Differential roles of NR4A2 (NURR1) paralogs in the brain and behavior of zebrafish.

Dopaminergic (DAnergic) dysfunction and imbalanced dopamine (DA) levels are known contributors to the pathogenesis of numerous psychiatric and neurodegenerative disorders. Of the many identified risk factors for DA-associated disorders, nuclear receptor subfamily 4 group A2 (NR4A2; or nuclear receptor related-1 protein (NURR1)), a transcription factor involved in DAnergic differentiation, has been associated with Parkinson's disease and attention deficit hyperactive disorder (ADHD). In zebrafish, transient loss of nr4a2 was previously shown to decrease tyrosine hydroxylase (TH) expression and impair locomotion. To further characterize the roles of the two zebrafish nr4a2 paralogs, nr4a2a, and nr4a2b, we produced targeted loss-of-function mutants and examined DAnergic neuron regeneration, oxidative respiration, and behavioral traits. The loss of nr4a2a function more closely recapitulated Parkinsonian phenotypes and affected neurotrophic factor gene expression. Conversely, nr4a2b mutants displayed behavioral symptoms reminiscent of mice deficient in Nr4a2 with increased neurotrophic output. In contrast, nr4a2b mutants also displayed increased metabolic input from non-mitochondrial sources indicative of high cytosolic reactive oxygen species and perturbed mitochondrial function. The nr4a2a mutants also showed increased maximal respiration, which may suggest a compensatory mechanism to meet the metabolic requirements of DAnergic neuron health. Overall, the zebrafish mutants generated in this study helped uncover molecular mechanisms involved in DA-related disease pathologies, and in the regeneration of DAnergic neurons.

CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.

PURPOSE: The functionality of many cellular proteins depends on cofactors; yet, they have only been implicated in a minority of Mendelian diseases. Here, we describe the first 2 inherited disorders of the cytosolic iron-sulfur protein assembly system. METHODS: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome. Studies in patient-derived skin fibroblasts and zebrafish models were performed to investigate the biochemical and cellular consequences. RESULTS: Metabolic analysis showed elevated uracil and thymine levels in body fluids but no pathogenic variants in DPYD, encoding dihydropyrimidine dehydrogenase. Genome sequencing identified compound heterozygosity in 2 patients for missense variants in CIAO1, encoding cytosolic iron-sulfur assembly component 1, and homozygosity for an in-frame 3-nucleotide deletion in MMS19, encoding the MMS19 homolog, cytosolic iron-sulfur assembly component, in the third patient. Profound alterations in the proteome, metabolome, and lipidome were observed in patient-derived fibroblasts. We confirmed the detrimental effect of deficiencies in CIAO1 and MMS19 in zebrafish models. CONCLUSION: A general failure of cytosolic and nuclear iron-sulfur protein maturation caused pleiotropic effects. The critical function of the cytosolic iron-sulfur protein assembly machinery for antiviral host defense may well explain the recurrent severe infections occurring in our patients.

Knock-out of vasotocin reduces reproductive success in female zebrafish, Danio rerio.

The vertebrate nonapeptide vasotocin/vasopressin is evolutionarily highly conserved and acts as neuromodulator and endocrine/paracrine signaling molecule. Circumstantial and mechanistic evidence from pharmacological manipulations of the vasotocin system in several teleost fishes suggest sex- and species-specific reproductive roles of vasotocin. While effects of vasotocin on teleost reproductive physiology involve both courtship behaviors and the regulation of the hypothalamic-pituitary-gonadal (HPG) axes, comprehensive studies investigating behavioral and physiological reproductive consequences of genetic ablation of vasotocin in a genetically tractable fish model, such as the zebrafish, are currently lacking. Here, we report the generation of homozygous CRISPR/Cas9-based vasotocin gene knock-out zebrafish. Breeding pairs of vasotocin knock-out fish produce significantly fewer fertilized eggs per clutch compared to wildtype fish, an effect coincident with reduced female quivering courtship behavior. Crossbreeding experiments reveal that this reproductive phenotype is entirely female-dependent, as vasotocin-deficient males reproduce normally when paired with female wild-type fish. Histological analyses of vasotocin knock-out ovaries revealed an overall reduction in oocytes and differential distribution of oocyte maturation stages, demonstrating that the reproductive phenotype is linked to oocyte maturation and release. Ovarian hormone quantification and gene expression analysis in mutant fish indicated reduced synthesis of Prostaglandin F2α, a hormone involved in ovarian maturation, egg release and regulation of female courtship behavior in some cyprinids. However, acute injection of vasotocin did not rescue the female mutant reproductive phenotype, suggesting a contribution of organizational effects of vasotocin. Together, this study provides further support for emerging roles of vasotocin in female teleost reproduction in an important teleost model species.

