotomy in four and median sternotomy in three cases. One patient required extraction and concurrent vertebral laminectomy due to cord compression. Twelve patients (30%) experienced complications (nine wound sepsis and three hospital-acquired pneumonia). There was one mortality (3%). The median length of hospital stay was 6 days. CONCLUSION: Uncontrolled extraction of a retained thoracic knife outside the operating room must be avoided. An unstable patient should proceed directly for operative exploration. For stable patients, cross-sectional imaging will allow for planned extraction in operating room.


Subject(s)
Wounds, Penetrating , Wounds, Stab , Adult , Humans , Male , Retrospective Studies , South Africa/epidemiology , Trauma Centers , Wounds, Penetrating/surgery , Wounds, Stab/epidemiology , Wounds, Stab/surgery , Young Adult
9.
Braz. j. oral sci ; 21: e226288, jan.-dez. 2022. ilus
Article in English | LILACS, BBO - Dentistry | ID: biblio-1366204

ABSTRACT

Aim: To describe the pattern of toothache experience in a cohort of children aged 2-5 over 21 years and to find the relationship between previous toothache experience and later reports of toothache to get finding on the most critical period of toothache as a problem in life. Methods: This is a secondary data analysis from Indonesia Family Life Survey (IFLS). A total of 1,927 children from IFLS-1 with complete data were included as baseline participants. They were followed up four times within 21 years (age 6-9y, age 9-12y, age 16-19y, age 23- 26y). Toothache was based on the question of self-reported toothache experience during the last four weeks. After 21 years, a total of 1,098 individuals could be traced and completed every cohort of the survey. Toothache experiences were reported for frequencies in every cohort and accumulative experiences over 21 years. Logistic regression tests were performed to analyze the association of previous toothache experience and later toothache experience. Results: Almost 40% of the respondents reported toothache at least once in their life. The age of 6-9 years is the period when a high percentage of children had teeth-related pain. The experience of toothache at this period was significantly related to every period of age in life. Conclusions: The period of early mixed dentition is important. Oral health status in this period is associated with future oral health. A comprehensive dental health prevention program targeting this population is essential to increase the quality of life


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Young Adult , Toothache/epidemiology , Oral Health , Socioeconomic Factors , Dental Health Surveys , Prevalence , Longitudinal Studies , Indonesia/epidemiology
10.
Int Arch Occup Environ Health ; 95(3): 701-708, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34626220

ABSTRACT

PURPOSE: Secondary metalworking carries exposure to relatively heavy levels of respirable particulate. We investigated the extent to which metalworking is associated with increased exhaled nitric oxide (FeNO), an established inflammatory biomarker. METHODS: We studied 80 metalworking factory employees in Kazakhstan. Informed by industrial hygiene data, we categorized them into three groups: (1) machine operators (41%); (2) welders or assemblers (33%); and (3) all others, including administrative and ancillary staff (26%). Participants completed questionnaires covering occupational history, smoking, home particulate sources, respiratory symptoms, and comorbidities. We measured exhaled carbon monoxide (CO), exhaled fractional nitric oxide (FeNO), and spirometric function. We used mixed-effects modeling to test the associations of occupational group with FeNO, adjusted for covariates. RESULTS: The median age was 51.5 (interquartile range 20.5) years; 7% were women. Occupational group (p < 0.01), daily current cigarette smoking intensity (p < 0.05), and age (p < 0.05), each was statistically associated with FeNO. Welders, or assemblers (Group 2), who had intermediate particulate exposure, manifested significantly higher exhaled FeNO compared to machinists (Group 1, with the highest particulate exposure) and all others (Groups 3, the lowest particulate): adjusted Group 2 mean 44.8 ppb (95% confidence interval (CI) 33.8-55.9) vs. Group 1 24.6 ppb (95% 20.5-28.7) and Group 3, 24.3 ppb (95% CI 17.7-30.9). Secondhand smoking and height were not associated with FeNO. CONCLUSION: In a metalworking industrial cohort, welders/assemblers manifested significantly higher levels of FeNO. This may reflect respiratory tract inflammation associated with airborne exposures specific to this group.


