Mental health and COVID-19 in a general population cohort in Spain (COVICAT study).

PURPOSE: Mental health conditions may affect outcome of COVID-19 disease, while exposure to stressors during the pandemic may impact mental health. The purpose of this study was to examine these factors in relation to ocurrence of depression and anxiety after the first outbreak in Spain. METHODS: We contacted 9515 participants from a population-based cohort study in Catalonia between May and October 2020. We drew blood samples to establish infection to the virus. Pre-pandemic mental health conditions were confirmed through Electronic Health Registries. We used the Hospital Anxiety and Depression Scale to assess severe depression and anxiety post-pandemic. Exposure to proximal, financial and wider environment stressors during the lockdown were collected. We calculated Relative Risks (RR), adjusting for individual- and contextual covariates. RESULTS: Pre-pandemic mental health disorders were not associated with SARS-CoV-2 infection , but were associated with severity of COVID-19 disease. People with pre-existing mental health disorders showed higher prevalence of severe depression (25.4%) and anxiety (37.8%) than those without prior mental disorders (4.9% and 10.1%). Living alone was a strong predictor of severe depression among mental health patients (RR = 1.6, 95% CI 1.2-2.2). Among those without prior mental health disorders, post-lockdown depression and anxiety were associated with household interpersonal conflicts (RR = 2.6, 95% CI 2.1-3.1; RR = 2.1, 95% CI 1.9-2.4) and financial instability (RR = 2.2, 95% CI 1.8-2.9; 1.9, 95% CI 1.6-2.2). CONCLUSIONS: The COVID-19 pandemic and the lockdown were associated with increased post-lockdown depression and anxiety. Patients with pre-existing mental health conditions are a vulnerable group for severe COVID-19 disease.

Effect of resveratrol on visceral white adipose tissue inflammation and insulin sensitivity in a mouse model of sleep apnea.

BACKGROUND: Sleep fragmentation (SF) increases food intake and the risk of obesity, and recruits macrophages to visceral white adipose tissue (VWAT) promoting tissue inflammation and insulin resistance. Administration of resveratrol (Resv) has been associated with significant improvements in high-fat diet-induced obesity, inflammation and insulin resistance. METHODS: Male mice were subjected to SF or sleep control conditions for 8 weeks, and treated with either Resv or vehicle (Veh). Fasting plasma levels of glucose, insulin and leptin were obtained and VWAT insulin sensitivity tests were performed (phosphorylated AKT/total AKT), along with flow-cytometric assessments for VWAT macrophages (M1 and M2) and T-cell lymphocytes (CD4+, CD8+ and T regulatory cell (Treg)). RESULTS: SF-Veh and SF-Resv mice showed increased food consumption and weight gain. However, although SF-Veh mice exhibited increased fasting insulin and leptin levels, and reduced VWAT p-AKT/AKT responses to insulin, such alterations were abrogated in SF-Resv-treated mice. Increases in M1, reduced M2 counts and increased tumor necrosis factor-α release emerged in SF-Veh macrophages compared with all other three groups. Similarly, increased CD8+ and reduced Treg lymphocyte counts were apparent in SF-Veh. CONCLUSIONS: Resveratrol does not reverse the SF-induced increases in food intake and weight gain, but markedly attenuates VWAT inflammation and insulin resistance, thereby providing a potentially useful adjunctive therapy in the context of sleep disorders manifesting metabolic morbidity.

Sleep fragmentation promotes NADPH oxidase 2-mediated adipose tissue inflammation leading to insulin resistance in mice.

BACKGROUND: Short sleep has been implicated in higher risk of obesity in humans, and is associated with insulin resistance. However, the effects of fragmented sleep (SF) rather than curtailed sleep on glucose homeostasis are unknown. METHODS: Wild-type and NADPH oxidase 2 (Nox2) null male mice were subjected to SF or sleep control conditions for 3 days to 3 weeks. Systemic and visceral adipose tissue (VAT) insulin sensitivity tests, glucose tolerance test, fluorescence-activated cell sorting and immunohistochemistry for macrophages and its sub-types (M1 and M2), and Nox expression and activity were examined. RESULTS: Here we show that SF in the absence of sleep curtailment induces time-dependent insulin resistance, in vivo and also in vitro in VAT. Oxidative stress pathways were upregulated by SF in VAT, and were accompanied by M1 macrophage polarization. SF-induced oxidative stress, inflammation and insulin resistance in VAT were completely abrogated in genetically altered mice lacking Nox2 activity. CONCLUSIONS: These studies imply that SF, a frequent occurrence in many disorders and more specifically in sleep apnea, is a potent inducer of insulin resistance via activation of oxidative stress and inflammatory pathways, thereby opening the way for therapeutic strategies.

