Array Comparative Genomic Hybridization in Sarcomas

Over the past years, much research on sarcomas based on low-resolution cytogenetic and molecular cytogenetic methods has been published, leading to the identification of genetic abnormalities partially underlying the tumourigenesis. Continued progress in the identification of genetic events such as copy number aberrations relies upon adapting the rapidly evolving high-resolution microarray technology, which will eventually provide novel insights into sarcoma biology, and targets for both diagnostics and drug development. The aim of this Thesis was to characterize DNA copy number changes that are involved in the pathogenesis of soft tissue leiomyosarcoma (LMS), dermatofibrosarcoma protuberans (DFSP), osteosarcoma (OS), malignant fibrous histiocytoma (MFH), and uterine leiomyosarcoma (ULMS) by applying fine resolution array comparative genomic hybridization (aCGH) technology. Both low- and high-grade LMS tumours showed distinct copy number patterns, in addition to sharing two minimal common regions of gains and losses. Small aberrations were detected by aCGH, which were beyond the resolution of chromosomal comparative genomic hybridization (cCGH). DFSP tumours analysed by aCGH showed gains in 17q, 22q, and 21 additional gained regions, but only one region (22q) with copy number loss. Recurrent amplicons identified in OS by aCGH were 12q11-q15, 8q, 6p12-p21, and 17p. Amplicons 12q and 17p were further characterized in detail. The amplicon at 17p was characterized by aCGH in low- and high-grade LMS, OS, and MFH. In all but one case this amplicon, with minimal common regions of gains at 17p11-p12, started with the distal loss of 17p13-pter. OS and high-grade LMS were grouped together as they showed a complex pattern of copy number gains and amplifications at 17p, whereas MFH and low-grade LMS showed a continuous pattern of copy number gains and amplification at 17p. In addition to the commonly gained and lost regions identified in ULMS by aCGH, various biological processes affected by these copy number changes were also indicated by pathway analysis. The three novel findings obtained in this work were: characterization of amplicon 17p in low- and high-grade LMS and MFH, profiles of DNA copy number changes in LMS, and detection of various pathways affected by copy number changes in ULMS. These studies have not been undertaken previously by aCGH technology, thus this Thesis adds new information regarding DNA copy number changes in sarcomas. In conclusion, the aCGH technique used in this Thesis has provided new insights into the genetics of sarcomas by detecting the precise regions affected by copy number changes and some potential candidate target genes within those regions, which had not been uncovered by previously applied low resolution techniques.no abstract avaliable

Study on maternal and perinatal outcome in eclampsia in a tertiary care hospital

Background: Eclampsia is an unpredictable multi-organ disease unique to pregnancy and is largely a preventable condition, responsible for high maternal and perinatal mortality. Methods: The present study was conducted in the Department of Obstetrics and Gynaecology in Maharani Laxmi Bai Medical College, Jhansi. It was a retrospective study conducted over a period of 12 months on all eclamptic cases attending our hospital and feto-maternal outcome data was analysed. Results: The incidence of eclampsia in our hospital was 2.22%. Most of the eclamptic cases were antepartum eclampsia constituting 81.48%. During the study period there were a total of 2430 obstetric admissions out of which 54 were eclamptic cases. There were 89 near miss cases and 21 maternal deaths. 16 (17.97%) near miss cases and 7(33.33%) maternal deaths were due to eclampsia. 37.03% patients had complications. Pulmonary edema/ARDS was the most common complication seen in our study. Early neonatal mortality in our study was 11.11%, 11 new-borns needed NICU care. Prematurity was the most common cause. Conclusions: Adequate screening, monitoring and routine check-up during and after pregnancy may prevent worsening the maternal and foetal outcome. Lack of antenatal care is a common risk factor for eclampsia is and this needs to be addressed to prevent this serious complication of pregnancy

A histopathological study of hysterectomy specimens and their clinical correlation in patients at tertiary health care setup in Bundelkhand region of Uttar Pradesh

