Zeitschrift für klinische und medizinische Genomik

In the 21^st century, the glamour of economic and technological development is not free from miseries particularly in the health domain. The quality of life of the people with increasing trend of non-communicable diseases is at great stake. Diabetes is one of the most dangerous killing diseases, which not only affect the individuals but the entire family and ultimately causing burden to the state. So far medical innovations have helped to diagnose the disease and maintain it throughout the life. Diabetes management is becoming market centric and it looks to suffer with deficits of cost effective and patient friendly perspective. The process involved in maintaining the disease is not friendly to human nature. The restrictions, cautions and precautions are much medicine centric; it does not suites completely to the human nature. The doctor treating the diabetic person may consider the fault on the part of patient but it is a natural for the patient to go beyond the prescriptions of Doctor. The medical approach of managing the diabetes carries unbearable cost on individual, family, society and even on the state itself.

Unless underling etiology of the disease is completely understood scientifically, using samples from variety of sections, regions and social groups, ethnic groups, we cannot get the profile of determinants which are rooted into diabetes. It is believed to be a disease of modern times, which is broadly embedded with host of stressors; and it is generally recognized that the environment in which people live is highly stress prone due to paradigm shift in the life style of people, e.g., eating, working, living, communicating etc. In order to get some insight about the disease, it is important to understand the causative factors embedded into the social system in which people are living. It is quite possible that host of incident shocking in nature to a particular individuals may play significant role in causing the diabetes. Keeping this into background retrospective narrative technique was used for in-depth interview with 20 diabetic persons with qualification ranging from primary school to Ph.D. having status of economically middle class. The salient findings are: 1) The in-depth case studies revealed micro level determinants in the changing dynamics of the relationship in the family, which play a critical role in facilitating non-communicable disease. 2) The drastic changes in the -expectation‘s profile‖ of the family members, unexpected changes in the behavior of the family members, unresolved conflicts among the family members, unexpected treatment on small matters like food, clothing, outing, property, etc. play a vital role in causing diabetes as reported in almost all the case studies. From the findings it looks that people need to be prepared from the early stages of life about upcoming situations emerging in the family of contemporary period. The coping skills and communication education about the dynamic changes in the expectations and behavior profile in the family and society should be taken up as preventive and promotive approach with complete intuitional design.

Citrobacter braakii (C. braakii) is widespread in nature, mainly found in human urinary tract. The current study was attempted to investigate the effect of Mr. Trivedi’s biofield treatment on C. braakii in lyophilized as well as revived state for antimicrobial susceptibility pattern, biochemical characteristics, and biotype number. Lyophilized vial of ATCC strain of C. braakii was divided into two parts, Group (Gr.) I: control and Gr. II: treated. Gr. II was further subdivided into two parts, Gr. IIA and Gr. IIB. Gr. IIA was analysed on day 10 while Gr. IIB was stored and analysed on day 159 (Study I). After retreatment on day 159, the sample (Study II) was divided into three separate tubes. First, second and third tube was analysed on day 5, 10 and 15, respectively. All experimental parameters were studied using automated MicroScan Walk-Away® system. The 16S rDNA sequencing of lyophilized treated sample was carried out to correlate the phylogenetic relationship of C. braakii with other bacterial species. The antimicrobial susceptibility and minimum inhibitory concentration showed 39.29% and 15.63% alteration respectively in treated cells of C. braakii as compared to control. Tetracycline showed improved sensitivity pattern, i.e., from resistant to susceptible after biofield treatment, with support of decreased MIC value (>8 to ≤ 4 μg/mL) by two-fold in all the treated samples as compared to the control. Biochemical reactions also showed significant (42.42%) alteration in the treated samples with respect to the control. Biotype numbers with species were substantially changed in Gr. IIA (53131052, Citrobacter freundii complex) on day 10 and in Gr. IIB, Study I (53111052; Citrobacter amalonaticus) on day 159 as compared to the control (77365776; Citrobacter braakii). Moreover, biotype numbers with species were substantially changed in Gr. IIB, Study II after retreatment on day 5 (53111042, Citrobacter amalonaticus) and (53131052; Citrobacter freundii complex) on day 10 and 15 as compared to the control. 16S rDNA analysis showed that the identified microbe as Citrobacter freundii (GenBank Accession Number: DQ517285) with 95% identity. The nearest homolog genus-species of C. braakii was found to be Citrobacter werkmanii (Accession No. AF025373). The results suggested that biofield treatment has a significant impact on C. braakii in lyophilized as well as revived state.

Recent reports have shown that during persistent HPV infections of the cervical epithelium the viral genome, of high risk HPV types, often integrate into the host chromosome, which results in an over expression of the viral proteins E6 and E7 of human papillomavirus. These oncoproteins induce immortalization and malignant transformation of cells conferring a certain growth advantage to the infected cells.

