Sphingosine is involved in PAPTP-induced death of pancreas cancer cells by interfering with mitochondrial functions.

Pancreas ductal adenocarcinoma belongs to the most common cancers, but also to the tumors with the poorest prognosis. Here, we pharmacologically targeted a mitochondrial potassium channel, namely mitochondrial Kv1.3, and investigated the role of sphingolipids and mutated Kirsten Rat Sarcoma Virus (KRAS) in Kv1.3-mediated cell death. We demonstrate that inhibition of Kv1.3 using the Kv1.3-inhibitor PAPTP results in an increase of sphingosine and superoxide in membranes and/or membranes associated with mitochondria, which is enhanced by KRAS mutation. The effect of PAPTP on sphingosine and mitochondrial superoxide formation as well as cell death is prevented by sh-RNA-mediated downregulation of Kv1.3. Induction of sphingosine in human pancreas cancer cells by PAPTP is mediated by activation of sphingosine-1-phosphate phosphatase and prevented by an inhibitor of sphingosine-1-phosphate phosphatase. A rapid depolarization of isolated mitochondria is triggered by binding of sphingosine to cardiolipin, which is neutralized by addition of exogenous cardiolipin. The significance of these findings is indicated by treatment of mutated KRAS-harboring metastasized pancreas cancer with PAPTP in combination with ABC294640, a blocker of sphingosine kinases. This treatment results in increased formation of sphingosine and death of pancreas cancer cells in vitro and, most importantly, prolongs in vivo survival of mice challenged with metastatic pancreas cancer. KEY MESSAGES: Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis. The mitochondrial Kv1.3 ion channel blocker induced mitochondrial sphingosine. Sphingosine binds to cardiolipin thereby mediating mitochondrial depolarization. Sphingosine is formed by a PAPTP-mediated activation of S1P-Phosphatase. Inhibition of sphingosine-consumption amplifies PAPTP effects on PDAC in vivo.

Acute nicotine administration reduces the efficacy of punishment in curbing remifentanil consumption in a seeking-taking chain schedule of reinforcement.

RATIONALE: Nicotine dependence is highly comorbid with opioid use disorders (OUDs). The use of nicotine-containing products increases the propensity to misuse prescription opioids and addressing both nicotine and opioid use simultaneously is more efficacious for treatment of OUDs than treating opioid use alone. OBJECTIVES: Given this extreme comorbidity, further elucidation of the effects of nicotine as a factor in promoting vulnerability to development of OUDs is needed. Here, we sought to further explore the effects of nicotine administration on operant self-administration of remifentanil (RMF), a fast-acting synthetic µ-opioid receptor agonist, using a heterogenous seeking-taking chain schedule of reinforcement in unpunished and punished conditions. METHODS: Male and female rats received nicotine (0.4 mg/kg) or saline prior to operant self-administration sessions. These sessions consisted of pressing a 'seeking' lever to gain access to a 'taking' lever that could be pressed for delivery of 3.2 µg/kg RMF. After acquisition, continued drug seeking/taking was punished through contingent delivery of foot-shock. RESULTS: Nicotine, relative to saline, increased RMF consumption. Furthermore, nicotine treatment resulted in significantly higher seeking responses and cycles completed, and this effect became more pronounced during punished sessions as nicotine-treated rats suppressed RMF seeking significantly less than controls. Nicotine treatment functionally reduced the efficacy of foot-shock punishment as a deterrent of opioid-seeking. CONCLUSIONS: Nicotine administration enhanced both appetitive and consummatory responding for RMF and engendered a punishment-insensitive phenotype for RMF that was less impacted by contingent administration of foot-shock punishment. These findings provide further support for the hypothesis that nicotine augments vulnerability for addiction-like behaviors for opioids.

Does Social Intelligence Training Improve Daily Well-Being and Responsiveness to Daily Negative and Positive Events in Custodial Grandmothers?

