Plasma levels of protein C pathway proteins and brain magnetic resonance imaging volumes in multiple sclerosis.

BACKGROUND AND PURPOSE: The involvement of protein C (PC) pathway components in multiple sclerosis (MS) has scarcely been explored. The aim was to investigate their levels in relation to clinical and neurodegenerative magnetic resonance imaging (MRI) outcomes in patients. METHODS: In all, 138 MS patients and 42 healthy individuals were studied. PC, protein S (PS) and soluble endothelial protein C receptor (sEPCR) were evaluated by multiplex assays and enzyme-linked immunosorbent assay. Regression analyses between 3 T MRI outcomes and PC pathway components were performed. ancova was used to compare MRI volumes based on protein level quartiles. Partial correlation was assessed amongst levels of PC pathway components and hemostasis protein levels, including soluble thrombomodulin (sTM), heparin cofactor II (HCII), plasminogen activator inhibitor 1 (PAI-1) and factor XII (FXII). The variation of PC concentration across four time points was evaluated in 32 additional MS patients. RESULTS: There was an association between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM) (P = 0.003), thalamus (P = 0.007), cortex (P = 0.008), deep GM (P = 0.009) and whole brain (P = 0.026). Patients in the highest PC level quartile were characterized by the lowest GM volumes. Correlations of PC-HCII, PC-FXII and sEPCR-sTM values were detectable in MS patients, whilst PC-PS and PS-PAI-1 correlations were present in healthy individuals only. CONCLUSIONS: Protein C plasma concentrations might be associated with neurodegenerative MRI outcomes in MS. Several differences in correlation amongst protein plasma levels suggest dysregulation of PC pathway components in MS patients. The stability of PC concentration over time supports a PC investigation in relation to GM atrophy in MS.

A Toe Flexion NIRS assisted Test for Rapid Assessment of Foot Perfusion in Peripheral Arterial Disease: Feasibility, Validity, and Diagnostic Accuracy.

OBJECTIVES: Feasibility, validity, and diagnostic accuracy of a non-invasive dynamic ambulatory test were assessed with near infrared spectroscopy (NIRS) evaluating foot perfusion in peripheral arterial disease (PAD). METHODS: This was a prospective observational study. Eighty PAD patients (63 males, 71 ± 9 years), including 41 patients with coexisting diabetes, participated. Thirteen healthy subjects (8 males, 26 ± 8 years) were also studied by echo colour Doppler providing 160 diseased and 26 non-diseased limbs. Under identical clinostatic conditions, participants performed a 10-repetition toe flexion tests with NIRS probes on the dorsum of each foot; the area under the curve of the oxygenated haemoglobin trace ("toflex area") was calculated and the ankle-brachial index (ABI) was measured. Time of execution, rate of wrong tests, and adverse reactions were recorded. Within session reliability was assessed by administering the test twice, with a 5 minute interval between tests. The validity was assessed determining whether the toflex area was (a) dependent on the oxygen delivery from the lower limb arteries simulating PAD conditions by a progressive blood flow restriction (40-120% of systolic pressure) in healthy subjects; (b) consistent with the degree of PAD ranked by ABI and correlated with ABI and ankle pressure values in PAD patients. The diagnostic accuracy in detecting PAD was compared with examination using echo colour Doppler ultrasound. RESULTS: All tests were rapidly, satisfactorily (<1% mistakes), and safely performed. Toflex area values, superimposable in the two sessions (intra-class correlation coefficient 0.92), were comparable to PAD values following blood flow restriction, consistent with PAD severity, correlated with dorsal pedis artery pressure (r = .21; p = .007) and ABI (r = .65; p < .001) in PAD, but not in the presence of diabetes. Toflex area was similar to echo colour Doppler for detecting PAD following receiver operating characteristic curve analysis (area = 0.987, p < .001; toflex area values ≤ -28 arbitrary units, sensitivity/specificity 95.6/100). CONCLUSION: The toe flexion test enables ambulatory assessment of foot perfusion and PAD detection, even in the presence of non-measurable ABI or diseases affecting the microcirculation.

