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Pre-eclampsia is a disorder of 2nd half of pregnancy, which is characterized by a combination of hypertension, proteinuria and edema, secondary to decreased placental perfusion. Clinical studies suggest that there are histopathological changes in the placenta of pre-eclamptic women, compared to normotensive pregnant women. In developing countries, pre-eclampsia causes an estimated 50,000 maternal deaths per year. Only a small number of studies have however, been conducted in Bangladesh. Objective: To compare the histopathology of placenta in selected pre-eclamptic and normotensive pregnant women. Methods: 220 pregnant women were selected with inclusion and exclusion criteria from 3 different medical colleges and divided into 2 groups – A study group, consisting of 110 pre-eclamptic women and a control group consisting of 110 normotensive pregnant women. Dietary information was collected by 7 days food frequency questionnaire and food score was determined. Anthropometric and biochemical tests were performed. To evaluate the histopathology of placenta, tissue samples were collected from the placenta after delivery, and were prepared for histopathological studies, by haemotoxylin and eosin stain method. The mean number of areas of syncytial knot formation, the mean number of areas of cytotrophoblastic cell proliferation, the mean number of areas of fibrinoid necrosis, and the mean number of areas of hyalinised villi of pre-eclamptic and normal pregnant women were evaluated. Results: The mean number of areas of syncytial knot formation, the mean number of areas of cytotrophoblastic cell proliferation, the mean number of areas of fibrinoid necrosis, and the mean number of areas of hyalinised villi were found to be significantly higher in the study group, compared to the control group. Conclusion: Therefore, mean number of areas of syncytial knot formation, the mean number of areas of cytotrophoblastic cell proliferation, the mean number of areas of fibrinoid necrosis is increased in the placenta of pre-eclamptic women, compared to normotensive pregnant women. J Dhaka Med Coll. 2021; 30(2) : 189-195

Transmission and distribution lines are used to transmit and distribute electrical power throughout load center. The problem with these lines are, because the loads are unbalanced and their attraction towards various faults as a results of lightning, short circuits, faulty equipment’s, miss-operation, human errors, overload, and aging. To avoid this case and that we need the precise location of fault occurrence. To avoid this situation, we need the exact location of fault occurrence. This problem is handled by a set of resistors representing cable length in KMs and fault creation is made by a set of switches at every known KM to cross check the accuracy of the same. Only way to solve this problem is to come up with a mechanism that can detect the fault in an electricity transmission line automatically and intimate the authorities with a precise location. Through this project we develop a device that uses sensors to sense the incoming & outgoing values and detect healthy and faulty condition. And, the system will be integrated with IoT mechanism, to intimate the responsible people real time with the location information. Moreover technical losses occur naturally and are caused because of power dissipation in transmission lines, transformers, and other equipments. The system prevents the illegal usage of electricity.

The status and feeding behavior of black kite (Milvus migrans) in Dhaka city were studied from July 2015 to June 2017. Road transects and morning roost-count method were used for population estimation and distribution, whereas focal sampling method was used to study the feeding and foraging behavior. Based on roosting and foraging areas, five transects were selected for population estimation. Moreover, six different feeding areas were selected for identifying various types of consumed food and assessing the feeding behavior of black kite. The black kite population was estimated at (1296±5.87) in Dhaka city. The population density was estimated at 21.8/km2. Among selected five different transects, the recorded population ranged from 108.12±6.70, 8.34%) at S-3 (Mirpur to Ramna Park) to 805±11.88, 62.11% of individuals at S-5 (Gulistan to Demra). The present study revealed that black kites were distributed throughout the study area and the distribution was influenced by availability of food, water and roosting place. Based on the annual records, the highest population (1510±6.92) was found in 2016. Majority of black kites fed on offal and insects in study area. In garbage dumps, the highest rate of feeding was recorded in afternoon followed by in morning and lowest in the noon. Whereas in non-garbage feeding areas, the highest rate was recorded in the morning followed by in the afternoon and lowest in the noon. Among four different foraging strategies, food collection by kites standing on the ground and intraspecific cleptoparasitism was never observed during study period while interspecific cleptoparasitism (against crows) was the highest number (193.67±2.77, 68.43%). Jahangirnagar University J. Biol. Sci. 9(1 & 2): 35-48, 2020 (June & December)