Subject(s)
Exhalation , Nitric Oxide , Adult , Breath Tests , Carbon Monoxide/analysis , Dust , Female , Humans , Spirometry , Young Adult
11.
Diabetes Metab Syndr ; 16(6): 102525, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35660933

ABSTRACT

BACKGROUND: Hypoglycemia unawareness designates failure to detect eminent hypoglycemia. Clarke's questionnaire is one of the most used systems to evaluate this problem. AIMS: To relate Clarke's questionnaire (QQ) results with continuous glucose monitoring data. METHODS: Application of the questionnaire in a sample of type 1 diabetes mellitus (T1DM) patients using intermittent continuous glucose monitoring (iCGM). RESULTS: 111 T1DM patients were evaluated, 56.8% female, mean age 35.0 ± 12.4 years and mean disease duration 18.8 ± 10.5 years. According to CQ, 13.5% had unawareness, 76.6% awareness and 9.9% indeterminate awareness to hypoglycemia. Those with unawareness had longer disease duration (25.1 ± 10.4 vs 18.2 ± 10.3 for awareness and 14.9 ± 9.9 for indeterminate awareness, p = 0.047), more time below range (10.3 ± 4.9% vs 6.3 ± 5.1 and 6.3 ± 4.8; p = 0.009) and higher mean duration of hypoglycemia (131.7 ± 38.6 vs 116.6 ± 49.6 and 131.7 ± 38.6; p = 0.008). In multivariate analysis, mean duration of hypoglycemia was an independent predictor of CQ results. In a receiver operating curve (AUC 0.746; p = 0.004) a mean duration of hypoglycemia ≥106.5 min showed 84.6% sensitivity/64.4% specificity for unawareness. CONCLUSIONS: Our sample had a significative prevalence of hypoglycemia unawareness which increased with longer diabetes duration. iCGM data can be indicative of this problem, with a mean hypoglycemia duration ≥106.5 min being suggestive, albeit unspecific.


Subject(s)
Diabetes Complications , Diabetes Mellitus, Type 1 , Hypoglycemia , Adult , Blood Glucose/analysis , Blood Glucose Self-Monitoring/adverse effects , Diabetes Complications/complications , Diabetes Mellitus, Type 1/complications , Female , Humans , Hypoglycemia/diagnosis , Hypoglycemia/etiology , Male , Middle Aged , Risk Factors , Young Adult
12.
Aliment Pharmacol Ther ; 56(2): 231-239, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35665521

ABSTRACT

BACKGROUND: Proton pump inhibitors (PPI) have no effect on non-acid reflux events which can continue to provoke gastro-oesophageal reflux disease (GERD) symptoms. Baclofen, a γ-aminobutyric acid agonist, can decrease non-acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied. AIMS: To assess the efficacy of baclofen 10 mg t.i.d. vs placebo as add-on therapy in PPI-refractory GERD symptoms, in a randomised, double-blind, placebo-controlled study. METHODS: Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10 mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance-pH monitoring on-PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models. RESULTS: About 60 patients were included (age 47.5 years [range 19-73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen-treated group compared to placebo (p = 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n = 25) group improved significantly with baclofen (pcorr  = 0.02), and worsened with placebo (pcorr  = 0.008). The total number of reflux events decreased over time (p = 0.01), mainly due to the baclofen condition (pcorr  = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr  = 0.009), but not placebo. CONCLUSION: Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH-impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.


Subject(s)
Gastroesophageal Reflux , Proton Pump Inhibitors , Adult , Aged , Baclofen/therapeutic use , Double-Blind Method , Esophageal pH Monitoring , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/drug therapy , Humans , Middle Aged , Proton Pump Inhibitors/therapeutic use , Treatment Outcome , Young Adult
13.
Clin Nutr ; 41(7): 1523-1531, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35667268

