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1.
Neuropsychopharmacology ; 49(6): 1024-1032, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38431758

RESUMEN

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in a total of 385 scans from 22qDel (n = 96, scans = 191, 53.1% female), 22qDup (n = 37, scans = 64, 45.9% female), and TD controls (n = 80, scans = 130, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the linear effects of 22q11.2 gene dosage and non-linear effects of age were characterized with generalized additive mixed models (GAMMs). Positive gene dosage effects (volume increasing with copy number) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.


Asunto(s)
Variaciones en el Número de Copia de ADN , Síndrome de DiGeorge , Dosificación de Gen , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Variaciones en el Número de Copia de ADN/genética , Adulto , Adolescente , Niño , Adulto Joven , Persona de Mediana Edad , Preescolar , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/patología , Síndrome de DiGeorge/diagnóstico por imagen , Estudios Longitudinales , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/crecimiento & desarrollo , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/patología , Tálamo/diagnóstico por imagen , Tálamo/crecimiento & desarrollo , Tálamo/patología , Tamaño de los Órganos
2.
Health Commun ; 39(2): 339-351, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36628486

RESUMEN

Social norm has been found to impact compliance with COVID-19 preventative behaviors, including handwashing, wearing a face mask, social distancing, and cleaning and disinfecting frequently touched surfaces. There is, however, a limited understanding of the social norm influence mechanisms and its boundary condition in the context of COVID-19. Guided by the theory of normative social behaviors (TNSB), this study conducted an online survey (N = 336) to examine whether perceived injunctive norms (PIN), outcome expectation (OE), group identity (GID), group orientation (GO), and cultural tightness-looseness (CTL) can moderate and/or mediate the relationship between perceived descriptive norms (PDN) and behavioral intentions (BI) to perform COVID-19 preventative behaviors in the United States. Results showed that whereas OE mediated the PDN-BI relationship to enact all four focal behaviors, PIN mediated the PDN-BI relationship for social distancing, wearing a face mask, and cleaning and disinfecting. However, inconsistent with the predictions, all five moderators (i.e. PIN, OE, GO, GID, and CTL) attenuated, instead of strengthening, the PDN-BI relationships for particular preventative behaviors. Theoretical and practical implications were discussed.


Asunto(s)
COVID-19 , Humanos , Estados Unidos , COVID-19/epidemiología , COVID-19/prevención & control , Conducta Social , Normas Sociales , Intención , Desinfección de las Manos
3.
Plast Reconstr Surg ; 153(1): 35-44, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37075288

RESUMEN

BACKGROUND: Infection following implant-based breast reconstruction can lead to devastating complications. Risk factors for infection include smoking, diabetes, and obesity. Intraoperative hypothermia may represent another modifiable risk factor. This study analyzed the effect of hypothermia in postmastectomy immediate implant-based reconstruction on postoperative surgical-site infection (SSI). METHODS: This was a retrospective review of 122 patients with intraoperative hypothermia, defined as less than 35.5°C, and 106 normothermic patients who underwent postmastectomy implant-based reconstruction between 2015 and 2021. Demographics, comorbidities, smoking status, hypothermia (and its duration), and length of surgery were collected. The primary outcome was SSI. Secondary outcomes included reoperation and delayed wound healing. RESULTS: A total of 185 patients (81%) underwent staged reconstruction with tissue expander placement and 43 patients (18.9%) had a direct-to-implant procedure. Over half (53%) of the patients experienced intraoperative hypothermia. In the hypothermic group, a higher proportion of patients had SSIs (34.4% versus 17% of normothermic patients; P < 0.05) and wound healing complications (27.9% versus 16%; P < 0.05). Intraoperative hypothermia predicted SSI (OR, 2.567; 95% CI, 1.367 to 4.818; P < 0.05) and delayed wound healing (OR, 2.023; 95% CI, 1.053 to 3.884; P < 0.05). Longer duration of hypothermia significantly correlated with SSI, with an average 103 minutes versus 77 minutes ( P < 0.05). CONCLUSIONS: This study demonstrates that intraoperative hypothermia is a significant risk factor for postoperative infection in postmastectomy implant-based breast reconstruction. Maintaining strict normothermia during implant-based breast reconstruction procedures may improve patient outcomes by reducing the risk of postoperative infection and delayed wound healing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Hipotermia , Mamoplastia , Humanos , Femenino , Implantes de Mama/efectos adversos , Incidencia , Hipotermia/complicaciones , Neoplasias de la Mama/etiología , Mastectomía/efectos adversos , Mastectomía/métodos , Mamoplastia/efectos adversos , Mamoplastia/métodos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control
4.
bioRxiv ; 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37961662

