Association of race and ethnicity with the development of cystic fibrosis-related diabetes.

BACKGROUND: CF-related diabetes (CFRD) is a common, life-expectancy limiting complication of CF. While Black race and Hispanic ethnicity in youth-onset type 1 and type 2 diabetes are well-recognized risk factors for worse diabetes complications, the potential for racial/ethnic disparities in CFRD has received limited attention. METHODS: We conducted a retrospective cohort study utilizing the CF Foundation Patient Registry from 2010 to 2019 to determine the prevalence and incidence of CFRD by race/ethnicity. Three age cohorts were identified at baseline in 2010 (11-20y, 21-30y, and 31-40y). Logistic regression and Cox regression stratified by age group were used to determine the prevalence and incidence, respectively, among Hispanic, non-Hispanic Blacks (NHB), and non-Hispanic whites (NHW) after adjustment for relevant confounders, including demographics, socioeconomic status, clinical factors, and chronic medication use. RESULTS: Among 14,660 registry participants, 510 were NHB and 890 Hispanic. NHB associated with higher odds of CFRD baseline prevalence in all age cohorts (11-20y: OR 2.53 (95 % CI: 1.88-3.41, P < 0.05), 21-30y: OR 1.80 (1.25-2.59, P < 0.05), and 31-40y: OR 1.93 (1.00-3.73, P < 0.05)) relative to NHW. In the 11-20y cohort, the hazard of new-onset CFRD was 40 % higher in NHB (HR 1.40 (1.09-1.8, P < 0.05)) and 19 % higher in Hispanics (HR 1.19 (1.01-1.41, P < 0.05)). CONCLUSION: NHB had a higher prevalence of CFRD across all age groups, with NHB and Hispanics showing higher incidence of CFRD in the youngest group. Multicenter studies performed in diverse CF populations are warranted to identify modifiable factors influencing earlier CFRD development in minoritized groups and their potential contribution to diabetes complication disparities.

2D array imaging system for mechanically-steered, forward-viewing ultrasound guidewire.

Approximately 4 million people with peripheral artery disease (PAD) present with critical limb ischemia each year, requiring urgent revascularization to avoid loss of limb. Minimally-invasive (i.e. endovascular) revascularization is preferable due to increased recovery time and increased risk of complications associated with open surgery. However, 40% of people with PAD also have chronic total occlusions (CTOs), resulting in > 20% of revascularization procedures failing when CTOs are present. A steerable robotic guidewire with integrated forward-viewing imaging capabilities would allow the guidewire to navigate through tortuous vasculature and facilitate crossing CTOs in revascularization procedures that currently fail due to inability to route the guidewire. The robotic steering capabilities of the guidewire can be leveraged for 3D synthetic aperture imaging with a simplified, low element count, forward-viewing 2D array on the tip of the mechanically-steered guidewire. Images can then be formed using a hybrid beamforming approach, with focal delays calculated for each element on the tip of the guidewire and for each physical location to which the robotically-steered guidewire is steered. Unlike synthetic aperture imaging with a steerable guidewire having only a single element transducer, an array with even a small number of elements can allow estimation of blood flow and physiological motion in vivo. A miniature, low element count 2D array transducer with 9 total elements (3 × 3) having total dimensions of 1.5 mm × 1.5 mm was designed to operate at 17 MHz. A proof-of-concept 2D array transducer was fabricated and characterized acoustically. The developed array was then used to image a wire target, a peripheral stent, and an ex vivo porcine iliac artery. Images were formed using the described synthetic aperture beamforming strategy. Acoustic characterization showed a mean resonance frequency of 17.6 MHz and a -6 dB bandwidth of 35%. Lateral and axial resolution were 0.271 mm and 0.122 mm, respectively, and an increase in SNR of 4.8 dB was observed for the 2D array relative to the single element case. The first 2D array imaging system utilizing both mechanical and electronic steering for guidewire-based imaging was developed and demonstrated. A 2D array imaging system operating on the tip of the mechanically-steered guidewire provides improved frame rate and increases field of view relative to a single element transducer. Finally, 2D array and single element imaging were compared for introduced motion errors, with the 2D array providing a 46.1% increase in SNR, and 58.5% and 17.3% improvement in lateral and axial resolution, respectively, relative to single element guidewire imaging.