X-ray production cross sections for Ir and Bi M-subshells induced by electron impact.

M-subshell X-ray production cross sections were indirectly measured for Ir and Bi targets irradiated with monoenergetic electron beams. The projectile energy range ran from 2.2 to 28 keV, impinging on Ir and Bi pure bulk targets in a scanning electron microscope. The resulting X-ray emission spectra were acquired with an energy dispersive spectrometer, and processed afterwards by means of a robust parameter optimization procedure developed previously. X-ray production cross sections were finally obtained through an approach involving an analytical prediction for the emission spectra, which relies on the ionization depth distribution function. The values obtained by this approach were compared with empirical and theoretical predictions, appealing to different relaxation data taken from the literature.

Effects of late gestational high-fat diet on body weight, metabolic regulation and adipokine expression in offspring.

AIMS/HYPOTHESIS: Gestational exposures such as dietary changes can alter offspring phenotype through epigenetic modifications and promote increased risk for specific diseases, such as metabolic syndrome. We hypothesized that high-fat diet (HFD) during late gestation would lead increased risk for insulin resistance and hyperlipidemia via associated epigenetic alterations in tissue adipocytokine genes. METHODS: Offspring mice of mothers fed a HFD during late gestation (HFDO) were weighed and their food intake measured weekly till age 20 weeks at which time glucose and insulin tolerance tests, plasma lipid and adipocytokine levels were assessed, as well as mRNA expression in visceral fat. Adipocytokine gene methylation levels in visceral fat, liver and muscle were also assayed. RESULTS: HFDO mice had increased weight accrual and food intake, and exhibited insulin resistance, hyperlipidemia and hyperleptinemia, as well as hypoadiponectinemia. Furthermore, increased methylation of adiponectin and leptin receptor, and decreased methylation of leptin genes with unchanged glucagon-like peptide-1 methylation patterns emerged in HFDO mice. CONCLUSIONS: Taken together, late gestational HFD induces increased risk of metabolic syndrome in the progeny, which is coupled with hypoadiponectinemia as well as with leptin resistance, and concomitant presence of selective tissue-based epigenetic changes among adipocytokine genes.

Prognosis and Outcomes in Early Stage Glottic Carcinoma Involving the Anterior Commissure Treated with Laser CO2 Surgery: A Retrospective Observational Analysis.

The anterior commissure (AC) is the area where the vocal cords attach to the thyroid cartilage through Broyles' ligament. Many authors argue that involvement of the anterior commissure in early stage glottic carcinoma (I, II) constitutes a risk factor for local recurrence. The objective of this study is to evaluate whether anterior commissure involvement in early stage glottis cancer is an independent risk factor for recurrence and mortality. The study included all those patients diagnosed with glottis carcinoma in stages I and II of the AJCC treated by transoral laser surgery at the Hospital San Pedro (Logroño, Spain) between 2005 and 2015. Patients were divided into two groups according to the presence (AC1) or absence (AC0) of involvement of the commissure. Of 29 patients treated, 44.8% were AC1. Patients with anterior commissure involvement had more local recurrence (p = 0.2701); higher mortality rate (p = 0.2256); lower disease-free survival (p = 0.0881) and a lower overall survival (p = 0.0331). The 5-year survival rate was 24.5% lower in patients with invasion of the anterior commissure. The involvement of the anterior commissure is an independent risk factor that should be considered in the prognosis of laryngeal cancer.

Paraneoplastic syndromes in ophthalmology.

Paraneoplastic syndromes consist on systemic manifestations associated with certain cancers which are not a direct consequence of tumor invasion or its metastases. It is known that autoimmunity and autoantibody synthesis play an important role in its pathophysiology due to a process of molecular mimicry. Paraneoplastic syndromes in ophthalmology are rare, but it is important to recognize them clinically because in some cases symptoms preceded the diagnosis of an underlying neoplasia. Most frequently involved cancer is small cell lung carcinoma, but there is also a relationship with other tumor etiologies such as thymoma, gynecological tumors or neuroblastoma in children. Paraneoplastic syndromes with ocular involvement can be divided into those that affect the afferent visual pathway, such as cancer-associated retinopathy, melanoma-associated retinopathy, or paraneoplastic optic neuropathy; and the ones that affect the efferent visual pathway, such as bilateral tonic pupils, Myasthenia Gravis, Lambert-Eaton syndrome or paraneoplastic cerebellar degeneration. The presence of autoantibodies is helpful in clinical practice but negativity does not exclude this diagnosis. Although evolution and prognosis is linked to primary disease, in some cases specific treatment, usually immunosuppressive therapy, can help improving patients quality of life.

