ABSTRACT
Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.
ABSTRACT
Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.
ABSTRACT
It is essential that communities at risk from TB are involved in TB research. Community advisory groups (CAGs) are one mechanism for involving communities in research and creating platforms for discussions between researchers and community members. We organised a CAG meeting with community members and people with lived experience in Ho Chi Minh City, Vietnam, to explore the community's knowledge about TB and their perspectives on different diagnostic tests in Vietnam, a low-middle-income country with a high TB burden. Researchers shared basic information and addressed questions about TB. CAG members commented on preference of TB screening tests, and suggested that chest X-rays and blood tests were more acceptable than sputum tests because of the difficulty in sputum expectoration. In addition, clinical studies that required fewer visits to the hospitals would be preferred, even if this meant a greater reliance on blood sampling.
Il est essentiel que les communautés exposées au risque de TB soient impliquées dans la recherche sur la TB. Les groupes consultatifs communautaires (CAG, pour l'anglais « community advisory groups ¼) constituent un mécanisme permettant d'impliquer les communautés dans la recherche et de créer des plateformes de discussion entre les chercheurs et les membres de la communauté. Nous avons organisé une réunion du CAG avec des membres de la communauté et des personnes ayant une expérience vécue à Ho Chi Minh Ville, au Viêt Nam, afin d'explorer les connaissances de la communauté sur la TB et leurs perspectives sur les différents tests de diagnostic au Viêt Nam, un pays à revenu faible et moyen où la charge de la TB est élevée. Les chercheurs ont partagé des informations de base et répondu à des questions sur la TB. Les membres du CAG ont fait part de leur préférence pour les tests de dépistage de la TB et ont suggéré que les radiographies pulmonaires et les analyses de sang étaient plus acceptables que les tests d'expectoration en raison de la difficulté d'expectoration des crachats. En outre, les études cliniques qui nécessitent moins de visites dans les hôpitaux seraient préférées, même si cela implique une plus grande dépendance à l'égard des prélèvements sanguins.
ABSTRACT
We have investigated the fragmentation dynamics of the organometallic ferrocene molecule after interaction with multiply charged ions using multicoincidence mass spectrometry and quantum chemistry calculations. We observed unexpected fragmentation dynamics of the two-body breakup channels from ferrocene dications revealing a charge screening effect from the iron atom and delayed fragmentation dynamics. These observations are rationalized through the population of a specific long-lived excited state, where one positive charge is located on each cyclopentadienyl ring.
ABSTRACT
Classical swine fever virus (CSFV) identification has witnessed significant advancements with the development of rapid reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays. However, conventional RT-LAMP assays for CSFV diagnosis are hindered by a laborious RNA extraction step. Moreover, the need for thermal incubators and expensive micropipettes has limited their application in field settings. Addressing these challenges, our study presents a groundbreaking solution-an electro-free and point-of-care (POC) tool known as the field-LAMP assay-for the rapid clinical detection of CSFV. By eliminating the RNA extraction requirement, advancing the colorimetric read-out and lyophilized reaction reagents, our field-LAMP assay streamlines the diagnostic process, saving valuable time and effort. This novel approach also overcomes the dependency on electric-dependent thermal incubators and expensive micropipettes, making it practical and accessible for use in the field. The successful development of the field-LAMP assay marks a significant milestone in CSFV detection. This electro-free and POC tool offers several advantages, including its ability to deliver rapid results without compromising accuracy, facilitating prompt response and containment measures.