RESUMEN

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in 22qDel (n=96, 53.1% female), 22qDup (n=37, 45.9% female), and TD controls (n=80, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the effect of 22q11.2 gene dosage was examined using linear mixed models. Age-related changes were characterized with general additive mixed models (GAMMs). Positive gene dosage effects (22qDel < TD < 22qDup) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

5.
Clin Gastroenterol Hepatol ; 21(13): 3405-3414.e4, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37482172

RESUMEN

BACKGROUND & AIMS: Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis. METHODS: We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates. RESULTS: Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P = .008), inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall symptom severity (P = .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients). CONCLUSIONS: CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES. CLINICALTRIALS: gov NCT #03941288.


Asunto(s)
Cannabidiol , Diabetes Mellitus Tipo 1 , Gastroparesia , Humanos , Gastroparesia/tratamiento farmacológico , Cannabidiol/efectos adversos , Agonismo Inverso de Drogas , Náusea/inducido químicamente , Vaciamiento Gástrico
6.
Genes (Basel) ; 14(6)2023 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-37372372

RESUMEN

Leveraging computation in the development of peptide therapeutics has garnered increasing recognition as a valuable tool to generate novel therapeutics for disease-related targets. To this end, computation has transformed the field of peptide design through identifying novel therapeutics that exhibit enhanced pharmacokinetic properties and reduced toxicity. The process of in-silico peptide design involves the application of molecular docking, molecular dynamics simulations, and machine learning algorithms. Three primary approaches for peptide therapeutic design including structural-based, protein mimicry, and short motif design have been predominantly adopted. Despite the ongoing progress made in this field, there are still significant challenges pertaining to peptide design including: enhancing the accuracy of computational methods; improving the success rate of preclinical and clinical trials; and developing better strategies to predict pharmacokinetics and toxicity. In this review, we discuss past and present research pertaining to the design and development of in-silico peptide therapeutics in addition to highlighting the potential of computation and artificial intelligence in the future of disease therapeutics.


Asunto(s)
Inteligencia Artificial , Plumas , Animales , Simulación del Acoplamiento Molecular , Plumas/metabolismo , Péptidos/farmacología , Péptidos/uso terapéutico , Péptidos/química , Proteínas/metabolismo
7.
Health Sociol Rev ; 32(3): 294-310, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37222411

RESUMEN

India's public health system aims to foster pluralism by integrating AYUSH (Ayurveda, Yoga & Naturopathy, Unani, Siddha, and Homeopathy) with mainstream biomedical care. This policy change provides an opportunity to explore the complexity of health system innovation, addressing the relationship between biomedicine and complementary or alternative medicine. Implementing health policy depends on local, societal, and political contexts that shape intervention in practice. This qualitative case study explores contextual features that have influenced AYUSH integration and examines the extent to which practitioners are able to exercise agency in these contexts. Health system stakeholders were interviewed (n = 37) and integration activities observed. The analysis identifies contextual factors in health administration, health facilities, community, and wider society which influence the integration process. In the administrative and facility spheres, pre-existing administrative measures, resource and capacity deficits limit access to AYUSH medicines and opportunities to build relationships between biomedical and AYUSH doctors. At the community and society levels, rural AYUSH acceptance facilitates integration into formal healthcare, while professional organisations and media support integrative processes by holding health services accountable. The findings also demonstrate how, amid these contextual influences, AYUSH doctors navigate the health system hierarchies, despite issues with system knowledge against a background of medical dominance.