[Efficacy of magnetotherapy in hand erosive osteoarthritis. A clinical trial]. / Eficacia de la magnetoterapia en artrosis erosiva de manos. Un ensayo clínico.

INTRODUCTION: Erosive arthritis is an unusual pathology. Despite using magnetotherapy as a treatment, there is no evidence supporting its use. The aim of the study is to evaluate magnetotherapy efficacy in patients suffering from hand erosive arthritis, compared to placebo, in terms of pain. Treatment safety will be also evaluated. METHOD: Prospective experimental double-blind randomized study consisting of an intervention group (IG: treatment with magnetotherapy: 15 20-minute-sesions 5 consecutive days per week) and a control group (CG: placebo). Treatment efficacy was evaluated at the end and 3 months after. We used Visual Analog Scale (VAS) for assess pain. Secondarily, functionality (The Disabilities of the Arm, Shoulder and Hand (DASH) score), rigidity (Modified Kapandji Index), grip strength (dynamometry) and quality of life (SF-36 questionnaire) were assessed. RESULTS: 29 patients were evaluated. Due to exclusion criteria, there were 19 patients left, all women with an average age of 59. After randomization, 10 were awarded to IG and 9 to CG, being both comparable groups. A higher percentage of patients with pain controlled (VAS<6) was found in IG post treatment and after 3-months (77.8% vs 33.3%, p=0.1 y 83.3% vs 33.3%, p=0.2; respectively). A tendency to decrease VAS for IG at 3-months (regression coefficient: -2.1 (95% CI: -5.7-1.5; p=0.2) was showed. There were no other statistically significant differences, except a higher dynamometry results in IG, in both hands (p<0.01 and p<0.04 respectively). There were neither adverse effects nor secondary effects. CONCLUSION: Magnetotherapy treatment for hand erosive arthritis patients is safe and probably leads to clinical improvement.

Visual impairment induced by prosthetic cobaltism.

The case of a 68-year-old patient with visual loss secondary to prosthetic cobaltism is reported. The degeneration of the metallic hip prosthesis can produce a systemic absorption of cobalt with cardiac, neurological, endocrine, auditory, and visual manifestations. The diagnostic suspicion is confirmed by serum cobalt measurements. Treatment with early surgery and chelating agents can lead to improvement of the visual, and the other disorders.

The upper extremity of the professional tennis player: muscle volumes, fiber-type distribution and muscle strength.

The effects of professional tennis participation on dominant and non-dominant upper extremity muscle volumes, and on fiber types of triceps brachii (lateral head) and vastus lateralis muscles were assessed in 15 professional tennis players. Magnetic resonance imaging (MRI, n=8) examination and dual-energy x-ray absorptiometry (DXA, n=7) were used to assess muscle volumes and lean body mass. Muscle fiber-type distribution assessed by biopsy sampling was similar in both triceps brachii (2/3 were type 2 and 1/3 type 1 fibers). The VL was composed of 1/3 of type 2 and 2/3 of type 1 fibers. The dominant had 12-15% higher lean mass (DXA/MRI) than the non-dominant (P<0.05). Type 1, 2a and 2x muscle fibers of the dominant were hypertrophied compared with the non-dominant by 20%, 22% and 34% (all P<0.01), respectively. The deltoid, triceps brachii, arm flexors and forearm superficial flexor muscles of the dominant were hypertrophied (MRI) compared with the non-dominant by 11-15%. These muscles represented a similar fraction of the whole muscle volume in both upper extremities. Dominant muscle volume was correlated with 1RM on the one-arm cable triceps pushdown exercise (r=0.84, P<0.05). Peak power during vertical jump correlated with VL muscle fibers's cross-sectional area (r=0.82-0.95, P<0.05).

Upper airway collapse and reopening induce inflammation in a sleep apnoea model.

