Impaired Reorganization of Centrosome Structure Underlies Human Infantile Dilated Cardiomyopathy.

BACKGROUND: During cardiomyocyte maturation, the centrosome, which functions as a microtubule organizing center in cardiomyocytes, undergoes dramatic structural reorganization where its components reorganize from being localized at the centriole to the nuclear envelope. This developmentally programmed process, referred to as centrosome reduction, has been previously associated with cell cycle exit. However, understanding of how this process influences cardiomyocyte cell biology, and whether its disruption results in human cardiac disease, remains unknown. We studied this phenomenon in an infant with a rare case of infantile dilated cardiomyopathy (iDCM) who presented with left ventricular ejection fraction of 18% and disrupted sarcomere and mitochondria structure. METHODS: We performed an analysis beginning with an infant who presented with a rare case of iDCM. We derived induced pluripotent stem cells from the patient to model iDCM in vitro. We performed whole exome sequencing on the patient and his parents for causal gene analysis. CRISPR/Cas9-mediated gene knockout and correction in vitro were used to confirm whole exome sequencing results. Zebrafish and Drosophila models were used for in vivo validation of the causal gene. Matrigel mattress technology and single-cell RNA sequencing were used to characterize iDCM cardiomyocytes further. RESULTS: Whole exome sequencing and CRISPR/Cas9 gene knockout/correction identified RTTN, the gene encoding the centrosomal protein RTTN (rotatin), as the causal gene underlying the patient's condition, representing the first time a centrosome defect has been implicated in a nonsyndromic dilated cardiomyopathy. Genetic knockdowns in zebrafish and Drosophila confirmed an evolutionarily conserved requirement of RTTN for cardiac structure and function. Single-cell RNA sequencing of iDCM cardiomyocytes showed impaired maturation of iDCM cardiomyocytes, which underlie the observed cardiomyocyte structural and functional deficits. We also observed persistent localization of the centrosome at the centriole, contrasting with expected programmed perinuclear reorganization, which led to subsequent global microtubule network defects. In addition, we identified a small molecule that restored centrosome reorganization and improved the structure and contractility of iDCM cardiomyocytes. CONCLUSIONS: This study is the first to demonstrate a case of human disease caused by a defect in centrosome reduction. We also uncovered a novel role for RTTN in perinatal cardiac development and identified a potential therapeutic strategy for centrosome-related iDCM. Future study aimed at identifying variants in centrosome components may uncover additional contributors to human cardiac disease.

Wastewater Surveillance for Poliovirus in Selected Jurisdictions, United States, 2022-2023.

Wastewater testing can inform public health action as a component of polio outbreak response. During 2022-2023, a total of 7 US jurisdictions (5 states and 2 cities) participated in prospective or retrospective testing of wastewater for poliovirus after a paralytic polio case was identified in New York state. Two distinct vaccine-derived poliovirus type 2 viruses were detected in wastewater from New York state and New York City during 2022, representing 2 separate importation events. Of those viruses, 1 resulted in persistent community transmission in multiple New York counties and 1 paralytic case. No poliovirus was detected in the other participating jurisdictions (Connecticut, New Jersey, Michigan, and Illinois and Chicago, IL). The value of routine wastewater surveillance for poliovirus apart from an outbreak is unclear. However, these results highlight the ongoing risk for poliovirus importations into the United States and the need to identify undervaccinated communities and increase vaccination coverage to prevent paralytic polio.

Global herpes zoster burden in adults with asthma: a systematic review and meta-analysis.

BACKGROUND: Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This is the first systematic review with the objective of summarising evidence on HZ burden in adults with asthma. METHODS: A global systematic literature review and meta-analysis was conducted (MEDLINE and Embase, 2003-2024) on HZ burden (incidence, risk and complications) in adults (≥18 years) with asthma. RESULTS: There were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% CI 4.68-6.96) in adults aged ≥18 years (4.20 (95% CI 3.09-5.70) in those aged <60 years versus 10.33 (95% CI 9.17-11.64) in those aged ≥60 years). The pooled rate ratio for developing HZ was 1.23 (95% CI 1.11-1.35) in those aged ≥18 years and 1.36 (95% CI 1.15-1.61) in those aged ≥50 years. The risk of HZ was higher in people with asthma using systemic corticosteroids, long-acting ß-agonists plus inhaled corticosteroids and "add-on therapy". Asthma was also associated with an increased risk of post-herpetic neuralgia (OR 1.21, 95% CI 1.06-1.37) and HZ ophthalmicus (OR 1.9, 95% CI 1.1-3.2). Differences in study design, setting, case definitions and follow-up durations led to heterogeneity. CONCLUSIONS: This systematic literature review and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care.