Subject(s)
Classical Swine Fever Virus , Classical Swine Fever , Swine Diseases , Swine , Animals , RNA , Sensitivity and Specificity , Classical Swine Fever/diagnosis , RNA, Viral , Swine Diseases/diagnosisABSTRACT
Our aim was to describe the research practices of doctoral students facing a dilemma to research integrity and to assess the impact of inappropriate research environments, i.e. exposure to (a) a post-doctoral researcher who committed a Detrimental Research Practice (DRP) in a similar situation and (b) a supervisor who did not oppose the DRP. We conducted two 2-arm, parallel-group randomized controlled trials. We created 10 vignettes describing a realistic dilemma with two alternative courses of action (good practice versus DRP). 630 PhD students were randomized through an online system to a vignette (a) with (n = 151) or without (n = 164) exposure to a post-doctoral researcher; (b) with (n = 155) or without (n = 160) exposure to a supervisor. The primary outcome was a score from - 5 to + 5, where positive scores indicated the choice of DRP and negative scores indicated good practice. Overall, 37% of unexposed participants chose to commit DRP with important variation across vignettes (minimum 10%; maximum 66%). The mean difference [95%CI] was 0.17 [- 0.65 to 0.99;], p = 0.65 when exposed to the post-doctoral researcher, and 0.79 [- 0.38; 1.94], p = 0.16, when exposed to the supervisor. In conclusion, we did not find evidence of an impact of postdoctoral researchers and supervisors on student research practices.Trial registration: NCT04263805, NCT04263506 (registration date 11 February 2020).
Subject(s)
Biomedical Research , Students , HumansABSTRACT
OBJECTIVE: Postoperative bowel movement dysfunction is a challenging problem greatly affecting patients' quality of life after low anterior resection. We aimed to evaluate the bowel movement function of patients undergoing laparoscopic low anterior resection for rectal cancer. PATIENTS AND METHODS: This retrospective study recruited 82 rectal cancer patients undergoing laparoscopic low anterior resection from July 2018 to July 2020 at 108 Military Central Hospital, Hanoi, Vietnam. RESULTS: The patients' mean age was 62.3±11.6 (28-84) years, 54 (65.9%) were males, and 28 (34.1%) were females. Bowel movement function changed significantly after one year: the average score for low anterior resection syndrome (LARS) after three months, six months, and one year was 17.6, 14.0, and 10.6, respectively. The rate of patients with major LARS decreased from 26.8% after three months to 14.6% after one year. The Wexner score also decreased from 5.9 after three months to 3.4 after one year. The rate of patients with normal bowel movement increased from 28.0% after three months to 46.3% after one year. The rate of patients with complete fecal incontinence decreased from 11.0% after three months to 7.3% after one year. Preoperative chemoradiotherapy (p=0.017), tumor location (p=0.02), method of anastomosis (p=0.01), and anastomosis location (p=0.000) were risk factors associated with major LARS after surgery. CONCLUSIONS: Bowel movement dysfunction in rectal cancer patients undergoing laparoscopic low anterior resection is a common and persistent problem after surgery. However, bowel function gradually recovers over time. Therefore, patients should be monitored and supported for a better quality of life.
Subject(s)
Intestinal Diseases , Laparoscopy , Rectal Neoplasms , Male , Female , Humans , Middle Aged , Aged , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Defecation , Retrospective Studies , Postoperative Complications/etiology , Quality of Life , Vietnam/epidemiology , Laparoscopy/adverse effectsABSTRACT
BACKGROUND: Evidence suggests that wearing permethrin-treated military uniforms is not associated with current adverse health conditions. However, exposure through this route results in permethrin biomarker concentrations considerably higher than those in the U.S. POPULATION: The U.S. Army is exploring different methods of uniform treatment that reduce exposure while maintaining effective protection from insect vector-borne diseases. OBJECTIVE: To compare permethrin exposure when wearing two types of permethrin-treated military uniforms. METHODS: Eight male soldiers participated in a 32-day crossover design study to compare permethrin exposure when wearing the current Army uniform (CurrU) and a uniform with a new applied fabric treatment (NewU). Each soldier wore the uniforms for designated 8 h/day time periods over 3 consecutive days separated by a 'wash-out' week of no exposure. Permethrin exposure was assessed from the urinary concentrations of 3-phenoxybenzoic acid (3-PBA) and of the sum of cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (∑DCCA). Estimated dose was determined based on ∑DCCA concentrations. RESULTS: Permethrin exposure biomarkers were 21% (3-PBA, p = 0.025) and 35% (∑DCCA, p < 0.001) lower when wearing the NewU compared to the CurrU; the dose was 33% lower (p = 0.05). SIGNIFICANCE: Findings suggest the new treatment reduces human permethrin exposure biomarkers resulting from wearing-treated military uniforms.