ABSTRACT

BACKGROUND AND AIMS: Whether early young adulthood dietary patterns predict the risk of metabolic syndrome (MetS) and diabetes-related endpoints prior to middle age remains unknown. We examined the prospective associations of dietary patterns in early young adulthood with MetS and diabetes-related endpoints at later young adulthood. METHODS: We used data of young adults from a long running birth cohort in Australia. The Western dietary pattern rich in meats, refined grains, processed and fried foods and the prudent dietary pattern rich in fruits and vegetables, whole grains and legumes were derived using principal component analysis at the 21-year follow-up from dietary data obtained by a food frequency questionnaire. Fasting blood samples at 30 years were collected from each participant and their blood biomarkers, anthropometric and blood pressure were measured. MetS, insulin resistance, and prediabetes were based on clinical cut-offs; increased ß-cell function and insulin resistance were based on upper quartiles. Log-binomial models were used to estimate diet-related risks of each outcome adjusting for potential confounders. RESULTS: Greater adherence to the Western pattern predicted higher risks of MetS (RR: 2.32; 95% CI: 1.34, 4.00), increased insulin resistance (1.69; 1.07, 2.65), high ß-cell function (1.60; 1.10, 2.31) and less likelihood of increased insulin sensitivity (0.57; 0.39, 0.84) in adjusted models. Conversely, adhering more to the prudent pattern predicted lower risks of MetS (RR: 0.47; 95% CI: 0.29, 0.75), increased insulin resistance (0.57; 0.39, 0.82), high ß-cell function (0.69; 0.50, 0.93) and a greater likelihood of increased insulin sensitivity (1.84; 1.30, 2.60). CONCLUSION: This prospective study of young adults indicates greater adherence to unhealthy Western diet predicted higher risks of MetS and increased insulin resistance, whereas healthy prudent diet predicted lower risks. Optimizing diets to improve later cardiometabolic health needs to occur in early adulthood.


Subject(s)
Insulin Resistance , Metabolic Syndrome , Adult , Diet , Diet, Western/adverse effects , Feeding Behavior , Humans , Insulin , Longitudinal Studies , Metabolic Syndrome/epidemiology , Middle Aged , Prospective Studies , Risk Factors , Vegetables , Young Adult
14.
Soc Sci Res ; 106: 102722, 2022 08.
Article in English | MEDLINE | ID: mdl-35680359

ABSTRACT

Research evaluating the relationship between work and crime has paid little attention to behavior in the workplace. We evaluate four hypotheses regarding the work-crime relationship: (1) Employment and crime are negatively related, (2) Employment displaces offending from the street to the workplace, (3) Work offending emboldens street offending, and (4) Work offending has no association with street offending. Drawing on longitudinal data from a high-risk sample of young adults from The Pathways to Desistance study, we use hybrid fixed effects models with measures of street property offending and workplace property offending to test the hypotheses. Our findings indicate a positive association between work property offending and street property offending with the inclusion of fixed effects. Findings also provide evidence that job quality moderates this relationship. We elaborate on the role of workplace behavior in the broader work-crime relationship and explore the mechanisms underlying the associations we identify.


Subject(s)
Crime , Workplace , Humans , Salaries and Fringe Benefits , Young Adult
15.
Target Oncol ; 17(3): 283-293, 2022 May.
Article in English | MEDLINE | ID: mdl-35715627

ABSTRACT

BACKGROUND: The MAPK pathway is an emerging target across a number of adult and pediatric tumors. Targeting the downstream effector of MAPK, MEK1, is a proposed strategy to control the growth of MAPK-dependent tumors. OBJECTIVE: iMATRIX-cobi assessed the safety, pharmacokinetics, and anti-tumor activity of cobimetinib, a highly selective MEK inhibitor, in children and young adults with relapsed/refractory solid tumors. PATIENTS AND METHODS: This multicenter Phase I/II study enrolled patients aged 6 months to < 30 years with solid tumors with known/expected MAPK pathway involvement. Patients received cobimetinib tablet or suspension formulation on Days 1-21 of a 28-day cycle. Dose escalation followed a rolling 6 design. The primary endpoint was safety; secondary endpoints were pharmacokinetics and anti-tumor activity. RESULTS: Of 56 enrolled patients (median age 9 years [range 3-29]), 18 received cobimetinib tablets and 38 cobimetinib suspension. Most common diagnoses were low-grade glioma (LGG; n = 32, including n = 12 in the expansion cohort) and plexiform neurofibroma within neurofibromatosis type 1 (n = 12). Six patients (11 %) experienced dose-limiting toxicities (including five ocular toxicity events), which established a pediatric recommended Phase II dose (RP2D) of 0.8 mg/kg tablet and 1.0 mg/kg suspension. Most frequently reported treatment-related adverse events were gastrointestinal and skin disorders. Steady state mean exposure (Cmax, AUC0-24) of cobimetinib at the RP2D (1.0 mg/kg suspension) was ~ 50 % lower than in adults receiving the approved 60 mg/day dose. Overall response rate was 5.4 % (3/56; all partial responses in patients with LGG). CONCLUSIONS: The safety profile of cobimetinib in pediatrics was similar to that reported in adults. Clinical activity was observed in LGG patients with known/suspected MAPK pathway activation. Cobimetinib combination regimens may be required to improve response rates in this pediatric population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02639546, registered December 24, 2015.