Pre – Eclampsia is a disorder of 2nd half of pregnancy, which is characterized by a combination of hypertension, proteinuria and edema, secondary to decreased placental perfusion. Clinical studies suggest that there are morphological changes in the placenta of pre-eclamptic women, compared to normotensive pregnant women. In developing countries, pre-eclampsia causes an estimated 50,000 maternal deaths per year. Only a small number of studies have however, been conducted in Bangladesh. Objective: To compare the morphology of placenta in selected pre-eclamptic and normotensive pregnant women. Methods: 220 pregnant women were selected with inclusion and exclusion criteria from 3 different medical colleges and divided into 2 groups – A study group, consisting of 110 pre-eclamptic women and a control group consisting of 110 normotensive pregnant women. Dietary information was collected by 7 days food frequency questionnaire and food score was determined. Anthropometric and biochemical tests were performed. To measure the weight of the placentas, the decidual part of the placentas were removed. The umbilical cords were then cut, nearest to the placenta, to drain the blood from the placental vessels, and the weight was recorded upto nearest gram with weighing machine. The diameters of placentas were measured by taking the average of two maximum diameters of placentas with measuring tape (cm).The cotyledons were counted from maternal side after removal of deciduas basalis. Number of placental infarcts were counted from fetal side. Results: The mean weights, diameters, number of cotyledons were found to be significantly lower in the study group, compared to the control group. The number of infarcted areas was significantly higher in the placentas of pre-eclamptic women Conclusion: Therefore, weight, diameter and number of cotyledons are decreased and number of infarcted areas are increased in the placenta of pre-eclamptic women, compared to normotensive pregnant women. J Dhaka Medical College, Vol. 29, No.2, October, 2020, Page 171-177

Pre -eclampsia is a disorder of 2nd half of pregnancy, which is characterized by a combination of hypertension, proteinuria and edema, secondary to decreased placental perfusion. Clinical studies suggest that antioxidant vitamins, such as Vit C and Vit. E can stabilize reactive free radicals, which are produced due to placental hypo perfusion, thereby preventing the development of pre-eclampsia. Pre-eclampsia remain a major cause of infant and maternal mortality and morbidity. In developing countries, pre-eclampsia causes an estimated 50,000 maternal deaths per year. Only a small number of studies have however, been conducted in Bangladesh. Objective: To compare the serum levels of antioxidants in selected pre-eclamptic and normotensive pregnant women. Methods: 220 pregnant women were selected with inclusion and exclusion criteria from 3 different medical colleges and divided into 2 groups – A study group, consisting of 110 pre-eclamptic women and a control group consisting of 110 normotensive pregnant women. Dietary information was collected by 7 days food frequency questionnaire and food score was determined. Anthropometric and biochemical tests were performed. Biochemical analysis such as serum vitamin C levels were measured by spectrophotometric method, and serum vitamin E levels were measured by HPLC (High Performance Liquid Chromatography) method. Results: The mean serum levels of Vit. C and Vit E were found to be significantly lower in the study group, compared to the control group. Anthropometric study revealed that the babies born to pre-eclamptic mothers had lower birth weight than those born to normotensive mothers. Conclusion: Therefore, low antioxidant levels do play a key role in the development of preeclampsia in pregnant women. J Dhaka Medical College, Vol. 29, No.1, April, 2020, Page 53-58