Limiting Access to Resistance Training Equipment During the Off-Season: The Impact on Collegiate Pitching Metrics.

ABSTRACT: Gdovin, JR, Hogan, B, and Williams, CC. Limiting access to resistance training equipment during the off-season: the impact on collegiate pitching metrics. J Strength Cond Res XX(X): 000-000, 2024-Resistance training has been shown to improve overhead throwing velocity, but it is unknown as to how limiting access to a strength and conditioning facility affects a baseball pitcher's readiness for the spring season. Therefore, the purpose of this study was to examine the influence of an individualized pitching program on pitching metrics during an 8-week fall season in collegiate baseball pitchers without a simultaneous structured strength training program. Twelve National Collegiate Athletic Association Division-I baseball pitchers completed the study and wore a PULSE Throw Workload Monitor to track peak arm slot angle, peak arm velocity, and peak elbow varus torque, while a radar gun measured ball velocity. An 8-week pitching program had subjects throw 30 and 50 maximum effort pitches in the first and eighth week, respectively, while workload increased by 5 maximum effort pitches every 2 weeks. Paired samples t-tests were conducted to compare variables of interest before and after an 8-week fall season with an alpha level set at 0.05. There was no significant difference in peak arm slot angle, peak arm velocity, and peak elbow varus torque (p > 0.05); however, there was a significant decrease in ball velocity (p < 0.001). These data indicate that 8-week pitching programs, not coupled with a resistance training regimen, negatively affect a pitcher's ball velocity. Sport coaches and practitioners should thus make accommodations to access the necessary equipment for a pitching and strength training program to be implemented simultaneously to ensure that pitchers are prepared to perform at an optimal level during the spring season.

Associations Between Relative Lower and Upper Body Strength and Hyperinsulinemia in US Adults: 1999-2002 and 2011-2014 NHANES.

ABSTRACT: Churilla, JR, Boyer, WR, Richardson, MR, and Williams, CC. Associations between relative lower and upper body strength and hyperinsulinemia in U.S. Adults: NHANES 1999-2002 and 2011-2014. J Strength Cond Res XX(X): 000-000, 2024-Skeletal muscle (SM) is an insulin-sensitive tissue that aids in glucose homeostasis. Insulin resistance leads to chronic hyperglycemia and type 2 diabetes. Previous evidence suggests that greater SM strength and size improve insulin dynamics. The primary aim of this study was to examine the association(s) between relative lower and upper body strength and hyperinsulinemia in a nationally representative sample of US adults. Samples of adult (≥50 years) subjects in the 1999-2002 (N = 1,097) and adults (≥20 years) in the 2011-2014 (N = 2,576) National Health and Nutrition Examination Survey were used in the analyses. Significance was set at p ≤ 0.05 for regression models. Quartiles (Q) of relative lower body strength (RLBS [N·BMI-1]) and relative grip strength (RGS [kg·BMI-1]) were created. Hyperinsulinemia was calculated using the weighted 75th percentile of log-fasted insulin among adults without diabetes. Inverse dose-response relationships were found for decreasing prevalence estimates of hyperinsulinemia by increasing Q of both RLBS and RGS. Similar dose-response associations were revealed for increasing Q of both RLBS and RGS and mean insulin concentrations. Following adjustment for demographic and lifestyle variables, subjects in Q2, Q3, and Q4 of RLBS were found to have significantly lower odds of hyperinsulinemia (OR 0.58 [P = 0.05], OR 0.38, OR 0.22 [p < 0.05 for both], respectively). Subjects in Q2, Q3, and Q4 of RGS were also found to have lower odds of hyperinsulinemia (OR 0.30; OR 0.14; OR 0.05 [p < 0.0001 for all]), respectively. These data suggest RLBS and RGS may both be favorably associated with insulin homeostasis.

The Casein kinase 1α agonist pyrvinium attenuates Wnt-mediated CK1α degradation via interaction with the E3 ubiquitin ligase component Cereblon.