The upper airway of obstructive sleep apnoea patients is subjected to recurrent negative pressure swings promoting its collapse and reopening. The aim of the present study was to ascertain whether this mechanical stress induces upper airway inflammation in a rat model. The upper airway of Sprague-Dawley rats was subjected to a periodic pattern of recurrent negative (-40 cmH2O, 1 s) and positive (4 cmH2O, 2 s) pressures inducing collapse and reopening for 5 h. Rats that were instrumented but not subjected to negative pressure swings were used as controls. The gene expression of the pro-inflammatory biomarkers macrophage inflammatory protein (MIP)-2, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and P-selectin in the soft palate and larynx tissues was assessed by real-time PCR. A marked overexpression of MIP-2, TNF-alpha, IL-1beta and P-selectin (approximately 40-, 24-, 47- and 7-fold greater than controls, respectively) was observed in the larynx tissue; similar results were found in the soft palate tissue (approximately 14-, 7-, 35- and 11-fold greater than controls, respectively). Recurrent upper airway collapse and reopening mimicking those experienced by obstructive sleep apnoea patients triggered an early local inflammatory process. These results could explain the inflammation observed in the upper airway of obstructive sleep apnoea patients.

[What would you do in front of a patient with a Horner syndrome?] / ¿Qué haría usted ante un paciente con síndrome de Horner?

Horner's syndrome (HS) occurs when there is disruption to the oculosympathetic pathway. Its features include eyelid ptosis, miosis and anhidrosis. The aetiology of this syndrome is varied and includes tumours, trauma, vascular disease and iatrogenic. Different pharmacologic tests are used for diagnosis, such as cocaine, hydroxyamphetamine and apraclonidine; while neuroimaging helps elucidating the aetiology. We present a case of a 63-year-old female referred to our service with a 4-month history of right eyelid ptosis. During examination right miosis was noted. The patient reported a history of multinodular goiter. Pharmacologic tests and neuroimaging confirmed the diagnosis of HS secondary to thyroid disease.

Superoxide dismutase in human sperm suspensions: relationship with cellular composition, oxidative stress, and sperm function.

Sensitive techniques have been developed for monitoring superoxide dismutase (SOD) activities in human sperm preparations. In contradiction to the protective role normally assigned to SOD, populations of defective spermatozoa recovered from the low density region of Percoll gradients were found to have three times more SOD than functionally competent preparations pelleting in high density Percoll. SOD activity was negatively correlated with the movement characteristics of human spermatozoa and their capacity for oocyte fusion, and positively associated with the induction of peroxidative damage. SOD activity was also highly correlated with other markers of the cytoplasmic space, creatine kinase (CK), and glucose-6-phosphate dehydrogenase (G-6-PDH). We conclude that while SOD may play a physiological role in maintaining a balance between O2.- and H2O2, high levels of this enzyme are associated with impaired sperm function because (a) the human spermatozoon is highly susceptible to the cytotoxic effects of H2O2, (b) O2.- is an important mediator of normal sperm function, and (c) high SOD activities reflect errors in spermatogenesis associated with germ cell exfoliation and the retention of excess residual cytoplasm by the spermatozoa.

Maximum respiratory pressures in trumpet players.

We studied whether experienced trumpet players can develop higher pressures with their inspiratory and expiratory muscles than untrained subjects. Twelve male trumpet players (mean age, 22.4 +/- 3.3 years) participated in the study. All of them had played the trumpet for at least 4 years and were nonsmokers. Twelve healthy male subjects (mean age, 23.3 +/- 3.1 years) participated as a control group. There were no differences in spirometric parameters between both groups. Maximum respiratory pressures were higher in the trumpet player group (trumpet players: Pmax 151.3 +/- 19.8 cm H2O; Pemax, 234.6 +/- 53.9 cm H2O; control group: Pemax, 106.7 +/- 10.4 cm H2O; Pemax, 189.6 +/- 14.6 cm H2O). We concluded that in young trumpet players, maximum respiratory pressures are higher than in young people who do not play wind instruments. This is most probably a consequence of respiratory muscle training with a wind instrument.

Expression of D-mannose binding sites on human spermatozoa: comparison of fertile donors and infertile patients.

OBJECTIVE: The hypothesis that defective expression of D-mannose binding sites (presumptive elements of the sperm-zona pellucida binding mechanism) is related to male infertility was tested. DESIGN: Experiments were performed on sperm samples from two groups of men classified, respectively, as fertile and infertile, based on their reproductive history. SETTING: The study was carried out in an andrologic laboratory of a University Hospital. PATIENTS, PARTICIPANTS: Fertile men were healthy sperm donors; infertile men were patients with fertility problems. INTERVENTIONS: D-mannose binding sites were visualized by fluorescence microscopy using a mannosylated neoglycoprotein probe. MAIN OUTCOME MEASURES: The hypothesis as reported in the objective section was formulated before data collection and was not modified thereafter. RESULTS: Sperm from fertile men displayed a characteristic pattern of changes in the expression of D-mannose binding sites during in vitro capacitation. This pattern was altered in sperm from infertile men. CONCLUSIONS: If the relationship between defective expression of D-mannose binding sites and decreased sperm fertilizing ability is validated by parallel tests of sperm-zona binding, it may be used for development of chemical tests replacing the current ones using human zonae pellucidae.