Asunto(s)
Terapias Complementarias , Homeopatía , Medicina Tradicional , Atención a la Salud , Política de Salud
9.
Gut ; 72(1): 54-65, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35580964

RESUMEN

OBJECTIVE: There are altered mucosal functions in irritable bowel syndrome with diarrhoea (IBS-D); ~30% of patients with IBS-D have abnormal bile acid (BA) metabolism (ABAM) and diarrhoea (summarised as BAD). AIM: To compare biochemical parameters, gastrointestinal and colonic transit, rectal sensation and pathobiological mechanisms in IBS-D without ABAM and in BAD (serum 7C4>52 ng/mL). DESIGN: In patients with Rome III criteria of IBS-D, we compared biochemical features, colonic transit, rectal sensation, deep genotype of five BA-related genes, ileal and colonic mucosal mRNA (differential expression (DE) analysis) and stool dysbiosis (including functional analysis of microbiome). Results in BAD were compared with IBS-D without ABAM. RESULTS: Compared with 161 patients with IBS-D without ABAM, 44 patients with BAD had significantly faster colonic transit, lower microbial alpha diversity, different compositional profile (beta diversity) and higher Firmicutes to Bacteroidetes ratio with evidence of decreased expression of bile acid thiol ligase (involved in transformation of primary to secondary BAs) and decreased sulfatases. In BAD (compared with IBS-D without ABAM), terminal ileal biopsies showed downregulation of SLC44A5 (a BA transporter), and ascending colon biopsies showed upregulation in barrier-weakening genes (CLDN2), serine protease inhibitors, immune activation, cellular differentiation and a cellular transporter (FABP6; BA binding). No DE of genes was documented in descending colon biopsies. The two groups had similar rectal sensation. CONCLUSION: Though sharing clinical symptoms with IBS-D, BAD is associated with biological differences and mechanisms that have potential to enhance diagnosis and treatment targeting barrier dysfunction, inflammatory and microbial changes.


Asunto(s)
Síndrome del Colon Irritable , Humanos , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/genética , Síndrome del Colon Irritable/metabolismo , Ácidos y Sales Biliares , Diarrea/genética , Diarrea/diagnóstico , Heces , ARN Mensajero/genética
10.
Diabetes Obes Metab ; 25(2): 377-386, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36193713

RESUMEN

AIM: To identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once-daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity. METHODS: One hundred and thirty-six obese adults (87% female) were randomized in a placebo-controlled, 16-week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET1/2 ); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model. RESULTS: Weight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide- and 16% of placebo-treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4-kg weight loss were GET1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57-3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602-0.864) per 100 kcal. Among only the 60 liraglutide-treated subjects, kcal intake at 16 weeks was associated with 4-kg weight loss (AUROC = 0.757). CONCLUSIONS: Slower GET1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide-treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.


Asunto(s)
Péptido 1 Similar al Glucagón , Liraglutida , Adulto , Humanos , Femenino , Masculino , Liraglutida/efectos adversos , Péptido 1 Similar al Glucagón/uso terapéutico , Obesidad/complicaciones , Pérdida de Peso , Vaciamiento Gástrico , Método Doble Ciego
11.
PLoS One ; 17(11): e0263910, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36331937