A total of 100 women undergoing routine cervical cytology samples joined this cohort study. A Thin Prep Pap Test sample was taken following consent for study participation and was tested for HPV. Cytological screening of the samples was done by trained cytologists. After sample collection, 1 ml aliquot was removed and prepared for flow cytometric analysis and the rest of the sample was sent for PCR analysis. In the total of 100 cases, 4 specimens were characterized as unsatisfactory.

For the rest 96 specimens, 82 specimens were found to be positive, for the HPV virus and 14 negative. In the total of 100 cases the analysis of flow cytometry and PCR detection gives the same results in most cases. As a conclusion, our results showed that the use of flow cytometry in the detection of HPV virus is a feasible method and requires only 1ml of sample specimen to give accurate results for the diagnosis.

Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmosis in human and animal. This parasite is worldwide spread and about one third of people are seropositive. Toxoplasmosis in immuno compromised patients causes serious symptoms. Toxoplasma gondii has a lot of various immunogenic antigens. Excreted/secreted antigens could stimulate of the cell mediated immune response and hence it appears to be a good candidate for vaccine in toxoplasmosis. In this study Microneme3 (MIC3) and GRA5 of Toxoplasma gondii are used as DNA vaccine.

The results indicated that survival rate of mice that immunized by recombinant plasmid have significant differences with control groups. IgG and IgG2a assay approved significant different between case and control groups (P<0.05). Cytokine assay indicated high level of IFN-γ and low level of IL4 for immunized groups.These results indicated DNA vaccine encoded MIC3 and GRA5 genes of Toxoplasma gondii capable to induced partially protection against toxoplasmosis.

The methyl-CpG-binding protein 2 gene (MECP2) on the X chromosome encodes an essential epigenetic regulator in human postnatal brain development. Increased dosage of MECP2 causes a severe syndromic form of intellectual disability, the MECP2 duplication syndrome. Males with this syndrome have a progressive neurological disorder, severe to profound intellectual disability, epilepsy and recurrent respiratory infections. We report three cases with copy number gain in Xq28 involving the MECP2 gene. The gains were detected by chromosomal microarray analysis and ranged in size from 300 kb to 4.96 Mb. The three boys were aged between 3 and 16 years old. All three had development delay and no speech. In addition, one patient was diagnosed with Lennox-Gastaut syndrome and another had a Dandy Walker variant. Their clinical features were compared with other reported cases. We concluded that all three patients’ clinical features were due to the Xq28 duplication, which confirmed the utility of chromosomal microarray analysis as a first-tier test in patients with unexplained intellectual disability. With a specific genetic diagnosis, we were able to provide appropriate anticipatory guidance for these patients and their families.

Background: Observational research associating methylenetetrahydrofolate reductase (MTHFR) polymorphisms with risk of autism, depression, cancer and cardiovascular disease has led to increased diagnoses of MTHFR, however, doctors lack knowledge about safety, effectiveness, and clinical implications of MTHFR treatment. Treatment strategies are hypothetical and mechanistically-based, including methylfolate with or without other B vitamins.

Aims: This study was designed to formally describe patient and healthcare provider experiences with the diagnosis and clinical management of MTHFR.

Methods: Guided by a structured interview guide, a qualitative study queried patients’ and providers’ observations regarding: testing indications, reaction to results, treatment protocols, and clinical response including adverse effects.

Results: Thirty patients and eight doctors participated. Patient themes included emotionality associated with diagnosis, classification of signs and symptoms, and challenges with treatment. They expressed confusion over their diagnosis, and frustration with the state of knowledge their providers had regarding MTHFR. Testing indications included: fatigue (21%), hormone imbalances (13%), and neurological symptoms (13%) including brain fog (8%). Patients reported improvements in physical (60%) and mental/behavioral symptoms (36%) following treatment. A minority of participants reported side effects but they occurred in almost every body system and ranged in severity. Doctors relied on trial and error to determine treatment doses, frequency and components.

Conclusions: MTHFR testing results in variable clinical processes in domains related to delivery of diagnosis and prognosis, and therapeutic options. However, patients report largely positive experiences. Clinicians and patients would benefit from therapeutic algorithms based on rigorous research.

Case Studies, as teaching strategies, have been described as an explanation of real situations confronted by a person or persons in an organization. It has been featured as a way to aggravate the learners’ critical thinking; to apply theory into practice; to train learners toward decision making; to enhance learner’s cooperative learning skills; and to build partnerships among learners and teachers. This paper presents a case study about the conflict of power. The real names of the persons involved in the scenario had been replaced with vague ones. This is to ensure the rigor of this work. The aim of this paper is to describe a situation in which leaders in nursing administrative positions faces a lot. Besides, the paper aims to provide a logical approach toward dealing with such situations. Furthermore, it aims to activate the critical thinking of the readers through providing a list of questions at the end of the paper in order to generate a discussion which in its turn enhances the learning process.

