Does ragging play a role in medical student depression — Cause or effect?

BackgroundMedical students experience a lot of stress what may contribute to symptoms of depression. In this study we set out to look at the environmental factors which may be contributing in one medical school in Brazil.MethodsWe assessed depressive symptoms using Beck's Depression Inventory in 465 and 267 medical students in 2001 and 2006 respectively. We explored possible social and environmental causes using qualitative data.ResultsNearly 15% scored above the cut off for depression in both the samples. Males in the pre-clinical stage in 2006 showed an increase in depressive symptoms than males in the same cycle in 2001 (aOR = 7.36 [95% CI = 0.85–63.5] p = 0.07). Qualitative data confirmed that factors such as ragging and low social involvement were correlated with depressive symptoms in pre-clinical stage males.LimitationsThe sample size was small both for quantitative and qualitative aspects of the study.ConclusionsIt appears that ragging plays an important role in the genesis of depressive symptoms in medical students.     

Does the cerebellum play a role in podokinetic adaptation?

After sustained stepping in-place on a rotating disc, healthy subjects will inadvertently turn in circles when asked to step in-place on a stationary surface with eyes closed. We asked whether the cerebellum is important for this adaptive phenomenon, called podokinetic after-rotation (PKAR). Subjects with cerebellar degeneration and age-matched control subjects performed 15 min of stepping in-place with eyes open on a rotating disc, then 30 min of attempting to step in-place with eyes closed on a stationary surface. Rotational velocity of PKAR was measured during this 30-min period. All control subjects demonstrated PKAR; average initial rotational velocity for control subjects was 16.4+/-3.5 degrees /s. Five of the eight cerebellar subjects demonstrated impaired PK adaptation, defined as PKAR with an initial velocity more than two standard deviations below the control mean initial velocity. Average initial rotational velocity for cerebellar subjects was 7.8+/-0.2 degrees /s. Impaired PK adaptation was not associated with impaired time constants of decay and was not correlated with variability of PKAR velocity. Our results suggest that the cerebellum is important for regulation of the amplitude of PK adaptation and that reduced PKAR amplitude is not likely the result of dyscoordination or variability of movement in the subjects tested.     

Does cyclophosphamide still play a role in glomerular diseases?

Cyclophosphamide is a prodrug that is converted to inactive carboxy-cyclophosphamide, acrolein and phosphoramide mustard, an agent that adds alkyl groups to oxygen and nitrogen atoms of guanine, one of the four nitrogen bases that form the DNA nucleotides, causing DNA cross-links and introducing DNA breaks. These cytotoxic and mutagenic effects mainly occur in proliferating cells. Repair mechanisms may prevent DNA damage in quiescent cells, but they may be insufficient to contrast the side effects of cyclophosphamide if high doses of the drug are used. Most adverse events are dose- and age-dependent. Phosphoramide mustard can cause bone marrow toxicity, gonadal toxicity, and may favor the development of leukemia, bladder cancer and other types of malignancy. Acrolein can produce hemorrhagic cystitis and even bladder fibrosis when given for prolonged periods. A number of precautional measures should be taken to prevent these untoward events. In particular, long-term administration and high doses of cyclophosphamide should be avoided whenever possible.Today the indications to cyclophosphamide in glomerular diseases are more restricted than in the past, but the drug is still used as a steroid-sparing agent in steroid-sensitive minimal change disease and focal segmental glomerulosclerosis. In membranous nephropathy, cyclophosphamide, alternated or associated with corticosteroids, proved to be beneficial in obtaining remission of nephrotic syndrome and preserving renal function. Cyclophosphamide is considered as a first-line treatment for rapidly progressive glomerulonephritis and the hectic phases of lupus nephritis. In conclusion, cyclophosphamide is a cheap drug that may be useful in a number of glomerular diseases but it may lead to severe side effects. A close monitoring of blood count and clinical conditions, as well as low cumulative doses of cyclophosphamide are strongly recommended when using the drug in patients with renal diseases.     

Does inadequate sleep play a role in vulnerability to obesity?

The prevalence of obesity is increasing rapidly worldwide, which is cause for concern because obesity increases the risk of cardiovascular disease and diabetes, reduces life expectancy, and impairs quality of life. A better understanding of the risk factors for obesity is therefore a critical global health concern, and human biologists can play an important role in identifying these risk factors in various populations. The objective of this review is to present the evidence that inadequate sleep may be a novel risk factor associated with increased vulnerability to obesity and associated cardiometabolic disease. Experimental studies have found that short-term sleep restriction is associated with impaired glucose metabolism, dysregulation of appetite, and increased blood pressure. Observational studies have observed cross-sectional associations between short sleep duration (generally <6 h per night) and increased body mass index or obesity, prevalent diabetes, and prevalent hypertension. Some studies also reported an association between self-reported long sleep duration (generally >8 h per night) and cardiometabolic disease. A few prospective studies have found a significant increased risk of weight gain, incident diabetes, and incident hypertension associated with inadequate sleep. Given the potential link between inadequate sleep and obesity, a critical next step is to identify the social, cultural, and environmental determinants of sleep, which would help to identify vulnerable populations. Future human biology research should consider variation in sleep characteristics among different populations and determine whether the associations between sleep and obesity observed in Western populations persist elsewhere.     

