Anisotropic satellite galaxy quenching modulated by black hole activity.

The evolution of satellite galaxies is shaped by their constant interaction with the circumgalactic medium surrounding central galaxies, which in turn may be affected by gas and energy ejected from the central supermassive black hole1-6. The nature of such a coupling between black holes and galaxies is, however, much debated7-9 and observational evidence remains scarce10,11. Here we report an analysis of archival data on 124,163 satellite galaxies in the potential wells of 29,631 dark matter halos with masses between 1012 and 1014 solar masses. We find that quenched satellite galaxies are relatively less frequent along the minor axis of their central galaxies. This observation might appear counterintuitive given that black hole activity is expected to eject mass and energy preferentially in the direction of the minor axis of the host galaxy. We show, however, that the observed anisotropic signal results precisely from the ejective nature of black hole feedback in massive halos, as outflows powered by active galactic nuclei clear out the circumgalactic medium, reducing the ram pressure and thus preserving star formation in satellite galaxies. This interpretation is supported by the IllustrisTNG suite of cosmological numerical simulations, even though the model's sub-grid implementation of black hole feedback is effectively isotropic12.

Black-hole-regulated star formation in massive galaxies.

Supermassive black holes, with masses more than a million times that of the Sun, seem to inhabit the centres of all massive galaxies. Cosmologically motivated theories of galaxy formation require feedback from these supermassive black holes to regulate star formation. In the absence of such feedback, state-of-the-art numerical simulations fail to reproduce the number density and properties of massive galaxies in the local Universe. There is, however, no observational evidence of this strongly coupled coevolution between supermassive black holes and star formation, impeding our understanding of baryonic processes within galaxies. Here we report that the star formation histories of nearby massive galaxies, as measured from their integrated optical spectra, depend on the mass of the central supermassive black hole. Our results indicate that the black-hole mass scales with the gas cooling rate in the early Universe. The subsequent quenching of star formation takes place earlier and more efficiently in galaxies that host higher-mass central black holes. The observed relation between black-hole mass and star formation efficiency applies to all generations of stars formed throughout the life of a galaxy, revealing a continuous interplay between black-hole activity and baryon cooling.

Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS.

Vascular aging is associated with the development of cardiovascular complications, in which endothelial cell senescence (ES) may play a critical role. Nitric oxide (NO) prevents human ES through inhibition of oxidative stress, and inflammatory signaling by mechanisms yet to be elucidated. Endothelial cells undergo an irreversible growth arrest and alter their functional state after a finite number of divisions, a phenomenon called replicative senescence. We assessed the contribution of NO during replicative senescence of human aortic (HAEC) and coronary (CAEC) endothelial cells, in which accumulation of the senescence marker SA-ß-Gal was quantified by ß-galactosidase staining on cultured cells. We found a negative correlation in passaged cell cultures from P0 to P12, between a reduction in NO production with increased ES and the formation of reactive oxygen (ROS) and nitrogen (ONOO-) species, indicative of oxidative and nitrosative stress. The effect of ES was evidenced by reduced expression of endothelial Nitric Oxide Synthase (eNOS), Interleukin Linked Kinase (ILK), and Heat shock protein 90 (Hsp90), alongside a significant increase in the BH2/BH4 ratio, inducing the uncoupling of eNOS, favoring the production of superoxide and peroxynitrite species, and fostering an inflammatory environment, as confirmed by the levels of Cyclophilin A (CypA) and its receptor Extracellular Matrix Metalloprotease Inducer (EMMPRIN). NO prevents ES by preventing the uncoupling of eNOS, in which oxidation of BH4, which plays a key role in eNOS producing NO, may play a critical role in launching the release of free radical species, triggering an aging-related inflammatory response.

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry.

BACKGROUND: Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. OBJECTIVES: To evaluate the response and tolerance of BV in a cohort of patients with CTCL. METHODS: We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). RESULTS: Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. CONCLUSIONS: These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.

Ultra Trail Performance is Differently Predicted by Endurance Variables in Men and Women.

The study aimed to assess the relationship between peak oxygen uptake, ventilatory thresholds and maximal fat oxidation with ultra trail male and female performance. 47 athletes (29 men and 18 women) completed a cardiopulmonary exercise test between 2 to 4 weeks before a 107-km ultra trail. Body composition was also analyzed using a bioelectrical impedance weight scale. Exploratory correlation analyses showed that peak oxygen uptake (men: r=-0.63, p=0.004; women: r=-0.85, p < 0.001), peak speed (men: r=-0.74, p < 0.001; women: r=-0.69, p=0.009), speed at first (men: r=-0.49, p=0.035; women: r=-0.76, p=0.003) and second (men: r=-0.73, p < 0.001; women: r=-0.76, p=0.003) ventilatory threshold, and maximal fat oxidation (men: r=-0.53, p=0.019; women: r=-0.59, p=0.033) were linked to race time in male and female athletes. Percentage of fat mass (men: r=0.58, p=0.010; women: r=0.62, p= 0.024) and lean body mass (men: r=-0.61, p=0.006; women: r=-0.61, p=0.026) were also associated with performance in both sexes. Subsequent multiple regression analyses revealed that peak speed and maximal fat oxidation together were able to predict 66% of male performance; while peak oxygen uptake was the only statistically significant variable explaining 69% of the variation in women's race time. These results, although exploratory in nature, suggest that ultra trail performance is differently predicted by endurance variables in men and women.