The Cullin-RING ligase 4 E3 ubiquitin ligase component Cereblon (CRBN) is a well-established target for a class of small molecules termed immunomodulatory drugs (IMiDs). These drugs drive CRBN to modulate the degradation of a number of neosubstrates required for the growth of multiple cancers. Whereas the mechanism underlying the activation of CRBN by IMiDs is well described, the normal physiological regulation of CRBN is poorly understood. We recently showed that CRBN is activated following exposure to Wnt ligands and subsequently mediates the degradation of a subset of physiological substrates. Among the Wnt-dependent substrates of CRBN is Casein kinase 1α (CK1α), a known negative regulator of Wnt signaling. Wnt-mediated degradation of CK1α occurs via its association with CRBN at a known IMiD binding pocket. Herein, we demonstrate that a small-molecule CK1α agonist, pyrvinium, directly prevents the Wnt-dependent interaction of CRBN with CK1α, attenuating the consequent CK1α degradation. We further show that pyrvinium disrupts the ability of CRBN to interact with CK1α at the IMiD binding pocket within the CRBN-CK1α complex. Of note, this function of pyrvinium is independent of its previously reported ability to enhance CK1α kinase activity. Furthermore, we also demonstrate that pyrvinium attenuates CRBN-induced Wnt pathway activation in vivo. Collectively, these results reveal a novel dual mechanism through which pyrvinium inhibits Wnt signaling by both attenuating the CRBN-mediated destabilization of CK1α and activating CK1α kinase activity.

Scaling eukaryotic cell-free protein synthesis achieved with the versatile and high-yielding tobacco BY-2 cell lysate.

Eukaryotic cell-free protein synthesis (CFPS) can accelerate expression and high-throughput analysis of complex proteins with functionally relevant post-translational modifications (PTMs). However, low yields and difficulties scaling such systems have prevented their widespread adoption in protein research and manufacturing. Here, we provide detailed demonstrations for the capabilities of a CFPS system derived from Nicotiana tabacum BY-2 cell culture (BY-2 lysate; BYL). BYL is able to express diverse, functional proteins at high yields in 48 h, complete with native disulfide bonds and N-glycosylation. An optimized version of the technology is commercialized as ALiCE® and advances in scaling of BYL production methodologies now allow scaling of eukaryotic CFPS reactions. We show linear, lossless scale-up of batch mode protein expression from 100 µL microtiter plates to 10 and 100 mL volumes in Erlenmeyer flasks, culminating in preliminary data from a litre-scale reaction in a rocking-type bioreactor. Together, scaling across a 20,000x range is achieved without impacting product yields. Production of multimeric virus-like particles from the BYL cytosolic fraction were then shown, followed by functional expression of multiple classes of complex, difficult-to-express proteins using the native microsomes of the BYL CFPS. Specifically: a dimeric enzyme; a monoclonal antibody; the SARS-CoV-2 receptor-binding domain; a human growth factor; and a G protein-coupled receptor membrane protein. Functional binding and activity are demonstrated, together with in-depth PTM characterization of purified proteins through disulfide bond and N-glycan analysis. Taken together, BYL is a promising end-to-end R&D to manufacturing platform with the potential to significantly reduce the time-to-market for high value proteins and biologics.

The Alzheimer's gene SORL1 is a regulator of endosomal traffic and recycling in human neurons.

BACKGROUND: Loss of the Sortilin-related receptor 1 (SORL1) gene seems to act as a causal event for Alzheimer's disease (AD). Recent studies have established that loss of SORL1, as well as mutations in autosomal dominant AD genes APP and PSEN1/2, pathogenically converge by swelling early endosomes, AD's cytopathological hallmark. Acting together with the retromer trafficking complex, SORL1 has been shown to regulate the recycling of the amyloid precursor protein (APP) out of the endosome, contributing to endosomal swelling and to APP misprocessing. We hypothesized that SORL1 plays a broader role in neuronal endosomal recycling and used human induced pluripotent stem cell-derived neurons (hiPSC-Ns) to test this hypothesis. We examined endosomal recycling of three transmembrane proteins linked to AD pathophysiology: APP, the BDNF receptor Tropomyosin-related kinase B (TRKB), and the glutamate receptor subunit AMPA1 (GLUA1). METHODS: We used isogenic hiPSCs engineered to have SORL1 depleted or to have enhanced SORL1 expression. We differentiated neurons from these cell lines and mapped the trafficking of APP, TRKB and GLUA1 within the endosomal network using confocal microscopy. We also performed cell surface recycling and lysosomal degradation assays to assess the functionality of the endosomal network in both SORL1-depleted and -overexpressing neurons. The functional impact of GLUA1 recycling was determined by measuring synaptic activity. Finally, we analyzed alterations in gene expression in SORL1-depleted neurons using RNA sequencing. RESULTS: We find that as with APP, endosomal trafficking of GLUA1 and TRKB is impaired by loss of SORL1. We show that trafficking of all three cargoes to late endosomes and lysosomes is affected by manipulating SORL1 expression. We also show that depletion of SORL1 significantly impacts the endosomal recycling pathway for APP and GLUA1 at the level of the recycling endosome and trafficking to the cell surface. This has a functional effect on neuronal activity as shown by multi-electrode array (MEA). Conversely, increased SORL1 expression enhances endosomal recycling for APP and GLUA1. Our unbiased transcriptomic data further support SORL1's role in endosomal recycling. We observe altered expression networks that regulate cell surface trafficking and neurotrophic signaling in SORL1-depleted neurons. CONCLUSION: Collectively, and together with other recent observations, these findings suggest that one role for SORL1 is to contribute to endosomal degradation and recycling pathways in neurons, a conclusion that has both pathogenic and therapeutic implications for Alzheimer's disease.