Subject(s)
Military Personnel , Pyrethrins , Humans , Male , Biomarkers , Clothing , Cross-Over Studies , Permethrin , Pyrethrins/adverse effectsABSTRACT
OBJECTIVE: Although the application of transcranial Doppler (TCD) ultrasonography in clinical diagnosis of cerebral vasospasm is popular in clinical practice in Vietnam, available evidence of the predictive value of vasospasm on TCD in the literature was mostly reported from large institutions in developed countries. Hence, this study was conducted to evaluate the value of TCD ultrasonography in the diagnosis of vasospasm in patients with subarachnoid hemorrhage (SAH) in Vietnam. PATIENTS AND METHODS: This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between 2008 and December 2011. TCD and 64-slice computed tomographic angiography (CTA) were used to cerebral vasospasm in SAH patients. RESULTS: 316 patients were analyzed (mean age = 52.97±12.27 years, 52.2% males). There were statistically significant difference rates of the cerebral vasospasm by Hunt and Hess Classification and Fisher classification (p <0.01). The proportion of the patients with cerebral vasospasm who were diagnosed exactly by TCD was 95.2%, while the proportion of the patients without cerebral vasospasm diagnosed exactly was 91.5%. TCD predictive diagnostic value was the highest, with the sensitivity of 0.95 (95% CI: 0.91-0.98), specificity of 0.91 (95% CI: 0.85-0.96), positive predictive value of 0.94 (5% CI: 0.90-0.97) and negative predictive value of 0.93 (95 CI: 0.87-0.97). Hemiplegia was the clinical symptom with the highest diagnostic value with the sensitivity of 0.34 (95% CI: 0.27-0.41), specificity of 0.92 (95% CI: 0.86-0.96), positive predictive value of 0.86 (95% CI: 0.76-0.93) and negative predictive value of 0.49 (95% CI: 0.41-0.54). CONCLUSIONS: Evidence of vasospasm diagnosis on TCD ultrasonography was found with high accuracy. Current study enables to suggest the wide application of TCD in Vietnam health facilities from central to grassroots levels instead of the CTA use.
Subject(s)
Subarachnoid Hemorrhage , Vasospasm, Intracranial , Adult , Aged , Cerebral Angiography , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Subarachnoid Hemorrhage/diagnostic imaging , Ultrasonography, Doppler, Transcranial/methods , Vasospasm, Intracranial/diagnostic imaging , VietnamABSTRACT
OBJECTIVES: Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry. METHODS: In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis. RESULTS: SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability = 4.9%, p = 6.83 × 10-8), East-Asian (R2 liability = 4.5%, p = 2.73 × 10-7) and European (R2 liability = 3.8%, p = 1.79 × 10-6) discovery samples. DISCUSSION: Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.
Subject(s)
Schizophrenia , Humans , Schizophrenia/genetics , Genome-Wide Association Study , Pilot Projects , Genetic Predisposition to Disease , Vietnam , Multifactorial InheritanceABSTRACT
The CD4 depletion model estimates diagnosis delays by approximating infection date from CD4 T-cell count at diagnosis, and back-calculation can compute the proportion of undiagnosed PLWHA. The model assumes the immigration of PLWHA to the U.S. is negligible and counts as a transmission event, which may be impractical outside high prevalence states. Duration of U.S. residency among foreign-born PLWHA and diagnosis delays were compared. The impact on estimates of undiagnosed PLWHA was tested through simulation with different proportions of foreign-born people assumed to have acquired HIV abroad. In 67% of foreign-born people, the mean (SD) years of delay (9.9 (6.3)) exceeded the duration of U.S. residency (2.0 (1.9)). Additionally, inaccuracies in the estimates for proportions of undiagnosed PLWHA were pronounced when foreign-born people who acquired HIV abroad comprised 30% of diagnoses. The CD4 model inadvertently misclassified some diagnoses as in-state transmission events. Consequently, simulated results demonstrated inaccuracies and unstable calculations.