Muscle Cramping in the Marathon: Dehydration and Electrolyte Depletion vs. Muscle Damage.

ABSTRACT: Martínez-Navarro, I, Montoya-Vieco, A, Collado, E, Hernando, B, Panizo, N, and Hernando, C. Muscle Cramping in the marathon: Dehydration and electrolyte depletion vs. muscle damage. J Strength Cond Res 36(6): 1629-1635, 2022-Our aim was to compare dehydration variables, serum electrolytes, and muscle damage serum markers between runners who suffered exercise-associated muscle cramps (EAMC) and runners who did not suffer EAMC in a road marathon. We were also interested in analyzing race pacing and training background. Nighty-eight marathoners took part in the study. Subjects were subjected to a cardiopulmonary exercise test. Before and after the race, blood and urine samples were collected and body mass (BM) was measured. Immediately after the race EAMC were diagnosed. Eighty-eight runners finished the marathon, and 20 of them developed EAMC (24%) during or immediately after the race. Body mass change, post-race urine specific gravity, and serum sodium and potassium concentrations were not different between crampers and noncrampers. Conversely, runners who suffered EAMC exhibited significantly greater post-race creatine kinase (464.17 ± 220.47 vs. 383.04 ± 253.41 UI/L, p = 0.034) and lactate dehydrogenase (LDH) (362.27 ± 72.10 vs. 307.87 ± 52.42 UI/L, p = 0.002). Twenty-four hours post-race also values of both biomarkers were higher among crampers (CK: 2,438.59 ± 2,625.24 vs. 1,166.66 ± 910.71 UI/L, p = 0.014; LDH: 277.05 ± 89.74 vs. 227.07 ± 37.15 UI/L, p = 0.021). The difference in the percentage of runners who included strength conditioning in their race training approached statistical significance (EAMC: 25%, non-EAMC: 47.6%; p = 0.074). Eventually, relative speed between crampers and noncrampers only differed from the 25th km onward (p < 0.05). Therefore, runners who suffered EAMC did not exhibit a greater degree of dehydration and electrolyte depletion after the marathon but displayed significantly higher concentrations of muscle damage biomarkers.

Recovery of Inflammation, Cardiac, and Muscle Damage Biomarkers After Running a Marathon.

ABSTRACT: Bernat-Adell, MD, Collado-Boira, EJ, Moles-Julio, P, Panizo-González, N, Martínez-Navarro, I, Hernando-Fuster, B, and Hernando-Domingo, C. Recovery of inflammation, cardiac and muscle damage biomarkers after running a marathon. J Strength Cond Res 35(3): 626-632, 2021-Physical endurance sports conditions the increase of blood biomarkers responsible for the acute inflammatory response. The purpose of this study was to observe the impact of intense physical exercise on these biomarkers and detect their recovery pattern. This is an experimental study of repeated measures (pre-post marathon). The biomarkers lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity troponin T (hs-TNT), and C-reactive protein (CRP) were analyzed in a total of 86 runners, 24 hours before the marathon, immediately after finishing the race and at 24, 48, 96, and 144 postrace hours. The comparative analyses were performed using the Friedman and Wilcoxon tests. The correlations between dependent and independent variables were analyzed using Spearman correlations. The data were processed through the IBM SPSS package, version 23. Significant value was p ≤ 0.05. The LDH increased and showed significant differences (p ≤ 0.001) for all times, compared with the initial LDH value, normalizing after 192 hours (p = 0.667) (effect size [ES], r = 0.807). The CK increased and showed significant differences (p ≤ 0.001) (ES, r = 0.975) up to 96 hours afterward, normalizing after 144 hours. The hs-TNT presented an increase and showed significant differences (p ≤ 0.001) between the pre-post race times, 24 and 48 hours, normalizing after 96 hours, although it showed a new significant value at 192 hours (p ≤ 0.001) (ES, r = 0.519). The CRP increased and showed significant differences (p ≤ 0.001) between the pre-post race times, at 24, 48, 96, 144, and 192 hours after race. The recovery after alterations produced by the marathon varies according to the biomarker. Blood levels of biomarkers decrease with longer race times. Greater energy expenditure increases the blood levels of LDH, CK, and hs-TNT.