Loss of dlx5a/dlx6a Locus Alters Non-Canonical Wnt Signaling and Meckel's Cartilage Morphology.

The dlx genes encode transcription factors that establish a proximal-distal polarity within neural crest cells to bestow a regional identity during craniofacial development. The expression regions of dlx paralogs are overlapping yet distinct within the zebrafish pharyngeal arches and may also be involved in progressive morphologic changes and organization of chondrocytes of the face. However, how each dlx paralog of dlx1a, dlx2a, dlx5a and dlx6a affects craniofacial development is still largely unknown. We report here that the average lengths of the Meckel's, palatoquadrate and ceratohyal cartilages in different dlx mutants were altered. Mutants for dlx5a-/- and dlx5i6-/-, where the entire dlx5a/dlx6a locus was deleted, have the shortest lengths for all three structures at 5 days post fertilization (dpf). This phenotype was also observed in 14 dpf larvae. Loss of dlx5i6 also resulted in increased proliferation of neural crest cells and expression of chondrogenic markers. Additionally, altered expression and function of non-canonical Wnt signaling were observed in these mutants suggesting a novel interaction between dlx5i6 locus and non-canonical Wnt pathway regulating ventral cartilage morphogenesis.

Spiking CMOS-NVM mixed-signal neuromorphic ConvNet with circuit- and training-optimized temporal subsampling.

We increasingly rely on deep learning algorithms to process colossal amount of unstructured visual data. Commonly, these deep learning algorithms are deployed as software models on digital hardware, predominantly in data centers. Intrinsic high energy consumption of Cloud-based deployment of deep neural networks (DNNs) inspired researchers to look for alternatives, resulting in a high interest in Spiking Neural Networks (SNNs) and dedicated mixed-signal neuromorphic hardware. As a result, there is an emerging challenge to transfer DNN architecture functionality to energy-efficient spiking non-volatile memory (NVM)-based hardware with minimal loss in the accuracy of visual data processing. Convolutional Neural Network (CNN) is the staple choice of DNN for visual data processing. However, the lack of analog-friendly spiking implementations and alternatives for some core CNN functions, such as MaxPool, hinders the conversion of CNNs into the spike domain, thus hampering neuromorphic hardware development. To address this gap, in this work, we propose MaxPool with temporal multiplexing for Spiking CNNs (SCNNs), which is amenable for implementation in mixed-signal circuits. In this work, we leverage the temporal dynamics of internal membrane potential of Integrate & Fire neurons to enable MaxPool decision-making in the spiking domain. The proposed MaxPool models are implemented and tested within the SCNN architecture using a modified version of the aihwkit framework, a PyTorch-based toolkit for modeling and simulating hardware-based neural networks. The proposed spiking MaxPool scheme can decide even before the complete spatiotemporal input is applied, thus selectively trading off latency with accuracy. It is observed that by allocating just 10% of the spatiotemporal input window for a pooling decision, the proposed spiking MaxPool achieves up to 61.74% accuracy with a 2-bit weight resolution in the CIFAR10 dataset classification task after training with back propagation, with only about 1% performance drop compared to 62.78% accuracy of the 100% spatiotemporal window case with the 2-bit weight resolution to reflect foundry-integrated ReRAM limitations. In addition, we propose the realization of one of the proposed spiking MaxPool techniques in an NVM crossbar array along with periphery circuits designed in a 130nm CMOS technology. The energy-efficiency estimation results show competitive performance compared to recent neuromorphic chip designs.

A Case Report of Occult Weak 'A' Subgroup: An Important Message for Renal Transplant Physicians.

Accurate ABO grouping is the cornerstone of a successful ABO-compatible organ transplant. While conventional methods identify blood groups accurately in most cases, rare and weak blood groups could occasionally be misread/missed. Weak A subgroups such as A3, Ax, Aend, Am, Ay, and Ael are often mistyped as group O. We present one interesting case of 'weak A' subgroup in a renal transplant donor, who was wrongly typed as 'O' Rh D positive by conventional grouping techniques. It was a near miss as the donor was almost selected for transplant for the patient with blood group B positive.