Subject(s)
HIV Infections , CD4 Lymphocyte Count , Emigration and Immigration , HIV Infections/diagnosis , HIV Infections/epidemiology , Humans , Incidence , PrevalenceABSTRACT
Importance: Hazardous and heavy alcohol use is common among people living with HIV and may decrease antiretroviral therapy (ART) adherence, but limited data exist from randomized clinical trials about the effects of interventions on viral load. Objective: To compare the efficacy of 2 scalable ART clinic-based interventions on alcohol use and viral suppression. Design, Setting, and Participants: This 3-group randomized clinical trial was conducted among 440 adults with HIV who were being treated at 7 ART clinics in Thai Nguyen, Vietnam. Adults receiving ART with hazardous alcohol use (Alcohol Use Disorders Identification Test-Consumption score ≥4 for men or ≥3 for women) and no plans to leave Thai Nguyen were included. Data were collected from March 2016 to May 2018 and analyzed from June 2018 to February 2020. Interventions: Participants were randomly assigned (1:1:1) to standard of care (SOC), a combined intervention of motivational enhancement therapy and cognitive behavioral therapy (6 in-person sessions of 1 hour each and 3 optional group sessions), or a brief intervention with similar components as the combined intervention but consisting of 2 shorter in-person sessions and 2 telephone sessions. Main Outcomes and Measures: The primary study outcomes were percentage of days abstinent from alcohol, confirmed using the alcohol biomarker phosphatidylethanol, and viral suppression at 12 months after enrollment. Results: A total of 440 eligible individuals (mean [SD] age, 40.2 [5.8] years; 426 [96.8%] men) were enrolled; 147 (33.4%) were assigned to the combined intervention, 147 (33.4%) to the brief intervention, and 146 (33.2%) to SOC. In the combined intervention group, 112 participants (76.2%) attended all 6 sessions, and in the brief intervention group, 124 (84.4%) attended all 4 sessions; in the whole sample, 390 (88.6%) completed 12 months of follow-up. At 12 months, the mean (SE) percentage of days abstinent was 65% (3.1%) among those in the combined intervention group, 65% (3.2%) among those in the brief intervention group, and 50% (3.4%) among those in the in the SOC group (Cohen d for combined intervention vs SOC and brief intervention vs SOC: 39%; 95% CI, 15% to 64%). Viral suppression (ie, <20 copies of HIV-1 RNA per milliliter) at 12 months was higher after the brief intervention than SOC (difference, 11%; 95% CI, 2% to 20%), but the difference between the combined intervention and SOC was not significantly different (difference, 5%; 95%, CI, -5% to 15%). Conclusions and Relevance: In this study, the brief intervention resulted in a significant increase in percentage of days abstinent from alcohol and a significant increase in viral suppression after 12 months. Future implementation science studies evaluating scale-up of the brief intervention are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02720237.