OBJECTIVES: Custodial grandparents are grandparents who raise grandchildren on a full-time basis in absence of the grandchild's birth parents. Compared to non-caregiving grandparents, custodial grandparents report poorer mental and physical health and stronger changes in daily well-being when experiencing negative and positive events. We examine whether an online social intelligence training (SIT) program improves custodial grandmothers' (CGM) daily well-being, socio-emotional skills, and changes in well-being when confronted with daily negative and positive events. METHOD: Multilevel models were applied to 200 CGM who were recruited from across the U.S. and completed a daily survey for 14 consecutive days prior to and following participation in a randomized clinical trial. Participants were randomized into the SIT program or an attention control condition focusing on healthy living habits. The outcomes of interest were daily well-being, social connectedness, emotional awareness, and perspective-taking. RESULTS: Multilevel analyses revealed that participants who participated in the SIT program, compared to the attention control condition, exhibited stronger emotional responsiveness (i.e., improvements) to daily positive events in the outcomes of positive affect, social engagement, and perspective-taking. DISCUSSION: Our findings illustrate that SIT improves key components of daily functioning in CGM, which may serve as a pathway linking the demands of custodial grandparenting to poorer mental and physical health. Our discussion focuses on the utility and accessibility of the SIT program for helping improve outcomes for this disadvantaged population.

Fatigue and Metabolic Responses during Repeated Sets of Bench Press Exercise to Exhaustion at Different Ranges of Motion.

This study compared the acute effects of different ranges of motion (ROM) on fatigue and metabolic responses during repeated sets of bench press exercise. Ten resistance trained men performed three sets to momentary failure with two-min rest intervals at three different ROM: full ROM (FULL), and partial ROM in which the barbell was moved either at the bottom half (BOTTOM) or the top half (TOP) of the full barbell vertical displacement. In TOP, a higher load was lifted, and a higher total number of repetitions was performed compared to FULL and BOTTOM (130 ± 17.6 vs. 102.5 ± 15.9 vs. 98.8 ± 17.5 kg; 55.2 ± 9.8, 32.2 ± 6.5 vs. 49.1 ± 16.5 kg, respectively p < 0.01). Work per repetition was higher in FULL than TOP and BOTTOM (283 ± 43 vs. 205 ± 32 vs. 164 ± 31 J/repetition, p < 0.01). Mean barbell velocity at the start of set 1 was 21.7% and 12.8% higher in FULL compared to TOP and BOTTOM, respectively. The rate of decline in mean barbell velocity was doubled from set 1 to set 3 (p < 0.01) and was higher in FULL than both TOP and BOTTOM (p < 0.001). Also, the rate of mean barbell velocity decline was higher in BOTTOM compared to TOP (p = 0.045). Blood lactate concentration was similarly increased in all ROM (p < 0.001). Training at TOP ROM allowed not only to lift a higher load, but also to perform more repetitions with a lower rate of decline in mean barbell velocity. Despite the lower absolute load and work per repetition, fatigue was higher in BOTTOM than TOP and this may be attributed to differences in muscle length.

The Impact of Range of Motion on Applied Force Characteristics and Electromyographic Activity during Repeated Sets of Bench Press Exercise.

This study examined the effects of range of motion (ROM) on applied force, power output and surface electromyographic (sEMG) responses during repeated sets of bench press exercise executed as fast as possible. Ten resistance trained men performed three sets to momentary failure with two-min rest intervals under three different ROM conditions: (a) full ROM (FULL), (b) TOP, at the top half of ROM, and (c) BOTTOM, at the bottom half of ROM. Mean and peak force were higher in TOP compared to FULL and BOTTOM (mean force: 817 ± 80 vs. 657 ± 98 vs. 623 ± 122 N, respectively, p < 0.001) with no differences between FULL and BOTTOM. During repeated sets, large decreases were found in peak (by 29.4 to 45.3%) and mean power (by 55.5 to 64.7%) from the first to the last repetitions. However, the decrease in mean force was only 2% (p < 0.01) and decreases in peak force ranged from 6.7 and 8.8% to zero, indicating the velocity loss was the main contributor to fatigue in power output. Although force and power output in set 3 were unchanged in BOTTOM, mean power output decreased significantly, suggesting that lower performance and fatigue may be related to the longer muscle length. Fatigue was accompanied by an increase in sEMG activity and a decrease in median frequency in all muscles, with triceps brachialis sEMG reflecting more the force and power differences among ROMs. In conclusion, fatigue depends on velocity rather than force loss during bench press exercise at different ROMs.