Pulmonary and Inspiratory Muscle Function Response to a Mountain Ultramarathon.

The study aimed to provide within-race data on the time course of pulmonary function during a mountain ultramarathon (MUM). Additionally, we wanted to assess possible sex differences regarding pre- to post-race change in pulmonary and inspiratory muscle function. Lastly, we were interested in evaluating whether changes in respiratory function were associated with relative running speed and due to general or specific fatigue. 47 athletes (29 males and 18 females; 41 ± 5 years) were submitted to a cardiopulmonary exercise test (CPET) before a 107-km MUM. Spirometric variables: forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC and peak expiratory flow (PEF); maximal inspiratory pressure (MIP); squat jump (SJ) and handgrip strength (HG) were assessed before and after the race. Additionally PEF was measured at three aid stations (33rd, 66th and 84th km) during the race. PEF declined from the 33rd to the 66th km (p = 0.004; d = 0.72) and from the 84th km to the finish line (p = 0.003; d = 0.90), while relative running speed dropped from the first (0-33 km) to the second (33-66 km) race section (p < 0.001; d = 1.81) and from the third (66-84 km) to the last race section (p < 0.001; d = 1.61). Post-race, a moderate reduction was noted in FVC (-13%; p < 0.001; d = 0.52), FEV1 (-19.5%; p < 0.001; d = 0.65), FEV1/FVC (-8.4%; p = 0.030; d = 0.59), PEF (-20.3%; p < 0.001; d = 0.58), MIP (-25.3%; p < 0.001; d = 0.79) and SJ (-31.6%; p < 0.001; d = 1.42). Conversely, HG did not change from pre- to post-race (-1.4%; p = 0.56; d = 0.05). PEF declined during the race in parallel with running speed drop. No sex differences were noted regarding post-race respiratory function, except that FEV1/FVC decay was significantly greater among women. The magnitude of pre- to post-race respiratory function decline was uncorrelated with relative running speed.

Immediate and 24-h post-marathon cardiac troponin T is associated with relative exercise intensity.

PURPOSE: We aimed at exploring whether cardiopulmonary fitness, echocardiographic measures and relative exercise intensity were associated with high-sensitivity cardiac troponin T (hs-TNT) rise and normalization following a marathon. METHODS: Nighty-eight participants (83 men, 15 women; 38.72 ± 3.63 years) were subjected to echocardiographic assessment and a cardiopulmonary exercise test (CPET) before the race. hs-TNT was measured before, immediately after and at 24, 48, 96, 144 and 192 h post-race. Speed and mean heart rate (HR) during the race were relativized to CPET values: peak speed (%VVMAX), peak HR (HR%MAX), speed and HR at the second ventilatory threshold (HR%VT2 and %VVT2). RESULTS: Hs-TNT increased from pre- to post-race (5.74 ± 5.29 vs. 50.4 ± 57.04 ng/L; p < 0.001), seeing values above the Upper Reference Limit (URL) in 95% of the participants. At 24 h post-race, 39% of the runners still exceeded the URL (High hs-TNT group). hs-TNT rise was correlated with marathon speed %VVT2 (r = 0.22; p = 0.042), mean HR%VT2 (r = 0.30; p = 0.007), and mean HR%MAX (r = 0.32; p = 0.004). Moreover, the High hs-TNT group performed the marathon at a higher Speed %VVT2 (88.21 ± 6.53 vs. 83.49 ± 6.54%; p = 0.002) and Speed %VVMAX (72 ± 4.25 vs. 69.40 ± 5.53%; p = 0.009). hs-TNT showed no significant associations with cardiopulmonary fitness and echocardiographic measures, except for a slight correlation with left ventricular end systolic diameter (r = 0.26; p = 0.018). CONCLUSION: Post-race hs-TNT was above the URL in barely all runners. Magnitude of hs-TNT rise was correlated with exercise mean HR; whereas, its normalization kept relationship with marathon relative speed.

Folliculocystic and collagenous hamartoma of tuberous sclerosis complex, not always a single cutaneous lesion.

Folliculocystic and collagenous hamartoma (FCCH) is a rare cutaneous manifestation characterized by the presence of single plaques studded with comedo-like openings and cysts. Although its pathophysiology is still unknown, it has generally been described in men with tuberous sclerosis complex (TSC). We report a case of a one-year-old child with two FCCH in the abdominal wall associated with TSC. In our case, a TSC2 mutation was identified.

From ED overcrowding to jail overcrowding: a cautionary tale of a Serial Inebriate Programme (SIP).

