New Insights into Disease and Pathogen Research Vol. 1

Molecular Basis of Pathogenesis of Diabetes Mellitus Type 2- a New Perspective

A. S. V. Prasad — Wed, 24 Jul 2019 00:00:00 +0000

Decreased insulin secretion due to beta cell dysfunction of the pancreas and defective utilization of insulin due to insulin resistance / Hyperinsulinemia are two important issues in the pathogenesis of DM2. There are many explanations in the literature to account for these two observed phenomena and their interrelationship. DM2 is believed to occur due to a complex interplay of environmental and Behavioural factors in genetically predisposed persons. Among the theories explaining the pathogenesis of DM2, the viscera- Portal hypothesis, the Ectopic fat hypothesis and the adipose tissue as an endocrinal gland are prominent. Besides, the role played by oxidative stress, metabolic stress, mitochondrial dysfunction, endoplasmic reticulum stress, etc. are also advanced. It is felt that basic to and at the core of all the observed facts, is the shift of energy metabolism from normal glycolysis to B- oxidation of fats. Hence, how B - oxidation prevails over glycolysis is the fundamental issue to be addressed together with its interrelationships with insulin resistance, as to which is the cause and which is the effect. At the molecular level, an attempt to find answers to the above questions is made in this paper.

To this extent, the Randle fatty acid cycle (Substrate competition theory of Randle) is suitably modified and applied to explain the switch of Energy metabolisms in DM2. Defective disulfide bond formation of the insulin receptor which makes it physiologically ineffective, is suggested as the cause of the insulin resistance where as the prevailing molecular mechanisms stress on post-receptor signaling defect. The cause and effect of both are discussed. This line is considered to be a departure from traditional approaches broached above and briefly outlined in this article.

Delirious Mania: Recognition and Successful Treatment with Donepezil in the Context of Historical and Contemporary Investigations of Delirium and Delirious Mania

Laurie Jo Moore, Mila Goldner-Vukov — Wed, 24 Jul 2019 00:00:00 +0000

Aims: Presentation of a case of severe delirious mania with resolution of delirium after treatment with donepezil.
Presentation of Case: KA was a 44 y/o Australian female with a history of bipolar affective disorder with psychotic manic episodes. Two weeks prior to her psychiatric admission she was admitted to a medical ward after an overdose (OD) of acetaminophen. On review, it appeared that this OD may have been the beginning of an unrecognized delirious mania. The patient was sent home and returned 2 weeks later for a prolonged psychiatric admission with multiple medical comorbidities. Psychiatric management and medical care were provided in intensive settings and despite adequate treatment and improvement in mood symptoms, her delirium did not resolve. Immediately upon institution of donepezil, her delirium resolved. After a period of stability, donepezil was stopped. Her delirium returned and donepezil was reinstituted with resolution of normal cognitive function.
Discussion: The DSM 5 criteria for Delirium and some inherent difficulties using these criteria are discussed. A review of the literature of delirious mania is presented which shows unresolved controversies but an evolving recognition of this disorder. A Cochrane Review shows no benefit in the use of acetylcholinesterases in the treatment of delirium. However, the multiple etiologies and pathological processes involved in delirium may require unique and individual recognition and management.
Conclusion: This case suggests that the use of donepezil is strongly recommended in the treatment of delirious mania. Further study is required to clarify in this challenging disorder.

The Role of Chromogenic Replica System for Isolation & Identification of Uropathogens in the Era of Molecular Diagnostics

Seema Bose — Wed, 24 Jul 2019 00:00:00 +0000

Multidrug resistance in uropathogens is a serious problem in a health care set up. To deal with that, rapid identification of the etiological agent from clinical urine sample is utmost important. Use of replica disc for presumptive identification of uropathogens is an easy to perform, cost effective and rapid method, which can be, adopted in the microbiology laboratories as a primary screening method.