Mitophagy is a quality control mechanism that eliminates damaged mitochondria, yet its significance in mammalian pathophysiology and aging has remained unclear. Here, we report that mitophagy contributes to mitochondrial dysfunction in skeletal muscle of aged mice and human patients. The early disease stage is characterized by muscle fibers with central nuclei, with enhanced mitophagy around these nuclei. However, progressive mitochondrial dysfunction halts mitophagy and disrupts lysosomal homeostasis. Interestingly, activated or halted mitophagy occur in a mosaic manner even in adjacent muscle fibers, indicating cell-autonomous regulation. Rapamycin restores mitochondrial turnover, indicating mTOR-dependence of mitochondrial recycling in advanced disease stage. Our evidence suggests that (1) mitophagy is a hallmark of age-related mitochondrial pathology in mammalian muscle, (2) mosaic halting of mitophagy is a mechanism explaining mosaic respiratory chain deficiency and accumulation of pathogenic mtDNA variants in adult-onset mitochondrial diseases and normal aging, and (3) augmenting mitophagy is a promising therapeutic approach for muscle mitochondrial dysfunction.

Idiopathic dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. The aim of this study was to assess the role of mitochondrial DNA (mtDNA) variations and haplogroups in Indian DCM patients. Whole mtDNA analysis of 221 DCM patients revealed 48 novel, 42 disease-associated and 97 private variations. The frequency of reported variations associated with hearing impairment, DEAF, SNHL and LHON are significantly high in DCM patients than controls. Haplogroups H and HV were over represented in DCM than controls. Functional analysis of two private variations (m.8812A>G & m.10320G>A) showed decrease in mitochondrial functions, suggesting the role of mtDNA variations in DCM.

The use of container-oriented orchestration platforms such as Kubernetes, is becoming more popular due to their ability to hide from developers the deployment details of the application and the capability of these platforms to support autoscaling and failure recovery. Most container orchestration environments have focused on supporting the HTTP protocol and are challenging to use in protocols such as SIP and RTP. When SIP/RTP services are deployed in the Kubernetes environment, failures related to port mapping and affinity occur. These failures are reflected as packets sent to the non-existent ports in either the overlay or underlay network in Kubernetes. This paper details these failures and presents solutions for resolving the SIP/RTP port mapping and the RTP affinity constraint failures. The SIP/RTP port mapping failure is solved by correctly mapping the internal SIP/RTP ports to those exposed externally by Kubernetes while the RTP affinity constraint solution leverages the concept of the creation of unique endpoints and labels for each RTP service port opened for a SIP call. The paper also offers some insight into the challenges faced in replicating the SIP constraint affinity failure. These solutions have been implemented in a Kubernetes aware SIP Proxy (SIP-K8S-Proxy) that supports port mapping and managing of the RTP affinity as well. The overhead associated with implementing this solution has been computed to be about 2 seconds in the establishment of a SIP call.

NAD(+) is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD(+) depletion occurs in patients with degenerative disorders and whether NAD(+) repletion improves their symptoms has remained open. Here, we report systemic NAD(+) deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD(+) booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD(+) increased in all subjects, up to 8-fold, and muscle-NAD(+) of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD(+) deficiency and points niacin to be an efficient NAD(+) booster for treating mitochondrial myopathy.

Objectives Studies exploring the outcome of epilepsy in patients with mitochondrial disorders are limited. This study examined the outcome of epilepsy in patients with mitochondrial disorders and its relation with the clinical phenotype, genotype and magnetic resonance imaging findings. Patients and methods The cohort was derived from the database of 67 patients with definite genetic diagnosis of mitochondrial disorders evaluated over a period of 11years (2006–2016). Among this, 27 had epilepsy and were included in final analysis. Data were analyzed with special reference to clinical phenotypes, genotypes, epilepsy characteristics, EEG findings, anti epileptic drugs used, therapeutic response, and magnetic resonance imaging findings. Patients were divided into three groups according to the seizure frequency at the time of last follow up: Group I- Seizure free; Group II- Infrequent seizures; Group III- uncontrolled seizures. For each group the clinical phenotype, genotype, magnetic resonance imaging and duration of epilepsy were compared. Results The phenotypes & genotypes included Mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes (MELAS) & m.3243A>G mutation (n = 10), Myoclonic Epilepsy Ragged Red Fiber syndrome (MERRF) & m.8344A>G mutation (n = 4), Chronic Progressive External Ophthalmoplegia plus & POLG1 mutation (CPEO, n = 6), episodic neuroregression due to nuclear mutations (n = 6; NDUFV1 (n = 3), NDUFA1, NDUFS2, MPV17-1 one each), and one patient with infantile basal ganglia stroke syndrome, mineralizing angiopathy & MT-ND5 mutations. Seven patients (25.9%) were seizure free; seven had infrequent seizures (25.9%), while thirteen (48.1%) had frequent uncontrolled seizures. Majority of the subjects in seizure free group had episodic neuroregression & leukoencephalopathy due to nuclear mutations (85.7%). Patients in group II with infrequent seizures had CPEO, POLG1 mutation and a normal MRI (71%) while 62% of the subjects in group III had MELAS, m.3243A>G mutation and stroke like lesions on MRI. Conclusions A fair correlation exists between the outcome of epilepsy, clinical phenotypes, genotypes and magnetic resonance imaging findings in patients with mitochondrial disorders. The recognition of these patterns is important clinically because of the therapeutic and prognostic implications.

