Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations.

Adult T-cell leukemia-lymphoma (ATLL) is an aggressive Human T-cell Leukemia Virus Type 1 (HTLV-1)-driven malignancy. Although Western hemisphere (Afro-Caribbean and South American) patients face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts. Recurrent deletion and/or damaging mutations involving FOXO3, ANKRD11, DGKZ, and PTPN6 implicate these genes as potential tumor suppressors. RNA-seq, published functional data and in vitro assays support the roles of ANKRD11 and FOXO3 as regulators of T-cell proliferation and apoptosis in ATLL, respectively. Survival data suggest ANKRD11 mutation may confer a worse prognosis. Japanese and Western cohorts, in addition to acute and lymphomatous subtypes, demonstrated distinct molecular patterns. GATA3 deletion was associated with unfavorable chronic cases. IRF4 and CARD11 mutations frequently emerged in relapses after interferon therapy. Our findings reveal novel putative ATLL driver genes and clinically relevant differences between Japanese and Western ATLL patients.

EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2024 update on the diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy. DIAGNOSIS: The diagnosis is established through meticulous pathological evaluation. Detection of EBV-encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO-HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others. RISK-STRATIFICATION: The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers. MANAGEMENT: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.

Acute sympathetic activation blunts the hyperemic and vasodilatory response to passive leg movement.

Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) has not been adequately addressed. This study sought to test the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 year). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) of maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after the cessation of exercise and central and peripheral hemodynamics were assessed. MSNA was directly recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+ 15 ± 5 burst/100 bpm) and ExPECO 40% (+ 22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Vasodilation, assessed by the change in leg vascular conductance during PLM, was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate that elevated MSNA attenuates the vasodilatory response to PLM and that the magnitude of reduction in vasodilation during PLM is graded in relation to the degree of sympathoexcitation.

Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management.

DISEASE OVERVIEW: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. DIAGNOSIS: The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. RISK STRATIFICATION: Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. MANAGEMENT: Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

Births: Final Data for 2022.

Objectives- This report presents 2022 data on U.S. births by selected characteristics. Trends in fertility patterns and maternal and infant characteristics are described. Methods-Descriptive tabulations based on birth certificates of the 3.67 million births registered in 2022 are shown by maternal age, live-birth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates also are shown. Trends for 2010 to 2022 are presented for selected items, and by race and Hispanic origin for 2016-2022. Results-A total of 3,667,758 births occurred in the United States in 2022, essentially unchanged from 2021. The general fertility rate declined 1% from 2021 to 56.0 births per 1,000 females ages 15-44 in 2022. The birth rate for females ages 15-19 declined 2% from 2021 to 2022; birth rates fell 7% for women ages 20-24, rose 1% to 5% for women ages 25-29 and 35-44, and rose 12% for women ages 45-49 (the first increase since 2016). The total fertility rate declined less than 1% to 1,656.5 births per 1,000 women in 2022. Birth rates declined for unmarried women but increased for married women from 2021 to 2022. Prenatal care beginning in the first trimester declined to 77.0% in 2022; the percentage of women who smoked during pregnancy declined to 3.7%. The cesarean delivery rate was unchanged in 2022 (32.1%); Medicaid was the source of payment for 41.3% of births. The preterm birth rate declined 1% to 10.38%; the low birthweight rate rose 1% to 8.60%. The twin birth rate was unchanged in 2022 (31.2 per 1,000 births); the 2% decrease in the triplet and higher-order multiple birth rate.

Muscle blood flow and vasodilation are blunted at the onset of exercise following an acute bout of ischemia-reperfusion.