Fatigue can influence the development of late-onset pain in post-COVID-19 syndrome: An observational study.

BACKGROUND: Late-onset pain is frequent following COVID-19, and many pathogenetic mechanisms have been proposed. Identifying the main features of patients may help in designing tailored rehabilitative interventions. METHODS: We enrolled post-COVID-19 patients with an increase in pain intensity of two points on the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) at 52 weeks compared to the pre-COVID-19 condition. All subjects were retrospectively monitored at 12, 26, and 52 weeks. A specific pain assessment was performed to determine the characteristics and mechanisms of pain. Catastrophizing, kinesiophobia, and other psychological symptoms were evaluated. The pressure pain threshold (PPT) and temporal summation (TS) were measured and compared in age- and sex-matched healthy controls to analyse pain characteristics. RESULTS: A total of 67 patients were recruited, with 20 of them presenting an increase in pain at 52 weeks. Subjects of the two subgroups were similar in demographic and clinical characteristics at baseline; significant differences in fatigue, anxiety, mobility, ability to perform daily activities, and general health perception were recorded at 26 weeks. Fatigue significantly predicted pain onset (ß = 0.54, p = 0.002). Sixteen different body regions were identified as painful, with a pain intensity of 6.0 ± 1.9. Most of the samples did not show neuropathic or nociplastic mechanisms. No differences in PPT and TS were recorded between patients and healthy controls. CONCLUSIONS: Almost one out of three patients hospitalized for COVID-19 developed pain 1 year later, and fatigue seems responsible for chronicity. An overlapping of conditions may explain late-onset post-COVID-19 pain, and a comprehensive approach must be considered for patient management. SIGNIFICANCE: Late-onset pain is frequent in post-COVID-19 syndrome and an overlapping of different mechanisms seems to be responsible for its development. Among many predisposing factors, fatigue in the months before seems to be one of the primary causes of pain one year following infection and its management may help to identify new strategies for prevention and treatment of late-onset pain.

From intensive care to rehabilitation: survey on the satisfaction with care received during prolonged hospitalization for COVID-19 at a northern Italian university hospital.

OBJECTIVE: Investigating the experiences perceived by COVID-19 inpatients is a fundamental research area that is starting to be explored. For this reason, our objective was to provide the first Italian survey on COVID-19 inpatients' satisfaction, obtained through a self-completed questionnaire previously used in a reference study in a UK cohort of COVID-19 patients. SUBJECTS AND METHODS: Hospitalized COVID-19 patients (>20 days) admitted to Ferrara University Hospital who underwent rehabilitation during their hospital stay were invited to complete an anonymous questionnaire. The survey's questions explored the patients' satisfaction with the health services received, and their completion took place approximately one year after hospitalization. Information on sex, number of wards, ICU stays, and hospital discharge dates was collected. RESULTS: Sixty-two completed questionnaires were analyzed. The average overall satisfaction score obtained from the answers indicated by the participants in the tenth question was 4.7 out of 5.0. Very positive responses were observed for information about discharge plans, privacy, management of pain, sleep quality, and feeling of safety. The possibility of being consulted about medications and side effects received a very low satisfaction score. Considering overall satisfaction, no significant differences were noted for sex or ICU stay. The obtained results were almost superimposable to those reported in the cohort of COVID-19 patients of the reference study. CONCLUSIONS: This survey suggested that COVID-19 patients' healthcare satisfaction was high. Nevertheless, some areas must be improved, such as the communication and involvement of the patients in the decision-making of care and the discussion about medications or possible side effects.

Can peripheral arterial disease be early screened for in a podiatric setting? A preliminary study in a cohort of asymptomatic adults.