NAD

Mitochondrial dysfunction elicits stress responses that safeguard cellular homeostasis against metabolic insults. Mitochondrial integrated stress response (ISRmt) is a major response to mitochondrial (mt)DNA expression stress (mtDNA maintenance, translation defects), but the knowledge of dynamics or interdependence of components is lacking. We report that in mitochondrial myopathy, ISRmt progresses in temporal stages and development from early to chronic and is regulated by autocrine and endocrine effects of FGF21, a metabolic hormone with pleiotropic effects. Initial disease signs induce transcriptional ISRmt (ATF5, mitochondrial one-carbon cycle, FGF21, and GDF15). The local progression to 2nd metabolic ISRmt stage (ATF3, ATF4, glucose uptake, serine biosynthesis, and transsulfuration) is FGF21 dependent. Mitochondrial unfolded protein response marks the 3rd ISRmt stage of failing tissue. Systemically, FGF21 drives weight loss and glucose preference, and modifies metabolism and respiratory chain deficiency in a specific hippocampal brain region. Our evidence indicates that FGF21 is a local and systemic messenger of mtDNA stress in mice and humans with mitochondrial disease.

Background Large studies analyzing magnetic resonance imaging correlates in different genotypes of mitochondrial disorders are far and few. This study sought to analyze the pattern of magnetic resonance imaging findings in a cohort of genetically characterized patients with mitochondrial disorders. Methods The study cohort included 33 patients (age range 18 months–50 years, M:F — 0.9:1) with definite mitochondrial disorders seen over a period of 8 yrs. (2006–2013). Their MR imaging findings were analyzed retrospectively. Results The patients were classified into three groups according to the genotype, Mitochondrial point mutations and deletions (n = 21), SURF1 mutations (n = 7) and POLG1 (n = 5). The major findings included cerebellar atrophy (51.4%), cerebral atrophy (24.2%), signal changes in basal ganglia (45.7%), brainstem (34.2%) & white matter (18.1%) and stroke like lesions (25.7%). Spinal cord imaging showed signal changes in 4/6 patients. Analysis of the special sequences revealed, basal ganglia mineralization (7/22), lactate peak on magnetic resonance spectrometry (10/15), and diffusion restriction (6/22). Follow-up images in six patients showed that the findings are dynamic. Comparison of the magnetic resonance imaging findings in the three groups showed that cerebral atrophy and cerebellar atrophy, cortical signal changes and basal ganglia mineralization were seen mostly in patients with mitochondrial mutation. Brainstem signal changes with or without striatal lesions were characteristically noted in SURF1 group. There was no consistent imaging pattern in POLG1 group. Conclusion Magnetic resonance imaging findings in mitochondrial disorders are heterogeneous. Definite differences were noted in the frequency of anatomical involvement in the three groups. Familiarity with the imaging findings in different genotypes of mitochondrial disorders along with careful analysis of the family history, clinical presentation, biochemical findings, histochemical and structural analysis will help the physician for targeted metabolic and genetic testing.

Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene ( MT-ND5 ) has been implicated as an important genetic cause of childhood mitochondrial encephalomyopathies. This study reports the clinical and magnetic resonance imaging findings in two pediatric patients with mutations in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G > A mutation presented with infantile basal ganglia stroke syndrome secondary to mineralizing angiopathy. The 7-year-old girl with the m.13514A > G mutation had episodic regression, progressive ataxia, optic atrophy, and hyperactivity. Magnetic resonance imaging of the brain showed bilateral symmetrical signal intensity changes in the thalamus, tectal plate, and inferior olivary nucleus, which subsided on follow-up image. Both the patients had a stable course. Familiarity with the various phenotypic and magnetic resonance imaging findings and the clinical course in childhood mitochondrial encephalomyopathies may help the physician in targeted metabolic–genetic testing and prognostication.

Background: Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. Methods: The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006–2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. Results: Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. Conclusions: Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients.

Hypertrophic cardiomyopathy (HCM) is a primary disorder, characterized by unexplained hypertrophy of the left ventricle that frequently involved in the inter-ventricular septum. Mitochondrial DNA (mtDNA) mutations and haplogroups have been found to be associated with several diseases. Therefore, in the present study, we have sequenced the complete mtDNA of 114 clinically well-characterized HCM patients to look for the role of mtDNA variations and haplogroups in HCM phenotype among Indian patients. Complete mtDNA analysis revealed 28 novel variations, 25 disease-associated and 50 private mutations. We found 13 (11.40%) HCM patients having novel non-synonymous and/or MT-tRNA variations, of which two (m.4797C > M and m.8728T > Y) were in heteroplasmic condition. In silico prediction showed that a few mutations are pathogenic, which may affect the energy production in the heart. Unlike some of the other studies, we did not find association of mitochondrial haplogroup with HCM.

Background: Barabanki one of the most populous districts of Uttar Pradesh with population growth rate being much higher than the national population growth rate. The objective of this study was to gain the knowledge about awareness and contraceptive practices in married women residing in Barabanki. To identify socio-demographic factors associated with unmet needs for contraceptionand also to ascertain the participation of husband in family planning.Methods: A cross sectional study was conducted in outpatient department of Obstetrics Gynecology and Department of Pediatrics in Medical college hospital in Barabanki. 144 females were enrolled in the study during the study period of one year. They were interviewed on the basis of a pre-structured proforma. Data obtained was then analyzed.Results: A total 144 women in the age group 18-45 years participated in the study of which 53% had knowledge of contraception. More than two thirds were not using any form of contraception. The most common method of contraception was barrier method followed by Depot medroxy progesterone acetate. Copper T was least used mode of contraception. The most common source of knowledge regarding contraception was from electronic media followed by friends and family. The most common reason behind the absence of contraception was lack of knowledge of contraception and husband disapproval.Conclusions: Poor knowledge of contraception led to decreased usage of contraceptive measures. Husband participation is virtually absent in family planning leading to high fertility. In order to make our family planning programs successful we must incorporate media for wider coverage to increase awareness and husbands for better implementation.

Although the Madras motor neuron disease (MMND) was found three decades ago, its genetic basis has not been elucidated, so far. The symptom at onset was impaired hearing, upper limb weakness and atrophy. Since some clinical features of MMND overlap with mitochondrial disorders, we analyzed the complete mitochondrial genome of 45 MMND patients and found 396 variations, including 13 disease-associated, 2 mt-tRNA and 33 non-synonymous (16 MT-ND, 10 MT-CO, 3 MT-CYB and 4 MT-ATPase). A rare variant (m.8302A>G) in mt-tRNA(Leu) was found in three patients. We predict that these variation(s) may influence the disease pathogenesis along with some unknown factor(s).