Neurocysticercosis and Psycho-social Trauma

Mila Goldner-Vukov, Laurie Jo Moore, Hesitha Abeysundera, Arulmathy Arunachalam — Wed, 24 Jul 2019 00:00:00 +0000

This chapter describes a patient with neurocysticercosis who presented with psychotic features. He came to Cairns, Queensland, Australia as a refugee following his experiences of civil unrest in Rwanda. A review of the current literature on neurocysticercosis is described including an introduction, clinical presentation of neurocysticercosis, diagnosis, treatment, case presentation, clinical course, Axis 1-IV diagnoses and discussion highlighting psychosocial trauma. A history of the genocide he survived in Rwanda in 1994 is summarised along with a discussion of traumatic or dissociative psychosis that was included in his differential diagnosis. The patient was admitted through the Emergency Department where he was assessed and treated in a medical ward with the involvement of the Psychiatric Liaison Team and Infectious Disease Team. CT and MRI of the brain confirmed the diagnosis of neurocysticercosis. Medical treatment was administered for neurocysticercosis and community psychiatric and medical follow-up were undertaken. Medical treatment of neurocysticercosis was successful but the patient subsequently developed a seizure disorder that was treated effectively and subsequently resolved without the need for continuing medication. The patient’s psychotic disorder was treated with medication and supportive psychotherapy. His delirium cleared quickly after two days treatment with an antipsychotic was given. Unresolved grief related to psycho-social trauma was addressed as an on-going process during his community psychiatric treatment.
Neurocysticercosis is rare and should be considered in immigrants from countries that have endemic neurocysticercosis. A small minority of patients present with psychosis. This patient who survived extensive trauma presented with psychosis that required assessment for traumatic or dissociative psychosis.

Effect of Verbal & Pictorial Materials on Memory Retention among Undergraduate Students - An Interventional Study

Wed, 24 Jul 2019 00:00:00 +0000

Aims: To compare the effectiveness of pictorial against verbal materials in memory retention among medical students.
Study Design: Crossover randomized controlled trial.
Place and Duration of Study: This study was conducted in Melaka-Manipal Medical College, Muar, Johor, Malaysia in April 2016.
Methodology: 38 right-handed medical students of Melaka-Manipal Medical College were volunteers and participants were divided into two groups equally via simple random sampling. One group of participants were to recall pictures shown first followed by words while the other group of participants were to recall words first followed by pictures. All the pictures and words shown were of everyday objects. Data were analysed using Epi Info version 7.
Results: There was a significant difference of memory retention between pictures and words (P-value =; p < 0.05) and of memory accuracy (P-value; p < 0.05). For memory retention, both groups were found to have higher scores for pictures than words as both groups obtained a mean score of 11.3 and 13.4 respectively for the pictures and 9.7 and 11.1 respectively for words. For memory accuracy, pictures were found to be recalled better than words as the mean scores for the pictures are higher than words in both groups.
Conclusion: Information in the form of pictures should be more utilized in medical schools so that medical students can have better memory retention which in turn will lead to better academic performances. This study shows that picture superiority effect has a remarkable effect in the memory retention of pictorial and verbal materials. Therefore, the results of this study support the need to implement and apply this theory in medical schools which require heavy memorization of informations in the form of pictures and text. Hence, the utilization of this method of study is essential for more efficient learning and improving academic performance.

Spotlight on Leucin-Rich Repeat Kinase 2 (LRRK2) G2019S Mutation and Parkinson's Disease in Egyptians

Ehab. S. El Desoky, Eman. M. Khedr, Mohamed. S. Khalil, Thomas Gasser — Wed, 24 Jul 2019 00:00:00 +0000

