VO2peak is a key health benefit of aerobic exercise; however, chronic hyperglycemia is associated with persistently low VO2peak due to an impaired adaptive response to training. Here, we tested whether reducing blood glucose with a low-carbohydrate/high-fat “ketogenic” diet could restore aerobic exercise adaptation in a mouse model of hyperglycemia. Hyperglycemia was induced by streptozotocin (STZ) and mice were stratified to standard chow (STZ-CHOW), or a ketogenic diet (STZ-KETO), which rapidly normalized blood glucose. After aerobic exercise training, improvements in VO2peak were blunted in STZ-CHOW, but exercise response was restored in STZ-KETO. Improved VO2peak in STZ-KETO was associated with enhanced aerobic remodeling of skeletal muscle, including a more oxidative fiber-type and increased capillary density, along with restoration of circulating angiogenic markers. Moreover, KETO induced exercise-independent effects on muscle mitochondrial remodeling and mitochondrial dynamics, significantly increasing fatty acid oxidation. Our results identify a ketogenic diet as a potential therapy to improve aerobic exercise response in the growing population with hyperglycemia due to diabetes and other metabolic conditions.

INTRODUCTION:A bout of vigorous endurance exercise transiently activates Toll-like receptor 4 (TLR4) and reduces TLR4 protein expressed on peripheral blood mononuclear cells (PBMCs). Endurance training, on the other hand, reduces TLR4-mediated signaling and minimizes the physiological stress imposed by exercise. Less is known about what occurs in skeletal muscle regarding TLR4 regulation and signaling. Therefore, this study aimed to investigate the regulation of TLR4 expressed in different tissue types (PBMCs and skeletal muscle samples) between endurance-trained and untrained men following vigorous endurance exercise and determine the effect of training status on cytokine responses associated with TLR4 activation. METHODS:Endurance-trained ( n = 7) and untrained ( n = 5) men cycled for 1 h at their respiratory compensation point, with blood and skeletal muscle samples collected pre- and 3 h post-exercise. RESULTS:In response to vigorous exercise, untrained men experienced a decrease in inhibitor of κBα (IκBα) protein (suggesting IκB degradation and the activation of TLR4-associated transcription factor NF-κB) and TLR4 protein levels, along with a simultaneous increase in TLR4 mRNA expression in both skeletal muscle and PBMCs. Moreover, this exercise session led to elevated levels of circulating interleukin-6, tumor necrosis factor-α, and interleukin-1β. Collectively, these results suggest a heightened TLR4-mediated signaling pathway in untrained men. However, no changes in these targets were observed in endurance-trained men, possibly indicating a potential mechanism by which regular endurance training blunts systemic inflammation. CONCLUSIONS:These findings highlight the potential of endurance training to mitigate TLR4-mediated signaling, such as systemic inflammation, and shed light on the effects of exercise on TLR4 expression in PBMCs and skeletal muscle.

Objective:Even though the COVID-19 emergency has concluded, its consequences are still relevant. Recent evidence suggests that a significant proportion of individuals experience persistent symptoms long after the initial infection has resolved, classified as "Long COVID" condition. Fear of COVID-19 increases anxiety and stress levels in healthy individuals and exacerbates the symptoms of those with pre-existing psychiatric disorders; therefore understanding the impact of the pandemic on psychiatric disorders remains of utmost importance. The present study aimed at assessing the prevalence and predictive factors of fear of COVID-19 in a sample of patients with different psychiatric conditions. Method:A sample of 269 psychiatric patients were recruited from two different tertiary clinics in Italy and assessed with the Fear of COVID-19 Scale (FCV-19S). In order to compare patients with a significant fear of COVID-19 or without (Fear+ vs. Fear-) and to identify the main features in terms of clinical dimension, exploratory and predictive analysis were performed. Results:Female gender, age at illness onset, and insight levels emerged as positive predictors of FCV-19S. Conversely, current substance abuse emerged as a negative predictor of fear levels. Moreover, significantly lower FCV-19S scores were observed in patients with a diagnosis of schizophrenia spectrum disorders. Conclusions:Specific sociodemographic and clinical factors predicted higher levels of fear of COVID-19 in psychiatric patients. Further studies are warranted to determine the potential long-term consequences of the COVID-19 impact on mental health.

