Hasil untuk "Specialties of internal medicine"

C. Sinsky, L. Colligan, Ling Li et al.

Kristine Godziuk, Mary Forhan, Flavio T. Vieira et al.

ABSTRACT Background Treatments aimed at improving physical function and body composition, including reducing fat mass (FM) and increasing muscle mass, may benefit individuals with advanced knee osteoarthritis (OA) and obesity. We investigated the feasibility and efficacy of a multimodal behavioural intervention compared to usual care to enhance physical function and muscle mass in this population. Methods The POMELO (Prevention Of MusclE Loss in Osteoarthritis) study is a two‐arm pilot randomized controlled trial; NCT05026385. Participants aged 40–75 years, with a BMI ≥ 35 kg/m2 and knee OA were randomized 1:1 to either the intervention group (POMELO) or usual care (UC). The 3‐month POMELO intervention incorporated progressive resistance exercise (3 sessions/week), individualized nutrition counselling targeted for OA, and 12 group education sessions on nutrition and arthritis self‐management. The UC group received standard clinical care. After the 3‐month supervised intervention, both groups were followed for 6 months without support. Assessments at baseline, 3 months and 9 months (primary endpoint) included body composition (DXA, measuring FM and appendicular lean soft tissue [ALST]), physical function (chair‐sit‐to‐stands [CSTS], 6‐min walk [6MWT], maximal handgrip strength [HGS]), and health‐related quality of life (Euroqol visual analog scale [EQ‐5D VAS]). Co‐primary outcomes were feasibility (intervention completion ≥ 80% and per‐protocol adherence ≥ 60% [i.e., attendance at 12 education sessions and exercise 3 ×/week]) and acceptability (4‐item Likert‐scale satisfaction survey, and open‐ended questions). Secondary outcomes included changes in physical function and ALST. Results Fifty participants were randomized (POMELO = 25, UC = 25), with 32 completing the study (69% female, mean age 64.9 ± 1.2 years, BMI 42.1 ± 1.0 kg/m2). The POMELO intervention group had 80% completion and 74% adherence, confirming feasibility. Higher satisfaction rates were observed in POMELO compared to UC (3.5 vs. 2.2, p < 0.001) indicating greater acceptability. The POMELO group had improvements in CSTS (mean difference [MD] 3.96, ES 1.2, p < 0.001), 6MWT (MD 31.6 m, ES 0.4, p = 0.039) and EQ‐5D VAS (MD 7.9 points, ES = 0.4, p = 0.01) compared to UC. Both groups experienced FM loss, but only the UC group lost ALST and HGS. Conclusion The POMELO intervention, combining personalized nutrition, resistance exercise and self‐management support, was feasible, acceptable and showed greater efficacy than usual care to improve physical function in patients with knee OA and obesity. Our pilot study of this intervention showed potential benefits on body composition and quality of life without focusing on weight reduction. A larger study is needed to confirm these results, as this approach may offer advantages over usual care, potentially leading to better mobility and health outcomes.

Kayla H Szymanik, Emily A Rex, Vamshikrishna R Pothireddy et al.

Proper recognition of viral pathogens is an essential part of the innate immune response. A common viral replicative intermediate and chemical signal that cells use to identify pathogens is the presence of a triphosphorylated 5' end (5'ppp) RNA, which activates the cytosolic RNA sensor RIG-I and initiates downstream antiviral signaling. While 5'pppRNA generated by viral RNA-dependent RNA polymerases (RdRps) can be a potent activator of the immune response, endogenous RNA polymerase III (RNAPIII) transcripts can retain the 5'ppp generated during transcription and induce a RIG-I-mediated immune response. We have previously shown that host RNA triphosphatase dual-specificity phosphatase 11 (DUSP11) can act on both host and viral RNAs, altering their levels and reducing their ability to induce RIG-I activation. Our previous work explored how experimentally altered DUSP11 activity can impact immune activation, prompting further exploration into natural contexts of altered DUSP11 activity. Here, we have identified viral DUSP11 homologs (vDUSP11s) present in some avipoxviruses. Consistent with the known functions of host DUSP11, we have shown that expression of vDUSP11s: 1) reduces levels of endogenous RNAPIII transcripts, 2) reduces a cell's sensitivity to 5'pppRNA-mediated immune activation, and 3) restores virus infection defects seen in the absence of DUSP11. Our results identify a context where DUSP11 activity has been co-opted by viruses to alter RNA metabolism and influence the outcome of infection.