Subject(s)
Alcohol Abstinence/statistics & numerical data , Alcoholism/therapy , Anti-Retroviral Agents/therapeutic use , Cognitive Behavioral Therapy/methods , HIV Infections/drug therapy , Motivational Interviewing/methods , Psychotherapy, Brief/methods , Sustained Virologic Response , Adult , Alcoholism/complications , Female , HIV Infections/blood , HIV Infections/complications , Humans , Male , Middle Aged , RNA, Viral/blood , Treatment Outcome , Vietnam , Viral LoadABSTRACT
A description and the molecular characterization of two new species in the Haploporidae and Haplosplanchnidae families are provided herein. Parasaccocoelium armatum n. sp. was collected from the intestine of a Mugil cephalus Linnaeus, 1758 from the Primorsky region, Russia, and Pseudohaplosplanchnus catbaensis n. g. n. sp. was collected from Moolgarda seheli (Forsskål, 1775) in the coastal waters of Cat Ba Island, Vietnam. The morphological features of P. armatum n. sp. closely resemble those of Parasaccocoelium polyovum, but these species differ from one another by hermaphroditic sac and vitellaria area length and by maximal egg size. The main difference between P. armatum n. sp. and P. polyovum is the presence of an armed hermaphroditic duct in the new species. Molecular data support the case for inclusion of the studied trematodes in P. armatum n. sp. Worms P. catbaensis n. g. n. sp. from the mullet from Vietnam are morphologically close to Haplosplanchnus (Haplosplosplanchninae). The only difference between P. catbaensis n. g. n. sp. and species of Haplosplanchnus is the presence of few (1-7) large eggs, measuring 135-142 × 92-104 µm, versus numerous small eggs with a maximal size of 75 × 50 µm. Phylogenetic analysis showed that there is a contradiction between the morphological similarity of the worms and their position in the Haplosplanchnidae system, based on the genetic data. Results of this study indicate that P. catbaensis n. g. n. sp. is genetically distant from other representatives of Haplosplanchnus, despite their morphological similarity. According to the molecular data, P. catbaensis n. g. n. sp. is close to Hymenocotta mulli Manter, 1961 (Hymenocottinae). However, these species are considerably different to each other morphologically. Molecular data argue for the possibility of establishing a new subfamily for P. catbaensis n. g. n. sp. However, considering earlier studies of Haplosplanchnidae, we support the view that creating new subfamilies within this family is unreasonable because of the lack of molecular data for most haplosplanchnid species, which are necessary to resolve the problematic systematics and phylogeny of this family.
Subject(s)
Fish Diseases/parasitology , Fishes/parasitology , Trematoda/anatomy & histology , Trematoda/classification , Animals , DNA, Helminth/genetics , DNA, Ribosomal/genetics , Phylogeny , RNA, Ribosomal, 28S/genetics , Russia , Sequence Analysis, DNA , Trematoda/genetics , VietnamABSTRACT
Two new species of Pseudohaploporinae, Pseudohaploporus pusitestis sp. n. and Parahaploporus elegantus n. g., sp. n., are described from intestines of the Vietnamese mullet fish Moolgarda seheli and Osteomugil cunnesius, respectively. Pseudohaploporus pusitestis sp. n. differs from two known Pseudohaploporus species, P. vietnamensis and P. planiliza, by the absence of a diverticulate hermaphroditic duct and muscular sphincters at the proximal end of the hermaphroditic sac. Metrically, P. pusitestis sp. n. is close to P. vietnamensis and differs from this species and from P. planilizum by lower maximum sizes of most parameters. Parahaploporus elegantus n. g., sp. differs from representatives of Pseudohaploporus by the presence of a single testis and the armament of hermaphroditic duct and is morphologically close to trematodes of the genus Haploporus. However, P. elegantus n. g differs from all known Haploporus species from mugilids of the Indo-West Pacific by the structure of the armament of the hermaphroditic duct and also by size of body, organs and eggs. The validity of designating two new species and a new genus of trematodes is supported by ITS and 28S rDNA sequence data. Phylogenetic reconstructions showed that the new trematodes belong to the Pseudohaploporinae, which formed a well-supported cluster within the monophyletic Haploporidae.
