New insight into the causes, consequences, and correction of hematopoietic stem cell aging

Aging of hematopoietic stem cells (HSCs) is characterized by lineage bias, increased clonal expansion, and functional decrease. At the molecular level, aged HSCs typically display metabolic dysregulation, upregulation of inflammatory pathways, and downregulation of DNA repair pathways. Cellular aging of HSCs, driven by cell-intrinsic and cell-extrinsic factors, causes a predisposition to anemia, adaptive immune compromise, myelodys, plasia, and malignancy. Most hematologic diseases are strongly associated with age. But what is the biological foundation for decreased fitness with age? And are there therapeutic windows to resolve age-related hematopoietic decline? These questions were the focus of the International Society for Experimental Hematology (ISEH) New Investigator Committee Fall 2022 Webinar. This review touches on the latest insights from two leading laboratories into inflammatory- and niche-driven stem cell aging and includes speculation on strategies to prevent or correct age-related decline in HSC function

Thin liquid water clouds: their importance and our challenge

Many clouds important to the Earth’s energy balance contain small amounts of liquid water, yet despite many improvements, large differences in retrievals of their liquid water amount and particle size still must be resolved

Low Intensity, High Frequency Vibration Training to Improve Musculoskeletal Function in a Mouse Model of Duchenne Muscular Dystrophy

The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice

Gender perspectives on views and preferences of older people on exercise to prevent falls: a systematic mixed studies review

Background: To offer fall prevention exercise programs that attract older people of both sexes there is a need to understand both womens and mens views and preferences regarding these programs. This paper aims to systematically review the literature to explore any underlying gender perspectives or gender interpretations on older peoples views or preferences regarding uptake and adherence to exercise to prevent falls. Methods: A review of the literature was carried out using a convergent qualitative design based on systematic searches of seven electronic databases (PubMed, CINAHL, Amed, PsycINFO, Scopus, PEDro, and OTseeker). Two investigators identified eligible studies. Each included article was read by at least two authors independently to extract data into tables. Views and preferences reported were coded and summarized in themes of facilitators and barriers using a thematic analysis approach. Results: Nine hundred and nine unique studies were identified. Twenty five studies met the criteria for inclusion. Only five of these contained a gender analysis of mens and womens views on fall prevention exercises. The results suggests that both women and men see women as more receptive to and in more need of fall prevention messages. The synthesis from all 25 studies identified six themes illustrating facilitators and six themes describing barriers for older people either starting or adhering to fall prevention exercise. The facilitators were: support from professionals or family; social interaction; perceived benefits; a supportive exercise context; feelings of commitment; and having fun. Barriers were: practical issues; concerns about exercise; unawareness; reduced health status; lack of support; and lack of interest. Considerably more women than men were included in the studies. Conclusion: Although there is plenty of information on the facilitators and barriers to falls prevention exercise in older people, there is a distinct lack of studies investigating differences or similarities in older womens and mens views regarding fall prevention exercise. In order to ensure that fall prevention exercise is appealing to both sexes and that the inclusion of both men and women are encouraged, more research is needed to find out whether gender differences exists and whether practitioners need to offer a range of opportunities and support strategies to attract both women and men to falls prevention exercise.Funding Agencies|Swedish Research Council [2015-03481]; Strategic Research Programme in Care Sciences, Umea University; Karolinska Institute, Sweden; Umea University</p

A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken

Author summaryVertebrates possess two types of melanin, red/yellow pheomelanin and black/brown eumelanin. In this study, we report that the recessive Inhibitor of gold phenotype in chicken, which causes a severe defect in pheomelanin pigmentation, is associated with a mutation that most likely inactivates the COMTD1 gene. This gene encodes an O-methyltransferase enzyme and is present throughout vertebrate evolution, but is one of the many genes in vertebrate genomes for which the biological function is still poorly understood. This is the first report of a COMTD1 mutation associated with a phenotypic effect. We show that the COMTD1 protein is present in mitochondria in pigment cells. Furthermore, inactivation of the gene in a mouse pigment cell line results in a significant reduction in metabolites that are important for the synthesis of pheomelanin. We hypothesize that COMTD1 activity protects pigment cells from oxidative stress and that inactivation of this function impairs the production of pheomelanin. It is likely that COMTD1 has a similar function in other cell types. This study establishes this chicken mutation as a model for further studies of COMTD1 function.The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5(th) exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin

Video-assisted thoracic surgery (VATS) for resection of metastatic adenocarcinoma as an acceptable alternative

Adenocarcinomas commonly metastasize to the lungs and can be resected using open thoracotomy or video-assisted thoracic surgery (VATS). This study reviews metastatic resections in primary adenocarcinoma patients, using both thoracotomy and VATS. We aim to compare long-term prognoses to test the efficacy and viability of VATS. A retrospective review of primary adenocarcinoma patients who underwent resection of pulmonary metastases from 1990 to 2006 was carried out. Information was obtained by chart review. Endpoints analyzed were disease-free interval (DFI), survival time, and recurrence-free survival (RFS). In a total of 42 (16 male, 26 female; median age 58.5 years) primary adenocarcinoma patients, 21 patients underwent first pulmonary metastatic resection using VATS (7 male, 14 female; median age 57 years) and 21 using thoracotomy (9 male, 12 female; median age 59 years). Primary adenocarcinomas were mainly 27 colorectal (64%) and 11 breast (26%). Two VATS (10%) and three open patients (14%) had local recurrences of the original cancer. Median postoperative follow was 13.3 months [interquartile range (IQR) 4.5–32.8 months] for VATS and 36.9 months (IQR 19.3–48.6 months) after thoracotomy. Median DFI–1 was 22.3 months (IQR 13.5–40.6 months) for VATS patients and 35.6 months (IQR 26.7–61.3 months) for open patients. Second thoracic occurrences were noted in six VATS patients (median DFI–2 9.2 months), and in seven open patients (median DFI-2 21.5 months). Third thoracic occurrences were noted in one VATS patient (DFI-3 18.7 months) and in one thoracotomy patient (DFI-3 21.8 months). Odds ratio of recurrence showed 12.5% less chance of developing recurrence in VATS patients. Five-year RFS was 53% in VATS and 57% in thoracotomy patients. VATS has become a viable alternative to open thoracotomy for resection of pulmonary metastases. In cases of primary adenocarcinoma, VATS showed no increase in number of thoracic recurrences, and comparable RFS. Short-term follow-up is encouraging; long-term follow-up will be needed to confirm these results

Chronic kidney-disease screening service quality: questionnaire survey research evidence from Taichung city

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is a serious public health problem in Taiwan and the world. The most effective, affordable treatments involve early prevention/detection/intervention, requiring screening. Successfully implementing CKD programs requires good patient participation, affected by patient perceptions of screening service quality. Service quality improvements can help make such programs more successful. Thus, good tools for assessing service quality perceptions are important. Aim: to investigate using a modified SERVQUAL questionnaire in assessing patient expectations, perceptions, and loyalty towards kidney disease screening service quality.</p> <p>Method</p> <p>1595 kidney disease screening program patients in Taichung City were requested to complete and return a modified kidney disease screening SERVQUAL questionnaire. 1187 returned them. Incomplete ones (102) were culled and 1085 were chosen as effective for use. Paired t-tests, correlation tests, ANOVA, LSD test, and factor analysis identified the characteristics and factors of service quality. The paired t-test tested expectation score and perception score gaps. A structural equation modeling system examined satisfaction-based components' relationships.</p> <p>Results</p> <p>The effective response rate was 91.4%. Several methods verified validity. Cronbach's alpha on internal reliability was above 0.902. On patient satisfaction, expectation scores are high: 6.50 (0.82), but perception scores are significantly lower 6.14 (1.02). Older patients' perception scores are lower than younger patients'. Expectation and perception scores for patients with different types of jobs are significantly different. Patients higher on education have lower scores for expectation (r = -0.09) and perception (r = -0.26). Factor analysis identified three factors in the 22 item SERVQUAL form, which account for 80.8% of the total variance for the expectation scores and 86.9% of the total variance for the satisfaction scores. Expectation and perception score gaps in all 22 items are significant. The goodness-of-fit summary of the SEM results indicates that expectations and perceptions are positively correlated, perceptions and loyalty are positively correlated, but expectations and loyalty are not positively correlated.</p> <p>Conclusions</p> <p>The results of this research suggest that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in kidney disease screening services, enabling the staff to identify where service improvements are needed from the patients' perspectives.</p