An ERK5-KLF2 signalling module regulates early embryonic gene expression and telomere rejuvenation in stem cells.

The ERK5 MAP kinase signalling pathway drives transcription of naïve pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ quantitative proteomic profiling to identify proteins whose expression is regulated by the ERK5 pathway in mESCs. This reveals a function for ERK5 signalling in regulating dynamically expressed early embryonic 2-cell stage (2C) genes including the mESC rejuvenation factor ZSCAN4. ERK5 signalling and ZSCAN4 induction in mESCs increases telomere length, a key rejuvenative process required for prolonged culture. Mechanistically, ERK5 promotes ZSCAN4 and 2C gene expression via transcription of the KLF2 pluripotency transcription factor. Surprisingly, ERK5 also directly phosphorylates KLF2 to drive ubiquitin-dependent degradation, encoding negative feedback regulation of 2C gene expression. In summary, our data identify a regulatory module whereby ERK5 kinase and transcriptional activities bi-directionally control KLF2 levels to pattern 2C gene transcription and a key mESC rejuvenation process.

N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV-Cell Interaction and Functional Activation of Endothelial Cells.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EV) are widely considered as a cell-free therapeutic alternative to MSC cell administration, due to their immunomodulatory and regenerative properties. However, the interaction mechanisms between EV and target cells are not fully understood. The surface glycans could be key players in EV-cell communication, being specific molecular recognition patterns that are still little explored. In this study, we focused on the role of N-glycosylation of MSC-EV as mediators of MSC-EV and endothelial cells' interaction for subsequent EV uptake and the induction of cell migration and angiogenesis. For that, EV from immortalized Wharton's Jelly MSC (iWJ-MSC-EV) were isolated by size exclusion chromatography (SEC) and treated with the glycosidase PNGase-F in order to remove wild-type N-glycans. Then, CFSE-labelled iWJ-MSC-EV were tested in the context of in vitro capture, agarose-spot migration and matrigel-based tube formation assays, using HUVEC. As a result, we found that the N-glycosylation in iWJ-MSC-EV is critical for interaction with HUVEC cells. iWJ-MSC-EV were captured by HUVEC, stimulating their tube-like formation ability and promoting their recruitment. Conversely, the removal of N-glycans through PNGase-F treatment reduced all of these functional activities induced by native iWJ-MSC-EV. Finally, comparative lectin arrays of iWJ-MSC-EV and PNGase-F-treated iWJ-MSC-EV found marked differences in the surface glycosylation pattern, particularly in N-acetylglucosamine, mannose, and fucose-binding lectins. Taken together, our results highlight the importance of N-glycans in MSC-EV to permit EV-cell interactions and associated functions.

Post-translational modification of SOX family proteins: Key biochemical targets in cancer?

Sox proteins are a family of lineage-associated transcription factors. They regulate expression of genes involved in control of self-renewal and multipotency in both developmental and adult stem cells. Overexpression of Sox proteins is frequently observed in many different human cancers. Despite their importance as therapeutic targets, Sox proteins are difficult to 'drug' using structure-based design. However, Sox protein localisation, activity and interaction partners are regulated by a plethora of post-translational modifications (PTMs), such as: phosphorylation, acetylation, sumoylation, methylation, and ubiquitylation. Here we review the various reported post-translational modifications of Sox proteins and their potential functional importance in guiding cell fate processes. The enzymes that regulate these PTMs could be useful targets for anti-cancer drug discovery.