Subject(s)
Fish Diseases/parasitology , Smegmamorpha , Trematoda/classification , Trematode Infections/veterinary , Animals , DNA, Helminth/analysis , DNA, Ribosomal Spacer/analysis , RNA, Ribosomal, 28S/analysis , Trematoda/anatomy & histology , Trematoda/genetics , Trematode Infections/parasitology , VietnamABSTRACT
BACKGROUND: In many countries, in-hospital survival from tetanus is increasing, but long-term outcome is unknown. In high-income settings, critical illness is associated with muscle wasting and poor functional outcome, but there are few data from resource-limited settings. In this study we aimed to assess muscle wasting and long-term functional outcome in adults with tetanus. METHODS: In a prospective observational study involving 80 adults with tetanus, sequential rectus femoris ultrasound measurements were made at admission, 7 days, 14 days and hospital discharge. Functional outcome was assessed at hospital discharge using the Timed Up and Go test, Clinical Frailty Score, Barthel Index and RAND 36-item Short Form Health Survey (SF-36) and 3 and 6 months after discharge using the SF-36 and Barthel Index. RESULTS: Significant muscle wasting occurred between hospital admission and discharge (p<0.01), particularly in severe disease, where a median 23.49% (interquartile range 10.01-26.07) reduction in rectus femoris cross-sectional area occurred in those with severe (Ablett grades 3 and 4) disease. Muscle mass at discharge was related to objective and subjective measures of physical and emotional function at discharge and 3 and 6 months after discharge. In patients >70 y of age, functional recovery at 6 months was reduced compared with younger patients. Hospital-acquired infection and age were risk factors for muscle wasting. CONCLUSIONS: Significant muscle wasting during hospitalization occurred in patients with tetanus, the extent of which correlates with functional outcome.
Subject(s)
Muscle Weakness/etiology , Muscle Weakness/physiopathology , Tetanus/complications , Tetanus/physiopathology , Adult , Critical Illness , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Prospective Studies , Time FactorsABSTRACT
Menisci act like shock absorbers and transmit load across the tibiofemoral joint by increasing congruency during movements or body weight load. This leads to decreasing the resultant stress on the articular cartilages. The meniscus has a dense extracellular matrix (ECM) composed of water, different types of collagens, and proteoglycans, such as decorin, aggrecan and biglycan. Decorin (DCN) regulates collagen fibrillogenesis acting on collagen fibrils diameter and fibrils orientation to achieve the proper assembly of its network. This work investigates the spatial disposition of this fundamental protein in pig meniscus' matrix by immunohistochemistry and western blot analysis. DCN shows an increasing trend, moving from neonatal to adult pig menisci. Adult meniscus, in porcine species, is the only one that could be considered fully mature and functional, and, even if an increasing trend is seen, no precise phenotypical switch points are seen in the age stages considered in this study.
Subject(s)
Age Factors , Decorin/physiology , Extracellular Matrix/physiology , Meniscus/physiology , Animals , SwineABSTRACT
The Osteoporosis Self Efficacy Scale was determined to equivalently measure calcium and exercise beliefs in both sexes. Despite data illustrating men's and women's similar self-efficacy, gender differences in clinical predictors of self-efficacy imply that efforts to improve care must account for more than self-efficacy. INTRODUCTION: To understand the extent to which the Osteoporosis Self Efficacy (OSE) Scale is reliable for both men and women. A secondary objective was to evaluate sex differences in OSE. METHODS: For this cross-sectional study, we analyzed data collected as part of the Patient Activation after DXA Result Notification (PAADRN) pragmatic trial which enrolled 7749 community-residing adults aged 50 and older reporting for bone densitometry. We used univariable methods, item analysis, exploratory and confirmatory factor analyses, and linear regression to evaluate sex differences in OSE responses and measurement. RESULTS: In this sample, the confirmatory factor analysis model for OSE both overall and within groups indicated a poor fit. The sex differences in the measurement model, however, were minor and reflected configural invariance (i.e., constructs were measuring the same things in both men and women), confirming that the OSE was measuring the same constructs in men and women. Men overall had higher exercise self-efficacy and women higher calcium self-efficacy. Overall, education, hip fracture, and self-reported health status predicted exercise self-efficacy whereas prior DXA, self-reported osteoporosis, and history of pharmacotherapy use did not. Predictors of calcium self-efficacy differed by gender. CONCLUSION: The OSE can be used to measure calcium and exercise self-efficacy in all older adults. However, gender differences in clinical predictors of self-efficacy and the lack of an association of prior DXA with self-efficacy imply that interventions to improve self-efficacy may be insufficient to drive significant improvement in rates of osteoporosis evaluation and treatment. TRIAL REGISTRATION: Patient Activation after DXA Result Notification (PAADRN), NCT01507662, https://clinicaltrials.gov/ct2/show/NCT01507662.