Estimating minimal clinically important difference (MCID) for gastrointestinal symptoms in cystic fibrosis.

BACKGROUND: Minimal clinically important difference (MCID) is important to establish as a meaningful outcome in research when using patient reported outcome measures (PROMs). We determined the MCID using the distribution-based approach for three measurements used as part of the GALAXY study, which is an observational prospective study on gastrointestinal (GI) symptoms in cystic fibrosis (CF). METHODS: Four hundred and two persons with cystic fibrosis (PwCF) participated in the GALAXY study, all with baseline values available for all questionnaires. Mean age was 20.9 years (2.1- 61.1) with 75 females and 94 males under the age of 18 (42.04 %) and 118 females and 115 males aged 18 or older (57.99 %). MCID was measured for Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL) and their subscales. Two distribution-based approaches, defined as multiplications of the standard deviation (SD) or standard error of the mean (SEM), were used to approximate the MCID. RESULTS: The two distribution-based approaches for determining the MCID estimates produced comparable results in trends in MCIDs across the subscales and total scores. In general, MCID estimates of subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire are as follows: PAC-SYM: 0.26 and 0.14; PAGI-SYM: 0.32 and 0.15; PAC-QOL: 0.27 and 0.18, respectively. CONCLUSION: This paper establishes initial MCIDs estimated by the distribution-based approach for the PAC-SYM, PAGI-SYM and PAC-QOL that can now be used to evaluate interventional studies that may impact gastrointestinal symptoms in PwCF.

Generation of a biliary tract cancer cell line atlas reveals molecular subtypes and therapeutic targets.

Biliary tract cancers (BTCs) are a group of deadly malignancies encompassing intrahepatic and extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinoma. Here, we present the integrative analysis of 63 BTC cell lines via multi-omics clustering and genome- scale CRISPR screens, providing a platform to illuminate BTC biology and inform therapeutic development. We identify dependencies broadly enriched in BTC compared to other cancers as well as dependencies selective to the anatomic subtypes. Notably, cholangiocarcinoma cell lines are stratified into distinct lineage subtypes based on biliary or dual biliary/hepatocyte marker signatures, associated with dependency on specific lineage survival factors. Transcriptional analysis of patient specimens demonstrates the prognostic significance of these lineage subtypes. Additionally, we delineate strategies to enhance targeted therapies or to overcome resistance in cell lines with key driver gene mutations. Furthermore, clustering based on dependencies and proteomics data elucidates unexpected functional relationships, including a BTC subgroup with partial squamous differentiation. Thus, this cell line atlas reveals potential therapeutic targets in molecularly defined BTCs, unveils biologically distinct disease subtypes, and offers a vital resource for BTC research.

Land-based plastic leakage into the aquatic environment from municipal solid waste - Waste flow diagram applied to Tuy Hoa City, Phu Yen, Vietnam.

Plastic mismanagement and its subsequent pollution by rapid economic development and urbanisation pose significant challenges for modern world society. Notwithstanding one of the main sources for macro plastic leakage into the ocean from land, precise assessment of plastic pollution origins from Southeast Asia is yet to be clearly examined. In order to make informed decisions and prioritise areas of improvement it is required to better understand the waste leakage dynamics at the local level. In this work, the Waste Flow Diagram (WFD) was applied to understand the sources and fates of plastics leaking from the solid waste management system for the case of Tuy Hoa City, Phu Yen, Vietnam. The study shows scenarios of leakage into the aquatic environment ranging from 0.8 to 2.7 kg/cap/year, which originates mainly from the collection system. Targeted improvements to this stage of the service could reduce leakages and the overall environmental impacts of mismanaged plastic waste. The results of this study show the necessity and importance of having up to date and reliable data to better inform stakeholders and service planning, facilitating efficient action against plastic pollution. As the first peer-reviewed scientific article critically applying the WFD, this work highlights the steps and challenges of the methodology and critically analyses different methodological pathways.

Metastatic melanoma to the urinary bladder with synchronous or metachronous metastasis to other organs: Clinicopathological characteristics and outcome.