Muscle mass is balanced between hypertrophy and atrophy by cellular processes, including activation of the protein kinase B-mechanistic target of rapamycin (Akt-mTOR) signaling cascade. Stressors apart from exercise and nutrition, such as heat stress, can stimulate the heat shock protein A (HSPA) and C (HSPC) families alongside hypertrophic signaling factors and muscle growth. The effects of heat stress on HSP expression and Akt-mTOR activation in human skeletal muscle and their magnitude of activation compared with known hypertrophic stimuli are unclear. Here, we show a single session of whole body heat stress following resistance exercise increases the expression of HSPA and activation of the Akt-mTOR cascade in skeletal muscle compared with resistance exercise in a healthy, resistance-trained population. Heat stress alone may also exert similar effects, though the responses are notably variable and require further investigation. In addition, acute heat stress in C2C12 muscle cells enhanced myotube growth and myogenic fusion, albeit to a lesser degree than growth factor-mediated hypertrophy. Though the mechanisms by which heat stress stimulates hypertrophy-related signaling and the potential mechanistic role of HSPs remain unclear, these findings provide additional evidence implicating heat stress as a novel growth stimulus when combined with resistance exercise in human skeletal muscle and alone in isolated murine muscle cells. We believe these findings will help drive further applied and mechanistic investigation into how heat stress influences muscular hypertrophy and atrophy. NEW & NOTEWORTHY We show that acute resistance exercise followed by whole body heat stress increases the expression of HSPA and increases activation of the Akt-mTOR cascade in a physically active and resistance-trained population.

Sugarcane cutters are vulnerable to extreme heat and are at risk for heat-related illness and chronic kidney disease, potentially due to high heat strain. We performed a comprehensive assessment of the physiological demands of sugarcane cutters via measurements of metabolic, thermal, and cardiovascular responses. In addition, we assessed cross-shift changes in markers of kidney function. Nine male sugarcane cutters were monitored while working during the spring harvest season in Brazil. Core temperature (Tcore) and heart rate (HR) were continuously recorded, and oxygen consumption was measured during the work shift. Urine and blood samples were collected pre- and postwork shifts. Total sweat loss was calculated using body weight changes and adjusting for water ingestion and urine output. A wet-bulb globe temperature (WBGT) station was used to monitor environmental heat stress. WBGT was ≥30°C on 7 of the 8 study days. Mean and peak Tcore during the work shift were 37.96 ± 0.47°C and 38.60 ± 0.41°C, respectively, with all participants surpassing a Tcore of 38°C. Mean and peak HR during the work shift were 137 ± 14 and 164 ± 11 beats/min, respectively. Percent of maximal oxygen consumption was, on average, 53 ± 11%. Workers had a total sweat loss of 7.63 ± 2.31 L and ingested 6.04 ± 1.95 L of fluid. Kidney function (estimated glomerular filtration rate) was reduced from pre- to postwork shift (Δ -20 ± 18 mL·min·1.73 m2). We demonstrated that sugarcane cutters performing prolonged work during a period of high environmental heat stress display high levels of heat strain, high water turnover, and reduced kidney function.NEW & NOTEWORTHY We demonstrate that a shift of sugarcane cutting performed outdoors during the spring harvest season results in a high level of heat strain. In fact, all the studied workers sustained core temperatures above 38°C and heart rates above 75% of the measured maximum heart rate. Additionally, workers displayed a high water turnover with sweat loss close to 10% of their body weight. Finally, we report elevated muscle damage and reductions in kidney function following the work shift.

Excessive Toll-like receptor 4 (TLR4) activation causes muscle atrophy. Muscle contractions can limit TLR4 activation on immune cells, but its impact on TLR4 expressed on skeletal muscle cells remains unclear. Here, we demonstrate in C2C12 myotubes for the first time that stimulated myotube contractions reduce membrane-bound TLR4 and increase soluble TLR4, preventing TLR4-mediated signaling and myotube atrophy. Further analyses revealed soluble TLR4 independently prevents myotube atrophy, supporting a potential therapeutic role in combating TLR4-mediated atrophy.

Treatment discontinuation is a major challenge in routine clinical settings. Despite poor adherence to antipsychotic medication, long acting injectable (LAI) formulations are an underutilized option in psychotic disorders. Recently, an earlier and broader use of LAIs has been emphasized. However, few studies have evaluated the factors associated with LAI antipsychotic discontinuation in ordinary clinical practice. The main purpose of the present study was, therefore, to identify the factors associated with LAI discontinuation in a real-world setting. Patients in treatment with LAI antipsychotics were recruited. A Cox regression analysis was applied considering a 12-month follow-up period. Moreover, a Kaplan-Meier survival analysis was applied to compare the single treatment LAI antipsychotic groups in terms of time to discontinuation. Our analysis showed an LAI discontinuation rate at 12 months, corresponding to 28.8%, with olanzapine and aripiprazole having a longer time to discontinuation compared to zuclopenthixol. The results of the present study can help clinicians with their choice of LAI antipsychotic according to patients' characteristics and in a context of precision medicine. Increasing knowledge about factors affecting discontinuation of LAI antipsychotics can improve the prescribing practices of these compounds. Individualized approaches may ameliorate long-term patients' treatment adherence, thus preventing the long-term disability caused by psychotic disorders.