SCS 6th Annual Meeting-EEVFA-11th International Congress of Biochemistry and Physiology of Exercise, Athens, Greece, 2023.

On behalf of the Strength and Conditioning Society (SCS) and the Hellenic Society of Biochemistry and Exercise Physiology (EEVFA), we are pleased to present the abstracts of the SCS 6th Annual Meeting and EEVFA-11th International Congress of Biochemistry and Physiology of Exercise. The event was held at the Hellenic Olympic Committee headquarters in Athens, Greece, on 19-22 October 2023, and comprised several invited sessions from international and national speakers on a variety of topics related to biochemistry and exercise physiology, strength and conditioning practices and their application to health, injury prevention and sports performance. These included strength training in high-performance sports, sport science and training-competition load management in elite environments, biochemistry and exercise physiology and prescription, nutrition and biomechanics, among others. The conference also included different practical workshops conducted by renowned academics and practitioners on eccentric training, change of direction ability and strength and power training in professional team-sports, and ergospirometry and exercise prescription in specific populations. Finally, the event disseminated up-to-date strength and conditioning research by providing practitioners and researchers with the opportunity to present their most recent findings. In this regard, all abstracts of the communications presented at the SCS 6th Annual Meeting-EEVFA-11th International Congress of Biochemistry and Physiology of Exercise can be found in this Conference Report.

Assessing the effectiveness of MRI, 18F-fluciclovine PET, SUVmax, and PSA in detecting local recurrence of prostate cancer after prostatectomy.

Purpose: The primary objective of this study was to evaluate the discriminatory utility of magnetic resonance imaging (MRI), 18F-fluciclovine positron emission tomography (PET), maximum standardized uptake value (SUVmax), prostate-specific antigen (PSA), and combinations of these diagnostic modalities for detecting local prostate cancer recurrence in the setting of rising PSA after radical prostatectomy. Material and methods: Patients were characterised for clinical features such as Gleason score, PSA at surgery, PSA at follow-up, follow-up MRI result, follow-up PET result, follow-up SUVmax, and follow-up disease status. The utility of diagnostic parameters for detecting disease recurrence at the prostatectomy bed was assessed using receiver operating characteristics (ROC) analysis to determine the area under the curve (AUC) for each model. Sensitivity, specificity, and positive/negative predictive values were also calculated. Optimal cut-off points for continuous variables were determined based on maximum Youden's J statistics. Results: The study found that MRI had the highest concordance (96%), sensitivity (100%), specificity (91%), positive predictive value (93%), and negative predictive value (100%) among the diagnostic modalities. The AUC for MRI was 0.9545, indicating a high discriminatory ability for detecting prostate cancer local recurrence. When combined, PET and SUVmax (cut-off value of 2.85) showed an improved performance compared to using them individually, with an AUC of 0.8925. Conclusions: The analysis suggests that MRI is the most effective imaging modality for detecting local prostate cancer recurrence, with 18F-fluciclovine PET and SUVmax also showing promising combined results. PSA has moderate discriminatory utility at follow-up but can still provide valuable information in detecting prostate cancer recurrence. Further research and recent references are needed to support these findings.

Symptoms of depression among outpatients with suspected COVID-19 in metropolitan Local Government Areas of Kaduna State, Nigeria.