Follow-up of SARS-CoV-2 positive subgroup from the Asymptomatic novel CORonavirus iNFection study.

A nested longitudinal study within theAsymptomatic novel CORonavirus iNFfection study followed participants with positive nasopharyngeal swab to query for development of symptoms and assess duration of positive reverse transcription-polymerase chain reaction (RT-PCR) test results. Of the 91 participants initially testing positive, 86 participated in follow-up approximately 14 days after study enrollment; of those 86 participants, 19 (22.1%) developed at least one symptom at any time after the initial positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result. The median number of days to symptom development after their initial positive test result was 6 (range 1-29 days). No participants reported a SARS-CoV-2-related hospitalization. The most frequently reported symptoms were fatigue or muscle aches (10.5%), headache (9.3%), fever (5.8%), and shortness of breath (5.8%). Of the 78 participants who submitted a nasopharyngeal swab for repeat RT-PCR testing, 17 (21.8%) remained positive at Day 14, 4 of which continued to test positive at Day 28. These findings reinforce the probable role of silent SARS-CoV-2 infections in community transmission, and that reliance on symptom development will miss a large proportion of infections. Broad testing programs not limited to individuals presenting with symptoms are critical for identifying persons with SARS-CoV-2 infection and ultimately slowing transmission.

TOTAL EAR CANAL ABLATION AND LATERAL BULLA OSTEOTOMY (TECA-LBO) IN ATLANTIC HARBOR SEALS (PHOCA VITULINA CONCOLOR) FOR SUCCESSFUL SURGICAL MANAGEMENT OF OTITIS MEDIA.

Chronic, severe otitis media was diagnosed in four Atlantic harbor seals (Phoca vitulina concolor), three of which were stranded animals undergoing rehabilitation. All seals presented with unilateral purulent aural discharge that would intermittently recur despite prolonged topical and systemic antimicrobial therapy. Aerobic culture from aural discharge isolated multidrug-resistant organisms in all seals, including Pseudomonas aeruginosa, Staphylococcus pseudintermedius, Klebsiella pneumoniae, and/or Enterococcus faecalis. Computed tomography was used in three cases to confirm otitis media and positive contrast ear canalography was used in one case to confirm tympanic membrane rupture. Given the persistent nature of otitis, surgical intervention in the form of a total ear canal ablation and lateral bulla osteotomy (TECA-LBO) was indicated. Surgery was successful in achieving complete clinical resolution of otitis in all seals. Postoperative complications included temporary unilateral paralysis of the left nare (2/4) and a transient left ptosis (1/4). Partial to complete surgical site dehiscence occurred in all cases; however, complete healing was achieved by second intention in 60 d or less. One rehabilitated seal was fitted with a satellite tag that confirmed normal swimming and diving patterns post release. In harbor seals, TECA-LBO can be performed safely to treat persistent cases of otitis media and should be considered in cases of chronic otitis that are not responsive to medical management.

Discovery, synthesis and characterization of a series of 7-aryl-imidazo[1,2-a]pyridine-3-ylquinolines as activin-like kinase (ALK) inhibitors.

The activin-like kinases are a family of kinases that play important roles in a variety of disease states. Of this class of kinases, ALK2, has been shown by a gain-of-function to be the primary driver of the childhood skeletal disease fibrodysplasia ossificans progressiva (FOP) and more recently the pediatric cancer diffuse intrinsic pontine glioma (DIPG). Herein, we report our efforts to identify a novel imidazo[1,2-a]pyridine scaffold as potent inhibitors of ALK2 with good in vivo pharmacokinetic properties suitable for future animal studies.

Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53-transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer.

Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3-48.6) and 43.3% of arm C (95% CI 23.9-65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7-46.3), 16.7% (95% CI 2.9-49.1), and 23.8% (95% CI 9.1-47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.

Transcription alterations of KCNQ1 associated with imprinted methylation defects in the Beckwith-Wiedemann locus.