BACKGROUND: Peripheral arterial disease (PAD) is a strong marker of cardiovascular disease but remains an under-diagnosed problem. Moreover, PAD frequently leads to foot problems requiring particular care and surveillance. AIM: The aims of this study were (1) to determine the prevalence of undiagnosed PAD in a cohort of asymptomatic subjects referred to a podiatric clinic and (2) to evaluate whether a four-item form assessing medical history for the presence of cardiovascular risk factors could identify subjects at high risk for asymptomatic PAD. PATIENTS AND METHODS: This study included 717 consecutive subjects (121 males, age 50.9±13.9 y) referring to a podiatric clinic who were asymptomatic for PAD and free of cardiovascular disease. The ankle brachial index (ABI) was measured in all subjects. Each subject also completed a self-administered form to identify cardiovascular risk factors. RESULTS: Among the entire cohort, the prevalence of PAD was 8.3% in males and 1.2% in females. Three subgroups were identified according to the number of risk factors reported (no risk factors, one risk factor, and two or more risk factors), and the prevalence of PAD differed between each subgroup (0.2%, 3.2%, and 18.9%, respectively; p < 0.001). CONCLUSIONS: In an unselected cohort of subjects referring to a podiatric clinic, who were asymptomatic for PAD and free from cardiovascular diseases, a remarkable prevalence of PAD was found among subjects reporting a minimum of two cardiovascular risk factors. In a podiatric setting, screening with a self-administered form for the presence of cardiovascular risk factors might lead to an early diagnosis of PAD.

[Return to work of the cardiac patient: work fitness evaluation in Occupational Medicine Division including an Occupational Cardiology Unit and Work-Physiology Lab in Bergamo]. / Unità Semplice di Cardiologia del Lavoro ed Ergometria degli Ospedali Riuniti di Bergamo: percorso per la valutazione dell'idoneità lavorativa del cardiopatico.

Cardiovascular disease in working age still represent a major cause of morbidity and account for a number of fitness to work certificates expressing several limitations and prescriptions. To present the medical assessment conducted in an Occupational Medicine Division including an Occupational Cardiology Unit and work-physiology lab. It is described the history and the structure of the Occupational Cardiology Unit. Our almost forty years long-lasting experience allow us to point out the precious contribution of the Occupational Cardiology Unit to the Occupational Medicine Division, due to a highly specialised and qualified assessment of cardiac patients.

Infodemiology of renal diseases: a novel opportunity to investigate public global interest.

OBJECTIVE: The aim of this study was to investigate the global community interest about renal diseases through relative search volumes (RSVs) of Google Trends (GT). MATERIALS AND METHODS: The online interest for the search terms hematuria (H), proteinuria (P), chronic kidney disease (CKD) and dialysis (D) was measured by evaluating RSVs from 2010 to 2019. All countries listed in GT were analysed and those presenting RSVs related to all search terms were considered following geographical position. RESULTS: Mean values of RSVs for D, CKD, H and P were 80±9%, 11±2%, 17±2% and 11±1%, respectively. D is the search term most frequently typed in English-speaking countries. On the other hand, in Latin Countries, the interest for P and H was higher than D. Searching for D, CKD and H are highly correlated whilst correlation coefficients between RSVs for D, CKD, and H with P are lower. Since 2010, the interest for renal diseases maintained stable. CONCLUSIONS: GT is a reliable tool in evaluating global interest for renal diseases in different geographical areas and temporal patterns. Although infodemiology represents a method for investigating the dissemination of information at a global level, our results suggest the need for increasing general population's interest for renal diseases especially, and move from simple interest to global awareness in the view of prevention strategies.

Infodemiology of solid organ transplantation: relationship to the Global Observatory on Donation and Transplantation data.

OBJECTIVE: Although transplantation medicine has been continuously improving, its impact on the general population needs to be evaluated. This study describes the global community interest in solid organ transplantation (SOT) using Google Trends, comparing relative search volumes (RSVs) and data from the World Health Organization (WHO) Global Observatory on Donation and Transplantation (GODT) regarding SOT activity all around the world. MATERIALS AND METHODS: The online interest for the search terms "kidney transplantation", "liver transplantation", "heart transplantation" and "lung transplantation" was measured, evaluating RSVs and the number of worldwide SOT recorded in the GODT website from 2008 to 2018. RESULTS: The mean values of RSVs were 51.7±16.8 for liver transplantation, 39.8±9.6 for kidney transplantation, 22.4±7.4 for heart transplantation and 15.4±5.2 for lung transplantation, and these values gradually reduced during the study period. Anglo Saxon countries had the highest interest for SOT, and the mean values of RSVs per year and annual numbers of SOT were inversely correlated. CONCLUSIONS: Despite the apparent interest and awareness, we found that public interest in SOT is decreasing. Access to information is crucial for improving understanding of transplantation and motivation to donate. Health care professionals could take advantage by using the internet, and evaluation of RSVs could represent valuable feedback.