Aim: Many causative genes and susceptibility loci have been identified to be associated with Parkinson's disease (PD) in different ethnic populations. One of these genes is the Leucin-rich repeat kinase 2 (LRRK2) gene. The G2019S substitution in that gene is the most common mutation identified to co-segregates with PD. One of the significant mutations in LRRK2 linked to PD is the G2019S which has been found associated with neuronal impairment and loss of dopaminergic neurons. Furthermore, new monoclonal antibody assay has been developed to quantify LRRK2 G2019S kinase pathway activity in Parkinson’s patients. This type of mutation has been investigated in the North part of Egypt (Alexandria and nearby region), which showed an incidence of 9.7% of heterozygous mutation in LRRK2 G2019S in a sample of Egyptians with sporadic PD. We investigated the same mutation in 69 Egyptian patients with sporadic PD and 96 ethnically matched controls who all were inhabitants of Upper Egypt to find out if it could be a susceptibility gene for PD among Egyptians.
Place and Duration of Study: Departments of pharmacology, neurology, and clinical pathology, Assiut University (Egypt) and Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany between June 2010 and September 2011.
Methodology: Sixty nine patients with PD of sporadic type and ninety six controls were included in the study and all were inhabitants of Assiut Governorate and nearby region in Upper Egypt. PCRgenotyping analysis for the point mutation G2019S in the exon 41 was performed and presence or absence of mutation was confirmed by direct sequencing of the probands identified of the DNA.
Results: Genotyping analysis and sequencing of DNA showed only one patient who was carrier to the mutation G2019S (1/69; incidence: 1.45%) and it was of heterozygous style. The rest of subjects (patients and control) were not carrying the mutation. This rarity of this kind of mutation among the Egyptian sample studied suggests that it may be a rare cause of PD in Upper Egypt region. However, if it is observed, it may have a trend of heterozygosity genotyping style as previously defined in the Egyptians living in the North region of Egypt.
Conclusion: The very low incidence of G2019S mutation in Egyptians living in Upper Egypt compared to Egyptians inhabitants in North Egypt suggests a prospective multicenter study on a large number of Egyptians with Parkinson’s disease to reach a real incidence of that mutation and if it has (or not) a correlation to causation and course of Parkinson’s disease among Egyptians. Also, genetic assessment of other points of mutations other than G2019S on LRRK2 is required among Egyptians with PD.

Aminoff Suffering Syndrome: A Challenge for Medical and Nursing Staff during End-of-Life Care: Open Letter and Proposals

Bechor Zvi Aminoff — Wed, 24 Jul 2019 00:00:00 +0000

The diagnosis of Aminoff Suffering Syndrome in advanced dementia determined by measuring the suffering level of patients according to the Mini Suffering State Examination (MSSE) scale—facilitates acceleration and intensity of care by the nursing staff in order to prevent and relieve suffering. Relief of Suffering Units for patients with Aminoff Suffering Syndrome should be an integral part of any medical department or nursing home that specializes in caring for elderly people. Aminoff Suffering Syndrome at the end of life could, and should be diagnosed, prevented and diminished. The treatment of patients with Aminoff Suffering Syndrome at the end of life is a genuine challenge for medical and nursing personnel. Our proposals for further experimental studies at the end of life are the diagnosis of Aminoff Suffering Syndrome in dying patients with cancer, AIDS, cardiac, pulmonary, kidney, liver and other terminal diseases. We recommend that such studies should be performed at the St Christopher's Hospice and all other settings.