Ischemia-reperfusion (I/R) injury can attenuate endothelial function and impair nitric oxide bioavailability. We tested the hypothesis that I/R also blunts the rapid and steady-state hyperemic and vasodilatory responses to handgrip exercise. Ten subjects (8M/2F; 24 ± 4 yr) performed handgrip exercises before and after I/R (20 min of ischemia/20 min of reperfusion) and time control (40-min supine rest) trials. Forearm blood flow (FBF) and forearm vascular conductance (FVC) were assessed with Doppler ultrasound during single forearm contractions and 3 min of rhythmic handgrip exercise. Venous blood samples were drawn at rest and during exercise to assess plasma [nitrite]. Peak ΔFBF (from baseline) and ΔFVC following single contractions were attenuated following I/R (134 ± 48 vs. 103 ± 42 mL·min-1; 160 ± 55 vs. 118 ± 48 mL·min-1·100 mmHg-1, P < 0.05 for both), but not following time control (115 ± 63 vs. 124 ± 57 mL·min-1; 150 ± 80 vs. 148 ± 64 mL·min-1·100 mmHg-1, P = 0.16 and P = 0.95, respectively). Steady-state ΔFBF and ΔFVC during rhythmic exercise were unchanged in both I/R (192 ± 52 vs. 190 ± 53 mL·min-1; 208 ± 56 vs. 193 ± 60 mL·min-1·100 mmHg-1) and time control (188 ± 54 vs. 196 ± 48 mL·min-1; 206 ± 60 vs. 207 ± 49 mL·min-1·100 mmHg-1) trials (group × time interactions P = 0.34 and 0.21, respectively). Plasma [nitrite] under resting conditions and during steady-state rhythmic exercise was attenuated following I/R (P < 0.05 for both), but not following time control (P = 0.54 and 0.93). These data indicate that I/R blunts hyperemia and vasodilation at the onset of muscle contractions but does not attenuate these responses during steady-state exercise.NEW & NOTEWORTHY Ischemia-reperfusion can impair endothelial function; however, it remains unknown whether exercise hyperemia and vasodilation are also impaired. This study presents novel findings that ischemia-reperfusion blunts the hyperemic and vasodilatory responses at the onset of muscle contractions but not during steady-state exercise. Plasma [nitrite] was also blunted at baseline and during steady-state exercise following ischemia-reperfusion compared with time control. These attenuated responses at the onset of exercise may be associated with ischemia-reperfusion reductions in NO bioavailability.

Intermittent versus continuous handgrip exercise and peripheral endothelial function: impact of shear rate fluctuations.

Sustained exercise-induced elevations in shear rate (SR) have been well established as beneficial for improving endothelial function. However, the impact of intermittent fluctuations in SR is not understood. We investigated the effect of intermittent SR elevations compared with sustained elevations on peripheral endothelial function. Brachial artery flow-mediated dilation (FMD) was assessed in 13 adults (9 M/4 F; 22 ± 4 yr) before and after 30 min of handgrip exercise. Three different rhythmic forearm exercise interventions were performed at a rate of 20 contractions/min. Intermittent exercises (6 × 3 min exercise interspersed by 2 min of rest) were performed at 25% (INT-25%) and 15% (INT-15%) maximum voluntary contraction (MVC), and continuous exercise was completed at 15% MVC. Brachial artery diameter and velocity were measured using Doppler ultrasound. The total increase in SR above baseline throughout exercise was greater during INT-25% (4,441 ± 516 s-1) and continuous (4,070 ± 407 s-1) compared with INT-15% (2,811 ± 342 s-1, P < 0.05). The %FMD increased following all exercises (INT-25%: 5.7 ± 1.2% to 8.1 ± 1.2%; INT-15%: 5.2 ± 1.2% to 7.0 ± 1.1%; continuous: 5.5 ± 1.3% to 6.8 ± 1.3%, P < 0.05 for all). The increase following INT-25% was significantly greater than INT-15% and continuous (P < 0.05 for both). Normalized FMD to shear rate area under the curve increased with intermittent exercise (INT-25%: 2.2 ± 0.2% to 3.4 ± 0.3%; INT-15%: 2.1 ± 0.2% to 3.2 ± 0.2%, P < 0.05 for both) but did not following continuous (2.1 ± 0.2% to 2.5 ± 0.1%, P = 0.06). The increase in normalized FMD with intermittent exercises were greater than continuous (P < 0.05 for both). These findings suggest intermittent fluctuations in SR during handgrip exercise may be more beneficial than sustained elevations on improving peripheral endothelial function.NEW & NOTEWORTHY Exercise-induced increases in shear rate is a well-established stimulus for improving peripheral endothelial function. This study presents novel findings that intermittent elevations in shear rate may be more effective at acutely improving endothelial function compared with continuous elevations. Despite similar increases in total shear rate during handgrip exercise intermittent elevations produced a significantly greater increase in endothelial function when compared with continuous elevations potentially indicating intermittent elevations as a more effective stimulus for acute improvements.

Births in the United States, 2022.

This report presents selected highlights from 2022 final birth data on key demographic, healthcare utilization, and infant health indicators. The number of births, general fertility rates (GFRs) (births per 1,000 females aged 15-44), age-specific birth rates (births per 1,000 women in specified age group), and cesarean delivery and preterm (less than 37 weeks of gestation) birth rates are presented. Results for 2020, 2021, and 2022 are shown for all births to describe changes in birth patterns during the COVID-19 pandemic years (1,2). Cesarean and preterm birth rates are shown for select race and Hispanic-origin groups.

The prognostic role of red cell distribution width on all-cause and cause-specific outcomes in peripheral T-cell lymphoma: a retrospective cohort study.