A dynamic objective evaluation of peripheral arterial disease by near-infrared spectroscopy.

OBJECTIVES: Near-Infrared Spectroscopy (NIRS), suitable for dynamic measurements, is not routinely used for peripheral arterial disease (PAD). We propose a dynamic NIRS-based measurement to quantify variations in muscle metabolism in PAD. METHOD: Sixty-seven consecutive PAD patients (males=56, age 71.6+/-8.7 years) and 28 healthy subjects (males=12, age 30.4+/-11.9 years) were studied. An echo-colour Doppler (ECD) was performed and the ankle-brachial index (ABI) was calculated. Participants performed an incremental treadmill test with NIRS probes on the gastrocnemius. Variations in oxygenated (HbO(2)), deoxygenated (HHb), total (tHb=HbO(2)+HHb), and differential (dHb=HbO(2)-HHb) haemoglobin were recorded and quantified as area-under-curve (AUC) within the range 1.7-3.0 km h(-1). Heart rate was recorded, and the number of beats in the same interval was calculated (dHr). RESULTS: O(2)Hb(AUC), HHb(AUC) and dHb(AUC) differed between diseased and non-diseased legs (P<0.0001) and exhibited different patterns related to PAD severity according to the ABI value. A compensatory heart rate increase was observed in PAD patients. Compared with the ECD positivity for occlusions/stenoses or multiple plaques, only the receiver-operating characteristic (ROC) analysis of dHb(AUC) (area=0.932, P<0.0001) showed a sensitivity/specificity of 87.6/93.4 for values

Exercise training and endothelial progenitor cells in haemodialysis patients.

Haemodialysis patients have few endothelial progenitor cells (EPCs) and an unfavourable cardiovascular outcome. The effects on peripheral blood CD34(+) cells and EPCs of a 6-month walking exercise programme were studied. Thirty dialysis patients (20 males, age 67 +/- 12 years) were prescribed exercise (two daily 10-min home walking sessions at moderate intensity, group E, n = 16) or not prescribed exercise (control, group C, n = 14). On entry and after 6 months peripheral blood CD34(+) cells, EPCs (assessed as CD34(+) cells co-expressing AC133 and vascular endothelial growth factor receptor 2 [VEGFR2], and as endothelial colony-forming units [e-CFU]) and exercise capacity (6-min walking distance, 6MWD) were evaluated. In group E, 6MWD and e-CFU increased significantly during the study period, with no significant changes in CD34(+) or CD34(+) AC133(+) VEGFR2(+) cell numbers. The change in e-CFU was directly and significantly correlated to patient-reported training load. Group C showed no significant change in any variable. In haemodialysis patients, moderate-intensity exercise selectively increased the number of e-CFU.

Blood parameters and biathlon performance.

AIM: Biathlon is a sport that combines cross-country skiing with rifle shooting. There is no well-described model of performance in this multi-sport event. This study aimed to identify the parameters influencing biathlon performance. In addition, the study aimed to search for a relationship between performance and measured blood parameters and to determine whether higher hemoglobin concentration [Hb] was associated with improved performance. METHODS: Eighty-three male biathletes underwent pre-competition blood sampling in selected World Cup competitions. For all athletes (N=83) and for a subgroup of top-athletes (N=37), performance parameters identified were related to final standings by univariate and multiple regression analyses and, subsequently, to blood parameters measured on the same day. In athletes tested twice with different [Hb], performance corresponding to competitions with lower and higher [Hb] was compared. RESULTS: Among the parameters considered, the percent variation for both groups in best skiing time and percent of missed targets were independent determinants of performance (R2=0.853, 0.834, respectively) and were not correlated to blood parameters. In athletes with two samples, despite significantly different (Hb), no corresponding changes in performance were observed. CONCLUSIONS: In this study, the determinants of biathlon performance were identified. A relationship between measured blood parameters was not found, and the individual (Hb) variations observed were not associated with improved performance.