INTRODUCTION AND IMPORTANCE: Bladder metastatic melanoma is a very uncommon condition. CASE PRESENTATION: On 62 reported cases, 55 studies have been done so far. We describe a 53-year-old woman with a hematuria who underwent transurethral resection of bladder lesions caused by metastatic melanoma for eight years ago after receiving her initial diagnosis of cutaneous malignant melanoma. CLINICAL DISCUSSION: We also review the medical literature to determine the prognosis of bladder metastatic melanoma. Synchronous metastases with metastatic melanoma to the bladder also reduces the mean survival compared with patients with metachronous metastases. CONCLUSION: Bladder metastatic melanoma combined with other factors, such as male, lymph node metastases, primary skin tumor, two or more bladder metastatic foci, and synchronous metastases are predictors of worse prognosis.

A giant metaplastic breast carcinoma with osseous differentiation: A rare case report and review of the literature.

INTRODUCTION: Metaplastic breast carcinoma (MBC) is a rare form of breast cancer, comprising less than 1 % of all breast malignancies. Osseous differentiation is an extremely rare subtype of MBC, accounting for only 0.003-0.12 % of all breast cancer cases. CASE PRESENTATION: We report a case of advanced-stage metaplastic breast carcinoma with osseous differentiation. The patient received neoadjuvant chemotherapy, but then the tumor progressed to metastasis. Despite palliative surgery, and chemotherapy, the disease did not respond; the patient died shortly later. CLINICAL DISCUSSION: Metaplastic breast carcinoma with osseous differentiation often rapidly progressive, resistant to chemotherapy, and associated with a poor prognosis. Some studies in the literature suggest that MBC tends to spread through the blood rather than lymphatic spread and therefore leads to lung and bone metastases. CONCLUSION: These findings suggest that the role of neoadjuvant chemotherapy in this histopathological group is limited and its use should be carefully considered.

CT imaging-derived phenotypes for abdominal muscle and their association with age and sex in a medical biobank.

The study of muscle mass as an imaging-derived phenotype (IDP) may yield new insights into determining the normal and pathologic variations in muscle mass in the population. This can be done by determining 3D abdominal muscle mass from 12 distinct abdominal muscle regions and groups using computed tomography (CT) in a racially diverse medical biobank. To develop a fully automatic technique for assessment of CT abdominal muscle IDPs and preliminarily determine abdominal muscle IDP variations with age and sex in a clinically and racially diverse medical biobank. This retrospective study was conducted using the Penn Medicine BioBank (PMBB), a research protocol that recruits adult participants during outpatient visits at hospitals in the Penn Medicine network. We developed a deep residual U-Net (ResUNet) to segment 12 abdominal muscle groups including the left and right psoas, quadratus lumborum, erector spinae, gluteus medius, rectus abdominis, and lateral abdominals. 110 CT studies were randomly selected for training, validation, and testing. 44 of the 110 CT studies were selected to enrich the dataset with representative cases of intra-abdominal and abdominal wall pathology. The studies were divided into non-overlapping training, validation and testing sets. Model performance was evaluated using the Sørensen-Dice coefficient. Volumes of individual muscle groups were plotted to distribution curves. To investigate associations between muscle IDPs, age, and sex, deep learning model segmentations were performed on a larger abdominal CT dataset from PMBB consisting of 295 studies. Multivariable models were used to determine relationships between muscle mass, age and sex. The model's performance (Dice scores) on the test data was the following: psoas: 0.85 ± 0.12, quadratus lumborum: 0.72 ± 0.14, erector spinae: 0.92 ± 0.07, gluteus medius: 0.90 ± 0.08, rectus abdominis: 0.85 ± 0.08, lateral abdominals: 0.85 ± 0.09. The average Dice score across all muscle groups was 0.86 ± 0.11. Average total muscle mass for females was 2041 ± 560.7 g with a high of 2256 ± 560.1 g (41-50 year old cohort) and a change of - 0.96 g/year, declining to an average mass of 1579 ± 408.8 g (81-100 year old cohort). Average total muscle mass for males was 3086 ± 769.1 g with a high of 3385 ± 819.3 g (51-60 year old cohort) and a change of - 1.73 g/year, declining to an average mass of 2629 ± 536.7 g (81-100 year old cohort). Quadratus lumborum was most highly correlated with age for both sexes (correlation coefficient of - 0.5). Gluteus medius mass in females was positively correlated with age with a coefficient of 0.22. These preliminary findings show that our CNN can automate detailed abdominal muscle volume measurement. Unlike prior efforts, this technique provides 3D muscle segmentations of individual muscles. This technique will dramatically impact sarcopenia diagnosis and research, elucidating its clinical and public health implications. Our results suggest a peak age range for muscle mass and an expected rate of decline, both of which vary between genders. Future goals are to investigate genetic variants for sarcopenia and malnutrition, while describing genotype-phenotype associations of muscle mass in healthy humans using imaging-derived phenotypes. It is feasible to obtain 3D abdominal muscle IDPs with high accuracy from patients in a medical biobank using fully automated machine learning methods. Abdominal muscle IDPs showed significant variations in lean mass by age and sex. In the future, this tool can be leveraged to perform a genome-wide association study across the medical biobank and determine genetic variants associated with early or accelerated muscle wasting.

