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Association of coexistence of frailty and depressive symptoms with mortality in community-dwelling older adults: Kashiwa Cohort Study

Arch Gerontol Geriatr. 2023 Dec 21;119:105322. doi: 10.1016/j.archger.2023.105322. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to determine the longitudinal associations of the coexistence of frailty and depressive symptoms with mortality among older adults.

METHODS: The study participants were community-dwelling older adults aged ≥65 years who participated in the baseline survey of the Kashiwa Cohort Study in Japan in 2012. We used Fried’s frailty phenotype criteria to classify participants as non-frail (score = 0), pre-frail (1 or 2), or frail (≥3). Depressive symptoms were assessed using the GDS-15 (≥6 points). Cox proportional hazards models were used to evaluate the association of co-occurring frailty and depressive symptoms with all-cause mortality, after adjusting for sociodemographic and clinical characteristics.

RESULTS: The study included 1920 participants, including 810 non-frail, 921 pre-frail, and 189 frail older adults, of which 9.0 %, 15.7 %, and 36.0 %, respectively, had depressive symptoms. Ninety-one (4.7 %) participants died during the average follow-up period of 4.8 years. Compared with non-frail participants without depressive symptoms, frail participants had greater adjusted hazard ratios for mortality: 2.47 (95 % CI, 1.16 to 5.25) for frail participants without depressive symptoms and 4.34 (95 % CI, 1.95 to 9.65) for frail participants with depressive symptoms. However, no statistically significant associations were observed in non-frail or pre-frail participants irrespective of depressive symptoms.

CONCLUSION: Frail older adults with depressive symptoms have a substantially greater risk of mortality. Screening for depressive symptoms and frailty in older adults should be incorporated into health checkups and clinical practice to identify high-risk populations.

PMID:38171032 | DOI:10.1016/j.archger.2023.105322

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The Impact of the Number of Sutures on Regeneration in Nerve Repair

Ann Plast Surg. 2023 Nov 20. doi: 10.1097/SAP.0000000000003700. Online ahead of print.

ABSTRACT

PURPOSE: The ideal number of sutures for epineural nerve repair is still unclear. Increased number of sutures increases secondary damage and inflammation to the nerve tissue, which negatively affects nerve regeneration. When the number of sutures decreases, the strength of the nerve repair site decreases and nerve endings are fringed, which also negatively affects nerve regeneration. Therefore, each additional suture is not only beneficial but also detrimental. The aim of this study was to find out the ideal number of sutures for nerve repair.

METHODS: Seventy rats were randomly divided into 5 groups. One of the groups was used as a control group, and right sciatic nerves of the rats in other 4 groups were repaired by using 2, 3, 4, or 6 epineural sutures, respectively, after nerve transection. Biomechanical assessment was performed on the nerves collected from these rats at 5 days of follow-up. Functional and histological analyses were evaluated after 12 weeks of follow-up.

RESULTS: It was found that an increase in the number of sutures enhances resistance to tensile force in general. However, there was no significant biomechanical difference between the 6-sutured group in which the most sutures were used and the 4-sutured group. In functional examinations, overall successful results were obtained in the group with 4 sutures. In histological examinations, there was no statistical difference between the control group, 2-sutured groups, and 4-sutured groups in terms of connective tissue index. However, it was observed that the group with 6 sutures had a higher connective tissue index than the control group and groups with 2 and 4 sutures. In terms of regeneration index, it was found that repair with 4 sutures was superior to repair with 2 and 6 sutures. No difference was found between any of the suture groups according to the diameter change index.

CONCLUSIONS: These results indicate that repair with 4 sutures is the best method of epineural repair that provides both strength and regeneration. These findings will contribute to both the repair of clinically similar nerves and the standardization of rat nerve studies.

PMID:38170975 | DOI:10.1097/SAP.0000000000003700

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Medicine for chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis

Ann Med. 2023;55(2):2299352. doi: 10.1080/07853890.2023.2299352. Epub 2024 Jan 3.