M. Jane Morwitzer, Ying Yi Zheng, Heather Friberg et al.

Dengue is caused by the four serotypes of dengue virus (DENV-1-4) and poses a significant global public health challenge, with an estimated 100–400 million infections annually. Severe dengue manifestations, such as Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), are influenced by immune responses, particularly during secondary infections with different serotypes. Antibody-dependent enhancement (ADE) of DENV infection is a critical mechanism in dengue immunopathogenesis, underscoring the need for comprehensive evaluation of antibody responses. Traditional cell lines used for DENV propagation exhibit variability and present logistical challenges for assessing non-neutralizing antibody functions. Here, we report the establishment of a stable CEM-NKR cell line expressing DC-SIGN, designated CEM2001, capable of supporting continuous infection with all four DENV serotypes. These cell lines allow for continuous DENV infection, enabling detailed immunoassays to evaluate serotype-specific and cross-reactive non-neutralizing antibody responses. Our approach offers a significant advancement in dengue research, providing a consistent and reliable system to study DENV immune responses and supporting future efforts to develop and evaluate dengue therapeutics and vaccines.

Lu Zhang, Xingjian Xiong, Muxi Zhang et al.

Abstract Background Elite female basketball players experience a high incidence of lower-limb injuries, yet evidence remains limited regarding the applicability of common functional performance tests in this population. This study aimed (1) to compare the performance of the Functional Movement Screen (FMS), Landing Error Scoring System (LESS), and Y-Balance Test (YBT) between athletes with and without knee or ankle/foot injuries, and (2) to examine the correlations among these three functional performance tests. Methods Eighteen elite female basketball players from the Chinese National Team completed three functional performance tests: FMS, LESS, and YBT. Differences in total and subtest scores between injured and non-injured athletes were analyzed using independent samples t-tests and the Mann–Whitney U test. Spearman correlation analysis was conducted to examine relationships among the three tests. Results No significant differences were found in total FMS, LESS, or YBT scores between injured and non-injured athletes. However, a large effect size suggested a potential clinical trend between knee injuries and total FMS scores, and the FMS Deep Squat subtest significantly differentiated athletes with knee injuries. No significant correlations were observed among FMS, LESS, and YBT scores. Conclusion The FMS Deep Squat component may help identify knee-related functional limitations in elite female basketball players, while the three tests collectively provide complementary perspectives on movement quality assessment in applied settings. However, given the small sample and cross-sectional design, these findings should be interpreted as exploratory and warrant validation in larger, prospective studies.

Tobias Leutritz, Maike Krauthausen, Anne Simmenroth et al.

Given the shortage and unequal distribution of physicians across specialties, we aimed to evaluate factors associated with medical students’ career choices, including background, personality traits, educational experience, personal interests, lifestyle considerations, and the awareness of work requirements. We conducted multiple cross-sectional surveys of students; a 159-item online questionnaire was designed and students from three different stages of the six-year medical degree course (outset, clinical phase, and on graduation) were invited to complete the survey. Data were collected between May 2021 and April 2023. The questionnaire was sent to 1406 students, of whom 683 replied (49%); 481 respondents were female (70%). The top specialty choices across the respondents were internal medicine, surgery, and general practice, with anaesthesiology, paediatric and adolescent medicine (ranging 11–15%), and obstetrics and gynaecology also receiving interest, with 6% undecided. In particular, female students lost interest in surgery during the course of study in favour of the other options. The choice of general practice was associated with more vocational training, prior positive experiences with the specialty, and lower grades in the university entry examination. Clinical clerkships in a specific (freely chosen) specialty aligned with career choice, while the final practical year did not have an impact on career decision-making. All students highly desired regulated working hours and work-life-balance; however, students choosing surgery rated these items as less important. Willingness to work in a hospital environment was highly associated with choosing anaesthesiology and surgery, whereas rural areas and practices were associated with general practice. Higher scores at agreeableness were associated with choosing paediatric and adolescent medicine by more female students, whereas lower neuroticism values were associated with the choice of anaesthesiology. The results highlight the intricate nature of decision-making and shed light on various aspects that contribute to the process of selecting a specialty. By identifying and addressing influencing factors, we can develop targeted interventions and policies to enhance diversity and distribution across medical specialisations and to aim for high-quality and equitable healthcare that matches the specific needs of both individuals and the population as a whole.