Mitochondrial oxidative phosphorylation (OXPHOS) disorders account for a variety of neuromuscular disorders in children. In this study mitochondrial respiratory chain enzymes were assayed in muscle tissue in a large cohort of children with varied neuromuscular presentations from June 2011 to December 2013. The biochemical enzyme deficiencies were correlated with the phenotypes, magnetic resonance imaging, histopathology and genetic findings to reach a final diagnosis. There were 85 children (mean age: 6.9±4.7years, M:F:2:1) with respiratory chain enzyme deficiency which included: isolated complex I (n=50, 60%), multiple complexes (n=24, 27%), complex IV (n=8, 9%) and complex III deficiencies (n=3, 4%). The most common neurological findings were ataxia (59%), hypotonia (59%) and involuntary movements (49%). A known mitochondrial syndrome was diagnosed in 27 (29%) and non-syndromic presentations in 57 (71%). Genetic analysis included complete sequencing of mitochondrial genome, SURF1, POLG1&2. It revealed variations in mitochondrial DNA (n=8), SURF1 (n=5), and POLG1 (n=3). This study, the first of its kind from India, highlights the wide range of clinical and imaging phenotypes and genetic heterogeneity in children with mitochondrial oxidative phosphorylation disorders.

Anemia in chronic kidney disease is a common clinical problem; it is primarily due to decreased production of erythropoietin or iron deficiency state. It is a ramification of decline in functional kidney mass. Recombinant Human Erythropoietin (rHuEPO) and it analogs are the greatest tools against the anemia in chronic kidney disease patients. Last two decades of clinical experience has greatly enhanced our understanding of the potentials as well as limitations of the current EPO based therapeutic practices. Recent studies have brought forth new therapies like HIF stabilizers, GATA inhibitor and erythropoietin gene therapy into active research in this field. These strategies are still in proof-of-concept stage and further evaluation is ongoing. This review also briefly touches on some other relevant issues such as pitfalls of iron therapy practices; present notions about iron mediated oxidative injury to residual renal function in PD patients and iatrogenic folic acid deficiency in HD patients.

Background There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders. Methods The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006–2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively. Results The study cohort included 18 patients (age range: 18 months–50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n = 11), SURF1 mutations (n = 4) and POLG1(n = 3). Axonal neuropathy was noted in 12 patients (sensori-motor:n = 4; sensory:n = 4; motor:n = 4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy. Conclusion A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder.

Summary Mitochondrial dysfunction affects cellular energy metabolism, but less is known about the consequences for cytoplasmic biosynthetic reactions. We report that mtDNA replication disorders caused by TWINKLE mutations—mitochondrial myopathy (MM) and infantile onset spinocerebellar ataxia (IOSCA)—remodel cellular dNTP pools in mice. MM muscle shows tissue-specific induction of the mitochondrial folate cycle, purine metabolism, and imbalanced and increased dNTP pools, consistent with progressive mtDNA mutagenesis. IOSCA-TWINKLE is predicted to hydrolyze dNTPs, consistent with low dNTP pools and mtDNA depletion in the disease. MM muscle also modifies the cytoplasmic one-carbon cycle, transsulfuration, and methylation, as well as increases glucose uptake and its utilization for de novo serine and glutathione biosynthesis. Our evidence indicates that the mitochondrial replication machinery communicates with cytoplasmic dNTP pools and that upregulation of glutathione synthesis through glucose-driven de novo serine biosynthesis contributes to the metabolic stress response. These results are important for disorders with primary or secondary mtDNA instability and offer targets for metabolic therapy.