HLA alleles associated with susceptibility and severity of the COVID-19 in Vietnamese.

The diversity of clinical manifestations in COVID-19 has been observed not only among individuals but also among various populations in globally. HLA molecules play a central role in physiology, protective immunity, and deleterious, disease-related autoimmune reactivity or overreaction. This study exploited the association between HLA frequencies and SARS-CoV-2 susceptibility and disease severity among the Vietnamese cohort (159 patients and 52 controls). A significant difference in frequency of both HLA class I and II in mild, moderate, and severe/fatal COVID-19 patients and negative exposure individuals - the controls were observed. Regarding SARS-CoV-2 sensitivity, HLA-A*03:01, 30:01, HLA-DQA1*01:02, DRB1*15:01, and DRB5*02:02 presented higher frequency in the control group compared with infected patients but DRB1 09:01 frequency was higher in infected patients. Regarding COVID-19 severity, HLA-F*01:01, 01:03 and DPA1*01:03 and 02:01, DPB1*04:01, DQA1*01:02, and DQB1*05:02 alleles were detected with higher frequency in severe patients but DOB*01:01, DRB1*05:01 and 09:01 had a significantly higher frequency in the mild group than remaining groups. Surprisingly, HLA-DQA1*01:02 and DRB1*09:01 alleles were identified with both inversely potential roles in protective function and severe risk. The obtained data herein will contribute to explore on the role of host genetic background in the pathology of COVID-19 disease.

Orthodontic Treatment for Borderline Class III Malocclusion in Adults: Nonextraction Treatment with Anterior Bite Turbo: A Case Report.

Retrusive upper lips, retroclined upper incisors, a shorter midface, and a larger maxillary-mandibular difference are the characteristics of borderline Class III malocclusion. Individuals with borderline Class III malocclusion frequently exhibit certain morphologic, dental, and skeletal traits, which should aid in the diagnosis of the condition. To report the case of a 22-year-old Vietnamese woman who complained of having tense front teeth and lacking confidence when smiling. Medical history did not find anything strange, there was root canal treatment of the first premolar on the left of the upper jaw, asymmetrical concave chin, and right deviation. Orthodontic camouflage treatment using anterior bite turbos in combination with early light short Class III elastics and box elastics was proposed since the patient declined to have orthognathic surgery. In just 10 months of treatment, a Class I molar and canine relationship was created, an anterior crossbite was corrected via mandibular retraction, and severe skeletal malocclusions were successfully treated without orthognathic surgery. Smiling currently showcases the patient's maxillary incisors more prominently, and her lower lip fullness has diminished, giving her a more attractive smile and a significant improvement to her facial profile.

Delayed duodenal/gastric fistula resulting in persistent perihepatic abscesses as a late complication of laparoscopic cholecystectomy.