Silent Myocardial Ischemia in Master Marathon Runner

Massimo Bolognesi, Diletta Bolognesi — Wed, 24 Jul 2019 00:00:00 +0000

Silent myocardial ischemia is defined as objective documentation of myocardial ischemia in the absence of angina or anginal equivalents. Silent myocardial ischemia is quite different from silent coronary artery disease. The symptomatic angina is the tip of the ischemic iceberg and it is less frequent in athletes than in non-athletes. Athletes change their perception of ischemic stimulus and increasing pain threshold from increased circulating endorphin levels. Silent myocardial ischemia is more prevalent than angina in patients with coronary artery disease, and athletes are not immune to it. In order to discover early stages of malignant neoplasia (e.g. breast and colon cancer) in the asymptomatic stage and thus prevent reaching final stages of the disease, screening participation has been widely accepted. Vice versa, although atherosclerotic cardiovascular disease causes more deaths and disabilities than all causes of death correlated to cancer, there are no precise guidelines concerning the screening of asymptomatic elements suffering from atherosclerosis. There are a number of reports of exercise-related sudden deaths and myocardial infarctions in aerobically trained athletes suffering from exercise - induced silent myocardial ischemia. The most appropriate and common method to discover silent myocardial ischemia is exercise stress testing. Therefore, in this chapter the authors describe three emblematic cases of silent myocardial ischemia detected in master marathon runners during systematic pre-participation screening. These marathon runners were asymptomatic but were suffering from a severe coronary artery disease that was detected only thanks to exercise treadmill stress test, and were then properly treated. Silent myocardial ischemia is not such a rare event in athletes, indeed quite the opposite. In fact, even though athletes are asymptomatic this does not exclude the possibility that they are suffering from severe coronary artery disease.

Metabolic Syndrome in Postmenopause: eNOS, p22 phox, CETP and ESR1 Gene Polymorphisms Related to Endocrine-Metabolic Changes

Wed, 24 Jul 2019 00:00:00 +0000

Aims: To investigate the endocrine-metabolic changes in postmenopausal women with MetS and examine relationship with the polymorphisms of eNOS-G894T, p22(phox)-930 A/G, CETP TaqIB, ESR1 (PvuII and XbaI) genes.
Methods: 280 postmenopausal apparently healthy women aged between 60 and 80 years were classified into non-MetS (212) and MetS (68). Clinical, anthropometric and endocrine-metabolic parameters were measured. The single nucleotide polymorphisms were determined and tested for interacting with these parameters.
Results: The weight, waist circumference, blood pressure, WBC, triglycerides, LDL-C, TG/HDL-C ratio, apolipoprotein (apo)B, apoB/apoA-I ratio, fasting glucose, insulin, HOMA, uric acid, were higher and HDL-C was lower in MetS group thus fulfilled the criteria for the MetS. The significant higher levels of E2, T3, GHBP, PTH and lower levels of cortisol, SHBG, FSH, LH, IGFBP1, cortisol/DHEA ratio were also detected. Genetic association studies showed that presence of A allele p22phoxA/G (OR=1.62; CI=1.08-2.42) and heterozygote AG-XbaI(ESR1) (OR=2.29; CI= 1.19-4.37) indicated a significant risk for MetS. The binary logistic regression (MetS vs Controls) showed an interaction of G894TeNOS polymorphism with MetS (OR>2.5; 95% CI =1.47-4.90) that associated with SBP, TG, apoB, uric acid, ASTGOT (OR>1) and HDL-C (OR<1). CETP TaqIB polymorphism associated with MetS (OR<1) in presence of SBP, GLU, TG with OR>1. ESR1 PvuII (T/C) associated with MetS (OR between 1.59-8.60) in presence of LDL-C, TG/HDL-C ratio, P with OD>1 and HDL-C, androstenedione, SHBG, FAI with OR<1.
In MetS group the carriers of -TT (eNOS-G894T) genotype had higher levels of blood pressure, glucose; -GG (p22phox A/G) had higher levels of BMI, apoB/apoA ratio; -B1B2 (CETP B1/B2) had higher levels of SBP, glucose, cholesterol, HDL-C, CRP, GHBP and lower levels of TSH; -CC (PvuII) and GG (XbaI) ESR1 genotypes showed higher levels of glucose.
Conclusions: These results sustain an interaction between the studied polymorphisms and the endocrine-metabolic changes in MetS pathogenesis. Our results sustain an interaction between the studied polymorphisms and their phenotypes in conferring a higher susceptibility to the endocrinemetabolic changes involved in pathogenesis of MetS. The elevated values of TG/HDL-C and apoB/apoA ratios could be risk indicators for calculation cardiovascular risk in of MetS.