ABSTRACT

PURPOSE: The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs).

METHODS: A predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials (RCTs) were included for meta-analysis to provide clinical evidence of the intervention effects. A network meta-analysis using Bayesian networks was conducted to observe the relative effects of different intervention measures and possible ranking of effects. The composition of the TCM formulation in the experimental group was analysed, and association rule mining was performed to identify hub herbal medicines. Target genes for CAG were searched in GeneCards, Online Mendelian Inheritance in Man, PharmGKB, Therapeutic Target Database and DrugBank. A regulatory network was constructed to connect the target genes with active ingredients of the hub herbal medicines. Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the central targets from a comprehensive viewpoint. Protein-protein interaction networks (PPINs) were constructed to identify hub genes and conduct molecular docking with differentially expressed genes (DEGs) and corresponding active molecules.

RESULTS: A total of 1140 participants from 12 RCTs were included in the statistical analysis, confirming that the experimental group receiving the addition of TCM intervention had better clinical efficacy. Seven hub TCMs (Paeonia lactiflora, Atractylodes macrocephala, Pinellia ternata, Citrus reticulata, Codonopsis pilosula, Salvia miltiorrhiza and Coptis chinensis) were identified through association rule analysis of all included TCMs. Thirteen hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14 and AKT1) were obtained from 90 gene PPINs. Differential gene expression analysis between the disease and normal gastric tissue identified MAPK1 and MAPK3 as the significant genes. Molecular docking analysis revealed that naringenin, luteolin and quercetin were the main active compounds with good binding activities to the two hub targets. GO analysis demonstrated the function of the targets in protein binding, while KEGG analysis indicated their involvement in important pathways related to cancer.

CONCLUSIONS: The results of a meta-analysis of 12 RCTs indicate that TCM intervention can improve the clinical treatment efficacy of CAG. NPAs identified seven hub TCM and 13 target genes associated with their actions, while bioinformatics analysis identified two DEGs between normal and CAG gastric tissues. Finally, molecular docking was employed to reveal the mechanism of action of the active molecules in TCM on the DEGs. These findings not only reveal the mechanisms of action of the active components of the TCMs, but also provide support for the development of new drugs, ultimately blocking the progression from chronic gastritis to gastric cancer.

PMID:38170849 | DOI:10.1080/07853890.2023.2299352

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Communicating about sexual activity and intimacy after a heart attack: a cross-sectional survey of Australian health professionals

Eur J Cardiovasc Nurs. 2024 Jan 3:zvad110. doi: 10.1093/eurjcn/zvad110. Online ahead of print.

ABSTRACT

AIMS: Sexual activity and intimacy improve quality of life for heart attack survivors. After a heart attack, patients frequently experience sexual dysfunction and anxiety about resuming sexual activity. However, most health professionals do not discuss sex or intimacy with their patients. The aim of this research was to explore the perceptions and practices of Australian health professionals in discussing sexual activity and intimacy with heart attack survivors and the barriers to achieving this.

METHODS AND RESULTS: This study employed a cross-sectional study design and online self-administered survey questionnaire. Study participants were a convenience sample of Australian health professionals working with cardiac patients, including general practitioners, cardiologists, cardiac rehabilitation specialists, registered nurses, and allied health professionals. Data were analysed using descriptive statistics and cross-tabulations to understand the different perspectives of health professional groups and the overall sample. Of 252 respondents, almost all believed discussing sex and intimacy with heart attack survivors was important, yet less than a quarter reported regularly doing so. About three-quarters reported feeling comfortable discussing sex and intimacy with either men or women, with half comfortable to do so with patients from diverse cultures. Barriers included lack of time, privacy, consumer resources, and protocols to guide discussions.