RESUMEN

OBJECTIVE: Women of reproductive age who have autoimmune rheumatic diseases [ARDs] have expressed a need to be better supported with making decisions about pregnancy. Women with ARDs want their motherhood identities and associated preferences to be taken into account in decisions about their healthcare. The aim of this study was to explore the interplay between illness and motherhood identities of women with ARDs during preconception decision making. METHODS: Timeline-facilitated qualitative interviews with women diagnosed with an ARD [18-49 years old]. Participants were purposively sampled based on the following three criteria: thinking about getting pregnant, currently pregnant, or had young children. Interviews were thematically analysed. RESULTS: Twenty-two women were interviewed face-to-face [N = 6] or over the telephone [N = 16]. Interview length ranged from 20 minutes to 70 minutes, with a mean length of 48 minutes. Three main themes were identified: prioritisation, discrepancy, and trade-off. Difficulties in balancing multiple identities in healthcare encounters were reported. Women used 'self-guides' as a reference for priority setting in a dynamic process that shifted as their level of disease activity altered and as their motherhood identity became more or less of a focus at a given point in time. Women's illness and motherhood identities did not present in isolation but were intertwined. CONCLUSIONS: Findings highlight the need for holistic person-centred care that supports women with the complex and emotive decisions relating to preconception decision-making. In practice, health professionals need to consider women's multiple and sometimes conflicting identities, and include both their condition and family associated goals and values within healthcare communication.


Asunto(s)
Síndrome de Dificultad Respiratoria , Enfermedades Reumáticas , Embarazo , Niño , Femenino , Humanos , Preescolar , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Responsabilidad Parental , Investigación Cualitativa , Personal de Salud
12.
Semin Arthritis Rheum ; 57: 152101, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36183478

RESUMEN

OBJECTIVES: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia. METHODS: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving <30% votes were rejected and those obtaining 30-70% votes were recirculated for up to two additional rounds. RESULTS: Seventeen experts participated (Europe (n = 10), North America (n = 6), and Israel (n = 1)) in the Delphi exercise and completed all three rounds. Aerobic exercise, education, sleep hygiene and cognitive behavioural therapy were recommended as core treatments for all symptoms. Mind-body exercises were recommended as core interventions for pain, fatigue and sleep problems. Mindfulness was voted core treatment for depression, and adjunctive treatment for other symptoms. Other interventions, namely music, relaxation, hot bath, and local heat were voted as adjunctive treatments, varying between symptoms. CONCLUSIONS: This study provided evidence-based expert consensus recommendations on non-pharmacological treatments for fibromyalgia that may be used to individualise treatments in clinical practice targeting the diverse symptoms associated with fibromyalgia.


Asunto(s)
Fibromialgia , Trastornos del Sueño-Vigilia , Humanos , Fibromialgia/terapia , Consenso , Técnica Delphi , Canadá , Fatiga/etiología , Fatiga/terapia , Dolor
13.
Obesity (Silver Spring) ; 30(8): 1608-1620, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35894080

RESUMEN

OBJECTIVE: This study aimed to determine the effects of a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, and placebo subcutaneously over 16 weeks on weight and gastric functions and to evaluate associations of single-nucleotide polymorphisms in GLP1R (rs6923761) and TCF7L2 (rs7903146) with effects of liraglutide. METHODS: The study conducted a randomized, parallel-group, placebo-controlled, 16-week trial of liraglutide, escalated to 3 mg subcutaneously daily in 136 otherwise healthy adults with obesity. Weight, gastric emptying of solids (GES), gastric volumes, satiation, and body composition measured at baseline and after treatment were compared in two treatment groups using analysis of covariance. RESULTS: Liraglutide (n = 59) and placebo (n = 65) groups completed treatment. Relative to placebo, liraglutide increased weight loss at 5 and 16 weeks (both p < 0.05), slowed time to half GES (T1/2 ) at 5 and 16 weeks (both p < 0.001), and increased fasting gastric volume (p = 0.01) and satiation (p < 0.01) at 16 weeks. GES T1/2 was positively correlated with weight loss on liraglutide (both p < 0.001). After 16 weeks of liraglutide, GLP1R rs6923761 (AG/AA vs. GG) was associated with reduced percent body fat (p = 0.062), and TCF7L2 rs7903146 (CC vs. CT/TT) was associated with lower body weight (p = 0.015). CONCLUSIONS: Liraglutide, 3 mg, induces weight loss with delay in GES T1/2 and reduces calorie intake. Slowing GES and variations in GLP1R and TCF7L2 are associated with liraglutide effects in obesity.