Since the early 1990's, laparoscopic cholecystectomy has become the gold standard for the treatment of symptomatic gallbladder disease. Although the incidence of postoperative complications is generally lower with this approach, gallbladder perforation represents a serious risk that is among the most common complications of laparoscopic cholecystectomy. The sequalae that can follow iatrogenic perforation have not been well documented and only a few case reports exist in the current literature. In this paper we discuss two case reports of delayed perihepatic abscesses following prior laparoscopic cholecystectomy, ultimately resulting in fistulous tracts. The course of the disease is discussed along with the diagnostic workup and eventual successful management of the aforementioned complications. Treating enteric fistulae requires a systematic approach and is carried out in phases. Enteric fistula formation following laparoscopic cholecystectomy is a rare complication of retained gallstones that can present months to years following the index operation. Significant care should be taken to avoid perforation and all efforts should be made to retrieve stones if spillage occurs.

Survey data of Gen Z customer behaviour using food delivery applications in Vietnam.

This study presents an analysis based on data collected via questionnaire, surveying Gen Z customers using food delivery applications in Vietnam. The purpose of the original research was to investigate factors influencing Gen Z customers' decision to continue using the applications. The data set presented in this paper includes 361 valid responses that were collected by convenience sampling method from Hanoi and Hochiminh City, which are the two most potential regions of e-commerce transactions in Vietnam. After being collected, sorted, and filtered, the data was calculated by SPSS 22 and AMOS 23 software to extract descriptive analysis, Cronbach's Alpha, and confirmatory factor analysis (CFA). The calculation results indicated that this data set ensures reliability, convergent, and discriminant validity, which can serve as a good reference for future studies.

Favorable outcome of a histiocytic sarcoma patient treated with immune checkpoint inhibitor: a case report.

Introduction and Importance: Histiocytic sarcoma (HS) is an extremely rare malignancy in which there has been no standard treatment approach. Some preclinical studies have provided rationales for the application of immunotherapy in advanced HS. Case Presentation: The authors reported a case of a 61-year-old patient with metastatic HS who had a rapid progression on ifosfamide, carboplatin, and etoposide chemotherapy. The authors performed PD-L1 testing, which showed a strong positivity in 90% of tumor cells. The patient was then treated with pembrolizumab 200 mg every 3 weeks. He refused palliative radiotherapy. A dramatic response in all sites was recorded on the PET-CT scan after three cycles. He was maintained on pembrolizumab, reaching over 30 months without disease progression. Clinical Discussion: Recent molecular data suggests there could be a role of immunotherapy in HS. In our patient, the disease was refractory to chemotherapy and pembrolizumab has been given based on the strong PD-L1 expression. Response to immunotherapy has also been recorded in several cases with malignant histiocytic neoplasm. Conclusion: Immunotherapy might bring sustained disease remission in PD-L1 high expression HS and further studies evaluating the role of immune checkpoint inhibitor in this disease are warranted.

Orally administered boldine reduces muscle atrophy and promotes neuromuscular recovery in a rodent model of delayed nerve repair.

Peripheral nerve injury often results in poor functional recovery due to a prolonged period of muscle denervation. In particular, absent axonal contact, denervated muscle can undergo irrevocable atrophy and diminished receptiveness for reinnervation over time, ultimately reducing the likelihood for meaningful neuromuscular recovery. While innovative surgical approaches can minimize the harmful effects of denervation by re-routing neighboring-otherwise uninjured-axons, there are no clinically-available approaches to preserve the reinnervation capacity of denervated muscles. Blocking intramuscular connexin hemichannel formation has been reported to improve muscle innervation in vitro and prevent atrophy in vivo. Therefore, the current study investigated the effects of orally administered boldine, a connexin hemichannel inhibitor, on denervated-related muscle changes and nerve regeneration in a rat model of delayed peripheral nerve repair. We found that daily boldine administration significantly enhanced an evoked response in the tibialis anterior muscle at 2 weeks after common peroneal nerve transection, and decreased intramuscular connexin 43 and 45 expression, intraneural Schwann cell expression of connexin 43, and muscle fiber atrophy up to 4 weeks post transection. Additional animals underwent a cross nerve repair procedure (tibial to common peroneal neurorrhaphy) at 4 weeks following the initial transection injury. Here, we found elevated nerve electrophysiological activity and greater muscle fiber maturation at 6 weeks post repair in boldine treated animals. These findings suggest that boldine may be a promising pharmacological approach to minimize the deleterious effects of prolonged denervation and, with further optimization, may improve levels of functional recovery following nerve repair.