Readily accessible biomarkers for risk stratification in settings with limited resources are lacking. We evaluated the effect of high red distribution width-coefficient of variation (RDW-CV) values (>14%) on all-cause and lymphoma-specific mortality outcomes among 118 patients with peripheral T-cell lymphoma (PTCL) who received systemic treatment at two tertiary centers between 2010 and 2019. With a median follow-up of 45 months, patients with a high RDW-CV had a lower 4-year overall survival rate (34% vs. 45%, p = 0.015) and higher cumulative incidence of lymphoma mortality (54% vs. 34%, p = 0.007). RDW-CV >14% was associated with all-cause (adjusted Hazard Ratio [aHR] 1.98, 95% confidence interval [CI] 1.10-3.56) and lymphoma-specific mortality (aHR 2.64, 95% CI 1.32-5.29). In our study, RDW-CV emerges as an easily accessible and complementary prognostic biomarker for risk stratification among treated patients with de novo PTCL. Further research should validate the predictive role of RDW-CV in prospective cohorts.

Births: Final Data for 2021.

Objectives-This report presents 2021 data on U.S. births according to a variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.

Isolated cardiac valve involvement in smoldering adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by infection with the Human T-cell Lymphotropic Virus Type 1 (HTLV-1). Cardiac involvement in patients with ATLL is infrequent, and when it happens it is usually seen in aggressive ATLL subtypes. However, ATLL presenting as isolated cardiac valve involvement is extremely rare. To date, only three histologically proven cases of ATLL with isolated cardiac valve involvement have been reported. Herein, we describe a 61-year-old Peruvian man who presented heart failure symptoms secondary to progressive cardiac valve infiltration. The patient underwent mitral valve replacement with a mechanical prosthesis. Histopathological evaluation of the resected valve revealed leaflet thickening with a nodular appearance due to fibrous tissue containing atypical T-lymphocytes with Foxp3 expression, infiltrating all layers of the resected valve. Interestingly, tumor cells were distributed around an incidental venous malformation (i.e., cavernous hemangioma). Postoperative evaluation demonstrated positive serology for HTLV-1, and a diagnosis of ATLL was established. Postoperative positron emission tomography/computed tomography did not show lesions outside the heart and cell blood counts were within normal range with low level of circulating CD4+ CD25+ lymphoma cell counts (7%); therefore, patient's disease was considered as smoldering ATLL and a "watch and wait" strategy was pursued. Currently, the patient is alive with no progression of disease after 18 months from diagnosis. Isolated cardiac valve involvement by ATLL should be considered in the differential diagnosis of HTLV-1 carriers with progressive heart failure, even when systemic lymphoma involvement is absent or not apparent.

Non-Hodgkin lymphoma treatment in middle-income countries in Latin America: perspective of the Latin American Study Group of Lymphoproliferative Disorders [Grupo de Estudio de Linfoproliferativos de Latino América (GELL)].

INTRODUCTION: Non-Hodgkin lymphomas (NHL) are the most frequently recognized entities among lymphoproliferative syndromes and rank fifth among neoplasms not associated with gender. There is scarce information on the clinical characteristics of the most frequent NHL, and no data on treatment regimens and their outcomes in Latin America. Although many factors affect a patient's possibilities of receiving treatment, the annual income per person/country is pivotal in Latin America. AIM: We present the clinical characteristics, risk groups, and treatment regimens of the three most frequent lymphoma subtypes in Latin America [diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and peripheral T-cell lymphoma (PTCL)], based on the data collected by the largest study group of lymphoproliferative diseases in Latin America: The Latin American Study Group of Lymphoproliferative Disease [Grupo de Estudio de Linfoproliferativos de Latino America (GELL)]. OUTCOMES: The most frequent treatment regimen for B-cell lymphomas is immunochemotherapy (R-CHOP ≥70%), and CHOP for PTCL. Survival is similar to that reported by industrialized nations. We have no solid data on the results of treatment with salvage regimens nor stem cell transplantation in refractory/ relapsed NHL. CONCLUSION: In Latin America, the same treatment regimens are used as in highly developed countries, although we lack the necessary technology to apply CAR T-cell therapies or a network of trials sponsored by the pharmaceutical industry.

Eight weeks of inorganic nitrate/nitrite supplementation improves aerobic exercise capacity and the gas exchange threshold in patients with type 2 diabetes.