Asunto(s)
Liraglutida , Farmacogenética , Adulto , Método Doble Ciego , Péptido 1 Similar al Glucagón/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Liraglutida/farmacología , Liraglutida/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/genética , Pérdida de Peso/genética
14.
Am J Physiol Gastrointest Liver Physiol ; 323(2): G88-G101, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35502856

RESUMEN

Altered mucosal functions are documented in jejunal or colorectal mucosa from patients with irritable bowel syndrome (IBS). Our aim was to quantify ileal, ascending, and rectosigmoid colon mucosal expression of genes in IBS-diarrhea (D) and IBS-constipation (C). Forty-four patients with IBS-D, 30 with IBS-C, and 30 healthy volunteers underwent colonoscopic ileal, ascending, and rectosigmoid colon biopsies. Biopsies were stored in RNAlater at -80 °C, purified with on-column DNase, cDNA libraries prepared from 100-200 ng of total RNA, sequenced on Illumina NovaSeq 6000, and analyzed on Illumina's RTA version 3.4.4. Normalized mRNA expression was obtained using MAP-RSeq bioinformatics pipeline. Differential expressions in the groups (Log2-fold change) were measured using the bioinformatics package edgeR 2.6.2, corrected for false discovery rate (PADJ <0.05). There were 30 females with IBS-C and 31 females and 13 males with IBS-D. In IBS-D and IBS-C groups, there were differential expressions of 181 genes in ascending colon and 199 genes in rectosigmoid colon. The majority were gene upregulations in IBS-D with functions reflecting activation of inflammation genes, TRPV1 (visceral hypersensitivity) and neurotransmitters/receptors (specifically purinergic, GABA, and cannabinoid). Although gene differential expressions in the ascending and rectosigmoid colon mucosa of the two groups were different, the diverse upregulated genes involved immune functions, receptors, transmitters, ion channels, and transporters. Conversely, there was reduced expression of PI15 and PI16 genes that inhibit proteases. In patients with IBS-D and IBS-C, differential expressions of genes related to immune, transmitter, nociceptive, protease inhibition, channel, and transporter functions suggest opportunities to reverse the pathobiology and treat patients with IBS.NEW & NOTEWORTHY This study compares gene expression in mucosa of the terminal ileum, right colon, and left colon in patients with diarrhea- or constipation-predominant irritable bowel syndrome (IBS) and contrasts expression between these two disease entities and also between each entity and mucosa from healthy controls. The study shows there is differential expression of genes related to immune, transmitter, nociceptive, ion channel, and transporter functions, as well as reduced serine protease inhibition, in patients with IBS.


Asunto(s)
Síndrome del Colon Irritable , Biopsia , Estudios de Casos y Controles , Colon/metabolismo , Estreñimiento/genética , Estreñimiento/metabolismo , Diarrea/metabolismo , Femenino , Humanos , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Síndrome del Colon Irritable/metabolismo , Masculino , ARN/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
15.
J Pharm Pract ; 35(5): 691-700, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33759609

RESUMEN

BACKGROUND: Patients living in rural communities often experience pronounced health disparities, have a higher prevalence of diabetes and hypertension, and poorer access to care compared to urban areas. To address these unmet healthcare service needs, an established, academic-based MTM provider created a novel, collaborative program to provide comprehensive, telephonic services to patients living in rural Arizona counties. OBJECTIVE: This study assessed the program effectiveness and described differences in health process and outcome measures (e.g., clinical outcomes, gaps in care for prescribed medications, medication-related problems) between individuals residing in different rural-urban commuting area (RUCA) groups (urban, micropolitan, and small town) in rural Arizona counties. METHODS: Subjects eligible for inclusion were 18 years or older with diabetes and/or hypertension, living in rural Arizona counties. Data were collected on: demographic characteristics, medical conditions, clinical values, gaps in care, medication-related problems (MRPs), and health promotion guidance. Subjects were analyzed using 3 intra-county RUCA levels (i.e., urban, micropolitan, and small town). RESULTS: A total of 384 patients were included from: urban (36.7%), micropolitan (19.3%) and small town (44.0%) areas. Positive trends were observed for clinical values, gaps in care, and MRPs between initial and follow-up consultations. Urban dwellers had significantly lower average SBP values at follow-up than those from small towns (p < 0.05). A total of 192 MRPs were identified; 75.0% were resolved immediately or referred to providers and 16.7% were accepted by prescribers. CONCLUSION: This academic-community partnership highlights the benefits of innovative collaborative programs, such as this, for individuals living in underserved, rural areas.