BACKGROUND: The novel SARS-CoV-2 virus that causes Coronavirus disease (COVID-19) has redefined global health and response to Acute Respiratory Infection (ARI). The outbreak of a cluster of influenza-like illnesses in Wuhan, China, has morphed into a pandemic in the last quarter of 2019, stretching from South East Asia to Europe, The Americas, Africa, and the Australian subcontinent. We evaluated the prevalence of depression among outpatients diagnosed with ARI. MATERIALS AND METHODS: We utilized a cross-sectional, observational design and investigated the prevalence of symptoms of depression among outpatients with ARI and described the characteristics of outpatients with ARI in Kaduna State. RESULTS: The prevalence of symptoms of depression was 19.6% for respondents with symptoms of ARI and 14.4% for those without symptoms of ARI. On no risk of depression, we had a higher proportion of the respondents without symptoms of ARI (86%) than those with symptoms of depression (80%) (M = 318.4, SD = 29.62 case, and M = 344.0, SD = 14.2 control, r = 0.88, CI = 13.5 to 6.5, P = 0.000952). Likewise, in the category with mild risk of depression, respondents without symptoms of ARI were fewer (10%) than those with symptoms of depression (15%) (M = 58.4, SD = 26.0 case, and M = 42.1, SD = 12.7 control, r = 0.86, CI = 11.8 to 5.8, P = 0.0136. There was no significant difference between respondents with symptoms of ARI and without symptoms of ARI in the categories of moderate (M = 13.6, SD = 5.1 case, and M = 11.6, SD = 4.6 control, r = 0.87, CI = 2.3 to 2.1, P = 0.178) and high (M = 5.6, SD = 2.5 case, and M = 4.4, SD = 3.2 control, r = 0.61, CI = 1.2 to 1.5, P = 0.174) risk of depression. CONCLUSION: Symptoms of depression were commoner among respondents who presented with symptoms of Acute Respiratory Infection (ARI) at the Outpatient Department (OPD). However, further explanatory research is needed to establish causality.

Statistics of Gaussian polymer chains in harmonic applied fields.

The model of an ideal polymer chain in a harmonic applied field has broad applicability in situations involving polymer confinement and deformation due to applied stress. In this work we (1) formulate a general analytical model for a continuous Gaussian chain under a harmonic applied potential and (2) evaluate the statistical mechanics of this model given the potential, obtaining partition functions and moment generating functions (MGFs) that describe the chain configurations. Closed-form expressions for the squared radius of gyration, potential energy, partition function, and MGF for the center of mass are obtained for a general and multidimensional harmonic field. The expressions are compared with results of Monte Carlo simulations of a discrete Gaussian chain as well as results for related systems obtained from the literature. The theory derived here is used to test the applicability of the current model assumptions to relations from the literature describing polymer confinement and deformation in experiment, theory, and simulations.

Free fatty acid receptor 4 in cardiac myocytes ameliorates ischemic cardiomyopathy.

Aims: Free fatty acid receptor 4 (Ffar4) is a receptor for long-chain fatty acids that attenuates heart failure driven by increased afterload. Recent findings suggest that Ffar4 prevents ischemic injury in brain, liver, and kidney, and therefore, we hypothesized that Ffar4 would also attenuate cardiac ischemic injury. Methods and Results: Using a mouse model of ischemia-reperfusion (I/R), we found that mice with systemic deletion of Ffar4 (Ffar4KO) demonstrated impaired recovery of left ventricular systolic function post-I/R with no effect on initial infarct size. To identify potential mechanistic explanations for the cardioprotective effects of Ffar4, we performed bulk RNAseq to compare the transcriptomes from wild-type (WT) and Ffar4KO infarcted myocardium 3-days post-I/R. In the Ffar4KO infarcted myocardium, gene ontology (GO) analyses revealed augmentation of glycosaminoglycan synthesis, neutrophil activation, cadherin binding, extracellular matrix, rho signaling, and oxylipin synthesis, but impaired glycolytic and fatty acid metabolism, cardiac repolarization, and phosphodiesterase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated impaired AMPK signaling and augmented cellular senescence in the Ffar4KO infarcted myocardium. Interestingly, phosphodiesterase 6c (PDE6c), which degrades cGMP, was the most upregulated gene in the Ffar4KO heart. Further, the soluble guanylyl cyclase stimulator, vericiguat, failed to increase cGMP in Ffar4KO cardiac myocytes, suggesting increased phosphodiesterase activity. Finally, cardiac myocyte-specific overexpression of Ffar4 prevented systolic dysfunction post-I/R, defining a cardioprotective role of Ffa4 in cardiac myocytes. Conclusions: Our results demonstrate that Ffar4 in cardiac myocytes attenuates systolic dysfunction post-I/R, potentially by attenuating oxidative stress, preserving mitochondrial function, and modulation of cGMP signaling.