Plasmodium Iron-Sulfur [Fe-S] cluster assembly protein Dre2 as a plausible target of Artemisinin: Mechanistic insights derived in a prokaryotic heterologous system.

Iron-sulfur (Fe-S) cluster containing proteins have been assigned roles in various essential cellular processes, such as regulation of gene expression, electron transfer, sensing of oxygen and balancing free radical chemistry. However, their role as the drug target remains sparse. Recently the screening of protein alkylation targets for artemisinin in Plasmodium falciparum led to identification of Dre2, a protein involved in redox mechanism for the cytoplasmic Fe-S cluster assembly in different organisms. In the present study, to further explore the interaction between artemisinin and Dre2, we have expressed the Dre2 protein of both P. falciparum and P. vivax in E. coli. The opaque brown colour of the IPTG induced recombinant Plasmodium Dre2 bacterial pellet, suggested iron accumulation as confirmed by the ICP-OES analysis. In addition, overexpression of rPvDre2 in E. coli reduced its viability, growth and increased the ROS levels of bacterial cells, which in turn led to an increase in expression of stress response genes of E. coli such as recA, soxS, mazF. Moreover, the overexpression of rDre2 induced cell death could be rescued by treatment with Artemisinin derivatives suggesting their interaction. The interaction between DHA and PfDre2 was later demonstrated by CETSA and microscale thermophoresis. Overall, this study suggests that Dre2 is the probable target of Artemisinin and the antimalarial activity of DHA/Artemether could also be due to yet unidentified molecular mechanism altering the Dre2 activity in addition to inducing DNA and protein damage.

Continuous Erector Spinae Plane Block in Paediatric VATS: A Case Series.

Decortication and stripping of infected pleura by video-assisted thoracoscopic surgery or thoracotomy is the treatment of choice in cases of empyema. The stripping is associated with intense post-operative pain. Erector spinae block is an excellent and safe alternative to thoracic epidural block. The experience in paediatric erector spinae plane block is very limited. We present our experience of continuous erector spinae block and one single-shot erector spinae plane block in paediatric video-assisted thoracoscopic surgeries. We had 5 patients aged 2-8 years with right-sided empyema, who were taken up for video-assisted thoracoscopic surgery decortication, and 2 patients aged 1-4 years with congenital diaphragmatic hernia (CDH) for video-assisted thoracoscopic surgery CDH repair. After induction and intubation, using high-frequency straight ultrasound probe, an erector spinae plane catheter was inserted and the local anaesthetic agent was administered. The patients were monitored for signs of effective analgesia. Post-extubation continuous erector spinae plane block was continued for 48 hours using bupivacaine and fentanyl. All patients had excellent postoperative analgesia for more than 48 hours. There were no side effects like motor block, nausea, vomiting, or respiratory depression. Continuous erector spinae plane block provides excellent analgesia in paediatric patients undergoing video-assisted thoracoscopic surgery, causing minimal side effects. Further, a prospective randomized control trial is suggested to establish the efficacy of this block in paediatric video-assisted thoracoscopic surgeries.

Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish.

AIM: Although zebrafish are gaining popularity as biomedical models of cardiovascular disease, our understanding of their cardiac control mechanisms is fragmentary. Our goal was to clarify the controversial role of the ß1-adrenergic receptor (AR) in the regulation of heart rate in zebrafish. METHODS: CRISPR-Cas9 was used to delete the adrb1 gene in zebrafish allowing us to generate a stable adrb1-/- line. Larval heart rates were measured during pharmacological protocols and with exposure to hypercapnia. Expression of the five zebrafish adrb genes were measured in larval zebrafish hearts using qPCR. RESULTS: Compared with genetically matched wild-types (adrb1+/+ ), adrb1-/- larvae exhibited ~20 beats min-1 lower heart rate, measured from 2 to 21 days post-fertilization (dpf). Nevertheless, adrb1-/- larvae exhibited preserved positive chronotropic responses to pharmacological treatment with AR agonists (adrenaline, noradrenaline, isoproterenol), which were blocked by propranolol (general ß-AR antagonist). Regardless of genotype, larvae exhibited similar increases in heart rate in response to hypercapnia (1% CO2 ) at 5 dpf, but tachycardia was blunted in adrb1-/- larvae at 6 dpf. adrb1 gene expression was abolished in the hearts of adrb1-/- larvae, confirming successful knockout. While gene expression of adrb2a and adrb3a was unchanged, adrb2b and adrb3b mRNA levels increased in adrb1-/- larval hearts. CONCLUSION: Despite adrb1 contributing to the setting of resting heart rate in larvae, it is not strictly essential for zebrafish, as we generated a viable and breeding adrb1-/- line. The chronotropic effects of adrenergic stimulation persist in adrb1-/- zebrafish, likely due to the upregulation of other ß-AR subtypes.