Subject(s)
Health Behavior , Osteoporosis/therapy , Self Efficacy , Absorptiometry, Photon , Aged , Calcium, Dietary/administration & dosage , Cross-Sectional Studies , Exercise Therapy/psychology , Female , Health Knowledge, Attitudes, Practice , Health Status , Humans , Independent Living , Male , Middle Aged , Osteoporosis/diagnosis , Osteoporosis/psychology , Patient Compliance/psychology , Patient Education as Topic/methods , Psychometrics , Self Report , Sex CharacteristicsABSTRACT
Adult specimens representing Pseudohaploporus vietnamensis n. g., sp. n., Pseudohaploporus planilizum n. g., sp. n., and Pseudohaploporus sp. were collected from the intestines of Osteomugil engeli (Bleeker, 1858), Moolgarda seheli (Forsskål, 1775), and Planiliza subviridis (Valenciennes, 1836) from Vietnam. The new genus Pseudohaploporus n. g. is similar to the genus Haploporus Looss, 1902 in morphology and host-specificity. Species of Pseudohaploporus and Haploporus both possess an elongated body, a long oesophagus, an intestinal bifurcation behind the ventral sucker, a large hermaphroditic bursa, vitellarium consisting of two compact accumulations, concretions in the excretory vesicle, and numerous small eggs that contain miracidia with a pigment eye, and both infect mullet. In contrast to Haploporus, both species of the genus Pseudohaploporus possess two testes. These species differ from each other morphometrically. Pseudohaploporus planilizum sp. n., in comparison with P. vietnamensis sp. n., possess a larger maximum and mean size for the body length, oral and ventral suckers, pharynx, oesophagus length, hermaphrodite bursa, and egg width. Molecular data (ITS and 28S rDNA sequences) support the validity of the new genus and the two new species and indicate the presence of another representative of this genus, Pseudohaploporus sp. Phylogenetic reconstructions show that Pseudohaploporus formed a well-supported clade within a large clade that represents the Haploporidae Nicoll, 1914. Based on morphological and molecular data for P. vietnamensis sp. n. and P. planilizum sp. n., we erected a new subfamily, Pseudohaploporinae subfam. n., which appears to be a sister taxon to Haploporinae Nicoll, 1914. Molecular data show that Pseudohaploporus differ from other haploporids at a level similar to that between other subfamilies.
Subject(s)
Smegmamorpha/parasitology , Trematoda/anatomy & histology , Trematoda/classification , Animals , DNA, Ribosomal Spacer/genetics , Intestines/parasitology , Ovum , Phylogeny , RNA, Ribosomal, 28S/genetics , Seafood/parasitology , Species Specificity , Trematoda/isolation & purification , Trematode Infections/veterinary , VietnamABSTRACT
HIV testing during pregnancy facilitates timely antiretroviral treatment for HIV-positive women. This study identifies reasons for late HIV testing among pregnant women delivering at a hospital in Ho Chi Minh City. We conducted a case-control study in which 160 cases were women who were tested for HIV late (i.e., at labor and delivery) and 160 controls were women who were tested during antenatal care (ANC). In multivariable logistic regression analysis, six variables were associated with late HIV testing: age less than 30 years, nine or fewer years of education, working as a homemaker or worker/farmer, living 20 km or more from the hospital, having received ANC at a private clinic/hospital only, and not believing that HIV testing is important during pregnancy. We recommend that national programs should provide additional effort for HIV testing during pregnancy to young women, less educated women, homemakers, and those receiving ANC at private clinics and hospitals.