Molecular simulation of flow-enhanced nucleation of polyethylene crystallites in biaxial flows.

Flow-enhanced nucleation (FEN) of n-pentacontahectane (C150) under biaxial extensional flows of varying strain rate ratios is studied using nonequilibrium molecular dynamics simulation. The nucleation rates thus calculated are used to test previously published FEN models based on invariants of the conformation tensor of Kuhn segments and the extra stress tensor. Models based on the conformation tensor provide a more accurate description of FEN observed in biaxial flow simulations than those based on the extra stress tensor. In addition, the formation of nematic domains previously reported to be stabilized by shear or extensional flow is absent in equibiaxial flows. However, such domains do form in non-equibiaxial flows, and nucleation occurs in these domains preferentially. The shape and orientation of nuclei formed under biaxial flows of various strengths and strain rate ratios are also reported.

Large, ulcerated infantile hemangioma of the chest wall complicated by life-threatening hemorrhage: Case report and literature review.

While ulceration is one of the most common infantile hemangioma (IH) complications, severe bleeding is a rare consequence, with a paucity of patients reported. We report a 5-month-old girl with a very large, mixed, partial segmental IH of the upper chest wall who, despite medical intervention, developed severe ulceration and multiple episodes of life-threatening bleeding that ultimately led to hemorrhagic shock. Experience in our patient and a review of six previous reports shows that severe bleeding is a risk when ulceration extends directly into an arterial feeding vessel that is often visible clinically. Other potential predictors for severe bleeding include large to very large IH size with extension of the tumor into underlying structures, segmental or partial segmental patterning, mixed and bulky morphology, and white discoloration as a sign of impending or worsening ulceration.

Reasons for multiple biologic and targeted synthetic DMARD switching and characteristics of treatment refractory rheumatoid arthritis.

OBJECTIVE: Switching biologic and targeted synthetic DMARD (b/tsDMARD) medications occurs commonly in RA patients, however data are limited on the reasons for these changes. The objective of the study was to identify and categorize reasons for b/tsDMARD switching and investigate characteristics associated with treatment refractory RA. METHODS: In a multi-hospital RA electronic health record (EHR) cohort, we identified RA patients prescribed ≥1 b/tsDMARD between 2001 and 2017. Consistent with the EULAR "difficult to treat" (D2T) RA definition, we further identified patients who discontinued ≥2 b/tsDMARDs with different mechanisms of action. We performed manual chart review to determine reasons for medication discontinuation. We defined "treatment refractory" RA as not achieving low disease activity (<3 tender or swollen joints on <7.5 mg of daily prednisone equivalent) despite treatment with two different b/tsDMARD mechanisms of action. We compared demographic, lifestyle, and clinical factors between treatment refractory RA and b/tsDMARD initiators not meeting D2T criteria. RESULTS: We identified 6040 RA patients prescribed ≥1 b/tsDMARD including 404 meeting D2T criteria. The most common reasons for medication discontinuation were inadequate response (43.3 %), loss of efficacy (25.8 %), and non-allergic adverse events (13.7 %). Of patients with D2T RA, 15 % had treatment refractory RA. Treatment refractory RA patients were younger at b/tsDMARD initiation (mean 47.2 vs. 55.2 years, p < 0.001), more commonly female (91.8% vs. 76.1 %, p = 0.006), and ever smokers (68.9% vs. 49.9 %, p = 0.005). No RA clinical factors differentiated treatment refractory RA patients from b/tsDMARD initiators. CONCLUSIONS: In a large EHR-based RA cohort, the most common reasons for b/tsDMARD switching were inadequate response, loss of efficacy, and nonallergic adverse events (e.g. infections, leukopenia, psoriasis). Clinical RA factors were insufficient for differentiating b/tsDMARD responders from nonresponders.

Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination.

We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (K D < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC 50 ∼0.1-1.75 nM) and provided robust protection in vivo . Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization. HIGHLIGHTS: ▪ Infection and vaccination elicit unique IgG antibody profiles at the molecular level▪ Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)▪ Hybrid immunity maintains the imprint of first infection or first vaccination▪ Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth.

Nickel-Catalyzed Enantioconvergent and Diastereoselective Allenylation of Alkyl Electrophiles: Simultaneous Control of Central and Axial Chirality.

In recent years, remarkable progress has been described in the development of methods that simultaneously control vicinal stereochemistry, wherein both stereochemical elements are central chirality; in contrast, methods that control central and axial chirality are comparatively rare. Herein we report that a chiral nickel catalyst achieves the enantioconvergent and diastereoselective coupling of racemic secondary alkyl electrophiles with prochiral 1,3-enynes (in the presence of a hydrosilane) to generate chiral tetrasubstituted allenes that bear an adjacent stereogenic center. A carbon-carbon and a carbon-hydrogen bond are formed in this process, which provides good stereoselectivity and is compatible with an array of functional groups.

Albumin is an important factor in the control of serum free fatty acid flux in both male and female mice.

Albumin knockout (Alb-/-) mice exhibit a low plasma free fatty acid (FFA) concentration, but it was not known if the suppressed concentration reflects a lower rate of appearance (Ra) of FFA in the circulation (i.e., lower FFA flux) or if the absence of albumin alters the relationship between FFA flux and concentration. For understanding the role of albumin in FFA transport through the bloodstream, it is not sufficient to rely on FFA concentration data alone. Therefore, we developed a method to study FFA kinetics in Alb-/- mice. Using an albumin-free formulation of [U-13C]palmitate tracer, serum FFA kinetics were tested in Alb-/- and wild-type (WT) mice. Results indicate that the flux of FFA in serum of Alb-/- mice was significantly lower than in WT mice (P < 0.05), while albumin deficiency did not alter the relationship between FFA flux and concentration. Next, to test if suppressed lipolysis might have also been involved in the suppressed FFA kinetics, gene expression of a lipolytic enzyme (adipose triglyceride lipase, Atgl) and a marker of lipolysis (phosphorylation of hormone-sensitive lipase, p-HSL) were measured in adipose tissue. In contrast to the low FFA flux in Alb-/-, both Atgl gene expression and p-HSL protein were significantly higher in adipose tissue of Alb-/- than in WT mice (P < 0.05). Thus, the low FFA flux in Alb-/- appeared to be driven by the absence of albumin's FFA binding functions rather than through regulation of lipolysis, indicating that albumin is an important factor in determining the flux of FFA in circulation.NEW & NOTEWORTHY To improve understanding of the albumin protein's function in vivo, we tested plasma free fatty acid kinetics in albumin knockout mice compared with wild-type mice. Using a new tracer formulation strategy, it was discovered that the appearance rate of free fatty acids in serum is lower in albumin knockout mice than in wild-type mice. The results indicate that albumin is a major controller of free fatty acid kinetics.

Longitudinal Molecular and Serological Evidence of SARS-CoV-2 Infections and Vaccination Status: Community-Based Surveillance Study (CONTACT).