PURPOSE: Beckwith-Wiedemann syndrome (BWS) is a developmental disorder caused by dysregulation of the imprinted gene cluster of chromosome 11p15.5 and often associated with loss of methylation (LOM) of the imprinting center 2 (IC2) located in KCNQ1 intron 10. To unravel the etiological mechanisms underlying these epimutations, we searched for genetic variants associated with IC2 LOM. METHODS: We looked for cases showing the clinical features of both BWS and long QT syndrome (LQTS), which is often associated with KCNQ1 variants. Pathogenic variants were identified by genomic analysis and targeted sequencing. Functional experiments were performed to link these pathogenic variants to the imprinting defect. RESULTS: We found three rare cases in which complete IC2 LOM is associated with maternal transmission of KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. As a consequence of KCNQ1 haploinsufficiency, these variants also cause LQTS on both maternal and paternal transmission. CONCLUSION: These results are consistent with the hypothesis that, similar to what has been demonstrated in mouse, lack of transcription across IC2 results in failure of methylation establishment in the female germline and BWS later in development, and also suggest a new link between LQTS and BWS that is important for genetic counseling.

The Effects of Various Weighted Implements on Baseball Swing Kinematics in Collegiate Baseball Players.

Williams, CC, Gdovin, JR, Wilson, SJ, Cazas-Moreno, VL, Eason, JD, Hoke, EL, Allen, CR, Wade, C, and Garner, JC. The effects of various weighted implements on baseball swing kinematics in collegiate baseball players. J Strength Cond Res 33(5): 1347-1353, 2019-The purpose of this study was to investigate the effects of different warm-up (WU) devices on bat swing parameters including maximal resultant velocity (MRV), resultant velocity at ball contact (RVBC), time difference between MRV and RVBC, bat angle at MRV, bat angle at RVBC, and perceptual differences of each WU implement used by National Collegiate Athletic Association Division-I baseball players. Fifteen varsity baseball players completed 1 experimental session during fall training. Retroreflective markers were placed on the bat and tee to measure basic bat kinematics during the swing. Participants completed a general calisthenics WU before being counter-balanced into 1 of 4 WU conditions: standard bat (SB) (33 in/30 oz), fungo (10.6 oz), weighted gloves with SB (weighted gloves) (55.6 oz) and donut with SB (donut) (55.6 oz). Each participant was asked to perform their normal on-deck routine over a 2-minute period, finishing with 5 practice swings with the designated condition. After completion of the WU, a 1-minute rest period (simulating normal game conditions) was given to allow each participant to get set to perform 5 maximal swings with a SB. Five, 1 × 4 (group × condition) repeated measures analysis of variance examined the aforementioned variables. There were no significant differences in MRV, RVBC, time difference between MRV and RVBC, and bat angle at MRV and RVBC between all WU conditions. If presented with the current options, athletes should choose the WU implement with which they are most comfortable using before an at-bat situation.

NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018.

The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on "Signs and Symptoms of SCLC" and "Principles of Pathologic Review."

Effects of Jaw Clenching and Jaw Alignment Mouthpiece Use on Force Production During Vertical Jump and Isometric Clean Pull.

Allen, CR, Fu, Y-C, Cazas-Moreno, V, Valliant, MW, Gdovin, JR, Williams, CC, and Garner, JC. Effects of jaw clenching and jaw alignment mouthpiece use on force production during vertical jump and isometric clean pull. J Strength Cond Res 32(1): 237-243, 2018-This study examined the effects of jaw clenching, a self-adapted, jaw-repositioning mouthpiece on force production during maximum countermovement vertical jump and maximum isometric midthigh clean pull assessments in an attempt to determine any ergogenic effect attributable to clenching, jaw-repositioning mouthpiece use, or the combination of both. Thirty-six male subjects performed vertical jump and isometric clean pull assessments from a force platform under various mouthpiece and clench conditions. A 3 × 2 (mouthpiece × clench) repeated-measures analysis of variance was conducted to analyze each of the following force production variables for both assessments: peak force, normalized peak force, and rate of force development. In addition, jump height was analyzed for the vertical jump. Results revealed improvements in peak force (F1,35 = 15.84, p ≤ 0.001, (Equation is included in full-text article.)= 0.31), normalized peak force (F1,35 = 16.28, p ≤ 0.001, (Equation is included in full-text article.)= 0.32), and rate of force development (F1,35 = 12.89, p = 0.001, (Equation is included in full-text article.)= 0.27) during the isometric clean pull assessment when participants maximally clenched their jaw, regardless of mouthpiece condition. There were no statistically significant differences in jump height, peak force, normalized peak force, or rate of force development during the vertical jump for any treatment condition. This study supports previous research demonstrating that the implementation of remote voluntary contractions such as jaw clenching can lead to concurrent activation potentiation and a resulting ergogenic effect during activities involving and requiring high-force production.