Role of hyperglycemia in cystic fibrosis pulmonary exacerbations.

BACKGROUND: Hyperglycemia could affect treatment response during cystic fibrosis (CF) exacerbations. We aimed to evaluate the prevalence and associations of hyperglycemia with exacerbation outcomes. We also evaluated feasibility of continuous glucose monitoring (CGM) during exacerbations. METHODS: The STOP2 study assessed efficacy and safety of different durations of intravenous antibiotics for CF exacerbations. We conducted a secondary data analysis of random glucose levels measured as part of clinical care during exacerbations. A small subset of participants also underwent CGM per research protocol. The associations between hyperglycemia, defined as random glucose ≥140 mg/dL, and changes in weight and lung function with exacerbation treatment were evaluated with linear regression after adjustment for confounding variables. RESULTS: Glucose levels were available for 182 STOP2 participants of mean (SD) age 31.6 (10.8) years, baseline percent predicted (pp) FEV1 53.6 (22.5); 37% had CF related diabetes and 27% were on insulin. Hyperglycemia was detected in 44% of participants. Adjusted mean difference (95% CI) was 1.34% (-1.39, 4.08) (p = 0.336) for change in ppFEV1 and 0.33 kg (-0.11, 0.78) (p = 0.145) for change in weight between hyperglycemic and non-hyperglycemic groups. Ten participants not on antidiabetic agents in the 4 weeks prior to enrollment underwent CGM; mean (SD) time spent >140 mg/dL was 24.6% (12.5) with 9/10 participants spending >4.5% time >140 mg/dL. CONCLUSIONS: Hyperglycemia identified with random glucose is prevalent during CF exacerbations but not associated with changes in lung function or weight with exacerbation treatment. CGM is feasible and may provide a useful tool for hyperglycemia monitoring during exacerbations.

Effectiveness of bee venom acupuncture for patients suffering from periarthritis humeroscapularis.

OBJECTIVE: To evaluate the efficacy of bee venom acupuncture in humeroscapularis (PHS) patients. METHODS: One hundred and twenty patients diagnosed with PHS were assigned into four groups: BV1 (0.01 mg/kg), BV2 (0.005 mg/kg), BV3 (0.0025 mg/kg), and control group (vitamin B1 plus novocain 3% injection) with 15 d of treatment. The outcomes of the study including visual analogue scale (VAS) score and ß-endorphin, inflammatory cytokines including interleukin-10 (IL-10), IL-1ß and tumor necrosis factor α (TNF-α) and shoulder function score were assessed at baseline, after 10 and 15 d of treatment. RESULTS: All four groups reported statistically significant improvement in VAS score, motion range, and shoulder function score ( < 0.01), only the BV3 group showed significant increase of anti-inflammatory (IL-10) and decrease of pro-inflammatory (IL-1ß, TNF-α) cytokines after treatment ( < 0.05). The BV3 group presented a significant difference between all outcomes compared to the control and other groups. CONCLUSION: BV3 groups showed better recovery including reduced pain, improved motor function and normalized inflammatory cytokines than current therapy used in Vietnam and other groups.

SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers.

Adult liver malignancies, including intrahepatic cholangiocarcinoma and hepatocellular carcinoma, are the second leading cause of cancer-related deaths worldwide. Most individuals are treated with either combination chemotherapy or immunotherapy, respectively, without specific biomarkers for selection. Here using high-throughput screens, proteomics and in vitro resistance models, we identify the small molecule YC-1 as selectively active against a defined subset of cell lines derived from both liver cancer types. We demonstrate that selectivity is determined by expression of the liver-resident cytosolic sulfotransferase enzyme SULT1A1, which sulfonates YC-1. Sulfonation stimulates covalent binding of YC-1 to lysine residues in protein targets, enriching for RNA-binding factors. Computational analysis defined a wider group of structurally related SULT1A1-activated small molecules with distinct target profiles, which together constitute an untapped small-molecule class. These studies provide a foundation for preclinical development of these agents and point to the broader potential of exploiting SULT1A1 activity for selective targeting strategies.