[Measurement of energy expenditure in a group of construction workers during work]. / Valutazione del dispendio energetico durante l'attività lavorativa in un gruppo di lavoratori edili.

The aim of this study is to show the results obtained from measuring energy expenditure (EE) during work in a group of male construction workers through a new portable device of practical use and low cost. The instrument consists of an electronic bracelet multisensor system for measuring EE, which is called Armband Sensewear Pro2 and is produced by Body Media. The disposal has 5 steel hypoallergenic sensors which detect the skin and the near body temperature, the environment temperature, the electrical skin conductance, and an internal two axes accelerometer which detects the transverse and longitudinal acceleration. The analysis of these parameters through software allows you to derive the individual EE. The study describes the results obtained by applying Armband to a group of 10 construction workers performing the following jobs: bricklayer, tiler, crane driver and "rock climber". The results allow to assess and confirm the high EE related to the work of the subjects enrolled in the study. In conclusion the authors argue that Armband, already validated experimentally in several areas of Medicine, can be a useful tool available to the Occupational Physician, in order to determine the EE for workers who perform heavy tasks, such as those that exist in the construction industry, which are characterised by high levels of EE and poor reproducibility of tasks. Moreover, Armband appears to be an useful tool in connection with the dual possibility on the one hand to assess fatigue related to certain skills and jobs, and on the other side to contribute to the metabolic evaluation of cardiac patients during rehabilitation at work.

Subtle effect of Xenos vesparum (Xenidae, Strepsiptera) on the reproductive apparatus of its male host: Parasite or parasitoid?

Parasitic castration is an adaptive strategy where parasites usurp the hosts' reproductive physiology to complete their life cycle. The alterations in the host traits vary in their magnitude, from subtle changes in the host morpho-physiology and behaviour to the production of complex aberrant phenotypes, which often depend on the host gender. The strepsipteran macroparasite Xenos vesparum induces dramatic behavioural and physiological changes in its female host, the paper wasp Polistes dominula, while its effect on the male phenotype is largely unknown. In this study we investigated how a single X. vesparum parasite influences the functional morphology of P. dominula male reproductive apparatus. We performed morphometry and ultrastructure characterization of corpora allata, testes, seminal vesicles and accessory glands in parasitized and unparasitized males, and also in young and old males to control for the effect of age on the natural deterioration of these organs. Our results show that age significantly affects the development of male reproductive apparatus. A low parasite load - one parasite per host is the common prevalence in the field - has only a marginal impact on the reproductive morphology of P. dominula males, affecting quantitatively but not qualitatively the protein content of male accessory glands. Thus, in male P. dominula wasps, X. vesparum appears to behave as a true "parasite", in clear opposition to the role of "parasitoid" that it takes in female hosts where castration causes the reproductive death.

Body mass index and metabolic syndrome impact differently on major clinical events in renal transplant patients.

OBJECTIVE: Kidney transplant recipients (KTRs) are bound to develop cardiovascular disease (CVD), and obesity represents a well-known risk factor for CVD. It has been reported that the metabolic syndrome (MetS) is a frequent finding in KTRs, and MetS could develop even if body mass index (BMI) is only mildly increased. We compared the impact of BMI and MetS on the development of major clinical events (MCEs) in a cohort of 107 KTRs during a follow-up of 63 ± 31 months. PATIENTS AND METHODS: Clinical characteristics were recorded at the time of enrollment and patients were classified on the basis of MCEs development. In a Cox model, MCEs were the dependent variable while age, sex, history of CVD, glomerular filtration rate, length of dialysis pre-transplantation, BMI classes and diagnosis of MetS were independent variables. Patients were classified into 3 groups: normal (BMI < 25 kg/m2), overweight (BMI of 25 to 30 kg/m2) and obese (BMI > 30 kg/m2). RESULTS: During follow-up, 55 MCEs were recorded: 16 patients died (15%), 19 (18%) had major cardiovascular events (CVEs), and 20 (19%) started dialysis due to graft failure. KTRs who had MCEs (n = 42) were older, had a lower renal function, longer dialysis vintage pre-transplantation, higher prevalence of history of CVD and higher BMI than those without MCEs. Cox regression analysis showed that length of dialysis pre-transplantation, renal function, previous CVD, and BMI classes (overweight and obesity) were related to MCEs. CONCLUSIONS: BMI, but not MetS, predicted MCEs in KTRs as well as non-traditional CVD risk factors such as length of dialysis pre-transplantation and graft function. Thus, a simple evaluation during clinic visits could identify KTRs at high risk for MCEs.