Subject(s)
Azetidines , Neoplasms , Piperidines , Adolescent , Adult , Azetidines/adverse effects , Azetidines/therapeutic use , Child , Child, Preschool , Enzyme Inhibitors/therapeutic use , Glioma/drug therapy , Humans , Maximum Tolerated Dose , Neoplasm Recurrence, Local , Neoplasms/drug therapy , Pediatrics , Piperidines/adverse effects , Piperidines/therapeutic use , Tablets , Young Adult
16.
Sci Data ; 9(1): 352, 2022 06 20.
Article in English | MEDLINE | ID: mdl-35725852

ABSTRACT

Brain atlases play important roles in studying anatomy and function of the brain. As increasing interests in multi-modal magnetic resonance imaging (MRI) approaches, such as combining structural MRI, diffusion weighted imaging (DWI), and resting-state functional MRI (rs-fMRI), there is a need to construct integrated brain atlases based on these three imaging modalities. This study constructed a multi-modal brain atlas for a Chinese aging population (n = 180, age: 22-79 years), which consists of a T1 atlas showing the brain morphology, a high angular resolution diffusion imaging (HARDI) atlas delineating the complex fiber architecture, and a rs-fMRI atlas reflecting brain intrinsic functional organization in one stereotaxic coordinate. We employed large deformation diffeomorphic metric mapping (LDDMM) and unbiased diffeomorphic atlas generation to simultaneously generate the T1 and HARDI atlases. Using spectral clustering, we generated 20 brain functional networks from rs-fMRI data. We demonstrated the use of the atlas to explore the coherent markers among the brain morphology, functional networks, and white matter tracts for aging and gender using joint independent component analysis.


Subject(s)
Brain , White Matter , Adult , Aged , Algorithms , Brain/anatomy & histology , Brain/diagnostic imaging , Brain Mapping , China , Diffusion Magnetic Resonance Imaging , Humans , Middle Aged , White Matter/anatomy & histology , White Matter/diagnostic imaging , Young Adult
17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(5): 449-453, 2022 May.
Article in Chinese | MEDLINE | ID: mdl-35728842

ABSTRACT

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients infected with novel coronavirus Omicron variant in Shanghai, as to provide a reference for epidemic prevention, clinical diagnosis, and treatment. METHODS: Altogether 4 264 novel coronavirus Omicron variant-infected patients with positive results of nucleic acid admitted to Shanghai New International Expo Center N3 Mobile Cabin Hospital from April 2 to May 7, 2022, were included. The demographic and baseline clinical characteristics, treatment strategy, prognosis, and different factors affecting the length of hospital stay were analyzed. RESULTS: A total of 4 264 novel coronavirus variant Omicron-infected cases were collected, including 3 111 cases (73.0%) asymptomatic infections and 1 153 cases (27.0%) mild infections. The overall median age was 45 (33, 55) years old with a range from 2 years old to 81 years old. The male to female ratio was 1.37:1. Altogether 3 305 cases (77.5%) had been vaccinated, of which 3 166 cases completed more than 2 doses. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical manifestations of these infected patients. During the course of the disease, patients with asymptomatic infection were mainly treated with traditional Chinese medicine (TCM, 55.1%) and clinical observation (36.8%), and those with mild infection were mainly treated with TCM (42.2%) or integrated Chinese and Western medicine (30.4%). All patients were cured and discharged. The overall median length of hospital stay and the negative conversion time of nucleic acid were 9 (6, 10) days and 8 (5, 9) days, respectively. Compared with the asymptomatic infected patients, the hospitalization duration and the nucleic acid negative conversion time of the mildly infected patients were slightly longer [days: 10 (8, 11) vs. 9 (5, 10); 8 (6, 10) vs. 7 (4, 9), both P < 0.001]. Multiple linear regression analysis showed that the increasing age and mild infection were associated with longer hospitalization duration, and the treatment of TCM or integrated Chinese and Western medicine was associated with shortened length of hospital stay (all P < 0.05). CONCLUSIONS: The current novel coronavirus Omicron variant epidemic in Shanghai mainly caused asymptomatic and mild infections. The young and middle-aged population had a relatively high infection rate. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical symptoms. Elderly and confirmed patients had prolonged hospitalization duration, while for patients receiving TCM treatment, the hospitalization duration was shortened.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Cough , Female , Hospitalization , Humans , Length of Stay , Male , Medicine, Chinese Traditional , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2 , Young Adult
18.
Int Immunopharmacol ; 108: 108898, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35729833