Chronic hyperglycemia is associated with low response to aerobic exercise training in rodent models and humans, including reduced aerobic exercise capacity and impaired oxidative remodeling in skeletal muscle. Here, we investigated whether glucose lowering with the sodium–glucose cotransporter 2 inhibitor (SGLT2i), canagliflozin (Cana; 30 mg/kg/day), could restore exercise training response in a model of hyperglycemia (low-dose streptozotocin [STZ]). Cana effectively prevented increased blood glucose in STZ-treated mice. After 6 weeks of voluntary wheel running, Cana-treated mice displayed improvements in aerobic exercise capacity, higher capillary density in striated muscle, and a more oxidative fiber-type in skeletal muscle. In contrast, these responses were blunted or absent in STZ-treated mice. Recent work implicates glucose-induced accumulation of skeletal muscle extracellular matrix (ECM) and hyperactivation of c-Jun N-terminal kinase (JNK)/SMAD2 mechanical signaling as potential mechanisms underlying poor exercise response. In line with this, muscle ECM accretion was prevented by Cana in STZ-treated mice. JNK/SMAD2 signaling with acute exercise was twofold higher in STZ compared with control but was normalized by Cana. In human participants, ECM accumulation was associated with increased JNK signaling, low VO2peak, and impaired metabolic health (oral glucose tolerance test–derived insulin sensitivity). These data demonstrate that hyperglycemia-associated impairments in exercise adaptation can be ameliorated by cotherapy with SGLT2i.

New Findings What is the central question of this study? What is the effect of hypobaric hypoxia on markers of exercise‐induced intestinal injury and symptoms of gastrointestinal (GI) distress? What is the main finding and its importance? Exercise performed at 4300 m of simulated altitude increased intestinal fatty acid binding protein (I‐FABP), claudin‐3 (CLDN‐3) and lipopolysaccharide binding protein (LBP), which together suggest that exercise‐induced intestinal injury may be aggravated by concurrent hypoxic exposure. Increases in I‐FABP, LBP and CLDN‐3 were correlated to exercise‐induced GI symptoms, providing some evidence of a link between intestinal barrier injury and symptoms of GI distress. AbstractWe sought to determine the effect of exercise in hypobaric hypoxia on markers of intestinal injury and gastrointestinal (GI) symptoms. Using a randomized and counterbalanced design, nine males completed two experimental trials: one at local altitude of 1585 m (NORM) and one at 4300 m of simulated hypobaric hypoxia (HYP). Participants performed 60 min of cycling at a workload that elicited 65% of their NORM . GI symptoms were assessed before and every 15 min during exercise. Pre‐ and post‐exercise blood samples were assessed for intestinal fatty acid binding protein (I‐FABP), claudin‐3 (CLDN‐3) and lipopolysaccharide binding protein (LBP). All participants reported at least one GI symptom in HYP compared to just one participant in NORM. I‐FABP significantly increased from pre‐ to post‐exercise in HYP (708 ± 191 to 1215 ± 518 pg ml−1; P = 0.011, d = 1.10) but not NORM (759 ± 224 to 828 ± 288 pg ml−1; P > 0.99, d = 0.27). CLDN‐3 significantly increased from pre‐ to post‐exercise in HYP (13.8 ± 0.9 to 15.3 ± 1.2 ng ml−1; P = 0.003, d = 1.19) but not NORM (13.7 ± 1.8 to 14.2 ± 1.6 ng ml−1; P = 0.435, d = 0.45). LBP significantly increased from pre‐ to post‐exercise in HYP (10.8 ± 1.2 to 13.9 ± 2.8 μg ml−1; P = 0.006, d = 1.12) but not NORM (11.3 ± 1.1 to 11.7 ± 0.9 μg ml−1; P > 0.99, d = 0.32). I‐FABP (d = 0.85), CLDN‐3 (d = 0.95) and LBP (d = 0.69) were all significantly higher post‐exercise in HYP compared to NORM (P ≤ 0.05). Overall GI discomfort was significantly correlated to ΔI‐FABP (r = 0.71), ΔCLDN‐3 (r = 0.70) and ΔLBP (r = 0.86). These data indicate that cycling exercise performed in hypobaric hypoxia can cause intestinal injury, which might cause some commonly reported GI symptoms.