CONCLUSION: This research supports the need for structural changes such as a clinical protocol, longer and more private consultations, staff training, and culturally appropriate patient-oriented resources to support health professionals to guide discussions about sexual activity and intimacy with patients who have had a heart attack.

PMID:38170837 | DOI:10.1093/eurjcn/zvad110

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Contraceptive Methods Women Have Ever Used:United States, 2015-2019

Natl Health Stat Report. 2023 Dec;(195):1-18.

ABSTRACT

Objective-This report describes methods of contraception ever used by U.S. women ages 15-49 who had ever had sexual intercourse with a male partner. Estimates are shown overall and by Hispanic origin and race, education, religious affiliation and importance, and urban-rural residence. Discontinuation of selected contraceptive methods is also described. Methods-This report focuses on information collected from the 11,695 women ages 15-49 interviewed in the 2015-2019 National Survey of Family Growth, a nationally representative survey conducted by the Centers for Disease Control and Prevention’s National Center for Health Statistics. Most estimates shown are based on data on contraceptive methods ever used by the 10,122 interviewed women who had ever had sexual intercourse with a male partner. Results-Based on 2015-2019 data, virtually all women of reproductive age who had ever had sexual intercourse with a male partner used at least one contraceptive method at some point in their life up to the time of interview (99.2%, or 63.2 million women ages 15-49), including 87.8% who had ever used a “most or moderately effective reversible method”: the pill, an injectable, contraceptive patch, contraceptive ring, contraceptive implant, or intrauterine device. Most women had used the male condom with a partner (94.5%), the pill (79.8%), or withdrawal (65.7%). About one in four women reported ever using long-acting reversible contraception (intrauterine device or contraceptive implant) (24.9%) or emergency contraception (23.5%). The type of methods ever used varied by Hispanic origin and race, nativity among Hispanic women, education, religious affiliation and importance, and urban-rural residence. Among women who had ever discontinued use of the pill or intrauterine devices due to dissatisfaction (and not for seeking a pregnancy), side effects were the most common reason.

PMID:38170816

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Changes in activities-specific balance confidence of active unilateral transtibial prosthesis users after provision of a self-aligning ankle foot

Prosthet Orthot Int. 2024 Jan 3. doi: 10.1097/PXR.0000000000000319. Online ahead of print.

ABSTRACT

BACKGROUND: Self-aligning ankle feet have an increased range of motion and are marketed to improve compliance over uneven terrain and increase function and balance; however, much of the existing literature focuses on the biomechanical aspect of these prostheses as opposed to patient-reported measures.

OBJECTIVE: To compare activities-specific balance confidence (ABC), health-related quality of life (HR-QoL), perceived mobility, gait speed, and step length before and after provision of a self-aligning ankle foot in the active unilateral transtibial prosthesis user.

STUDY DESIGN: Retrospective analysis of prospectively collected data.

METHODS: Patient-reported and functional measures were captured for 85 users who were provided with a self-aligning ankle foot. Measures were recorded immediately before self-aligning ankle foot provision and again at 6 months afterward. The primary outcome was the ABC Score, along with the following secondary measures; HR-QoL using EQ-5D-5L Health Index Prosthetic Limb User Survey of Mobility and 10-meter timed walk test.

RESULTS: The median age of the cohort was 55.2 years old and 71% were males, with the majority having their transtibial amputation due to trauma. There was a statistically significant improvement in ABC from 76 to 86% (p < 0.001) with a medium effect size. There was no statistically significant improvement in HR-QoL (p = 0.051), Prosthetic Limb User Survey of Mobility (p = 0.043), time taken to walk 10 m (p = 0.15) and step length (p = 0.003).

CONCLUSIONS: Self aligning ankle feet increased ABC and step length with no detrimental effect on HR-QoL, perceived mobility or walking speed in those with a unilateral trans-tibial amputation.