ABSTRACT

Cognitive aging is a major risk factor for neurodegenerative diseases and has a great impact on the living quality of older individuals. However, the precise mechanisms underlying cognitive aging remain elusive. Accumulating evidence has demonstrated that interleukin 17A (IL-17A) is responsible for cognitive decline in the process of various neurological diseases. Thus, we conducted this study aiming to investigate the role of IL-17A in cognitive aging. In the present study, 31 aging (65-85 years) and 25 young (18-35 years) patients scheduled for elective removal of internal fixation surgery with spinal anesthesia were included for measurements of preoperative cognitive function, serum and cerebrospinal fluid (CSF) levels of IL-17A. For animal study, RNAseq and Kyoto Encyclopedia of Genes and Genomes pathways were used to identify differentially expressed genes between young and aging mice. For the treatment groups, young (2-3 months) and aging (16-18 months) mice received intraperitoneally with IL-17A and anti-IL-17A antibody, respectively. Twenty-four hours later, neurocognitive behavioral tests were conducted. Our results suggested that differentially expressed genes between young and aging mice were mainly enriched in IL-17 pathways. Serum and CSF levels of IL-17A increased significantly in aging patients and were negatively correlated with mini-mental state examination scores. Both young mice receiving IL-17A and aging mice showed impaired memory, increased blood-brain barrier permeability, overactivated microglia and increased inflammatory mediators in the hippocampus. Additionally, aging mice showed a significantly decreased θ power in the task-related neural oscillations. Notably, intraperitoneal injection of anti-IL-17A antibody alleviated increased blood-brain barrier permeability, microglial activation, neuroinflammation, θ oscillation disruption and cognitive decline of aging mice. In conclusion, our study demonstrated that IL-17A may be an initiating factor of cognitive aging.


Subject(s)
Cognitive Aging , Interleukin-17 , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Hippocampus/metabolism , Humans , Interleukin-17/metabolism , Mice , Mice, Inbred C57BL , Microglia/metabolism , Young Adult
19.
Eur Rev Med Pharmacol Sci ; 26(11): 3958-3966, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35731066

ABSTRACT

OBJECTIVE: Serum gamma-glutamyl transferase (GGT), an indicator of oxidative stress and/or a chronic inflammatory process, is associated with the levels of leukotrienes and other inflammatory mediators that play a critical role in the pathogenesis of asthma. This study aimed at investigating whether apparently healthy subjects with higher serum GGT levels at a national health check-up are at an increased risk of developing asthma in the near future. PATIENTS AND METHODS: We analyzed 564,213 Korean adults, aged 20-80 years who underwent a national general health examination, including measurement of baseline serum GGT between 2003 and 2015, using data from a large-scale representative cohort of the Korean population. Data were analyzed using a Cox proportional hazards regression analysis. RESULTS: In total, 516,956 participants were included in the final analysis. During the mean follow-up period of 8 years (standard deviation, 4.0), 7,439 incident asthma events occurred. We then classified the male and female participants according to quartiles of blood GGT levels (males: ≤ 20, 21-30, 31-51, and ≥ 52 IU/L; females: ≤ 12, 13-16, 17-22, and ≥ 23 IU/L, respectively). The adjusted hazard ratio (aHR) for incident asthma was significantly greater for subjects in the highest GGT quartile than for those in the lowest GGT quartile (aHR, 1.47; 95% confidence intervals, 1.36-1.59). Further, there was a significant linear trend across quartiles with regard to asthma (ptrend<0.001). We estimated the optimal cut-off values (using the minimum p-value approach) as 35 IU/L for the total population, 35 IU/L for males, and 36 IU/L for females, respectively. CONCLUSIONS: Clinicians should be aware of the risk of incident asthma in healthy subjects with elevated GGT levels. Our findings advance our understanding of asthma pathogenesis.