[Prevalence of risk factors and prevention of coronary disease in a population of construction workers of the Province of Bergamo]. / Prevalenza dei fattori di rischio e prevenzione della coronaropatia in una popolazione di lavoratori edili della provincia di Bergamo.

Authors describe the prevalence of cardiovascular risk factors among 1.348 construction workers, enrolled in a five years lasted health surveillance program. Our results confirm both the high prevalence of cardiovascular risk factors and the need of further examinations other the clinical, laboratory, electrocardiogram and chest X, in order to point out a correct diagnosis and evaluate the fitness to job. Furthermore, we underline the usefulness of training in health education for the prevention of cardiovascular disease, considering the low extent to which individuals perceive their own risk.

The power output/heart rate relationship in cycling: test standardization and repeatability.

PURPOSE: The purpose of this study was to update and standardize the test for determining the power output/heart rate (PO/HR) relationship in cycling. METHODS: The current protocol was developed in the laboratory using a wind-load cycling simulator. Five hundred incremental tests were carried out by 290 male cyclists during a 2-yr period (1995-1997). The subjects' own bicycles, equipped with a standard crankset with a built-in power measuring system, were used for testing. The test protocol consisted of time-based increments in cadence that were uniform up to submaximal speeds and progressively greater in the final phase. RESULTS: The PO/HR relationship obtained was linear at low to submaximal PO and curvilinear from submaximal to maximal PO. A method was developed for the mathematical identification of the point of transition from the linear to the curvilinear phase (deflection point or heart rate break point). In 484 of the 500 tests performed, the deflection was independent of the final acceleration (PO at deflection 318.4 +/- 42.4 W, PO at final acceleration 351.6 +/- 43.2 W, P < 0.001), whereas in 16 tests the deflection and the start of the final acceleration coincided. To evaluate test repeatability and precision, 15 subjects repeated the test twice within a few days. No significant differences were found for the heart rate at deflection, power output at deflection, or slope of the linear part of the PO/HR relationship obtained in the two tests. CONCLUSION: It is concluded that the deflection point obtained by determining the PO/HR relationship on a wind-load simulator is not an artifact dependent on the incremental test protocol but rather a repeatable physiological phenomenon.

Training guided by pain threshold speed. Effects of a home-based program on claudication.

AIM: To verify the effectiveness of a 120 day home-based program guided by the pain threshold speed (PTS). METHODS: Twenty-nine patients with stable claudication were measured for ankle pressure (AP), ankle-brachial index (ABI), PTS, maximal speed (Smax) on treadmill. Daily walking sessions at a speed 20-30% below PTS were prescribed. Determination of the training speed was supervised and facilitated at home. The program included a daily record of exercise data and symptoms, an intermediate PTS re-evaluation to adjust the training speed, and the reassessment of all the parameters after 120 days. RESULTS: Overall patients showed a reduction of systemic blood pressure (151.3+/-14.3 to 147.6+/-18.3 mmHg; 77.1 +/-9.1 to 72.4+/-8, p=0.008) while AP did not. ABI increased from 0.65+/-0.13 to 0.71+/- 0.18 (p=0.01). PTS and Smax rose from 3.2+/-1.1 to 4.2+/-1.5 km/h (p=0.0001) and from 3.9+/-1.3 to 4.6+/-1.3 km/h (p=0.0001), respectively. According to their compliance, patients were divided into 3 groups: 1) trained (T, n=14): exercise at the prescribed speed, 2) free-walkers (FW, n=7): walking speed markedly below PTS and 3) untrained (U, n=8): incomplete program compliance. T group showed symptom reduction up to pain disappearance. The ABI change (0.72+/-0.09 to 0.82+/- 0.16, p<0.02) was correlated to AP increase (r= 0.879). PTS and Smax rose from 3.6+/-1.1 to 5.4+/-0.8 km/h (p<0.02) and from 4.7+/-1.2 to 5.7+/-0.7 (p<0.02), respectively. FW showed improvement of all parameters, and U a better walking efficiency. CONCLUSIONS: In patients with claudication, a low-cost home-based program driven by PTS allows dramatic improvements of functional parameters.

