What’s All the Racket? Comparing Physical Health Outcomes Between Pickleball and Tennis in Older Athletes

Background: Pickleball is rising in popularity, especially among older adults. Pickleball boasts psychological and physical benefits to aging athletes. Singles pickleball has been found to approximate brisk walking in metabolic equivalents (METs) at 4.1, while the METs level for singles tennis is 7.0-8.0. The physical health benefits of tennis are known to be positive while those of pickleball are still being explored. With objective differences in MET level it may be surmised that health outcomes might vary between the two sports. Purpose: The purpose of this study was to use the Senior Athlete Fitness Exam (SAFE) to quantify and compare the health characteristics of older pickleball athletes to older tennis athletes. Methods: Senior athletes who completed the SAFE at the National Senior Games between 2013 and 2019 and were exclusively registered to compete in pickleball or tennis were analyzed. Screening was conducted by trained personnel and included subtests for cardiovascular health, strength, mobility, flexibility, and balance. Demographic information and SAFE subtest results were compared between tennis and pickleball groups. Results: Significant differences were found between tennis and pickleball athletes in the categories of single leg balance with eyes open (p = 0.03), fast gait speed (p = 0.02), and shoulder range of motion (p \u3c 0.01). Pickleball players performed better than tennis in all significantly different outcome measures. Conclusion: Pickleball and tennis provide similar health benefits to older athletes, leaving more options for older adults interested in staying healthy. Previously reported intensity levels for pickleball may be underestimated

Developing public health clinical decision support systems (CDSS) for the outpatient community in New York City: our experience

<p>Abstract</p> <p>Background</p> <p>Developing a clinically relevant set of quality measures that can be effectively used by an electronic health record (EHR) is difficult. Whether it is achieving internal consensus on relevant priority quality measures, communicating to EHR vendors' whose programmers generally lack clinical contextual knowledge, or encouraging implementation of EHR that meaningfully impacts health outcomes, the path is challenging. However, greater transparency of population health, better accountability, and ultimately improved health outcomes is the goal and EHRs afford us a realistic chance of reaching it in a scalable way.</p> <p>Method</p> <p>In this article, we summarize our experience as a public health government agency with developing measures for a public health oriented EHR in New York City in partnership with a commercial EHR vendor.</p> <p>Results</p> <p>From our experience, there are six key lessons that we share in this article that we believe will dramatically increase the chance of success. First, define the scope and build consensus. Second, get support from executive leadership. Third, find an enthusiastic and competent software partner. Fourth, implement a transparent operational strategy. Fifth, create and test the EHR system with real life scenarios. Last, seek help when you need it.</p> <p>Conclusions</p> <p>Despite the challenges, we encourage public health agencies looking to build a similarly focused public health EHR to create one both for improved individual patient as well as the larger population health.</p

Genome-Wide Survey of MicroRNA - Transcription Factor Feed-Forward Regulatory Circuits in Human

In this work, we describe a computational framework for the genome-wide identification and characterization of mixed transcriptional/post-transcriptional regulatory circuits in humans. We concentrated in particular on feed-forward loops (FFL), in which a master transcription factor regulates a microRNA, and together with it, a set of joint target protein coding genes. The circuits were assembled with a two step procedure. We first constructed separately the transcriptional and post-transcriptional components of the human regulatory network by looking for conserved over-represented motifs in human and mouse promoters, and 3'-UTRs. Then, we combined the two subnetworks looking for mixed feed-forward regulatory interactions, finding a total of 638 putative (merged) FFLs. In order to investigate their biological relevance, we filtered these circuits using three selection criteria: (I) GeneOntology enrichment among the joint targets of the FFL, (II) independent computational evidence for the regulatory interactions of the FFL, extracted from external databases, and (III) relevance of the FFL in cancer. Most of the selected FFLs seem to be involved in various aspects of organism development and differentiation. We finally discuss a few of the most interesting cases in detail.Comment: 51 pages, 5 figures, 4 tables. Supporting information included. Accepted for publication in Molecular BioSystem