We appreciate the effort shown by the authors and their comments on our article ‘‘Leber’s Hereditary Optic Neuropathy-Specific Mutation m.11778G>A Exists on Diverse Mitochondrial Haplogroups in India.’’ Leber’s hereditary optic neuropathy (LHON) is the most common, well-diagnosed, and maternally inherited mitochondrial disease. In this case, we would emphasize the statement that LHON is one of the most well characterized maternally inherited mitochondrial disease. We do agree with the statement that penetrance may depend on the age of individuals who carry the mutation. To date, our follow-up data do not reveal nonsymptomatic mutation carriers to have developed visual impairment and LHON. The data presented are to the best of our knowledge, till the time the manuscript was written. However, most of the families are in contact with the clinicians and have been informed about their genetic diagnosis. The families were followed up for the period of study (2005–2016), and patients were included if they developed visual disturbance. As discussed in the article, 13 out of 64 LHON families with m.11778G>A mutation were observed in heteroplasmic condition, and the remaining 51 were homoplasmic. In total (22 out of 145), 15% of manifesting mutation carriers was present with heteroplasmic form, while 31% of mutation carriers (124 out of 398) were present with homoplasmic condition. We do agree with the authors that knowledge of environmental factors (tobacco smoke) would greatly help in answering the penetrance of these LHON pedigrees. However, we realized during the study that quite a significant percentage of participants were not ready to share the details about their smoking and alcohol consumption history in an accurate way. At present, we lack proper details of the tobacco smoke and alcohol consumption for all the pedigrees and the amount of information, which we have, is not sufficient to make any specific conclusion about this issue. Keeping this in mind, we have decided to exclude this information from this study. During the initial analysis, 41 out of 64 index cases had positive family history of LHON. Seven affected individuals have mothers clinically manifesting LHON. During the course of this study, all the index cases were investigated for multiorgan involvement. We observed one patient from the index case had mild hepatosplenomegaly, while the other patients from index cases do not have any organ involvement. Hence, we would not be able to make conclusions about the multiorgan involvement and heteroplasmy level. None of the tRNA variants scored >11 on the Yarham score. One of the limitations was that we do not have all the information required for predicting the Yarham score for each patient due to absence of histology and transmitochondrial cybrid study for all the mutations. During initial clinical diagnosis of LHON-like symptoms for the patients, blood samples were collected for genetic diagnosis, which was confirmed by the presence of mutation. We, therefore, do not agree with collection of invasive samples like muscle biopsy in all the cases, but it was collected for a few cases where patients gave their consent. Hence, we were not able to perform all the analysis for predicting the Yarham score for additional variants observed together with m.11778G>A mutation. We also think it would be very difficult to segregate the effect of additional variant, since patients already have pathogenic mutation. We do agree with authors that pathogenicity of variants may be confirmed by using single fiber and cybrid analysis. However, it is not possible for us to make cybrids for all the variants; nevertheless, for the continuation of this project, we have a plan to select a few of the potential variants to study their role in different haplogroup backgrounds.

Mitochondrial dysfunction elicits various stress responses in different model systems, but how these responses relate to each other and contribute to mitochondrial disease has remained unclear. Mitochondrial myopathy (MM) is the most common manifestation of adult-onset mitochondrial disease and shows a multifaceted tissue-specific stress response: (1) transcriptional response, including metabolic cytokines FGF21 and GDF15; (2) remodeling of one-carbon metabolism; and (3) mitochondrial unfolded protein response. We show that these processes are part of one integrated mitochondrial stress response (ISRmt), which is controlled by mTORC1 in muscle. mTORC1 inhibition by rapamycin downregulated all components of ISRmt, improved all MM hallmarks, and reversed the progression of even late-stage MM, without inducing mitochondrial biogenesis. Our evidence suggests that (1) chronic upregulation of anabolic pathways contributes to MM progression, (2) long-term induction of ISRmt is not protective for muscle, and (3) rapamycin treatment trials should be considered for adult-type MM with raised FGF21.

Mitochondrial disorders resulting from an isolated deficiency of complex II of the respiratory chain is rarely reported. The phenotypic spectrum associated with these disorders is heterogeneous and still expanding. This report describes a patient who presented with myopathy, dilated cardiomyopathy, and pontine signal changes on magnetic resonance imaging. Muscle biopsy showed total absence of succinate dehydrogenase on enzyme histochemistry, negative succinate dehydrogenase subunit A (SDHA) activity on immunohistochemistry, and ultrastructural evidence of mitochondrial aggregates of varying sizes confirming the diagnosis of complex II deficiency. A unique phenotype with complex II deficiency is reported.