Within North East India, the people of Mizoram are mongoloid in origin and Cancer is a major disease condition among this tribal populace. A peculiar habit of consuming ‘‘tuibur’’ (tobacco smoke–infused aqueous solution) has been practiced in Mizoram. Blood and oral swab samples were collected from stomach cancer patients, tuibur consumers and healthy people. DNA was extracted followed by PCR amplification of the D-loop region of mtDNA. Restriction enzyme digestion of 1050 bp of the hyper variable control region of mtDNA was performed in order to gain an insight into the phylogenetic relationship of populace of Mizoram besides the genetic variations among tuibur consumers. The phylogram based on restriction enzyme analysis (AluI, HaeIII, MspI and KpnI) of the D-loop region subsumed within same mtDNA haplogroups and the markers resulted in a similar clustering of the population. The polymorphic samples were sequenced, analyzed and compared with the MITOMAP database. In the hypervariable control region, 292A>AA and 316C>CC are novel microsatellites instability as they have been reported for the first time as it has not been found in the mitochondrial database. 292A>AA position of MT-HV II region is a locus for the mtTF1 binding site Y. Due to the microsatellite instability of this position, the binding of mtTF1 may be altered. 316C>CC is present at the conserved sequence block II in MT-HV II region of human mitochondrial control region. The present study revealed a variety of mtDNA D-loop region mutations and polymorphisms among tuibur consumer besides stomach cancer patients of Mizoram, some of which might be involved in the development of carcinogenesis in stomach for the tuibur consumer.

Acute mountain sickness (AMS) occurs in up to 50% of individuals ascending to high altitudes greater than 2600 meters. An AMS Han Chinese and a normal Han group were compared for 17 simple nucleotide polymorphisms (SNPs) within 9 genes that have been associated with AMS. The SNPs were analyzed with respect to linkage disequilibrium (LD) between intra- and intergenic SNP alleles and alterations in transcriptional factor binding sites (TFBS). Included in the study was the angiotensin-converting enzyme (ACE) (rs4340), the angiotensinogen (AGT) (rs699) and the angotensin II type 1 receptor (AGTR1) (rs5186) SNPs from the renin-angiotension system (RAS) as well as the GNB3 (rs2071057) SNP from G-protein signaling and a LDL apolipoprotein B (APOB) (rs693) SNP. The endothetal Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) SNP and two egl nine homolog 1 (EGLN1) SNPS (rs480902 and rs516651) from the hypoxia-inducible factor (HIF) oxygen signaling pathway were included. SNPs analyzed in the vascular endothelial growth factor (VEGF) signaling pathway are the v-akt murine thymoma viral oncogene homolog 3 (AKT3) (rs4590656 and rs2291409), the endothelial cell nitric oxide synthase 3 (eNOS3) (rs1007311 and rs1799983) and the (VEGFA) (rs79469752, rs13207351, rs28357093, rs1570360 and rs3025039). These SNP alleles alter the TFBS for TF binding. Pair-wise LD was computed between SNPs. An increase in LD occurred in 32 pair-wise comparisons while a decrease was found in 22 pair-wise comparisons between the AMS and controls. Increases and decreases in LD pairs were found within and between signaling pathways and systems indicating the interaction of SNP alleles or potential TFBS from different areas of the genome. The most drastic change in TFBS occurs with ACE (I/D) SNP (rs4340) where the ACE-I allele generates 84 potential TFBS while the ACE-D allele generates only four binding sites. The alteration in TFBS generated by the 17 SNPs is discussed with respect to AMS.

Esophageal and gastric cancers are two of the most common malignancies worldwide with particularly high mortality rates. Esophageal and gastric cardia cancers share certain environmental risk factors, but it is unclear if these cancers share similar gene mutation patterns. To improve patient diagnosis, treatment, and outcome, identification and characterization of the unique molecular mutation profiles of these cancers are needed to develop more effective target therapies. Until recently, personalized DNA sequencing to identify individual cancer mutations was unrealistic for clinical applications. But technological advancements in next-generation DNA sequencing, including the semiconductor-based Ion Torrent sequencing platform, have made DNA sequencing more cost and time effective with reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in esophageal adenocarcinoma, esophageal squamous cell carcinoma, and gastric cardia cancer samples from Chinese patients. The sequencing analysis revealed frequent mutations in PIK3CA and TP53 genes, and less frequent mutations in several other genes. Thus, this study demonstrates the feasibility of using Ion Torrent sequencing on individual human cancers to detect patient-specific gene mutations with the goal of directing mutation-specific targeted therapies or aid in targeted drug development to more effectively treat cancer patients.

Cardiac resynchronization therapy (CRT) improves systolic performance in heart failure (HF). However, the effects of CRT on left ventricular diastolic function were variable and not fully understood.

The available studies used different diastolic parameters derived from pulse and tissue Doppler techniques and more recently from deformation data.

The most studies showed that CRT improves diastolic function (data are more controversial regarding relaxation) but this seems to be dependent on improvement in systolic function.