Fetuin A: A Newer Marker for Pre Diabetes

Sukhraj Kaur, Mridula Mahajan — Wed, 24 Jul 2019 00:00:00 +0000

Objective: To evaluate the role of Fetuin A levels in predicting glycemic outcome in individuals with impaired fasting glucose.
Research Design and Methods: A total of 742 young individuals were recruited for the study out of which 177 had impaired fasting glucose, 468 had normoglycemia and 97 individuals with diabetes. These individuals were offsprings of diabetics (either mother or father or both) and were siblings amongst themselves belonging to age group of 18-35 years. Various biochemical investigations such as fasting plasma glucose, glycosylated Hb, serum insulin, C-peptide and Fetuin A were carried out. People with impaired fasting glucose were followed and analyzed according to glycemic outcome and quartile of Fetuin A level.
Results: A total of 66 individuals with prediabetes reverted back to normal, 28 progressed to diabetes and 83 remained with prediabetes over a mean±S.D follow up of 24±4.1 months. People in the highest quartile of fetuin A had the highest Insulin, Insulin Resistance, Increased loss of beta cell activity, decreased sensitivity to insulin and a higher rate of progression to diabetes (relative risk 11.96, 95% CI 5.9 to 24.01, p<0.001) and a significantly lower rate of reversion to normoglycemia (relative risk 5.62, 95% CI 3.16 to 9.9, p<0.001) than those in other Fetuin A quartiles. fetuin A correlated positively with Insulin (r= +0.289, p<0.001), C-peptide (r=+ 0.177, p<0.001), %β cell function(r= -0.368, p<0.001), insulin resistance (r= +0.436, p<0.001) and glycosylated Hb (r=+0.958, p<0.05) and negatively with % sensitivity to insulin( r= -0.287, p<0.001). Cox regression analysis showed that baseline fetuin A, insulin levels and fasting glucose levels were predictive of reversion to normoglycemia.
Conclusions: Increased fetuin A levels had an adverse impact on glycemic outcomes thus suggesting that fasting plasma glucose and Fetuin A can be used as a tool to determine the susceptibility of an individual to develop pre-diabetes and thus diabetes mellitus.

Ethical Dilemmas in Orthodontics

Maen Mahfouz, Yara Mahfouz — Wed, 24 Jul 2019 00:00:00 +0000

Introduction: Doctors and dentists possess special training and expertise which patients and their families do not. This special knowledge and skillset, which has the potential to benefit as well as harm patients, places on the medical or dental professional the moral obligation to act in the interests of the patient.
Aim: To present a clinical case as an example of an ethical dilemma that orthodontists may face when advocating for the best interests of a child.
Case Presentation: A five-year-old girl attended my private orthodontic clinic with a main complaint of lower anterior teeth overlapping her upper anterior teeth. She was in the primary dentition stage. There was a conflict between the orthodontist’s interests of the child and the need to respect parental autonomy. Her mother had doubts and misgivings about the effectiveness of orthodontic treatment and was reluctant to have her daughter begin treatment at this age.
Discussion: Factually, there are ethical problems continuously encountered by orthodontists during orthodontic interventions, even though there are important human values at stake in the course of treatment. These values may include preventing pain, maintaining and restoring oral function for normal speech and eating, preserving and restoring the patient’s physical appearance, and promoting a sense of control over and responsibility for one’s own health. Last but definitely not least, orthodontists deal largely with children, and ethical problems arise especially when there is moral uncertainty.
Conclusion: The ethical traditions and codes of conduct of medicine and dentistry require orthodontists to act in the interest of their patients regardless of financial arrangements, and even, at times, with risk to themselves. In the case of children, this interest in the patient becomes even more pronounced and may conflict with the orthodontist’s interests to respect the wishes of the patient.