Epidemiology of Traumatic Posterior Hip Instability in the National Football League.

BACKGROUND: There is a paucity of literature regarding injury incidence, mechanism, and return to play in National Football League (NFL) players who have sustained traumatic posterior hip instability. PURPOSE: To describe the incidence of traumatic posterior hip instability and the rate of return to play in NFL players across 18 seasons. STUDY DESIGN: Descriptive epidemiology study. METHODS: We retrospectively assessed all traumatic posterior hip dislocations/subluxations that occurred during football-related activities in the NFL seasons from 2000 through 2017. Player demographics and injury data (injury mechanism, season of injury, treatment, days missed, and return to play time) were collected from all 32 NFL teams prospectively through a leaguewide electronic health record system. Descriptive statistics are presented. RESULTS: Across the 18 NFL seasons, 16 posterior hip instability injuries in 14 players were reported, with a maximum incidence of 4 (25%) in 2013. Posterior hip instability was predominantly sustained by offensive players (64.3%), with tight ends being the most affected (31.3%). Half of the injuries occurred during the regular season, 43.8% in the preseason, and 6.2% in the offseason. Of all injuries, 37.5% were noncontact, while 56.3% involved contact (direct or indirect), and 6.2% were of unknown mechanism. Among noncontact injuries, 66.7% occurred during cutting and change of direction while sprinting. The time of return to full participation was documented for 11 of the 16 reported injuries (68.8%); among them, the mean time loss was 136.7 ± 83.8 days-143.3 ± 99.6 days if the player underwent surgery (n = 4) and 116.7 ± 76.2 days missed by players without surgery (n = 6)-the treatment modality was unknown in 1 player. CONCLUSION: Although the incidence of traumatic posterior hip instability during the study period was low, all injured athletes missed time from football activities and competitions. Injuries that required surgery led to more missed time than those that did not. Ongoing research to understand risk factors and mechanisms of this injury, in conjunction with improvements to prevention and rehabilitation protocols, is necessary to ensure the safety of professional American football players.

Perfusion index as a predictor of working pediatric caudal block under general anesthesia- A prospective observational study.

Background and Aims: Advances in pulse oximeter technology have enabled us to measure parameters such as perfusion index (PI). We aimed to ascertain the utility of PI in the lower limb for evaluating the onset and adequacy of the pediatric caudal block under general anesthesia. The primary objective was to monitor PI trends after caudal block. The secondary objective was to compare the role of PI, heart rate (HR), and mean arterial pressure (MAP) in detecting onset and adequacy of caudal block and to ascertain whether PI was an earlier indicator in detecting adequate block. Material and Methods: Twenty-five children between 1 and 6 years, who underwent general anesthesia (GA) with caudal block were included. Baseline PI, HR, and MAP were recorded prior to and post caudal block at 5, 10, 15, 20 min and on skin incision. The onset of adequate block was defined as 100% increase of PI from baseline, 15% decrease of MAP or HR from baseline. T-test was used to compare trends of PI with baseline and the number of patients who met or failed these criteria for each of these three parameters at various time intervals wasnoted. Results: PI increased at all time intervals in 23 of 25 patients with working caudal block (P < 0.0001). By 10 min all those with a working caudal showed a 100% increase in PI. In contrast, 15% decrease in HR was not attained until 15 min where only 8 out of 23 achieved the above criteria, reaching a maximum of 20 patients at the time of incision; a 15% decrease in MAP was observed only in one patient at 5 min, reaching a maximum of eight patients at the time of incision. Conclusion: PI is an earlier and more sensitive indicator of the onset of the caudal block under general anesthesia (GA) than HR and MAP.

Rethinking the routine: Preoperative laboratory testing among American Society of Anesthesiologists class 1 and 2 patients before low-risk ambulatory surgery in the 2017 National Surgical Quality Improvement Program cohort.