Asunto(s)
Diabetes Mellitus , Hipertensión , Humanos , Administración del Tratamiento Farmacológico , Evaluación de Programas y Proyectos de Salud , Población Rural , Estados Unidos , Población Urbana
16.
Clin Gastroenterol Hepatol ; 20(9): 2083-2090.e1, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34871814

RESUMEN

BACKGROUND & AIMS: Bile acid diarrhea (BAD) affects approximately a quarter of patients with irritable bowel syndrome with diarrhea (IBS-D). We aimed to compare the demographics, bowel and somatic symptoms, and quality of life of patients with IBS-D, with or without BAD. METHODS: On one occasion, patients with IBS-D (positive for Rome III criteria) completed the following questionnaires: bowel disease questionnaire, Hospital Anxiety and Depression inventory, general quality of life (Symptom Checklist-90), and IBS-specific quality of life. A fasting serum C4 level higher than 52.5 ng/mL was used as a biomarker for BAD. Statistical analysis included a multiple variable logistic model to identify strong predictors of BAD in IBS-D. RESULTS: Among 219 patients (79% female) with IBS-D, 44 had BAD; the BAD group was significantly older and had a higher body mass index than the patients without BAD. Patients with BAD had more severe bowel dysfunction and impact on IBS-specific quality of life (need of toilet proximity) compared with patients with IBS-D without BAD. Patients with BAD were more likely than other IBS-D groups to receive antidiarrheals, bile acid binders, and antacid secretory agents. The severity of diarrhea and need of toilet proximity were predictors of BAD in IBS-D (P < .01). Patients with BAD were more likely to have a depression score higher than 8 on the Hospital Anxiety and Depression inventory. CONCLUSIONS: There is a greater impact on bowel and somatic symptoms and quality of life in IBS-D with BAD compared with IBS-D without BAD. Screening for BAD in IBS-D is especially relevant, with more severe and frequent diarrhea along with urgency.


Asunto(s)
Síndrome del Colon Irritable , Síntomas sin Explicación Médica , Ácidos y Sales Biliares , Diarrea , Femenino , Humanos , Masculino , Calidad de Vida , Encuestas y Cuestionarios
17.
J Health Psychol ; 27(12): 2744-2762, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34933582

RESUMEN

This study examined risk perceptions, efficacy beliefs, social norms, and their interactions as predictors of people's intention to practice four COVID-19 preventative behaviors among a U.S. sample with quotas on age, sex, ethnicity, and region (N = 336). This online survey found that perceived injunctive norms predicted intentions to clean and disinfect (ß = 0.20), practice social distancing (ß = 0.14), and wear a face mask (ß = 0.24). Additionally, efficacy beliefs were found to attenuate the association between descriptive norm perceptions and intention to wash hands (B = -0.15) and wear a face mask(B = -0.12). The results revealed the importance of considering both psychological and social factors to promote COVID-19 preventative behaviors.


Asunto(s)
COVID-19 , Intención , Actitud , COVID-19/prevención & control , Humanos , Percepción , Conducta Social , Normas Sociales , Estados Unidos
18.
Soc Sci Med ; 286: 114152, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34465489