Does "autoreactivity" play a role in atopic dermatitis?

The role of autoimmunity in atopic dermatitis (AD) is unclear. We sought to critically examine the occurrence, correlation with severity, and possible causative role of autoreactivity in patients with AD. Our systematic review of studies identified from MEDLINE included 31 experiments that described autoreactivity in patients with AD. We defined autoreactivity as in vitro or in vivo evidence of immune response to autologous human, generic human, or recombinant human proteins or other tissue/cellular components. Autoreactivity prevalence in patients with AD ranged from 23% to 91% in 14 studies involving 2644 participants, although it did not appear to vary with age, sex, or disease duration. In contrast to studies of AD, IgE autoreactivity was not found in healthy subjects or in those with allergic rhinoconjunctivitis, psoriasis, systemic lupus erythematosus, or other inflammatory diseases (8 studies of 816 participants). Two reports found a positive correlation between autoreactivity and AD severity. We suggest that autoreactivity might be playing a causative role in AD based on the magnitude and specificity of the associations found; plausible mechanisms through IgE autoantibodies, IgG autoantibodies, and T(H)1 autoreactivity; and experimental elicitation of eczematous lesions after provocation. Whether autoantibodies contribute to AD chronicity now needs to be examined in longitudinal studies.     

Does complement play a role in bone development and regeneration?

The skeletal and the immune system are not two independent systems, rather, there are multifaceted and complex interactions between the different cell types of both systems and there are several shared cytokines. As a part of the innate immunity, the complement system was found to be an important link between bone and immunity. Complement proteins appear to be involved in bone development and homeostasis, and specifically influence osteoblast and osteoclast activity. This review describes the complex mutual regulation of the two systems, and indicates some of the negative side effects as a result of inappropriate or excessive complement activation.     

Does cellular iron dysregulation play a causative role in Parkinson's disease?

Selective dopaminergic cell loss in Parkinson's disease is correlated with increased levels of cellular iron. It is still hotly debated as to whether the increase in iron is an upstream event which acts to promote neurodegeneration via formation of oxidative stress or whether iron accumulates as a by-product of the neuronal cell loss. Here we review evidence for loss of iron homeostasis as a causative factor in disease-associated neurodegeneration and the primary players which may be involved. A series of recent studies suggest that iron regulatory proteins (IRPs) coordinate both cellular iron levels and energy metabolism, both of which are disrupted in Parkinson's disease (PD) and may in turn contribute to increased levels of oxidative stress associated with the disease. Iron has also been recently been implicated in promotion of alpha-synuclein aggregation either directly or via increasing levels of oxidative stress suggesting an important role for it in Lewy body formation, another important hallmark of the disease.     

Does Toll-like receptor 3 play a biological role in virus infections?

The Toll-like receptor (TLR) family functions to recognize conserved microbial and viral structures with the purpose of activating signal pathways to instigate immune responses against infections by these organisms. For example, in vitro studies reveal that the TLR3 ligand is a double-stranded RNA (dsRNA), a product of viral infections. From this observation, it has been proposed that TLR3 is likely an important first signal for virus infections. We approached this issue by investigating the role of TLR3 in four different infectious viral models (lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), murine cytomegalovirus (MCMV), and reovirus) and in TLR3 genetically deficient ((-/-)) mice. Our results indicate that TLR3 is not universally required for the generation of effective antiviral responses because the absence of TLR3 does not alter either viral pathogenesis or impair host's generation of adaptive antiviral responses to these viruses.     

Does CA1 dopaminergic system play a role in cholestasis induced hypothermia?

ObjectiveThere is some of evidence describing that cholestasis induces hypothermia. Meanwhile, there is paucity of comprehensive data on the mechanism(s) governing this phenomenon. The present study was undertaken to determine the effect of CA1 dopaminergica system on cholestasis induced hypothermia.MethodsMale NMRI mice weighing 25–30 g, were used. Bilateral cannulae were implanted in dorsal hippocampi (CA1) for drug microinjection. Animals were randomly divided into non-operated control, sham-operated and bile duct-ligated (BDL) groups. Cholestasis was induced by means of main bile duct ligation. Body temperatures were measured before, two and four days after BDL.ResultsData indicated that, two and four days post BDL, the body temperature decreases as compared to the sham-operated animals, which indicates hypothermia. Intra-CA1 injection of different doses of sulpiride (SUL; 0.25, 0.5 and 0.75 μg/mouse), SCH23390 (SCH; 0.125, 025 and 0.5 μg/mouse), SKF38393 (SKF; 0.25, 0.5 and 1 μg/mouse) and quinpirole (QUI; 0.25, 05 and 0.75 μg/mouse) exerted no effect on body temperature in non-operated and sham operated mice, by themselves. Moreover, intra-CA1 injection of SUL, QUI or SKF blocked, whereas, SCH tended to increase BDL induced hypothermia.ConclusionsThe present data revealed that the CA1 dopaminergic system is possibly involved in the BDL induced impairment of thermoregulation.     