Magdalena Sevilla-González, Maria Fernanda Garibay-Gutiérrez, Arsenio Vargas-Vázquez et al.

Background: A risk haplotype in SLC16A11 characterized by alterations in fatty acid metabolism emerged as a genetic risk factor associated with increased susceptibility to type 2 diabetes (T2D) in Mexican population. Its role on treatment responses is not well understood. Objectives: We aimed to determine the impact of the risk haplotype on the metabolomic profile during a lifestyle intervention (LSI). Methods: We recruited Mexican-mestizo individuals with ≥1 prediabetes criteria according to the American Diabetes Association with a body mass index between 25 and 45 kg/m2. We conducted a 24-wk quasiexperimental LSI study for diabetes prevention. Here, we compared longitudinal plasma liquid chromatography/mass spectrometry metabolomic changes between carriers and noncarriers. We analyzed the association of risk haplotype with metabolites leveraging repeated assessments using multivariable-adjusted linear mixed models. Results: Before the intervention, carriers (N = 21) showed higher concentrations of hippurate, C16 carnitine, glycine, and cinnamoylglycine. After 24 wk of LSI, carriers exhibited a deleterious metabolomic profile. This profile was characterized by increased concentrations of hippurate, cinnamoglycine, xanthosine, N-acetylputrescine, L-acetylcarnitine, ceramide (d18:1/24:1), and decreased concentrations of citrulline and phosphatidylethanolamine. These metabolites were associated with higher concentrations of total cholesterol, triglycerides, and low density lipoprotein cholesterol. The effect of LSI on the risk haplotype was notably more pronounced in its impact on 2 metabolites: methylmalonylcarnitine (β: −0.56; P-interaction = 0.014) and betaine (β: −0.64; P-interaction = 0.017). Interestingly, lower consumption across visits of polyunsaturated (β: −0.038; P = 0.017) fatty acids were associated with higher concentrations of methylmalonylcarnitine. Covariates for adjustment across models included age, sex, genetic ancestry principal components, and body mass index. Conclusions: Our study highlights the persistence of deleterious metabolomic patterns associated with the risk haplotype before and during a 24-wk LSI. We also emphasize the potential regulatory role of polyunsaturated fatty acids on methylmalonylcarnitine concentrations suggesting a route for improving interventions for individuals with high-genetic risk.

Robert J. Gallo, Steven M. Asch, David C. Chan

Shuhei Yoshida, Haruki Matsumoto, Jumpei Temmoku et al.

Temporal arteritis (TA) is a large-vessel vasculitis mostly seen in older patients. Amyloid A (AA) amyloidosis secondary to a chronic inflammation induces multiple organ dysfunctions, including a dysfunction of the gastrointestinal tract. Herein, we present a case of TA complicated by AA amyloidosis that was resistant to oral and intravenous steroids. An 80-year-old man with a history of new-onset headache, jaw claudication, and distended temporal arteries was referred to our department. On admission, the patient presented with tenderness and a subcutaneous temporal nodule in both temple arteries. Ultrasonography of the nodule revealed an anechoic perivascular halo surrounding the right temporal artery. Following the diagnosis of TA, high-dose prednisolone therapy was initiated. However, the patient presented with recurrent abdominal pain and refractory diarrhea. Due to the unclear origin of refractory diarrhea, an extensive workup, including biopsy of the duodenal mucosa, was performed. Endoscopy revealed chronic inflammation in the duodenum. Immunohistochemical analysis of duodenal mucosal biopsy samples revealed AA amyloid deposition resulting in the diagnosis of AA amyloidosis. After tocilizumab (TCZ) administration, refractory diarrhea reduced; however, the patient died of intestinal perforation 1 month after the start of TCZ administration. Gastrointestinal involvement was the main clinical manifestation of AA amyloidosis in the present case. This case highlights the importance of bowel biopsy screening for amyloid deposition in patients with unexplained gastrointestinal tract symptoms, even in a recent onset of large-vessel vasculitis. In the present case, the carriage of the SAA1.3 allele likely contributed to the rare association of AA amyloidosis with TA.