Patients with type 2 diabetes mellitus (T2DM) have reduced exercise capacity, indexed by lower maximal oxygen consumption (V̇o2max) and achievement of the gas exchange threshold (GET) at a lower % V̇o2max. The ubiquitous signaling molecule nitric oxide (NO) plays a multifaceted role during exercise and, as patients with T2DM have poor endogenous NO production, we investigated if inorganic nitrate/nitrite supplementation (an exogenous source of NO) improves exercise capacity in patients with T2DM. Thirty-six patients with T2DM (10F, 59 ± 9 yr, 32.0 ± 5.1 kg/m2, HbA1c = 7.4 ± 1.4%) consumed beetroot juice containing either inorganic nitrate/nitrite (4.03 mmol/0.29 mmol) or a placebo (0.8 mmol/0.00 mmol) for 8 wk. A maximal exercise test was completed before and after both interventions. V̇o2max was determined by averaging 15-s data, whereas the GET was identified using the V-slope method and breath-by-breath data. Inorganic nitrate/nitrite increased both absolute (1.96 ± 0.67 to 2.07 ± 0.75 L/min) and relative (20.7 ± 7.0 to 21.9 ± 7.4 mL/kg/min, P < 0.05 for both) V̇o2max, whereas no changes were observed following placebo (1.94 ± 0.40 to 1.90 ± 0.39 L/min, P = 0.33; 20.0 ± 4.2 to 19.7 ± 4.6 mL/kg/min, P = 0.39). Maximal workload was also increased following inorganic nitrate/nitrite supplementation (134 ± 47 to 140 ± 51 W, P < 0.05) but not placebo (138 ± 32 to 138 ± 32 W, P = 0.98). V̇o2 at the GET (1.11 ± 0.27 to 1.27 ± 0.38L/min) and the %V̇o2max in which GET occurred (56 ± 8 to 61 ± 7%, P < 0.05 for both) increased following inorganic nitrate/nitrite supplementation but not placebo (1.10 ± 0.23 to 1.08 ± 0.21 L/min, P = 0.60; 57 ± 9 to 57 ± 8%, P = 0.90) although the workload at GET did not achieve statistical significance (group-by-time P = 0.06). Combined inorganic nitrate/nitrite consumption improves exercise capacity, maximal workload, and promotes a rightward shift in the GET in patients with T2DM. This manuscript reports data from a registered Clinical Trial at ClinicalTrials.gov ID: NCT02804932.NEW & NOTEWORTHY We report that increasing nitric oxide bioavailability via 8 wk of inorganic nitrate/nitrite supplementation improves maximal aerobic exercise capacity in patients with type 2 diabetes mellitus. Similarly, we observed a rightward shift in the gas exchange threshold. Taken together, these data indicate inorganic nitrate/nitrite may serve as a means to improve fitness in patients with type 2 diabetes mellitus.

Hypoxia offsets the decline in brachial artery flow-mediated dilation after acute inactivity.

Intermittent (IH), as opposed to continuous hypoxia (CH), is thought to have beneficial effects on cardiovascular function and health. In the present study, we examined the acute effects of IH and CH (∼80% pulse oxygen saturation via 10% oxygen tank) on peripheral vascular function. Brachial artery flow-mediated dilation (FMD) was used to assess vascular function in 12 young adults (23 ± 5 yr; 8 M/4 F) before and after 50 min of IH (5 cycles; 4-min normoxia/6-min hypoxia per cycle), CH (20-min normoxia followed by 30-min hypoxia), or time control (50-min normoxia) interventions. Brachial artery diameter and velocity were measured using Doppler ultrasound to assess blood flow and shear rate. The total change in shear rate was greater during IH (634 ± 1,073·s-1, P < 0.05) and CH (321 ± 833·s-1, P = 0.05) than during time control (-412 ± 789·s-1). %FMD was reduced following time control (7.4 ± 1.2 to 5.9 ± 1.1%, P < 0.05) but was maintained following both hypoxia trials (IH: 7.2 ± 1.5 to 7.5 ± 1.5%, P = 0.52; CH: 6.9 ± 1.6 to 6.8 ± 1.4%, P = 0.73). Normalized %FMD for shear rate area under the curve (%FMDSRAUC) was reduced following the time control trial (4.2 ± 1.4 to 3.7 ± 0.9%, P < 0.05) with no change observed with CH (4.0 ± 1.5 to 3.9 ± 1.4%, P = 0.71). However, %FMDSRAUC increased with IH (3.8 ± 1.1 to 4.5 ± 1.5%, P < 0.05). Our data suggest that acute exposure to hypoxia (both intermittently and continuously) offsets the decline in vascular function after brief inactivity. The potential beneficial effect of hypoxia on peripheral vascular function observed in the current study may be associated with enhanced brachial artery shear in response to the hypoxic challenge.

Births in the United States, 2021.