PMID:38170795 | DOI:10.1097/PXR.0000000000000319

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HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence

Proc Natl Acad Sci U S A. 2024 Jan 9;121(2):e2306454120. doi: 10.1073/pnas.2306454120. Epub 2024 Jan 3.

ABSTRACT

Mitochondrial and lysosomal functions are intimately linked and are critical for cellular homeostasis, as evidenced by the fact that cellular senescence, aging, and multiple prominent diseases are associated with concomitant dysfunction of both organelles. However, it is not well understood how the two important organelles are regulated. Transcription factor EB (TFEB) is the master regulator of lysosomal function and is also implicated in regulating mitochondrial function; however, the mechanism underlying the maintenance of both organelles remains to be fully elucidated. Here, by comprehensive transcriptome analysis and subsequent chromatin immunoprecipitation-qPCR, we identified hexokinase domain containing 1 (HKDC1), which is known to function in the glycolysis pathway as a direct TFEB target. Moreover, HKDC1 was upregulated in both mitochondrial and lysosomal stress in a TFEB-dependent manner, and its function was critical for the maintenance of both organelles under stress conditions. Mechanistically, the TFEB-HKDC1 axis was essential for PINK1 (PTEN-induced kinase 1)/Parkin-dependent mitophagy via its initial step, PINK1 stabilization. In addition, the functions of HKDC1 and voltage-dependent anion channels, with which HKDC1 interacts, were essential for the clearance of damaged lysosomes and maintaining mitochondria-lysosome contact. Interestingly, HKDC1 regulated mitophagy and lysosomal repair independently of its prospective function in glycolysis. Furthermore, loss function of HKDC1 accelerated DNA damage-induced cellular senescence with the accumulation of hyperfused mitochondria and damaged lysosomes. Our results show that HKDC1, a factor downstream of TFEB, maintains both mitochondrial and lysosomal homeostasis, which is critical to prevent cellular senescence.

PMID:38170752 | DOI:10.1073/pnas.2306454120

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Exploring the incidence and etiopathogenesis of pathological yawning as adverse side effect of psychotropic drugs

Neuropsychopharmacol Hung. 2023 Dec;25(4):194-205.

ABSTRACT

INTRODUCTION: Yawning is a normal, stereotyped physiological event in humans and animal kingdom. When excessive (>3 per 15 minutes), it is termed as pathological yawning (PY). PY could be due to many causes but more commonly associated with side-effect of drugs, notably involving those used in psychopharmacology. Though there are isolated case reports and case-series, there are no large-scale reports of PY. This work attempted to address this lacuna.

MATERIAL AND METHODS: The current work attempted to identify characteristics of PY as collated from adverse drug effect databases of Australia (Database of Adverse Event Notifications), Canada (Canada Vigilance Adverse Reaction Online Database) and the United States of America (FDA Adverse Event Reporting System – FAERS). These databases collect and provide public access to reports of adverse events related to drugs and therapeutic goods. They act as a prime pharmacovigilance tool as well as a first-line resource for healthcare professionals, researchers, and the public to monitor the safety of these products and make informed decisions. In the first week of June 2023, open access, unrestricted adverse effect of drug databases were explored, using the word “YAWNING” as the only search term for the side effect of any drug without any restrictions. The collected details of PY cases with their gender, age, reason for drug use, other concomitant complaints as well as the nature of adverse event(s) and its treatment requirements were assessed. Descriptive statistics were used.

RESULT: Of the 2655 instances in USA database, 398(15%) had more than 1 suspect drug and in total 578 medications involved. The most commonly involved drugs were apomorphine, sertraline, fluoxetine and paroxetine. In all 341(12.8%) cases reported of YAWN alone or with one another sleep disorder, the most common off ending drug were fluoxetine hydrochloride.