Akram Amani

Testicular cancer (TC) is among the specific clinical problems of our time. Current therapy is highly effective, confirming 5-year disease-free survival in approximately 95% of ill people. TC is a prevalent type of cancer diagnosed in males between 14 and 44 ages, with an incidence of less than 1 in 9.9 cases per 100,000 men nationwide, but the total number of TC. Increase worldwide. In addition, the danger of expanding cancer in people with cancer during 15 years after diagnosis is 2%. These complicated and different conditions must be found in the clinical evidence base. Genetic, environmental, and hormonal elements are related to developing diseases and disorders in response to treatment and danger of relapse. This research discusses current topics that explain the relative contribution of the problems mentioned above to TC development. Additionally, we pay attention to environmental chemicals and heat exposure, their function in cancer development, and recent advances at the molecular level have been studied.

Danang Dwi Cahyadi, Tomoko Warita, Nanami Irie et al.

ABSTRACTNormalization is a crucial step in gene expression analysis to avoid misinterpretation. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of 10 candidate housekeeping genes in non-differentiated (ND) and differentiated (DI) 3T3-L1 cells on days 5 and 10. We used geNorm, NormFinder, BestKeeper, RefFinder, and the ∆Ct method to evaluate expression stability. The findings revealed that (1) the expression levels of the reference genes changed over time, even in non-differentiating cells, and (2) peptidylprolyl isomerase A (Ppia) and TATA box-binding protein (Tbp) were stable reference genes for 10 days in both undifferentiated and differentiated 3T3-L1 cells. Notably, the expression of known reference genes in non-differentiating cells was altered throughout the experiment.

Minhan Yi, Minhan Yi, Minhan Yi et al.

BackgroundInflammation proteins including interleukins (ILs) have been reported to be related to obstructive sleep apnea (OSA). The aims of this study were to estimate the levels for several key interleukins in OSA and the causal effects between them.MethodWeighted mean difference (WMD) was used to compare the expression differences of interleukins between OSA and control, and the changed levels during OSA treatments in the meta-analysis section. A two-sample Mendelian randomization (MR) was used to estimate the causal directions and effect sizes between OSA risks and interleukins. The inverse-variance weighting (IVW) was used as the primary method followed by several other MR methods including MR Egger, Weighted median, and MR-Robust Adjusted Profile Score as sensitivity analysis.ResultsNine different interleukins—IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23—were elevated in OSA compared with control to varying degrees, ranging from 0.82 to 100.14 pg/ml, and one interleukin, IL-10, was decreased by 0.77 pg/ml. Increased IL-1β, IL-6, and IL-8 rather than IL-10 can be reduced in OSA by effective treatments. Further, the MR analysis of the IVW method showed that there was no significant evidence to support the causal relationships between OSA and the nine interleukins—IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, and IL-18. Among them, the causal effect of OSA on IL-5 was almost significant [estimate: 0.267 (−0.030, 0.564), p = 0.078]. These results were consistent in the sensitivity analysis.ConclusionsAlthough IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-17, IL-18, and IL-23 were increasing and IL-10 was reducing in OSA, no significant causal relationships were observed between them by MR analysis. Further research is needed to test the causality of OSA risk on elevated IL-5 level.

Vinicius C. Iamonti, Gerson F. Souza, Antonio A. M. Castro et al.