Family Risk of Metabolic Disorder; A Parameter for Timely Screening of Vascular Endothelial Health

Preeti Kanawjia, Sunita Tiwari, Manish Bajpai — Wed, 24 Jul 2019 00:00:00 +0000

Aim: To study the correlation of vascular endothelial health with family risk of metabolic disorders, in healthy overweight, obese and non obese subjects.
Study Design: A case-control (pilot) study.
Place and Duration of Study: The study was conducted in Cardiovascular Physiology lab, Department of Physiology, K.G.M.U
Methods: Cases and controls comprised from January 2009 to February 2010. of 30 overweight / obese healthy subjects (BMI >= 25 kg/m 2 and/or WHR (female>0.85; male>1) and 30 non-obese healthy subjects respectively (BMI< 25 kg/m 2 and/or WHR (female<0.85; male<1) excluding subjects with secondary cause of abnormal blood flow. Vascular endothelial health was assessed via reactive hyperemic response measured via impedance plethysmography in the subject’s forearm. Fasting plasma glucose and serum lipid profile was also done.
Results: On comparison of biochemical variables, lipid derangement was recorded in both the groups. Significant difference in VLDL (control 21.84±9.68, case 29.01±16.83) (p=0.048) and TG (control 101.22±-43.33; case145.21±84.02) (p=0.013), could be seen. VLDL & TG was deranged in 15 (6 cases + 9 controls) (P=0.371) and 14 (5 cases + 9 controls) (P=0.222) subjects respectively with no inter-group significant statistical difference. Inter-group reactive hyperemia at 1, 2, 3, 5, 7, 9 min post occlusion time showed no significant difference. Peak hyperemic response was seen at 2 minutes in both the groups. Though independent family history in first degree relatives of diabetes, coronary artery disease and/or hypertension showed a significant association with % RH at 2 min. (P =0.049), yet in group wise exploration, no significant association was seen.
Conclusion: Adverse anthropometry is universally not associated with deranged lipid profile and vice versa. Raised RH response associated with positive family risk could be either due to hyperinsulinemia and/or some yet undeciphered cause but not solely as add-on sequelae of deranged anthropometry (BMI & WHR). In the light of our findings, we conclude that what seems as a favourable response i.e. a raised hyperemic response in subjects with a positive family history of risk factors, may be last ditch escape response before the vascular system succumbs to the inflammatory insult. Some yet undeciphered causes could thus be suspected of an adverse outcome and thus accordingly timely modified by lifestyle modifications or pharmacological interventions.

New Insights into Gastric Pressure Activity

Rongguo Yan — Wed, 24 Jul 2019 00:00:00 +0000

Diseases in the gastric cavity are, to some extent, related to with gastric motility. Using a telemetric device, which is composed of a capsule robot, an in-vitro pocket data recorder, an ultrasonic locating unit, and an in-vitro data processing computer, to obtain gastric physiological digestive or interdigestive pressure activity is a good way to get the pattern of gastric motility. This chapter of the book first presents such a telemetric device. Then, general data processing and analysis method, as well as reasonable interpretation on how to generate such gastric pressure activity are given. Such general process for processing pressure recordings includes removal of abnormal values, five-threeHanning (53H) weighted average smoothing and estimation of pressure activity fluctuation frequency. Finally, an analysis method for detecting quadratic phase coupling (QPC) behavior of human gastric interdigestive pressure activity is proposed. They are the Fourier transforms of the diagonal slices of the triple correlations, and can actually detect the phase coupling and coupled components respectively by expanding the real process into the complex counterpart through Hilbert transform. In order to learn more about the QPC structure in a certain frequency band that we are mostly interested in and obtain higher frequency resolution, the method, named the wavelet packet based diagonal slice spectrum, is introduced. It shows that the nonlinear QPC behavior occurs during gastric contractions (phase II), whereas no distinct phase coupling occurs during gastric motor quiescence (phase I). It is the nonlinear cell-to-cell coupling mechanisms, existence of fast and slow waves and their interactions that nonlinear QPC structure of the gastric pressure activity occurs. These findings in this chapter could be considered as some new insights into gastric pressure activity.