Effectiveness on post-stroke hemiplegia in patients: electroacupuncture plus cycling electroacupuncture alone.

OBJECTIVE: To evaluate the effectiveness of cycling in combination with electroacupuncture in treatment of post-stroke hemiplegia patients at National Hospital of Acupuncture, Vietnam. METHODS: The study was designed as a single-centre, outcome-assessor-blinded parallel randomised controlled trial with 120 post-stroke hemiplegia patients randomly assigned into two groups: electroacupuncture plus cycling (CT group) and electroacupuncture (AT group). Patients were assessed before and after the treatment (using muscle grading, modified Rankin, Barthel, Orgorozo scores and electromyography). Statistical Man-Whitney U test, and Fisher's exact tests were used to compare between CT and AT groups. RESULTS: The results reported statistically significant improvement in motor function in patients suffering from hemiplegia following ischemic stroke in both CT and AT groups. Patients in CT group experienced a greater improvement compared to those in AT group including better muscle contraction (increased frequency and amplitude of electromyography and increased muscle grading scale); increased recovery (Orgogozo scale), increased independency (Barthel scale) and decreased disability (Modified Rankin scale) (< 0.01). CONCLUSIONS: Combination with cycling training significantly improves the recovery of post-stroke patients treated with electroacupuncture.

Genetic variations of antioxidant genes and their association with male infertility in Vietnamese men.

BACKGROUND: Antioxidant genes, such as superoxide dismutase (SOD), catalase (CAT), and nitric oxide synthase (NOS), play critical roles in spermatogenesis and sperm functions. Polymorphisms of antioxidant genes have been shown to be strongly associated with sperm quality which affects male fertility. METHODS: To investigate the association of antioxidant gene polymorphisms to male infertility in Vietnamese men, in this case-control study, using Sanger sequencing, we genotyped four variants SOD1:7958G>A, SOD2:c.47T>C, CAT:-262C>T, and NOS3:-786C>T. RESULTS AND CONCLUSIONS: We identified SOD1:7958GA genotype and NOS3:-786CT genotype in the infertility group were significantly higher than in the control with OR = 2.191 (95% CI: 1.226-3.915, p = 0.004) and OR = 3.135 (95% CI: 1.591-6.180, p < 0.001), respectively. We also detected that the frequency of the SOD2:c.47TC genotype was significantly higher in the male infertility group than in fertile men (OR = 1.941, 95% CI: 1.063-3.595, p = 0.029). Gene-gene interactions between the SNPs of SOD1, SOD2, and CAT might increase the risk of male infertility patients. In particular, patients carrying the SOD1:GA+AA, SOD2:TC+CC, and CAT:CT/TT genotype pattern have an increased risk of male infertility (OR = 7.614, p = 0.007). To our knowledge, this is the first study to evaluate the association between the SOD1:7958G>A polymorphism and male infertility. Further studies with larger sample sizes and more genes are needed to better assess the association between variants of antioxidant genes and male infertility.

Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms.

Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. Yet, their downstream oncogenic signaling mechanisms are poorly understood. We used global phosphoproteomics and kinase activity profiling to map conserved signaling outputs driven by a range of genetic changes that activate PKA in human cancer. Two signaling networks were identified downstream of PKA: RAS/MAPK components and an Aurora Kinase A (AURKA)/glycogen synthase kinase (GSK3) sub-network with activity toward MYC oncoproteins. Findings were validated in two PKA-dependent cancer models: a novel, patient-derived fibrolamellar carcinoma (FLC) line that expresses a DNAJ-PKAc fusion and a PKA-addicted melanoma model with a mutant type I PKA regulatory subunit. We identify PKA signals that can influence both de novo translation and stability of the proto-oncogene c-MYC. However, the primary mechanism of PKA effects on MYC in our cell models was translation and could be blocked with the eIF4A inhibitor zotatifin. This compound dramatically reduced c-MYC expression and inhibited FLC cell line growth in vitro. Thus, targeting PKA effects on translation is a potential treatment strategy for FLC and other PKA-driven cancers.