INTRODUCTION: This prospective, longitudinal, community-based study, EpidemiologiCal POpulatioN STudy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Lake CounTy, Illinois (CONTACT), investigated coronavirus disease 2019 (COVID-19) immunity, occupational risks related to SARS-CoV-2 exposure, and long-term immunoglobulin G (IgG) seroconversion kinetics. METHODS: At baseline and follow up (3, 6, and 9 months), non-hospitalized adult participants provided nasal and blood serum specimens for molecular [reverse transcription polymerase chain reaction (RT-PCR)] and serological (IgG) testing (4 November 2020-30 October 2021). RESULTS: At baseline, 6.4% (65/1008) had evidence of current/prior SARS-CoV-2 infection. At 3, 6, and 9 months, positive PCR tests were obtained from 0.4% (3/781), 0.4% (3/733), and 0% (0/673) of participants, respectively. Positive IgG occurred at baseline and 3, 6, and 9 months in 4.5% (45/1008), 6.0% (48/799), 5.4% (39/733), and 2.8% (19/673) of participants, respectively. Of participants positive for IgG at baseline, 28 had a negative IgG test at a follow-up visit; of those 28, 21 had their first negative IgG test within 6 months. Participants were more likely to retain positive IgG if they were 18-29 years of age, were male, or had medium-high/high-risk occupations. A high vaccination rate (70% received ≥ 1 dose by 9 months) was observed. Influence of occupational status or characteristics on transmission and IgG, and COVID-19 vaccination trends, are shown. CONCLUSIONS: This study expands on prior studies assessing COVID-19 immunity and IgG seroconversion by including both RT-PCR and serologic testing and longitudinal follow-up of study participants. We observed decreased infection rates over the 9 month follow-up period as well as a decline in IgG persistency after 6 months. The findings from this community-based study regarding vaccinate rates, infection rates by PCR, and IgG persistency over time can help improve our understanding of COVID-19 immunity, occupational risks related to SARS-CoV-2 exposure, and the kinetics of long-term IgG seroconversion, which is important to help guide local and national mitigation strategies. CLINICAL TRIAL REGISTRATION: NCT04611230.

Physiological Responses and Performance during an Integrated High-Intensity Interval Aerobic and Power Training Protocol.

This study compared the acute physiological responses and performance changes during an integrated high-intensity interval aerobic and power protocol. Sixteen moderately trained athletes (age: 20.1 ± 2.2 years, body height: 180.0 ± 6.5 cm, body mass: 75.7 ± 6.4 kg, VO2max: 55.8 ± 4.3 mL/kg/min) performed a 2 × 6 min interval training protocol with 2 min passive recovery between sets on two different occasions in random and counterbalanced order. Each 6 min set included repeated periods of 15 s exercise interspersed with 15 s passive rest. On one occasion (RUN), all exercise periods included running at 100% of maximal aerobic speed, while on the other occasion an integrated protocol was used (INT) in which each of the two 6 min sets included 4 × 1.5 min periods of running exercise at 100% of maximal aerobic speed in combination with jumping (i.e., 2 × 15 running with 15 s rest and 1 × 15 s drop jumping with 15 s rest). Time spent above 85% HRmax was two-fold higher in INT compared to RUN (8.5 ± 3.6 vs. 4.3 ± 3.9 min, respectively, p = 0.0014). Interestingly, heart rate increased above 95% HRmax only in INT and almost no time was spent above 95% HRmax in RUN (1.4 ± 1.9 vs. 0.1 ± 0.2 min, respectively, p = 0.008). Blood lactate concentration at the end of the second set of INT was higher than RUN (7.3 ± 3.2 vs. 4.6 ± 2.7 mmol/L, p = 0.002). Countermovement jump was higher in INT after the end of second set by 6.4% (p = 0.04), 6.7% (p = 0.04), 7.8% (p < 0.01) and 7.3% (p < 0.001), at 2, 6 and 8 min after set 2. In conclusion, the comparison between INT and RUN shows that INT not only elicits higher physiological and metabolic responses, but also acutely enhances neuromuscular performance for at least 8 min after the end of exercise. The integrated running/jumping high-intensity interval exercise approach could be a very useful and time efficient method for strength and conditioning coaches, especially in team sports, in which the time available for the improvement of physical parameters is limited.