Background: Women in their life time are prone to develop several neoplastic and non-neoplastic lesions in her uterus and cervix basically due to hormone responsiveness of female genital tract system. The aim of the study was to evaluate all hysterectomy specimens and to study the pattern of pathological changes of different lesions occurring in cervix and uterus associated with different age groups. Methods: This retrospective cross-sectional, study was conducted on patients undergoing hysterectomy in department of obstetrics and gynecology in MLB Medical College Jhansi and hysterectomized specimens reported to department of pathology for further evaluation. Total 35 hysterectomy specimens were included in the study with age of patients varying from 30 years to 60 years. Detailed clinical and other relevant history were taken followed by thorough gross examination and histopathological evaluation. Results: Majority of hysterectomy specimens were sent for histopathological examination in the department of pathology, out of these 30 (85%) were total abdominal hysterectomy specimen, 5 (14.28%) were of vaginal hysterectomy specimens. Out of all these cases, in 7 (20%) cases bilateral or unilateral salpingopherectomy done. Conclusions: In our study, most common surgical procedure for hysterectomy was abdominal hysterectomy 30 (85.7%) followed vaginal hysterectomy 5 (14.28%) All the vaginal hysterectomy was done for second- and third-degree utero-vaginal prolapse. Most prevalent endometrial histopathological finding in our study is non-secretive 15 (42.8%), secretive 7 (20%) followed by atrophic 6 (17.1%) as most of the patients in our study presents with abnormal uterine bleeding and menorrhagia 23 (65.7%)

Assessing critical gaps in COVID-19 testing capacity : the case of delayed results in Ecuador

Background: Testing is crucial for COVID-19 response and management, however, WHO's preparedness index omits estimations of actual testing capabilities, which influence the ability to contain, mitigate and clinically manage infectious diseases. With one of the highest excess death rates globally, Ecuador had a comparatively low number of confirmed COVID-19 cases, which may have been influenced by limited availability of data for decision-making due to low laboratory capacity. Methods: We examine de-identified data on 55,063 individuals with suspected COVID-19 between February 27 and April 30, 2020 included in the RT-PCR testing database collected by the Ministry of Health. Processing times and rates per province, and the number of pending tests, were tallied cumulatively. We assessed the relationship between sample shipping, laboratory capacity and case completion using a negative binomial generalized linear model. Results: The national average time for case completion was 3 days; 12.1% of samples took ≥10 days to complete; the national average daily backlog was 29.1 tests per 100,000 people. Only 8 out of 24 provinces had authorized COVID-19 processing laboratories but not all processed samples. There was an association between samples coming from outside the processing laboratory province, the number of other samples present at the laboratory during processing, and the amount of time needed to process a sample. Samples from another province took 1.29 times as long to process, on average. The percentage of pending results on April 30 was 67.1%. Conclusion: A centralized RT-PCR testing system contributes to critical delays in processing, which may mask a case burden higher than reported, impeding timely awareness, and adequate clinical care and vaccination strategies and subsequent monitoring. Although Ecuador adapted or authorized existing facilities to address limitations in laboratory capacity for COVID-19, this study highlights the need to estimate and augment laboratory capabilities for improved decision making and policies on diagnostic guidelines and availability. Support is needed to procure the necessary human and physical resources at all phases of diagnostic testing, including transportation of samples and supplies, and information management. Strengthening emergency preparedness enables a clear understanding of COVID-19 disparities within and across the country.Publisher PDFPeer reviewe

