Psychological morbidity, sources of stress and coping strategies among undergraduate medical students of Nepal

<p>Abstract</p> <p>Background</p> <p>In recent years there has been a growing appreciation of the issues of quality of life and stresses involved medical training as this may affect their learning and academic performance. However, such studies are lacking in medical schools of Nepal. Therefore, we carried out this study to assess the prevalence of psychological morbidity, sources and severity of stress and coping strategies among medical students in our integrated problem-stimulated undergraduate medical curriculum.</p> <p>Methods</p> <p>A cross-sectional, questionnaire-based survey was carried out among the undergraduate medical students of Manipal College of Medical Sciences, Pokhara, Nepal during the time period August, 2005 to December, 2006. The psychological morbidity was assessed using General Health Questionnaire. A 24-item questionnaire was used to assess sources of stress and their severity. Coping strategies adopted was assessed using brief COPE inventory.</p> <p>Results</p> <p>The overall response rate was 75.8% (407 out of 525 students). The overall prevalence of psychological morbidity was 20.9% and was higher among students of basic sciences, Indian nationality and whose parents were medical doctors. By logistic regression analysis, GHQ-caseness was associated with occurrence of academic and health-related stressors. The most common sources of stress were related to academic and psychosocial concerns. The most important and severe sources of stress were staying in hostel, high parental expectations, vastness of syllabus, tests/exams, lack of time and facilities for entertainment. The students generally used active coping strategies and alcohol/drug was a least used coping strategy. The coping strategies commonly used by students in our institution were positive reframing, planning, acceptance, active coping, self-distraction and emotional support. The coping strategies showed variation by GHQ-caseness, year of study, gender and parents' occupation.</p> <p>Conclusion</p> <p>The higher level of psychological morbidity warrants need for interventions like social and psychological support to improve the quality of life for these medical students. Student advisors and counselors may train students about stress management. There is also need to bring about academic changes in quality of teaching and evaluation system. A prospective study is necessary to study the association of psychological morbidity with demographic variables, sources of stress and coping strategies.</p

The homozygous K280N troponin T mutation alters cross-bridge kinetics and energetics in human HCM

Hypertrophic cardiomyopathy (HCM) is a genetic form of left ventricular hypertrophy, primarily caused by mutations in sarcomere proteins. The cardiac remodeling that occurs as the disease develops can mask the pathogenic impact of the mutation. Here, to discriminate between mutation-induced and disease-related changes in myofilament function, we investigate the pathogenic mechanisms underlying HCM in a patient carrying a homozygous mutation (K280N) in the cardiac troponin T gene (TNNT2), which results in 100% mutant cardiac troponin T. We examine sarcomere mechanics and energetics in K280N-isolated myofibrils and demembranated muscle strips, before and after replacement of the endogenous troponin. We also compare these data to those of control preparations from donor hearts, aortic stenosis patients (LVHao), and HCM patients negative for sarcomeric protein mutations (HCMsmn). The rate constant of tension generation following maximal Ca2+ activation (kACT) and the rate constant of isometric relaxation (slow kREL) are markedly faster in K280N myofibrils than in all control groups. Simultaneous measurements of maximal isometric ATPase activity and Ca2+-activated tension in demembranated muscle strips also demonstrate that the energy cost of tension generation is higher in the K280N than in all controls. Replacement of mutant protein by exchange with wild-type troponin in the K280N preparations reduces kACT, slow kREL, and tension cost close to control values. In donor myofibrils and HCMsmn demembranated strips, replacement of endogenous troponin with troponin containing the K280N mutant increases kACT, slow kREL, and tension cost. The K280N TNNT2 mutation directly alters the apparent cross-bridge kinetics and impairs sarcomere energetics. This result supports the hypothesis that inefficient ATP utilization by myofilaments plays a central role in the pathogenesis of the disease

Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy

Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' — a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed

Vitalism in contemporary chiropractic: a help or a hinderance?

Background: Chiropractic emerged in 1895 and was promoted as a viable health care substitute in direct competition with the medical profession. This was an era when there was a belief that one cause and one cure for all disease would be discovered. The chiropractic version was a theory that most diseases were caused by subluxated (slightly displaced) vertebrae interfering with “nerve vibrations” (a supernatural, vital force) and could be cured by adjusting (repositioning) vertebrae, thereby removing the interference with the body’s inherent capacity to heal. DD Palmer, the originator of chiropractic, established chiropractic based on vitalistic principles. Anecdotally, the authors have observed that many chiropractors who overtly claim to be “vitalists” cannot define the term. Therefore, we sought the origins of vitalism and to examine its effects on chiropractic today. Discussion: Vitalism arose out of human curiosity around the biggest questions: Where do we come from? What is life? For some, life was derived from an unknown and unknowable vital force. For others, a vital force was a placeholder, a piece of knowledge not yet grasped but attainable. Developments in science have demonstrated there is no longer a need to invoke vitalistic entities as either explanations or hypotheses for biological phenomena. Nevertheless, vitalism remains within chiropractic. In this examination of vitalism within chiropractic we explore the history of vitalism, vitalism within chiropractic and whether a vitalistic ideology is compatible with the legal and ethical requirements for registered health care professionals such as chiropractors. Conclusion: Vitalism has had many meanings throughout the centuries of recorded history. Though only vaguely defined by chiropractors, vitalism, as a representation of supernatural force and therefore an untestable hypothesis, sits at the heart of the divisions within chiropractic and acts as an impediment to chiropractic legitimacy, cultural authority and integration into mainstream health care

Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy

Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO2), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). Twenty patients with HCM (12 men, mean age: 55.2 +/- 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 +/- 10 years) were studied with [C-11]acetate PET to assess MVO2. CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. Between study groups, MVO2 (controls: 0.12 +/- 0.04 ml center dot min(-1)center dot g(-1), HCM: 0.13 +/- 0.05 ml center dot min(-1)center dot g(-1), p = 0.64) and EW (controls: 9,139 +/- 2,484 mmHg center dot ml, HCM: 9,368 +/- 2,907 mmHg center dot ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 +/- 21 g, HCM: 200 +/- 76 g, p < 0.001) and MEE was decreased in HCM patients (controls: 35 +/- 8%, HCM: 21 +/- 10%, p < 0.001). MEE was related to stroke volume (SV), LV outflow tract gradient, NH2-terminal pro-brain natriuretic peptide (NT-proBNP) and serum free fatty acid levels (all p < 0.05). Multivariate analysis revealed that SV ( = 0.74, p < 0.001) and LVM ( = -0.43, p = 0.013) were independently related to MEE. HCM is characterized by unaltered MVO2, impaired EW generation per gram of myocardial tissue and subsequent deteriorated myocardial efficiency. Mechanical external efficiency could independently be predicted by SV and LVM

Modulation of thin filament activation by breakdown or isoform switching of thin filament proteins: physiological and pathological implications.

In the heart, the contractile apparatus is adapted to the specific demands of the organ for continuous rhythmic contraction. The specialized contractile properties of heart muscle are attributable to the expression of cardiac-specific isoforms of contractile proteins. This review describes the isoforms of the thin filament proteins actin and tropomyosin and the three troponin subunits found in human heart muscle, how the isoform profiles of these proteins change during development and disease, and the possible functional consequences of these changes. During development of the heart, there is a distinctive switch of isoform expression at or shortly after birth; however, during adult life, thin filament protein isoform composition seems to be stable despite protein turnover rates of 3 to 10 days. The pattern of isoforms of actin, tropomyosin, troponin I, troponin C, and troponin T is not affected by aging or heart disease (ischemia and dilated cardiomyopathy). The evidence for proteolysis of thin filament proteins in situ during ischemia and stunning is evaluated, and it is concluded that C-terminal cleavage of troponin I is a feature of irreversibly injured myocardium but may not play a role in reversible stunning

The E117K mutation in β-tropomyosin disturbs concerted conformational changes of actomyosin in muscle fibers.

The effect of the skeletal myopathy-causing E117K mutation in human β-tropomyosin on actomyosin structure during the ATPase cycle was studied using fluorescent probes bound to actin subdomain 1 and the myosin head. Multistep changes in flexural rigidity of actin filament and in spatial arrangement of actin subdomain 1 and myosin SH1 helix in troponin-free ghost muscle fibers were revealed. During the ATPase cycle E117K tropomyosin inhibited the rotation of subdomain 1 by 46% and the tilt of the SH1 helix by 49% compared with wild-type. At strong-binding stages the proportion of strong binding sub-states in the actomyosin population is decreased by the mutation. At weak-binding stages abnormally high numbers of switched-on actin monomers were observed, thus indicating a disturbance in concerted conformational changes of actomyosin. These structural alterations are likely to underlie the contractile deficit observed with this mutation

Altered regulatory properties of human cardiac troponin I mutants that cause hypertrophic cardiomyopathy.

Cardiac troponin I (cTnI) is the inhibitory component of the troponin complex and is involved in the calcium control of heart muscle contraction. Recently, specific missense mutations of the cTnI gene (TNNI3) have been shown to cause familial hypertrophic cardiomyopathy (HCM). We have analyzed the functional effects of two HCM mutations (R145G and R162W) using purified recombinant cTnI. Both mutations gave reduced inhibition of actin-tropomyosin-activated myosin ATPase, both in experiments using cTnI alone and in those using reconstituted human cardiac troponin under relaxing conditions. Both mutant troponin complexes also conferred increased calcium sensitivity of ATPase regulation. Studies on wild type/R145G mutant mixtures showed that the wild type phenotype was dominant in that the inhibition and the calcium sensitivity conferred by a 50:50 mixture was more similar to wild type than expected. Surface plasmon resonance-based assays showed that R162W mutant had an increased affinity for troponin C in the presence of calcium. This observation may contribute to the increased calcium sensitivity found with this mutant and also corroborates recent structural data. The observed decreased inhibition and increased calcium sensitivity suggest that these mutations may cause HCM via impaired relaxation rather than the impaired contraction seen with some other classes of HCM mutants