Endoscopic treatment of prepatellar bursitis

Operative treatment of prepatellar bursitis is indicated in intractable bursitis. The most common complication of surgical treatment for prepatellar bursitis is skin problems. For traumatic prepatellar bursitis, we propose a protocol of outpatient endoscopic surgery under local anaesthesia. From September 1996 to February 2001, 60 cases of failed nonoperative treatment for prepatellar bursitis were included. The average age was 33.5 ± 11.1 years (range 21–55). The average operation duration was 18 minutes. Two to three mini-arthroscopic portals were used in our series. No sutures or a simple suture was needed for the portals after operation. After follow-up for an average of 36.3 months, all patients are were symptom-free and had regained knee function. None of the population had local tenderness or hypo-aesthesia around their wound. Their radiographic and sonographic examinations showed no recurrence of bursitis. Outpatient arthroscopic bursectomy under local anaesthesia is an effective procedure for the treatment of post-traumatic prepatellar bursitis after failed conservative treatments. Both the cosmetic results and functional results were satisfactory

Service quality of private hospitals: The Iranian Patients' perspective

<p>Abstract</p> <p>Background</p> <p>Highly competitive market in the private hospital industry has caused increasing pressure on them to provide services with higher quality. The aim of this study was to determine the different dimensions of the service quality in the private hospitals of Iran and evaluating the service quality from the patients' perspective.</p> <p>Methods</p> <p>A cross-sectional study was conducted between October and November 2010 in Tehran, Iran. The study sample was composed of 983 patients randomly selected from 8 private general hospitals. The study questionnaire was the SERVQUAL questionnaire, consisting of 21 items in service quality dimensions.</p> <p>Results</p> <p>The result of factor analysis revealed 3 factors, explaining 69% of the total variance. The total mean score of patients' expectation and perception was 4.91(SD = 0.2) and 4.02(SD = 0.6), respectively. The highest expectation and perception related to the tangibles dimension and the lowest expectation and perception related to the empathy dimension. The differences between perception and expectation were significant (p < 0.001). There was a significant difference between the expectations scores based on gender, education level, and previous hospitalization in that same hospital. Also, there was a significant difference between the perception scores based on insurance coverage, average length of stay, and patients' health conditions on discharge.</p> <p>Conclusion</p> <p>The results showed that SERVQUAL is a valid, reliable, and flexible instrument to monitor and measure the quality of the services in private hospitals of Iran. Our findings clarified the importance of creating a strong relationship between patients and the hospital practitioners/personnel and the need for hospital staff to be responsive, credible, and empathetic when dealing with patients.</p

The United States of America and Scientific Research

To gauge the current commitment to scientific research in the United States of America (US), we compared federal research funding (FRF) with the US gross domestic product (GDP) and industry research spending during the past six decades. In order to address the recent globalization of scientific research, we also focused on four key indicators of research activities: research and development (R&D) funding, total science and engineering doctoral degrees, patents, and scientific publications. We compared these indicators across three major population and economic regions: the US, the European Union (EU) and the People's Republic of China (China) over the past decade. We discovered a number of interesting trends with direct relevance for science policy. The level of US FRF has varied between 0.2% and 0.6% of the GDP during the last six decades. Since the 1960s, the US FRF contribution has fallen from twice that of industrial research funding to roughly equal. Also, in the last two decades, the portion of the US government R&D spending devoted to research has increased. Although well below the US and the EU in overall funding, the current growth rate for R&D funding in China greatly exceeds that of both. Finally, the EU currently produces more science and engineering doctoral graduates and scientific publications than the US in absolute terms, but not per capita. This study's aim is to facilitate a serious discussion of key questions by the research community and federal policy makers. In particular, our results raise two questions with respect to: a) the increasing globalization of science: “What role is the US playing now, and what role will it play in the future of international science?”; and b) the ability to produce beneficial innovations for society: “How will the US continue to foster its strengths?