Does COX2-dependent PGE2 play a role in neuropathic pain?

Neuropathic pain (NeP) is a common chronic pain state with unmet medical needs. Due to poorly defined underlying mechanisms, current therapies for NeP are far from satisfactory. Mounting evidence suggests that long-term plasticity in pain signaling pathways underpins the pathogenesis of NeP. Inflammatory responses in injured nerves have been recognized as important events initially sensitizing nociceptive neurons and subsequently inducing long-term plasticity in the dorsal root ganglion. Inflammatory cells such as invading macrophages and Schwann cells produce a wide array of inflammatory mediators. Cyclooxygenase 2-dependent prostaglandin E2 (COX2/PGE2) is one of the important mediator abundantly produced in injured nerves and involved in the genesis of NeP. In this mini-review, we highlight possible novel mechanisms underlying the role of COX2/PGE2 in injured nerves in the genesis of NeP. Long lasting COX2/PGE2 in injured nerves may induce chronic effects on nociceptors to facilitate the synthesis of pain-related molecules by stimulating 'en passant' injured or spared axons. COX2/PGE2 may also induce chronic effects on local inflammatory cells in injured nerves to facilitate the synthesis of inflammatory mediators via autocrine and paracrine pathways. COX2/PGE2 in injured nerves and downstream PGE2 EP receptor signaling should be considered as therapeutic targets to more effectively treat chronic NeP.     

Does oxidative stress play a critical role in cardiovascular complications of kawasaki disease?

Abstract The aim of the present work was to evaluate the contribution of the different reactive oxidizing species to systemic oxidative stress in the whole blood of patients with Kawasaki disease (KD). This is a rare generalized systemic vasculitis typical of the early childhood characterized by inflammation and endothelial dysfunction with a high risk for cardiovascular fatal events. We found that, compared to age-matched healthy donors, blood from KD patients showed increased production of oxygen- and nitrogen-derived species as detected by electron paramagnetic resonance (EPR) spin probing with the cyclic hydroxylamine 1-hydroxy-3-carboxy-pyrrolidine. The (?)NO pathway involvement was also confirmed by the decreased concentrations of the endogenous (?)NO synthase inhibitor asymmetric dimethyl-arginine and the increased amounts of 3-nitrotyrosine in plasma. Further, increased plasma yields of the proinflammatory enzyme myeloperoxidase were also observed. The appearance of circulating red blood cell alterations typically associated with oxidative imbalance and premature aging (e.g., decrease of total thiol content, glycophorin A, and CD47 expression, as well as increase of phosphatidylserine externalization) has also been detected. Collectively, our observations lead to hypothesize that the simultaneous oxidative and nitrative stress occurrence in the blood of KD patients may play a pathogenetic role in the cardiovascular complications often associated with this rare disease. Antioxid. Redox Signal. 17, 1441-1446.     

Does experience with role play activate "mindreading" in a perspective-taking task?

This study investigated the development of "mindreading" in young adults. Forty university students were divided into two groups (role-play group and no-role-play group). Then they participated in a perspective-taking task in which the use of mindreading is essential. The participants viewed a computer display of eight familiar objects in different compartments of a wall divider with four rows of four compartments. Some of the compartments were open to see through, while others had back panels and thus which, if any, object was present could only be seen from the participant's side. They were instructed to touch the display corresponding to an object in a compartment in accord with the instructions of a "manager" who stood behind the divider and thus could not see into all of the compartments. The no-role-play group made more errors than the role-play group, and took longer to respond. The effects of role play lasted during five successive task blocks. These results suggest that experience with role play activates mindreading in this perspective-taking task.     

Does mitochondrial DNA play a role in Parkinson's disease? A review of cybrid and other supportive evidence

SIGNIFICANCE: Mitochondria are currently believed to play an important role in the neurodysfunction and neurodegeneration that underlie Parkinson's disease (PD). RECENT ADVANCES: While it increasingly appears that mitochondrial dysfunction in PD can have different causes, it has been proposed that mitochondrial DNA (mtDNA) may account for or drive mitochondrial dysfunction in the majority of the cases. If correct, the responsible mtDNA signatures could represent acquired mutations, inherited mutations, or population-distributed polymorphisms. CRITICAL ISSUES AND FUTURE DIRECTIONS: This review discusses the case for mtDNA as a key mediator of PD, and especially focuses on data from studies of PD cytoplasmic hybrid (cybrid) cell lines.