Standard melatonin intake and circadian rhythms of elite athletes after a transmeridian flight.

Many transmeridian travellers, including top athletes, regularly take melatonin to reduce negative jet lag symptoms. Standard (rather than individually tailored) doses are often used. We examined the effects of a standard dose of melatonin on the body temperature rhythms of 12 elite biathletes (eight men and four women) after an eastward transmeridian flight to an international competition. The different effects on body temperature rhythms in men versus women underscore the need for personalized dosing schedules to avoid potential undesirable consequences.

Cocaine and acute vascular diseases.

Cocaine is one of the most widely used drugs of abuse. Chest pain is the most common side effect requiring emergency visits after cocaine use. Vasoconstriction and platelet activation are the main effects of cocaine in the vasculature. In this brief review, we consider the most important clinical effects of cocaine abuse on the heart, brain and kidney. Symptoms related to cocaine toxicity such as myocardial infarction, congestive heart failure, arrhythmias, aortic dissection, stroke, renal failure, are similar to the clinical picture of atherosclerotic vascular damage, even if the age of cocaine abusers is usually in the second and third decades. Clinicians (especially emergency department physicians) should consider substance abuse among the differential diagnosis of chest pain in young people.

Is chronic fatigue the symptom of venous insufficiency associated with multiple sclerosis? A longitudinal pilot study.

AIM: Chronic fatigue (CF) severely affects patients with multiple sclerosis (MS), but its pathogenesis remains elusive and the effectiveness of available treatments is modest. We aimed to evaluate the effect on CF of the balloon dilatation of stenosing lesions affecting the main extracranial veins configuring the chronic cerebrospinal venous insufficiency (CCSVI), a condition strongly associated with MS. METHODS: Thirty-one MS consecutive patients (16 males, age 46.2+/-9.4 years) with associated CCSVI and CF underwent the endovascular procedure. Fatigue was assessed using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) at baseline (T0) and one (T1), six (T6) and twelve (T12) months after the procedure. In ambulatory patients (N.=28), mobility was evaluated using the 6-min walking test at T0 and T1. RESULTS: and MFIS scores significantly improved from preoperative values, and the positive trend was maintained at one year (FSS: T0=5.1+/-1.0 to T12=3.5+/-1.8, P<0.001; MFIS-total score: T0=34.9+/-14.8 to T12=22.5+/-13.7, P<0.001; MFIS-Physical subscale: T0=21.2+/-8.0 to T12=13.5+/-9.7 P<0.001; MFIS-Cognitive subscale: T0=9.2+/-9.5 to T12=6.0+/-6.3, P=0.03; MFIS-Psychosocial subscale: T0=4.5+/-2.1 to T12=2.5+/-2.1, P<0.001). Six-min walking distance (6MWD) at T1 improved significantly (332+/-190m to 378+/-200m, P=0.0002). In addition, an inverted correlation between 6MWD and MFIS-physical subscale variations was found in the subgroup of patients (N.=8) with no lower limb motor impairment (r=-0.74, P=0.035). CONCLUSION: The reestablishment of cerebral venous return dramatically reduced CF perception in a group of MS patients with associated CCSVI, suggesting that CF is likely the symptom of CCSVI.