Evidence suggests that hyperglycemia can blunt improvements in aerobic capacity (VO2peak) with exercise training. Accordingly, people with diabetes have lower VO2peak than normoglycemic controls, increasing their risk of complications and mortality. We hypothesized that reducing blood glucose levels with a dietary intervention would restore exercise training-induced improvements in VO2peak in hyperglycemic mice. To test this, we induced hyperglycemia in male CD-1 mice with streptozotocin (STZ) , which increased random blood glucose to 220 ± 31 mg/dL on a standard diet (80% carbohydrate, 10% fat & protein) . A subset of STZ mice was fed a ketogenic (KETO) diet consisting of 90% fat and 10% protein, which reduced blood glucose to 177 ± 26 mg/dL. Eight weeks after starting the dietary intervention, STZ and KETO mice underwent voluntary wheel running or remained sedentary for 8 weeks. Exercise training improved VO2peak and time to exhaustion during a graded exercise test in KETO-fed mice while no significant improvement was observed in STZ mice. Trained STZ and KETO mice had similar fat and lean mass, indicating improved VO2peak in trained KETO mice was independent of body composition. Our data demonstrate that reducing blood glucose using a carbohydrate-restricted diet may restore training-induced improvements in exercise capacity that are prevented by hyperglycemia. Disclosure R.C.Nava: None. E.M.Cooney: None. S.J.Lessard: None. Funding National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) RDK124258 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) T32 Postdoctoral Training Fellowship 5T32DK007260-45

Our aim was to determine the effect of repeated sprint exercise in hypoxia on HIF-1 and HIF-1-regulated genes involved in glycolysis, mitochondrial turnover and oxygen transport. We also determined whether genes upregulated by exercise in hypoxia were dependent on the activation of HIF-1 in an in vitro model of exercise in hypoxia. Eight endurance athletes performed bouts of repeated sprint exercise in control and hypoxic conditions. Skeletal muscle was sampled pre, post and 3 h post-exercise. HIF-1α protein and HIF1A, PDK1, GLUT4, VEGFA, BNIP3, PINK1 and PGC1A mRNA were measured. C2C12 myotubes were exposed to hypoxia and muscle contraction following treatment with a HIF-1α inhibitor to determine whether hypoxia-sensitive gene expression was dependent on HIF-1α. Sprint exercise in hypoxia increased HIF-1α protein expression immediately post-exercise [fold change (FC) = 3.5 ± 2.0]. Gene expression of PDK1 (FC = 2.1 ± 1.2), BNIP3 (FC = 2.4 ± 1.4) and VEGFA (FC = 2.7 ± 1.7) increased 3 h post-exercise in hypoxia but not control. PGC1A mRNA increased 3 h post-exercise in control (FC = 5.16) and hypoxia (FC = 5.7 ± 4.1) but there was no difference between the trials. Results from the in vitro experiment showed that hypoxia plus contraction also increased PDK1, BNIP3, and VEGFA gene expression. These responses were inhibited when HIF-1 protein activity was suppressed. Repeated sprint exercise in hypoxia upregulates some genes involved in glycolytic metabolism, mitochondrial turnover, and oxygen transport. HIF-1α is necessary for the expression of these genes in skeletal muscle cells.

Vaccination is widely considered the most effective preventative strategy to protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. An individual’s exercise habits, and physical fitness have been shown to impact the immune response following vaccination using traditional vaccine platforms, but their effects are not well characterized following administration of newer vaccination technology (mRNA vaccines). We investigated these effects on the magnitude of antibody responses following SARS-CoV-2 mRNA vaccination while accounting for known covariates (age, sex, time since vaccination, and the type of vaccine administered). Adults of varying fitness levels (18–65 years; N = 50) who had received either the Moderna or Pfizer SARS-CoV-2 mRNA vaccine between 2 weeks and 6 months prior, completed health history and physical activity questionnaires, had their blood drawn, body composition, cardiorespiratory fitness, and strength assessed. Multiple linear regressions assessed the effect of percent body fat, hand grip strength, cardiorespiratory fitness, and physical activity levels on the magnitude of receptor binding domain protein (RBD) and spike protein subunit 1 (S1) and 2 (S2) while accounting for known covariates. Body fat percentage was inversely associated with the magnitude of S1 ( p = 0.006, β = − 366.56), RBD ( p = 0.003, β = − 249.30), and S2 ( p = 0.106, β = − 190.08) antibodies present in the serum following SARS-CoV-2 mRNA vaccination. Given the increasing number of infections, variants, and the known waning effects of vaccination, future mRNA vaccinations such as boosters are encouraged to sustain immunity; reducing excess body fat may improve the efficacy of these vaccinations.