INTRODUCTION: Community-based programmes have been implemented to curtail ED use by individuals with chronic public intoxication. Among these programmes is the Serial Inebriate Programme (SIP), which aims to reduce use of ED and emergency medical services. We present the results of an evaluation of the SIP in Santa Cruz, California, including data on the participants' police and jail history, information not considered in prior analyses of SIPs. METHODS: In the present study, we used a retrospective cohort to evaluate the effectiveness of the SIP in Santa Cruz, California from 2013 to 2015. Specifically, we looked at the programme effects on participants' arrests, nights in jail, use of the local ED and ambulance services after programme adjudication. RESULTS: The median number of visits to the ED for participants before and after adjudication was reduced from 4 to 1, and participants showed a significant decrease in their number of jail bookings following adjudication (-4.5 bookings; p=0.004). However, the average number of nights in jail served by participants after adjudication was 2.1 times the average number of nights spent in jail spent before programme adjudication (58.5 vs 27.6 nights in jail for postadjudication and preadjudication groups, respectively; p=0.009). CONCLUSIONS: Our findings suggest that the Santa Cruz SIP had some impact in reducing participants' use of emergency services, but at the cost of increased jail time. The burdens of placing chronically intoxicated individuals in jail for extended periods of time are not trivial and should not be overlooked when designing and implementing a SIP.

Pancreatic panniculitis.

Pancreatic panniculitis (PP) is an infrequent manifestation of pancreatic pathology (2%). This condition has mainly been described in association with acute and chronic pancreatitis, in males aged 40-60 years with chronic alcoholism, as was the case of this patient. However, it might also be the outset manifestation of a pancreatic neoplasm.

Cardiac Damage Biomarkers and Heart Rate Variability Following a 118-Km Mountain Race: Relationship with Performance and Recovery.

This study aimed to assess the release of cardiac damage biomarkers jointly with cardiac autonomic modulation after a mountain ultramarathon. Such knowledge and the possible relationship of these markers with race time is of primary interest to establish possible recommendations upon athletes' recovery and return to training following these competitions. Forty six athletes enrolled in the Penyagolosa Trails CSP115 race (118 km and a total positive elevation of 5439 m) took part in the study. N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin T (hs-TNT) concentrations as well as linear and nonlinear heart rate variability (HRV) were evaluated before and after the race. NT-proBNP and hs-TNT significantly increased post-race; fifty percent of the finishers surpassed the Upper Reference Limit (URL) for hs-TNT while 87% exceeded the URL for NT-proBNP. Overall and vagally-mediated HRV were diminished and cardiac autonomic modulation became less complex and more predictable following the race. More pronounced vagal modulation decreases were associated with higher levels of postexertional NT-proBNP. Moreover, rise in hs-TNT and NT-proBNP was greater among faster runners, while pre-race overall and vagally-mediated HRV were correlated with finishing time. Participation in a 118-km ultratrail induces an acute release of cardiac damage biomarkers and a large alteration of cardiac autonomic modulation. Furthermore, faster runners were those who exhibited a greater rise in those cardiac damage biomarkers. In light of these findings, an appropriate recovery period after ultraendurance races appears prudent and particularly important among better performing athletes. At the same time, HRV analysis is shown as a promising tool to assess athletes' readiness to perform at their maximum level in an ultraendurance race.

Hydration Status, Executive Function, and Response to Orthostatism After a 118-km Mountain Race: Are They Interrelated?

Martínez-Navarro, I, Chiva-Bartoll, O, Hernando, B, Collado, E, Porcar, V, and Hernando, C. Hydration status, executive function and response to orthostatism after a 118-km mountain race: are they interrelated? J Strength Cond Res 32(2): 441-449, 2018-The present study aimed to explore whether blood pressure (BP) and heart rate (HR) variability (HRV) responsiveness to orthostatism, jointly with executive function (EF) performance, was diminished after an ultra-endurance mountain race. Besides, we wanted to assess whether hydration status was related to either performance or the abovementioned alterations. Fifty recreational ultra-endurance athletes participating in the Penyagolosa Trails CSP115 race (118 km and a total positive elevation of 5,439 m) were evaluated before and after the competition. The HRV and BP were measured in response to an orthostatic challenge. The EF was evaluated using the color-word interference task of the Stroop test. Body mass (BM) and urine specific gravity (USG) changes were used to assess hydration status. The HRV and BP responsiveness to orthostatism was diminished after the race. Besides, a significant BM loss of 3.51 ± 2.03% was recorded. Conversely, EF and USG showed no significant changes from prerace to postrace. Eventually, BM loss was inversely related to finishing time (r = -0.34) and postrace orthostatic HR and EF were positively associated (r = 0.60). The USG and BM loss appear to provide different insights into hydration status, and our results challenge the well-established criteria that BM losses >2% are detrimental to performance. Coaches are advised to consider athletes' performance level when interpreting their BM changes during an ultra-endurance competition. Similarly, coaches should be aware that increased vulnerability to orthostatism is a common phenomenon after ultra-endurance races, and diminished HR responsiveness to orthostatism could constitute a practical indicator of EF worsening.