This report presents selected highlights from 2021 final birth data on key demographic, healthcare use, and infant health indicators. The number of births, general fertility rates (GFRs) (births per 1,000 females aged 15-44), age-specific birth rates (births per 1,000 females in specified age group), vaginal birth after cesarean (VBAC) delivery rates, and preterm (less than 37 weeks of gestation) birth rates are presented. Results for 2019, 2020, and 2021 are shown for all births to provide context for changes in birth patterns noted during 2020, the first year of the COVID-19 pandemic (1,2). VBAC and preterm birth rates are shown for the three largest race and Hispanic-origin groups: non-Hispanic White, non-Hispanic Black, and Hispanic.

Treatment and Survival Outcomes of Waldenstrom Macroglobulinemia in Latin American Patients: A Multinational Retrospective Cohort Study.

PURPOSE: Waldenstrom Macroglobulinemia (WM) is a rare lymphoma with distinct clinical features, and data from Latin American patients are lacking. Therefore, we aim to investigate the clinical, therapy, and outcome patterns of WM in Latin America. METHODS: We retrospectively analyzed patients with WM diagnosed between 1991 and 2019 from 24 centers in seven Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 159 cases (median age 67 years, male 62%). Most patients (95%) were symptomatic at diagnosis. The International Prognostic Scoring System for WM (IPSSWM) at diagnosis was available in 141 (89%) patients (high-risk 40%, intermediate-risk 37%, and low-risk 23%). Twenty-seven (17%) patients were tested for MYD88L265P, with 89% (n = 24 of 27) carrying the mutation. First-line and second-line therapies were administered to 142 (89%) and 53 (33%) patients, respectively. Chemoimmunotherapy was the most commonly used first-line (66%) and second-line (45%) approach; only 18 (11%) patients received ibrutinib. With a median follow-up of 69 months, the 5-year OS rate was 81%. In treated patients, the 5-year OS and PFS rates were 78% and 59%, respectively. High-risk IPSSWM at treatment initiation was an independent risk factor for OS (adjusted hazard ratio: 4.73, 95% CI, 1.67 to 13.41, P = .003) and PFS (adjusted hazard ratio: 2.43, 95% CI, 1.31 to 4.50, P = .005). CONCLUSION: In Latin America, the management of WM is heterogeneous, with limited access to molecular testing and novel agents. However, outcomes were similar to those reported internationally. We validated the IPSSWM score as a prognostic factor for OS and PFS. There is an unmet need to improve access to recommended diagnostic approaches and therapies in Latin America.

Impact of Interrepetition Rest on Muscle Blood Flow and Exercise Tolerance during Resistance Exercise.

Background and Objectives: Muscle blood flow is impeded during resistance exercise contractions, but immediately increases during recovery. The purpose of this study was to determine the impact of brief bouts of rest (2 s) between repetitions of resistance exercise on muscle blood flow and exercise tolerance. Materials and Methods: Ten healthy young adults performed single-leg knee extension resistance exercises with no rest between repetitions (i.e., continuous) and with 2 s of rest between each repetition (i.e., intermittent). Exercise tolerance was measured as the maximal power that could be sustained for 3 min (PSUS) and as the maximum number of repetitions (Reps80%) that could be performed at 80% one-repetition maximum (1RM). The leg blood flow, muscle oxygenation of the vastus lateralis and mean arterial pressure (MAP) were measured during various exercise trials. Alpha was set to p ≤ 0.05. Results: Leg blood flow was significantly greater, while vascular resistance and MAP were significantly less during intermittent compared with continuous resistance exercise at the same power outputs (p < 0.01). PSUS was significantly greater during intermittent than continuous resistance exercise (29.5 ± 2.1 vs. 21.7 ± 1.2 W, p = 0.01). Reps80% was also significantly greater during intermittent compared with continuous resistance exercise (26.5 ± 5.3 vs. 16.8 ± 2.1 repetitions, respectively; p = 0.02), potentially due to increased leg blood flow and muscle oxygen saturation during intermittent resistance exercise (p < 0.05). Conclusions: In conclusion, a brief rest between repetitions of resistance exercise effectively decreased vascular resistance, increased blood flow to the exercising muscle, and increased exercise tolerance to resistance exercise.

Sphingolipids and Lymphomas: A Double-Edged Sword.

Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical targets might be hiding within these pathways. Many comprehensive reviews describing their role in cancer exist, but because most research has been conducted in solid malignancies, evidence in lymphomagenesis is somewhat limited. In this review, we summarize key aspects of sphingolipid biochemistry and discuss their known impact in cancer biology, with a particular focus on lymphomas and possible therapeutical strategies against them.