Subject(s)
Asthma , gamma-Glutamyltransferase/blood , Adult , Aged , Aged, 80 and over , Asthma/epidemiology , Cohort Studies , Female , Humans , Male , Middle Aged , Republic of Korea/epidemiology , Risk Factors , Young Adult
20.
JAMA Netw Open ; 5(6): e2218297, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35731513

ABSTRACT

Importance: Few studies have examined the dietary trends in Korea beyond evaluating selected food groups. To help prevent cardiometabolic disease burdens, a comprehensive investigation of the trends in overall diet quality and identification of possible contributing factors would be useful. Objective: To investigate the trends and independent associations of age, period, and birth cohort with diet quality and cardiometabolic risk factors among Korean adults. Design, Setting, and Participants: Serial cross-sectional and age-period-cohort analyses were conducted of nationally representative 24-hour dietary recall data from the Korea National Health and Nutrition Examination Survey 2007-2018. The study population included 65 416 Korean adults aged 19 to 79 years. Data analyses were conducted from March 1, 2020, through April 30, 2021. Exposures: Age, calendar year, birth cohort, and population sociodemographic characteristics. Main Outcomes and Measures: Korean Healthy Eating Index (KHEI), a validated diet quality score (range, 0-90, with higher scores indicating greater diet quality), and 8 cardiometabolic risk factors (waist circumference and systolic blood pressure, diastolic blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and fasting blood glucose levels). Results: Among 65 416 participants, mean age (SD) was 44.5 (0.1) years and 36 631 were women (55.8%). In 2007-2018, the age-standardized mean (SE) KHEI score increased from 51.0 (0.4) to 52.1 (0.5), which was associated with reduced sodium intake and increased whole grain, dairy, and protein-rich food intakes. The mean (SE) KHEI score was lowest at age 39 years (50.1 [0.3]) and increased at older ages (58.0 [0.3] at 79 years). Controlling for age and period effects, the highest KHEI score was observed among the birth cohorts of 1960-1964 (53.6 [0.9]) and decreased in subsequent cohorts (45.5 [1.2] in the 1990-1999 birth cohort). Similar cohort effects in cardiometabolic risk factors were observed, showing the lowest waist circumference, blood pressure, and total cholesterol levels among the birth cohorts of the 1960s and 1970s and higher levels among more recent birth cohorts (1990-1999 vs 1960-1964: waist circumference, 83.8 [0.5] vs 81.4 [0.4] cm; systolic blood pressure, 118.7 [0.7] vs 116.4 [0.4] mm Hg; total cholesterol, 200.2 [0.9] vs 198.9 [0.7] mg/dL). At most ages, periods, and birth cohorts, the mean KHEI score was consistently higher in adults living in urban areas (at age 45 years: 50.5 [1.0] vs 49.7 [0.9] rural) and among high-income (at age 45 years: 50.7 [1.1] vs 49.3 [0.9] low income) and educational levels (at age 45 years: 53.1 [0.9] vs 49.1 [1.0] low educational level). Conclusions and Relevance: The findings of this study suggest that, from 2007 to 2018, the diet quality of Korean adults modestly improved. Despite the improvement, inequalities in diet among age, birth cohort, and socioeconomic subgroups persisted, suggesting that more intense interventions may be needed to target the susceptible groups.


Subject(s)
Cardiometabolic Risk Factors , Diet , Adult , Aged , Cholesterol, LDL , Cross-Sectional Studies , Diet/adverse effects , Female , Humans , Male , Middle Aged , Nutrition Surveys , Young Adult
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