Effects of phosphodiesterase inhibitors caffeine and pentoxifylline on spontaneous and stimulus-induced acrosome reactions in human sperm.

OBJECTIVE: To determine whether the phosphodiesterase inhibitors caffeine and pentoxifylline influence the acrosome reaction in the conditions in which they are currently used as sperm movement enhancers. DESIGN: The frequency of acrosome reaction occurring spontaneously in capacitating media or induced by physiological (follicular fluid [FF]) and artificial (ionophore A23187) stimuli was compared in the presence and absence of the phosphodiesterase inhibitors. SETTING: Private hospital and research laboratory. PATIENTS, PARTICIPANTS: Patients undergoing routine semen examination before in vitro fertilization (no pathology detected) and healthy sperm donors. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Percentage of acrosome-reacted sperm determined with the use of fluorescein-labeled Pisum sativum agglutinin as acrosomal stain. RESULTS: Caffeine alone augmented the frequency of acrosome reaction, but this effect was not observed with pentoxifylline alone. However, pentoxifylline increased sperm responsiveness to the acrosome reaction-inducing stimuli, FF and ionophore A23187. CONCLUSIONS: The promotion of spontaneous acrosome reaction may counteract the benefits from application of caffeine as motility stimulant. On the other hand, the sensitization to physiological acrosome reaction stimuli is expected to contribute to the improvement of sperm fertilizing ability by pentoxifylline and make this drug a potential candidate for the treatment of acrosome reaction anomalies.

Fast acrosome reaction measure: a highly sensitive method for evaluating stimulus-induced acrosome reaction.

OBJECTIVE: To test a new method for evaluation of stimulus-induced acrosome reaction (AR). To determine whether this method, based on the definition of a specific staining pattern of recently reacted spermatozoa, brings an advantage of increased sensitivity as compared with a standard procedure. DESIGN: The hypothesis that a specific staining pattern with fluorescein-labeled Pisum sativum agglutinin corresponds to recently acrosome-reacted spermatozoa was tested by analyzing the frequency of this pattern at different time points after addition of ionophore A23187, an artificial AR inducer. The AR results obtained with a new method based on this relationship were compared with those obtained with a standard method of AR evaluation. SETTING: Private hospital, public research center, and a university-based research laboratory. PARTICIPANTS: Healthy sperm donors. MAIN OUTCOME MEASURE: Changes in the frequency of specific sperm-staining patterns. RESULTS: A specific sperm-staining pattern with P. sativum agglutinin was shown to be associated with a recently occurred AR, whereas the absence of staining was typical of reactions having occurred a longer time ago. This phenomenon was used to define a formula for fast AR measure after stimulus addition. An increased sensitivity provided by this formula as compared with a standard evaluation was demonstrated. CONCLUSIONS: Fast AR measure is a simple, easy-to-perform method for AR evaluation. It is particularly suitable for testing the effects of rapidly acting stimuli.

Selective expression of a progesterone receptor on the human sperm surface.

OBJECTIVE: To visualize progesterone (P) binding sites on the sperm surface, examine the relationship between hormone binding and hormone action (acrosome reaction), and determine the size of the hormone-responsive sperm subpopulation. DESIGN: Kinetic analysis of P binding was combined with the assessment of the hormone effect using a fluorescent acrosomal marker. SETTING: Private hospital, medical research center, and a university-based andrological laboratory. PATIENTS, PARTICIPANTS: Sperm samples were from healthy volunteers with normal spermiogram values. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Progesterone binding was analyzed by fluorescence microscopy and flow cytometry using P coupled to fluorescein isothiocyanate-labeled bovine serum albumin. Tetramethylrhodamine isothiocyanate-labeled Pisum sativum agglutinin was used as acrosomal marker in double-labeling experiments. RESULTS: After in vitro capacitation, only few spermatozoa (approximately 10%) were able to bind P to the cell surface, but most of these cells subsequently generated the acrosome reaction in response to hormone binding. CONCLUSIONS: The expression of P receptor sites on the human sperm surface is a major factor controlling the P-induced acrosome reaction. Further studies are warranted to explore if defective expression of the receptor can compromise fertility.