We investigated the effect of cardiorespiratory fitness (CRF) on the probability of achieving the verification criterion to confirm that VO2max was obtained in a sample of middle-aged to older adults. Data from twelve men and nine women (60.7±8.5 years, VO2max: 34.8±9.4 mL/kg/min) were used for analysis. Participants had their VO2max measured via a maximal graded exercise test and confirmed using a verification bout on a cycle ergometer. Logistic regression was used to evaluate the effect of CRF (VO2max) on the probability a participant would successfully achieve the verification criterion. Odds ratios are reported to quantify the effect size. No statistically significant relationship was observed between CRF and achieving the verification criterion (β=.081, SE=.0619, Wald=1.420, p=.156). Estimated odds ratio for the effect of CRF on the verification criterion indicated an increase of 8% [Exp(β)=1.08, 95% CI (0.96, 1.22)] in the probability of achieving the verification criterion given a one unit increase in VO2max. Each 1 mL/kg/min increase in VO2max results in an 8% increase in the chance that an individual achieves the verification criterion confirming that VO2max was obtained. Therefore, CRF is likely of practical significance and should be considered when deciding to use a verification trial.

The purpose of the study was to investigate the combined effect of downhill running and heat stress on muscle damage, as well as on heat strain and kidney stress during subsequent running in the heat. In a randomized cross-over study, ten non-heat-acclimated, physically active males completed downhill running in temperate (EIMD in Temp) and hot (EIMD in Hot) conditions followed by an exercise-heat stress (HS) test after 3-h seated rest. Blood and urine samples were collected immediately pre- and post-EIMD and HS, and 24 h post-EIMD (post-24 h). Core temperature and thermal sensation were measured to evaluate heat strain. Serum creatine kinase (CK), maximal voluntary isometric contraction of the quadriceps (MVC) and perceived muscle soreness were measured to evaluate muscle damage. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels were measured to indicate acute kidney stress. CK, MVC and perceived soreness were not different between conditions at any timepoints. In the EIMD in Hot condition, urinary NGAL was significantly elevated from pre- to post-HS (pre-HS: 6.56 {1.53–12.24} ng/min, post-HS: 13.72 {7.67–21.46} ng/min, p = 0.034). Such elevation of NGAL or KIM-1 was not found in the EIMD in Temp condition. As compared with downhill running in a temperate environment, downhill running in a hot environment does not appear to aggravate muscle damage. However, elevated NGAL levels following EIMD in a hot environment suggest such exercise may increase risk of mild acute kidney injury during subsequent endurance exercise in the heat.

The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant, promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients—already receiving intranasal ESK but showing an instable course—who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.

Implementing permissive dehydration (DEH) during short-term heat acclimation (HA) may accelerate adaptations to the heat. However, HA with DEH may augment risk for acute kidney injury (AKI). This study investigated the effect of HA with permissive DEH on time-trial performance and markers of AKI. Fourteen moderately trained men (age and VO2max = 25 ± 0.5 yr and 51.6 ± 1.8 mL.kg−1.min−1) were randomly assigned to DEH or euhydration (EUH). Time-trial performance and VO2max were assessed in a temperate environment before and after 7 d of HA. Heat acclimation consisted of 90 min of cycling in an environmental chamber (40 °C, 35% RH). Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were assessed pre- and post-exercise on day 1 and day 7 of HA. Following HA, VO2max did not change in either group (p = 0.099); however, time-trial performance significantly improved (3%, p < 0.01) with no difference between groups (p = 0.485). Compared to pre-exercise, NGAL was not significantly different following day 1 and 7 of HA (p = 0.113) with no difference between groups (p = 0.667). There was a significant increase in KIM-1 following day 1 and 7 of HA (p = 0.002) with no difference between groups (p = 0.307). Heat acclimation paired with permissive DEH does not amplify improvements in VO2max or time-trial performance in a temperate environment versus EUH and does not increase markers of AKI.