Limited information is available regarding the role of anaerobic metabolism capacity on GOLD 1 and 2 COPD patients during upper limb exercise. We aimed to compare the upper limb anaerobic power capacity, blood lactate concentration, cardiovascular and respiratory responses, in male COPD patients versus healthy subjects during the 30-s Wingate anaerobic test (WAnT). The rate of fatigue and time constant of the power output decay (τ, tau) were also calculated and a regression analysis model was built to assess the predictors of τ in these patients. Twenty-four male COPD patients (post-bronchodilator FEV1 73.2 ± 15.3% of predicted) and 17 healthy subjects (FEV1 103.5 ± 10.1% of predicted) underwent the WAnT. Measurements were performed at rest, at the end of the WAnT, and during 3′ and 5′ of recovery time. Peak power (p = 0.04), low power (p = 0.002), and mean power output (p = 0.008) were significantly lower in COPD patients than in healthy subjects. Power output decreased exponentially in both groups, but at a significantly faster rate (p = 0.007) in COPD patients. The time constant of power decay was associated with resistance (in ohms) and fat-free mass (r2 = 0.604, adjusted r2 = 0.555, and p = 0.002). Blood lactate concentration was significantly higher in healthy subjects at the end of the test, as well as during 3′ and 5′ of recovery time (p < 0.01). Compared with healthy subjects, COPD patients with GOLD 1 and 2 presented lower upper limb anaerobic capacity and a faster rate of power output decrease during a maximal intensity exercise. Also, the WAnT proved to be a valid tool to measure the upper limb anaerobic capacity in these patients.

Kasande M, Natwijuka A, Katushabe E Snr et al.

Meble Kasande, Andrew Natwijuka, Eve Katushabe Snr, Anne Tweheyo Otwine Snr Faculty of Nursing and Health Sciences, Bishop Stuart University, Mbarara, UgandaCorrespondence: Meble Kasande, Bishop Stuart University, Faculty of Nursing and Health Sciences, P.O Box 09, Mbarara, Uganda, Tel +256 7812551, Email meblekasande@gmail.com; aotweheyo@nhs.bsu.ac.ugPurpose: This study aims at exploring experiences of people caring for adolescents living with HIV, also known as caregivers. By 2021, 150,000 adolescents were living with HIV and 32,000 adolescents were dying of AIDS related causes. HIV/AIDS remains one of the most serious public health problems, especially among the adolescents. This has placed a heavy burden on many caregivers, yet they are essential in caring for ALHIV. However, focus of all interventions has excluded caregivers of ALHIV. Thus, this is the reason why this study is being conducted to find out caregivers’ experience in caring for ALHIV.Participants and Methods: A phenomenological study was carried out. Purposive sampling was used to select a total of 15 caregivers to participate in the study. These participants were subjected to in-depth semi-structured interviews. Their responses were recorded, transcribed and translated for thematic analysis.Results: While analyzing the results, six themes emerged. They include: diagnosis and reaction to diagnosis, experiences on adolescent’s HIV serostatus disclosure, stigma and discrimination, care disengagement, and lastly, challenges during care and coping strategies. Caregivers experienced feelings of fear, Guilt, suicidal thoughts after diagnosis. Stigma and discrimination of adolescents living with HIV which was common at school and from the neighbors and the adolescent stage were some of the challenges experienced by the caregivers and it makes it hard to retain ALHIV in care.Conclusion: Families are the main source of caregiving to the adolescents living with HIV (ALHIV). The study’s findings indicate that caregivers in the families experience challenges related to family needs, and psychological challenges resulting from the adolescence stage. So, families should not be left to shoulder the burden of caring for ALHIV. As a way forward, social network and financial support should also be strengthened for most caregivers as a coping strategy.Keywords: ALHIV, adolescents living with HIV, caregivers and experiences

Jiawei Zhuang, Gangyi Cheng, Jian Huang et al.