BACKGROUND: Routine preoperative laboratory testing is not recommended for American Society of Anesthesiologists classification 1 or 2 patients before low-risk ambulatory surgery. METHODS: The 2017 National Surgical Quality Improvement Program data set was retrospectively queried for American Society of Anesthesiologists class 1 and 2 patients who underwent low-risk, elective outpatient anorectal, breast, endocrine, gynecologic, hernia, otolaryngology, oral-maxillofacial, orthopedic, plastic/reconstructive, urologic, and vascular operations. Preoperative laboratory testing was defined as any chemistry, hematology, coagulation, or liver function studies obtained ≤30 days preoperatively. Demographics, comorbidities, and outcomes were compared between those with and without testing. The numbers needed to test to prevent serious morbidity or any complication were calculated. Laboratory testing costs were estimated using Centers for Medicare and Medicaid Services data. RESULTS: Of 111,589 patients studied, 57,590 (51.6%) received preoperative laboratory testing; 26,709 (46.4%) had at least 1 abnormal result. Factors associated with receiving preoperative laboratory testing included increasing age, female sex, non-White race/ethnicity, American Society of Anesthesiologists class 2, diabetes, dyspnea, hypertension, obesity, and steroid use. Mortality did not differ between patients with and without testing. The complication rate was 2.5% among tested patients and 1.7% among patients without tests (P < .01). The numbers needed to test was 599 for serious morbidity and 133 for any complication. An estimated $373 million annually is spent on preoperative laboratory testing in this population. CONCLUSION: Despite American Society of Anesthesiologists guidelines, a majority of American Society of Anesthesiologists class 1 and 2 patients undergo preoperative laboratory testing before elective low-risk outpatient surgery. The differences in the rates of complications between patients with and without testing is low. Preoperative testing should be used more judiciously in this population, which may lead to cost savings.

Delineating the Role of Aedes aegypti ABC Transporter Gene Family during Mosquito Development and Arboviral Infection via Transcriptome Analyses.

Aedes aegypti acts as a vector for several arboviral diseases that impose a major socio-economic burden. Moreover, the absence of a vaccine against these diseases and drug resistance in mosquitoes necessitates the development of new control strategies for vector-borne diseases. ABC transporters that play a vital role in immunity and other cellular processes in different organisms may act as non-canonical immune molecules against arboviruses, however, their role in mosquito immunity remains unexplored. This study comprehensively analyzed various genetic features of putative ABC transporters and classified them into A-H subfamilies based on their evolutionary relationships. Existing RNA-sequencing data analysis indicated higher expression of cytosolic ABC transporter genes (E & F Subfamily) throughout the mosquito development, while members of other subfamilies exhibited tissue and time-specific expression. Furthermore, comparative gene expression analysis from the microarray dataset of mosquito infected with dengue, yellow fever and West Nile viruses revealed 31 commonly expressed ABC transporters suggesting a potentially conserved transcriptomic signature of arboviral infection. Among these, only a few transporters of ABCA, ABCC and ABCF subfamily were upregulated, while most were downregulated. This indicates the possible involvement of ABC transporters in mosquito immunity.

A retrospective multi-center experience of renal transplants from India during COVID-19 pandemic.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic led to a sudden drop in renal transplant numbers across India in the initial months of 2020. Although the transplant numbers increased with easing of lockdown, the outcome of these transplants remains unknown. METHODS: This was a retrospective, observational, multi-center study done across eight different transplant centers in India. All the transplants done from January 30, 2020 to December 31, 2020 were included. The primary outcomes studied were patient and death censored graft survival as well as incidence of COVID-19 infection and its outcomes. RESULTS: During the study period a total of 297 kidney transplants were done. After a median follow up of 265 days the patient and death censored graft survival was 95.3% and 97.6%, respectively. Forty-one patients (13.8%) developed COVID-19 post-transplant. Majority (58.5%) were asymptomatic to mildly symptomatic and the case fatality ratio was 14.6%. On multivariable logistic regression analysis older age was associated with higher likelihood of COVID-19 infection (odds ratio 1.038; CI 1.002-1.077). CONCLUSIONS: Patient and graft outcome of kidney transplants done during the COVID-19 pandemic in India was acceptable. The incidence of COVID-19 was 13.8% with a high case fatality ratio.

Novel cross-regulation interactions between dlx genes in larval zebrafish.