Bangladesh is one of the most promising developing countries of the third world. Majority of the population do not have access to electricity. Due to industrial development, Bangladesh has maintained its economic growth above 6% since the last few years. Energy crisis is the most significant barrier for its economic development. Ever increasing utilization of fossil fuel for generation of electricity increasing consumption cost. In this circumstance, renewable energy sources must be incorporated with traditional power plants to meet energy demand. This paper discussed about the present situation of renewable energy practices in Bangladesh. It presents an extensive overview of suitable renewable energies (solar, wind, biomass and hydroelectric) for Bangladesh, their prospects and socio economic impacts.

We performed an extensive study on mitochondrial dysfunction in chronic periodontitis (CP). Electron microscopic analysis of gingival cells revealed abnormal mitochondria in 60% of the patients. Mitochondrial membrane potential and oxygen consumption of gingival cells were reduced by 4 fold and 5.8 fold, respectively; whereas ROS production was increased by 18%. The genetic analysis by complete mitochondrial DNA sequencing revealed the identification of 14 novel mutations only in periodontal tissues but not in the blood, suggesting a role of oxidative stress on periodontal tissues. Thus, our functional and genetic analysis provided an evidence for the mitochondrial dysfunction in CP.

Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.

Bilateral hypertrophic olivary degeneration on brain MRI has been reported in a few metabolic, genetic and neurodegenerative disorders, including mitochondrial disorders. In this report, we sought to analyse whether bilateral symmetrical inferior olivary nucleus hypertrophy is specifically associated with mitochondrial disorders in children.This retrospective study included 125 children (mean age, 7.6 ± 5 years; male:female, 2.6:1) diagnosed with various metabolic and genetic disorders during 2005-2012. The routine MRI sequences (T1 weighted, T2 weighted and fluid-attenuated inversion-recovery sequences) were analysed for the presence of bilateral symmetrical olivary hypertrophy and central tegmental tract or dentate nuclei signal changes. The other imaging findings and the final diagnoses were noted.The cohort included patients with Leigh and Leigh-like syndrome (n = 25), other mitochondrial diseases (n = 25), Wilson disease (n = 40), Type 1 glutaric aciduria (n = 14), maple syrup urine disease (n = 13), giant axonal neuropathy (n = 5) and L-2 hydroxy glutaric aciduria (n = 3). Bilateral inferior olivary nucleus hypertrophy was noted in 10 patients, all of whom belonged to the Leigh and Leigh-like syndrome group.Bilateral hypertrophic olivary degeneration on MRI is relatively often, but not routinely, seen in children with Leigh and Leigh-like syndrome. Early detection of this finding by radiologists and physicians may facilitate targeted metabolic testing in these children.This article highlights the occurrence of bilateral hypertrophic olivary nucleus degeneration on MRI in children with Leigh and Leigh-like syndrome, compared with other metabolic disorders.

Purpose To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber hereditary optic neuropathy (LHON) patients carrying the m.14484T>C mutation. Methods Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants. Results In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male: female = 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e., F1c1, M31a, U2a, M*, I1, M6, M3a1, and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON. Conclusions Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease.

Context: Testosterone is the male sex hormone responsible for growth of secondary sexual character and accessory sex organs. Despite the effectiveness as a male sex hormone, testosterone causes Benign Prostatic Hyperplasia (BPH) resulting in urinary dysfunction. On the other hand, flutamide is a pure antitestosterone, which blocks the effects of Dihydro testosterone (DHT) at the testosterone receptor and prevents BPH. Therefore the present study was designed to observe the protective role of flutamide on testosterone induced prostatic hyperplasia. Objective: To observe the effects of flutamide on testosterone induced prostatic hyperplasia in Long Evans rats. Study design: An experimental study. Place and period of study: The study was carried out in the Department of Anatomy, Sir Salimullah Medical College, Dhaka during the period of July 2006 to June 2007. Materials & Methods: Forty five matured male long Evans rats of age 8-10 weeks and weighing 200-300 gms were used in this study. They were divided into three equal groups. Group A was vehicle (olive oil) control group, Group B was testosterone treated group and Group C was testosterone & flutamide treated group. Comparative study in different groups were done microscopically. Results: There was significant reduction (P