DISCUSSION AND CONCLUSION: The neural mechanism and physiology of yawning are explained. This study stresses that a health care professional, particularly mental health professionals and neurologists, should be aware of the importance of PY to deliver the best for the patients under their care. (Neuropsychopharmacol Hung 2023; 25(4): 194-205)

PMID:38170730

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Naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation: A retrospective, single-center cohort study

PLoS One. 2024 Jan 3;19(1):e0295952. doi: 10.1371/journal.pone.0295952. eCollection 2024.

ABSTRACT

INTRODUCTION: There are few reports describing the association of naldemedine with defecation in critically ill patients with opioid-induced constipation. The purpose of this study was to determine whether naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

METHODS: In this retrospective cohort study, patients admitted to the Intensive Care Unit (ICU) without defecation for 48 hours while receiving opioids were eligible for enrollment. The primary endpoint was the time of the first defecation within 96 hours after inclusion. Secondary endpoints included presence of diarrhea, duration of mechanical ventilation, ICU length of stay, ICU mortality, and in-hospital mortality. The Cox proportional hazard regression analysis with time-dependent covariates was used to evaluate the association naldemedine with earlier defecation.

RESULTS: A total of 875 patients were enrolled and were divided into 63 patients treated with naldemedine and 812 patients not treated. Defecation was observed in 58.7% of the naldemedine group and 48.8% of the no-naldemedine group during the study (p = 0.150). The naldemedine group had statistically significantly prolonged duration of mechanical ventilation (8.7 days vs 5.5 days, p < 0.001) and ICU length of stay (11.8 days vs 9.2 days, p = 0.001) compared to the no-naldemedine group. However, the administration of naldemedine was significantly associated with earlier defecation [hazard ratio:2.53; 95% confidence interval: 1.71-3.75, p < 0.001].

CONCLUSION: The present study shows that naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

PMID:38170714 | DOI:10.1371/journal.pone.0295952

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Outcomes of possible and probable rheumatic fever: A cohort study using northern Australian register data, 2013-2019

PLOS Glob Public Health. 2024 Jan 3;4(1):e0002064. doi: 10.1371/journal.pgph.0002064. eCollection 2024.

ABSTRACT

In Australia, there is a high burden of acute rheumatic fever (ARF) among Aboriginal and Torres Strait Islander peoples. Clinical diagnostic criteria can result in a diagnosis of ‘definite’, ‘probable’ or ‘possible’ ARF and outcomes range from recovery to severe rheumatic heart disease (RHD). We compared outcomes by ARF diagnosis, where the main outcome was defined as disease progression from: possible to probable ARF, definite ARF or RHD; probable to definite ARF or RHD; or definite ARF to definite ARF recurrence or RHD. Data were extracted from the Northern Territory RHD register for Indigenous Australians with an initial diagnosis of ARF during the 5.5-year study period (01/01/2013-30/06/2019). Descriptive statistics were used to describe cohort characteristics, probability of survival, and cumulative incidence risk of disease progression. Cox proportional hazards regression was used to determine whether time to disease progression differed according to ARF diagnosis. Sub-analyses on RHD outcome, clinical manifestations, and antibiotic adherence were also performed. In total there were 913 cases with an initial ARF diagnosis. Of these, 92 (13%) experienced disease progression. The probability of disease progression significantly differed between ARF diagnoses (p = 0.0043; log rank test). Cumulative incidence risk of disease progression at 5.5 years was 33.6% (95% CI 23.6-46.2) for definite, 13.5% (95% CI 8.8-20.6) for probable and 11.4% (95% CI 6.0-21.3) for possible ARF. Disease progression was 2.19 times more likely in those with definite ARF than those with possible ARF (p = 0.026). Progression to RHD was reported in 52/732 (7%) of ARF cases with normal baseline echocardiography. There was a significantly higher risk of progression from no RHD to RHD if the initial diagnosis was definite compared to possible ARF (p<0.001). These data provide a useful way to stratify risk and guide prognosis for people diagnosed with ARF and can help inform practice.

PMID:38170692 | DOI:10.1371/journal.pgph.0002064