The homeodomain-containing transcription factors dlx1a, dlx2a, dlx5a and dlx6a are expressed in the zebrafish brain in overlapping patterns and are important in vertebrate development. Previous work in mice have suggested the overlapping expression pattern is in part due to cross-regulatory interactions among the aforementioned dlx genes. However, the extent of these interactions and whether they are conserved among vertebrates remains to be determined. Through whole-mount in situ hybridization in zebrafish dlx mutants produced by CRISPR-Cas9 mutagenesis, cross-regulatory interactions between dlx1a, dlx2a, dlx5a and dlx6a were examined from 24 to 72 h post fertilization (hpf). Notably, and different from previous work done in mouse, zebrafish dlx2a-/- mutants continue to express dlx5a until 72hpf, whereas deletion of both enhancers within the dlx5a/dlx6a locus resulted in delayed dlx5a/dlx6a expression and relative increased dlx2a expression. These results suggest alternative regulatory elements and pathways exist to mediate dlx expression in zebrafish and may highlight evolutionary differences in gene interactions between vertebrates.

gdnf affects early diencephalic dopaminergic neuron development through regulation of differentiation-associated transcription factors in zebrafish.

Glial cell line-derived neurotrophic factor (GDNF) has been reported to enhance dopaminergic neuron survival and differentiation in vitro and in vivo, although those results are still being debated. Glial cell line-derived neurotrophic factor (gdnf) is highly conserved in zebrafish and plays a role in enteric nervous system function. However, little is known about gdnf function in the teleost brain. Here, we employed clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 to impede gdnf function in the maintenance of dopaminergic neuron development. Genotyping of gdnf crispants revealed successful deletions of the coding region with various mutant band sizes and down-regulation of gdnf transcripts at 1, 3 and 7 day(s) post fertilization. Notably, ~20% reduction in ventral diencephalic dopaminergic neuron numbers in clusters 8 and 13 was observed in the gdnf-deficient crispants. In addition, gdnf depletion caused a modest reduction in dopaminergic neurogenesis as determined by 5-ethynyl-2'-deoxyuridine pulse chase assay. These deleterious effects could be partly attributed to deregulation of dopaminergic neuron fate specification-related transcription factors (otp,lmx1b,shha,and ngn1) in both crispants and established homozygous mutants with whole mount in-situ hybridization (WISH) on gdnf mutants showing reduced otpb and lmx1b.1 expression in the ventral diencephalon. Interestingly, locomotor function of crispants was only impacted at 7 dpf, but not earlier. Lastly, as expected, gdnf deficiency heightened crispants vulnerability to 1-methyl-4-phenylpyridinium toxic insult. Our results suggest conservation of teleost gdnf brain function with mammals and revealed the interactions between gdnf and transcription factors in dopaminergic neuron differentiation.

mtDNA Analysis: A Valuable Tool to Establish Relationships in Live Related Organ Transplants.

INTRODUCTION: In India, 90% kidneys for transplantation are obtained from living donor while only 10% come from deceased donors. Since the rate of living organ donors is high, it therefore leads to the problem of organ trafficking.To minimize the chances of organ trafficking, the Transplantation of Human Organ Act (THOA) 2014 was enacted in India that makes it mandatory to prove the relationship between patient and donor by DNA testing. The present study was undertaken to evaluate the degree of matching between maternally related patients and donors, performed using mitochondrial DNA (mtDNA). METHODS: After taking an informed consent, a total of 84 subjects were recruited in the study, 42 kidney transplant recipients and 42 their corresponding donors. An attempt was made to establish and confirm the claimed relationship betweenrecipient and donor using mtDNA analysis. RESULTS: Out of the total 42 cases, mtDNA analysis supported the claimed relationship in 33 (78.57%) cases, whereas in 9 (21.42%) cases claimed relationship could not be supported. CONCLUSION: mtDNA can be used as valuable tool to support the claimed relationships of maternal lineage. It is important that more and more organ transplant physicians, surgeons and committees are made aware of this diagnostic modality.

Neoplastic Pathogenesis Associated with Cigarette Carcinogens.

Cigarette smoke is widely regarded as a carcinogenic agent; thus, the incidence of relative neoplasms correlates to cigarette smoking (CS) on a global level. While CS is most commonly associated with carcinomas of the upper and lower respiratory tracts, studies have also associated CS with the pathogenesis of a variety of non-respiratory related neoplasms. The tobacco smoke emitted from cigarettes contains carcinogenic substances that can be harmful to the normal physiology of the human body. This study will elaborate on the incidence and etiology of carcinomas, as well as discuss, in detail, the role of tobacco in the pathogenesis of oral, esophageal, lung, gastric, pancreatic, renal, and bladder carcinomas.