Effects of physical activity participation on cognitive impairment in older adults population with disabilities

BackgroundExisting research on the association between cognitive function and physical activity in the older adults population with disabilities is limited. Additionally, there is a need to explore avenues for enhancing the longevity and quality of life among these individuals.ObjectiveThis study aimed to investigate the independent and joint associations between cognitive function and levels of physical activity in the older adults population with disabilities.MethodsA total of 315 older adults adults (men = 182, women = 133), identified with disabilities based on medical evaluation, were recruited from the first survey of the Korean Longitudinal Study of Aging (KLoSA). Participants underwent assessments for cognitive function, physical activity (PA), activities of daily living (ADLs), instrumental activities of daily living (IADLs), and grip strength.ResultsADLs (p < 0.001) and IADLs (p < 0.001) scores were significantly higher in the male normal cognitive group compared to both the male and female cognitive impairment groups. In an unadjusted model, disabled older adults individuals who did not meet the recommended PA guidelines showed an increased odds ratio for cognitive dysfunction (OR = 2.29, 95% CI = 1.32–3.97). Those participating in PA at least 1 day per week also demonstrated an elevated odds ratio (OR = 1.22, 95% CI = 1.08–1.38) for cognitive dysfunction compared to those who engaged in regular PA. A negative correlation was observed between K-MMSE scores and grip strength (r = 0.448, p < 0.001).ConclusionThis study provides robust evidence that disabled older adults individuals who do not meet the recommended guidelines for PA or who do not participate in PA at least once a week have an increased likelihood of cognitive impairment compared to those who are regularly active

Molecular Subgroup Analysis of Clinical Outcomes in a Phase 3 Study of Gemcitabine and Oxaliplatin with or without Erlotinib in Advanced Biliary Tract Cancer

AbstractBACKGROUND: We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX) resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers (BTCs). Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken. METHODS: Epidermal growth factor receptor (EGFR), KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid–locked nucleic acid polymerase chain reaction clamp reactions. Survival and response rates (RRs) were analyzed according to the mutational status. Sixty-four patients (48.1%) were available for mutational analysis in the chemotherapy alone group and 61 (45.1%) in the chemotherapy plus erlotinib group. RESULTS: 1.6% (2/116) harbored an EGFR mutation (2 patients; exon 20), 9.6% (12/121) harbored a KRAS mutation (12 patients; exon 2), and 9.6% (12/118) harbored a PIK3CA mutation (10 patients, exon 9 and 2 patients, exon 20). The addition of erlotinib to GEMOX in patients with KRAS wild-type disease (n = 109) resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs 12.5%, P = .024). In 95 patients with both wild-type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to RR as compared with GEMOX alone (P = .04). CONCLUSION: This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in BTCs. Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild-type BTCs

One-Dimensional Hydrogen-Bonded Infinite Chain from Nickel(II) Tetraaza Macrocyclic Complex and 1,2-Cyclopentanedicarboxylate Ligand

The reaction of [Ni(L)]Cl2·2H2O (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo [14,4,01.18,07.12]docosane) with trans-1,2-cyclopentanedicarboxylic acid (H2-cpdc) yields a 1D hydrogen-bonded infinite chain with formula [Ni(L)(H-cpdc−)2] (1). This complex has been characterized by X-ray crystallography, spectroscopy and cyclic voltammetry. The crystal structure of 1 exhibits a distorted octahedral geometry about Ni atom with four nitrogen atoms of the macrocycle and two oxygen atoms of the H-cpdc− ligand at the axial position. Compound 1 crystallizes in the monoclinic system P21/c with a = 8.7429(17), b = 10.488(2), c = 18.929(4) Å, β = 91.82(2), V = 1734.8(6) Å3, Z = 2. Electronic spectrum of 1 reveals a high-spin octahedral environment. Cyclic voltammetry of 1 undergoes two waves of a one-electron transfer corresponding to NiII/NiIII and NiII/NiI processes

Severe Pulmonary Adverse Effects in Lymphoma Patients Treated with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) Regimen Plus Rituximab

BACKGROUND/AIMS: The aim of our study was to determine the incidence and clinical features of severe pulmonary complications in patients receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) as the initial treatment for lymphoma. METHODS: A retrospective analysis of pulmonary infection and drug-induced interstitial pneumonitis (DIIP) was performed using lymphoma registry data. R-CHOP was administered in 71 patients and CHOP in 29 patients. RESULTS: The severe pulmonary adverse events tended to occur more frequently with R-CHOP (18.3%) than CHOP alone (13.8%), although the difference was not significant (p = 0.771). DIIP occurred in five patients in the R-CHOP arm (7%) and in one in the CHOP arm (3%). The continuous use of steroids for conditions other than lymphoma significantly increased the risk of pulmonary infection including Pneumocystis jiroveci pneumonia (p = 0.036) in the multivariate analysis. International prognostic index, tumor stage, smoking, previous tuberculosis, chronic obstructive pulmonary disease, and lymphoma involvement of lung parenchyma were not related to pulmonary adverse events. Patients who experienced severe pulmonary events showed shorter survival when compared to those without complications (p = 0.002). CONCLUSIONS: Our experiences with serial cases with DIIP during chemotherapy and the correlation of continuous steroid use with pulmonary infection suggest that the incidence of pulmonary complications might be high during lymphoma treatment, and careful monitoring should be performed.ope

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management : Perspectives from Europe, Latin America, Asia, and The United States

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work–life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur–investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

Laboratory information management system for COVID-19 non-clinical efficacy trial data

Background : As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results : In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions : This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.This research was supported by the National research foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020M3A9I2109027 and 2021M3H9A1030260)

Changing Levels of Myokines after Aerobic Training and Resistance Training in Post-Menopausal Obese Females: A Randomized Controlled Trial

The purpose of this study was to investigate changes in the levels of myokines in post- menopausal obese females (PMOF) after regular aerobic and resistance training. A community-based, randomized controlled trial study of 41 PMOF from Buk-gu Community Center in Chuncheon, Gangwon-do, Republic of Korea, was conducted from November 2017 through October 2018. These participants were randomly assigned to an aerobic exercise group (n = 21) or a resistance exercise group (n = 20). The 12-week exercise program was conducted three days a week (Monday, Wednesday, and Friday). Body composition, physical fitness, and myokines were measured at baseline, 6 weeks, and 12 weeks. The two-way within-factor ANOVA revealed group × time interaction for body mass index (BMI, p < 0.05). In the resistance exercise group, muscle endurance (p < 0.001), power (p < 0.01), and agility (p < 0.001) improved significantly at 12 weeks compared to baseline and 6 weeks. In the aerobic exercise group, muscle strength (p < 0.05), flexibility (p < 0.05), muscle endurance (p < 0.001), and agility (p < 0.001) were greater at 12 weeks compared to baseline and 6 weeks. The levels of IL-6 (p < 0.001), IL-15 (p < 0.001), and BDNF (p < 0.001) were greater at 12 weeks compared to baseline and 6 weeks in both exercise groups. Aerobic exercise training and resistance exercise training changed the levels of myokines and improved body composition and physical fitness in PMOF. These findings provide preliminary evidence that PMOF need to exercise or perform physical activity to improve or maintain their levels of myokines and physical fitness