RESUMEN

Hierarchies of power among healthcare professionals are well documented, nonetheless, power remains neglected, understudied and under-theorised in health systems analysis and policy discussions, especially in the domain of Traditional, Complementary and Alternative Medicine (TCAM). Sociological and public health scholarship has documented the persistence of medical dominance in the health system, theorised as the limitation, subordination, exclusion and incorporation of other professions. This paper explores how interprofessional power dynamics shape the integration of TCAM into Indian primary healthcare centres, as part of a nationwide policy of TCAM integration and medical pluralism implemented since 2005. We conducted interviews (n = 37) with health system administrators, nurses, pharmacists, TCAM and biomedicine doctors, and observed day-to-day activities of primary healthcare centres for six months in Odisha state, India. Thematic analysis enabled the identification of themes and exploration of sub-themes. The analysis revealed multilayered forms of medical dominance within the primary healthcare system and identified multiple sites where everyday power is mobilised. Biomedicine practitioners exercised authoritative power and restricted TCAM doctors' access to facility-level resources, i.e. financial and workforce support, which inhibited the integration policy implementation. Significantly, TCAM doctors were 'ordered' to practice biomedicine at primary healthcare centres, which was beyond the scope of the integration policy. However, TCAM doctors were also able to exercise countervailing power in their day-to-day activities in the primary healthcare centres and sought to assist patients' health behaviour change through their authoritative knowledge about 'how to live a healthy life'. The health system actors involved in policy implementation hold a range of forms of power specific to the circumstances, influencing the integration processes. We explain these dynamics in relation to existing theories of medical dominance and countervailing power, while introducing a previously unreported dimension of dominance: 'co-optation', which enrols TCAM practitioners in the practice of biomedicine.


Asunto(s)
Terapias Complementarias , Médicos , Actitud del Personal de Salud , Personal de Salud , Humanos , Salud Pública
19.
Medicine (Baltimore) ; 100(35): e27143, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34477169

RESUMEN

ABSTRACT: Limited evidence exists regarding the relationships between adherence, as defined in Pharmacy Quality Alliance (PQA) medication adherence measures, health care utilization, and economic outcomes. PQA adherence measures for hypertension, cholesterol, and diabetes are of particular interest given their use in Medicare Star Ratings to evaluate health plan performance.The objective of this study was to assess the relationship between adherence and utilization and cost among Medicare Supplemental beneficiaries included in the aforementioned PQA measures over a 1-year period.Retrospective cohort study.Three cohorts (hypertension, cholesterol, and diabetes) of eligible individuals from the Truven Health MarketScan Commercial Claims and Encounters Research Databases (2009-2015) were used to assess associations between adherence and health care expenditure and utilization for Medicare Supplemental beneficiaries.Generalized linear models with log link and negative binomial (utilization) or gamma (expenditure) distributions assessed relationships between adherence (≥80% proportion of days covered) and health care utilization and expenditure (in 2015 US dollars) while adjusting for confounding variables. Beta coefficients were used to compute cost ratios and rate ratios.Adherence for all 3 disease cohorts was associated with lower outpatient and inpatient visits. During the 1-year study period, adherence was associated with lower outpatient, inpatient, and total expenditures across the cohorts, ranging from 9% lower outpatient costs (diabetes cohort) to 41.9% lower inpatient costs (hypertension cohort). Savings of up to $324.53 per member per month in total expenditure were observed for the hypertension cohort.Our findings indicate adherence is associated with lower health care utilization and expenditures within 1 year.


Asunto(s)
Antihipertensivos/economía , Gastos en Salud/estadística & datos numéricos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/economía , Hipoglucemiantes/economía , Cumplimiento de la Medicación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Medicare , Estudios Retrospectivos , Estados Unidos
20.
Biochem Mol Biol Educ ; 49(5): 707-719, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34080750

RESUMEN

Proteopedia (proteopedia.org) is an open resource to explore the structure-function relationship of proteins and other biomolecules. This guide provides practical advice on how to incorporate Proteopedia into teaching the structure and function of proteins and other biomolecules. For 11 activities, we discuss desired outcomes, setting expectations, preparing students for the tasks, using resources within Proteopedia, and evaluating student work. We point out features of Proteopedia that make it especially suitable for teaching and give examples of how to avoid common pitfalls.


Asunto(s)
Proteínas , Estudiantes , Humanos , Enseñanza
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