Abstract Background Myocarditis is a cardiomyopathy associated with the inflammatory response. Rosuvastatin (RS) demonstrates cardioprotective effect in the clinical setting, although its cellular and molecular mechanisms in ameliorating myocarditis are largely unknown. MG53 (muscle-specific E3 ligase Mitsugumin 53), a newly identified striated muscle-specific protein, is involved in skeletal muscle membrane repair. We aimed to explore whether RS mediated the repair of cardiomyocytes in an MG53-dependent manner. Methods The RS-induced upregulation of MG53 was determined using RT-qPCR and western blotting. A lipopolysaccharide (LPS)-induced cell inflammatory model was constructed using rat cardiac muscle cell H9C2. Inflammatory injury was evaluated according to the alterations of cell viability, mitochondrial membrane potential, cell apoptosis, and expression of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1). Small interfering RNAs (siRNAs) were used to silence MG53. The cardioprotective effect of RS and the inhibition of this protection by MG53 silence were evaluated in the forementioned in vitro model. The underlying mechanism was finally investigated using western blotting to detected the expressions of apoptotic markers (Bcl-2, Bax, Cleaved caspase-9, Cleaved caspase-3), cell cycle regulatory factors (Cyclin A, Cyclin E1, Cyclin D1, CDK2), and components involved in NF-κB signaling pathway (p-IκBa, Iκba, p-p65, p65). Results RS ameliorated LPS-induced inflammatory injury. RS upregulated the expression of MG53. MG53 was crucial for the RS-mediated repair response in vitro. Ablation of MG53 inhibited the RS-mediated protective effect. Furthermore, RS and MG53 interact in multiple signaling pathways to modulate recovery. Conclusion RS exerts cardioprotective effect in an MG53-dependent manner. MG53 may serve as a novel drug target for myocarditis treatment.

Jiao Jian, Shanshan Zhang, Jun Zhang et al.

Avrum Gillespie

Xiaoqing Shi, Xiaoqing Shi, Chuan Wang et al.

Pulmonary artery sling (PAS) is a rare but fatal malformation. Patients with PAS tend to develop obstructive symptoms in few weeks of life. Conversely, some patients may be otherwise mild or asymptomatic in their early life. Currently, no consensus on the intervention timing and treatment strategy for asymptomatic and mild cases has been reached. Moreover, the extent of tracheal stenosis is another determining factor for the choice of intervention timing since clinical symptoms might not correspond well with the degree of stenosis. Lack of comprehensive assessment of entire airways confer underestimation of disease severity and in turn improper choice of treatment regimens and poor outcomes. Herein, we described an infantile case of PAS, who was scheduled initially for periodic outpatient follow-up on account of the absence of symptoms and inadequate imaging assessment at diagnosis. The patient developed recurrent wheezing and progressive respiratory distress at 7 months of age. After left pulmonary artery (LPA) reimplantation without tracheal intervention, bronchoscopy was performed due to failure to wean from mechanical ventilation, which demonstrated complete tracheal cartilage rings, a long segment tracheal stenosis, a low tracheal bifurcation at T6, and the absence of a separate right middle lobe bronchus. The patient was finally diagnosed with type IIb PAS and extubated successfully following conservative treatment. Miserably, neurological sequelae were devastating, leading to poor outcomes. Comprehensive airway evaluation using bronchoscopy is substantial to early identification of all components responsible for airway compromise in PAS anatomic subtypes. Considering severe concomitant maldevelopment of the bronchial tree in children with type IIb PAS, early and complete correction by surgery might decrease perioperative morbidities and mortalities of these patients.

Diana L. Learoyd, Stephen J. Clarke

AbstractOver careers spanning 35 years each, we have witnessed great advances in medicine especially in genetics, imaging, immunotherapies and targeted cancer therapies. Our respective specialties of endocrinology and medical oncology have come to overlap significantly necessitating better communication and skills across both specialties. We will highlight common scenarios that straddle endocrinology and medical oncology. The same broad issues apply to other closely related specialties, albeit with different clinical challenges. At present, we see expensive and inefficient cross‐referrals to other subspecialists or sometimes no referral at all, leading to significant clinical omissions. Opportunities for dual advanced training, or for more comprehensive single advanced training could more efficiently lead to enhanced patient care and communication.

Stephen Gauthier, Lindsay Melvin, M. Mylopoulos et al.

Direct observation is the foundation of assessment and learning in competency‐based medical education (CBME). Despite its importance, there is significant uncertainty about how to effectively implement frequent and high‐quality direct observation. This is particularly true in specialties where observation of non‐procedural skills is highly valued and presents unique challenges. It is therefore important to understand perceptions of direct observation to ensure successful acceptance and implementation. In this study, we explored perceptions of direct observation in internal medicine.