OBJECTIVE:To assess the long-term impact of early COVID-19 lockdown phase on emergency psychiatric consultations in two psychiatric emergency departments located in Italy. METHODS:We conducted a cross-sectional study comparing the number and characteristics of emergency psychiatric consultations during post-lockdown with respect to the lockdown period. Sociodemographic data, clinical characteristics, referred symptoms, diagnosis, information on multiple psychiatric consultations and hospitalisation were collected. RESULTS:A rise of almost 60% in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed. Emergency psychiatric consultations in the post-lockdown period were associated with lower rates of cannabis (aOR = 0.42, p = 0.011) and cocaine use (aOR = 0.39, p = 0.011). Despite a lower occurrence of two or more psychiatric consultations was observed during post-lockdown phase (aOR = 0.44, p = 0.008), subjects who had anxiety disorders (aOR = 3.91, p = 0.000) and substance intoxication or withdrawal (aOR = 6.89, p = 0.000) were more likely to present to emergency psychiatric consultations during post-lockdown period compared to the lockdown one. CONCLUSIONS:Substance intoxication or withdrawal and anxiety disorders increased after the COVID-19 lockdown. The findings of this study suggest to address more economic and professional sources to the mental health areas potentially more affected by the different phases of a pandemic.KEYPOINTSCOVID-19 pandemic and lockdown measures increased mental health unmet needs.According to our findings, a rise in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed.Patients with substance intoxication or withdrawal syndrome and anxiety disorders were significantly more likely to present to emergency psychiatric consultations during post-lockdown.Lockdown was associated with higher rates of both cannabis and cocaine use disorders as well as of multiple psychiatric consultations.Alternative strategies to improve mental health such as e-health technologies should be promoted.

Background Major depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive–compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration. The etiology of OCD has not yet been fully elucidated but there is a growing evidence that glutamate signaling dysfunction in the cortico-striatal–thalamo-cortical circuitry plays an essential role. This case report exemplifies possible clinical effects of esketamine on both depressive and OCD symptoms. Case presentation We present the case of a 39-year-old man suffering from TRD. During the first evaluation at our clinic, he also reported the presence of OCD spectrum symptoms, causing him to perform time-consuming mental rituals due to pathological doubts regarding the relationship with his wife as well as intrusive thoughts regarding his mental conditions. He underwent psychometric evaluations, therapeutic drug monitoring analysis, and pharmacogenomic tests. The overall results helped to explain patient’s treatment-resistance. Moreover, we observed a significant reduction in both depressive and OCD symptoms after administration of esketamine. Conclusion This case underlines the importance of pharmacogenomic tests in profiling TRD patients and confirms the possible use of esketamine in the treatment of comorbid OCD.

Autophagy is an evolutionary conserved cellular degradation system that underlies the positive effects of exercise. Currently, few human data exist investigating the autophagic response to exercise including the response to high-intensity interval training (HIIT), response in divergent tissues, and if sex differences exist. The purpose of this study was to investigate the autophagy response in skeletal muscle and peripheral blood mononuclear cells (PBMCs) following an acute bout of HIIT and moderate-intensity continuous training (MICT) with treadmill running in males and females. Using a crossover design, ten recreationally-active males (n = 5; 25.2 ± 1.1 yrs) and females (n = 5; 21.6 ± 3.6 yrs) performed a bout of MICT (60 min at 55% of max velocity [Vmax]]) and HIIT (12 bouts of 1 min at 100% Vmax and 1 min at 3 miles per hour) in a fasted state separated by ≥ 72 h. Muscle biopsy samples from the vastus lateralis and PBMCs were collected pre- and 3 h post-exercise and analyzed for differences in protein expression of LC3I, LC3II, and p62 via western blot analysis. Expression of LC3II:LC3I was significantly different from pre-exercise 3 h post-exercise in MICT in skeletal muscle (64.3 ± 47.3%; p = 0.024). A significant time effect was found for p62 3 h post-exercise compared to pre-exercise (135.23 ± 84.6%; p = 0.043) in skeletal muscle. No differences in markers of autophagy were observed in PBMCs. When sexes were analyzed separately there was a condition x time x sex interaction in LC3II (p = 0.007) and LC3II:LC3I (p = 0.043) in PBMCs. Post hoc analyses revealed a difference in LC3II pre vs. 3 h post exercise in males, but not females, in both HIIT (144.2 ± 89.7%; p = 0.024) and MICT (61.8 ± 36.1%; p = 0.043). Our findings show that HIIT results in changes in markers of autophagy and that the exercise-induced autophagy response varies in tissues and between sexes.