The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer

PURPOSE: To investigate SGI-110 as a "chemosensitizer" in ovarian cancer and to assess its effects on tumor suppressor genes (TSG) and chemoresponsiveness-associated genes silenced by DNA methylation in ovarian cancer. EXPERIMENTAL DESIGN: Several ovarian cancer cell lines were used for in vitro and in vivo platinum resensitization studies. Changes in DNA methylation and expression levels of TSG and other cancer-related genes in response to SGI-110 were measured by pyrosequencing and RT-PCR. RESULTS: We demonstrate in vitro that SGI-110 resensitized a range of platinum-resistant ovarian cancer cells to cisplatin (CDDP) and induced significant demethylation and reexpression of TSG, differentiation-associated genes, and putative drivers of ovarian cancer cisplatin resistance. In vivo, SGI-110 alone or in combination with CDDP was well tolerated and induced antitumor effects in ovarian cancer xenografts. Pyrosequencing analyses confirmed that SGI-110 caused both global (LINE1) and gene-specific hypomethylation in vivo, including TSGs (RASSF1A), proposed drivers of ovarian cancer cisplatin resistance (MLH1 and ZIC1), differentiation-associated genes (HOXA10 and HOXA11), and transcription factors (STAT5B). Furthermore, DNA damage induced by CDDP in ovarian cancer cells was increased by SGI-110, as measured by inductively coupled plasma-mass spectrometry analysis of DNA adduct formation and repair of cisplatin-induced DNA damage. CONCLUSIONS: These results strongly support further investigation of hypomethylating strategies in platinum-resistant ovarian cancer. Specifically, SGI-110 in combination with conventional and/or targeted therapeutics warrants further development in this setting

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Locale and chemistry of spermine binding in the archetypal inward rectifier Kir2.1

Polyamine block of inwardly rectifying potassium (Kir) channels underlies their steep voltage dependence observed in vivo. We have examined the potency, voltage dependence, and kinetics of spermine block in dimeric Kir2.1 constructs containing one nonreactive subunit and one cysteine-substituted subunit before and after modification by methanethiosulfonate (MTS) reagents. At position 169C (between the D172 “rectification controller” and the selectivity filter), modification by either 2-aminoethyl MTS (MTSEA) or 2-(trimethylammonium)ethyl MTS (MTSET) reduced the potency and voltage dependence of spermine block, consistent with this position overlapping the spermine binding site. At position 176C (between D172 and the M2 helix bundle crossing), modification by MTSEA also weakened spermine block. In contrast, MTSET modification of 176C dramatically slowed the kinetics of spermine unblock, with almost no effect on potency or voltage dependence. The data are consistent with MTSET modification of 176C introducing a localized barrier in the inner cavity, resulting in slower spermine entry into and exit from a “deep” binding site (likely between the D172 rectification controller and the selectivity filter), but leaving the spermine binding site mostly unaffected. These findings constrain the location of deep spermine binding that underlies steeply voltage-dependent block, and further suggest important chemical details of high affinity binding of spermine in Kir2.1 channels—the archetypal model of strong inward rectification

Genetic Variation in the Inflammation and Innate Immunity Pathways and Colorectal Cancer Risk

It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways

Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)

Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9

The X-ray Polarization Probe mission concept

The X-ray Polarization Probe (XPP) is a second generation X-ray polarimeter following up on the Imaging X-ray Polarimetry Explorer (IXPE). The XPP will offer true broadband polarimetery over the wide 0.2-60 keV bandpass in addition to imaging polarimetry from 2-8 keV. The extended energy bandpass and improvements in sensitivity will enable the simultaneous measurement of the polarization of several emission components. These measurements will give qualitatively new information about how compact objects work, and will probe fundamental physics, i.e. strong-field quantum electrodynamics and strong gravity.Comment: submitted to Astrophysics Decadal Survey as a State of the Profession white pape