Asynchronous Inhibition in Neocortical Microcircuits

Neurons are constantly integrating information from external and internal sources, causing them to spike at particular times. The exact timing of spikes is determined by a neuron's intrinsic properties, as well as the interplay between local excitatory and inhibitory inputs. Although inhibitory interneurons have been extensively studied, their contribution to neuronal integration and spike timing remains poorly understood. To elucidate the functional role of GABAergic interneurons during cortical activity, we combined molecular identification of interneurons, two photon imaging and electrophysiological recordings in mouse thalamocortical slices. In this preparation, cortical UP states, a network state characterized by prolonged periods of depolarization and synchronized spiking, can be evoked by thalamic stimulation and can also occur spontaneously. To assay the role of inhibition, we first characterized the firing properties of Parvalbumin (PV) and Somatostatin (SOM) interneurons during UP states activity, and found a higher probability and rate of spiking in these two subtypes compared to excitatory cells. These subtypes did not display differential timing of activation during the evoked response. Furthermore, calcium imaging showed low correlations among PV and SOM interneurons, indicating that neurons sharing these neurochemical markers do not coordinate their firing. Intracellular recordings confirmed that nearby interneurons, known to be electrically coupled, do not display more synchronous spiking than excitatory cells, suggesting that this coupling may not function to synchronize the activity of interneurons on fast time scales¬¬¬. After characterizing inhibitory interneuron outputs, we next studied the timing and correlation of inhibitory inputs, which we isolated from excitatory inputs by voltage clamping at the reversal for excitation (0mV) or inhibition (-70mV). In both thalamically triggered and spontaneous activations, IPSCs between cell pairs were remarkably well correlated, with correlation coefficients reaching over .9 in some cases. This high degree of correlation has previously been assumed to be due to interneuron synchrony, but our population imaging and paired recordings did not support this view. In addition, we found that the connection rate between interneurons is very high (~80%), and quantal analysis revealed that each IPSC recorded in neighboring cells during an UP state could be due to a single presynaptic interneuron. Therefore, we explain the high IPSCs correlations in nearby pyramidal cells are emerging from the common input from individual interneurons, rather than from synchronization of interneuron activity across the population. In a final set of experiments, we found that a partial pharmacological block of inhibitory signaling increased EPSC correlations. Our data support a model in which inhibitory neurons do not fire in a correlated fashion but have strong, dense connections to pyramidal neurons that serve to prevent local excitatory synchrony during UP states. This would mean that inhibition may not, as previously thought, serve to synchronize the firing of excitatory cells, but have precisely the opposite effect, decorrelating their activity by breaking down their coordinated firing. This is consistent with the hypothesis that pyramidal cells are carrying out an essentially integrative function in the circuit and that interneurons expand the temporal dynamic range of this integration

Interesting rare case of recurrent puerperal uterine inversion: a case report

Uterine inversion is a rare obstetric emergency that may lead to severe haemorrhage, shock and eventually death. The incidence of uterine inversion varies from one in 2,000-20,000 deliveries. Recurrent uterine inversion is still rare with no exact reported incidence so far. We report a case of a near miss patient, 28 years old primiparous with complete uterine inversion with atonic postpartum haemorrhage and shock, managed by manual repositioning and tamponade insertion which got corrected. Patient had recurrent uterine inversion twice in the puerperal period on 5th and 7th postpartum day. A new approach to management was taken. Rather than going for laparotomy, vaginal manual correction followed by intrauterine tri-way foley catheter insertion was done. Gradual deflation was done leading to final permanent correction. Uterine inversion is a rare but potentially deadly complication post vaginal delivery. Mortality and morbidity can be reduced by rapid recognition and immediate replacement. For recurrent inversion prolonged intrauterine balloon placement may be needed in rare cases

A Review on Role of Advanced Glycation End products (AGEs) in Rheumatoid Arthritis

Rheumatoid arthritis (RAa) is a systemic inflammatory connective tissue disease with polyarthritis as a prominent feature; however, extra-articular symptoms and signs are always present. Aadvanced glycation end products with ability of cross-linking of proteins characteristic fluorescence and reaction with AaGEe-specific receptor RAaGEe (receptor for AaGEes). AaGEes action as well as AaGEe formation is directly related to both to inflammation and oxidative stress. RAaGEe is a 35-kDa polypeptide whose gene is located at the junction of the class II and III HLAla regions on chromosome. ligation of RAaGEe has been shown to activate p21ras and mitogen-activated protein (MAaP) kinase, and stimulate nuclear translocation of the transcription factor NF-κB, thereby, resulting in the transcription of target genes thus may induce chronic cellular activation and tissue damage

A comparative study on maternal and foetal outcome between low and normal amniotic fluid index in term pregnancies

Background: Amniotic fluid index (AFI) approximates amniotic fluid volume. It measures the overall well-being of the foetus. objective of the study was to determine Maternal and Foetal outcome in oligohydramnios pregnancies and compare them with cases of normal amniotic fluid volume full term pregnancies. Methods: This hospital based prospective comparative study included 300 pregnant women with full term pregnancies. Distributed equally into two groups, cases (AFI ≤5 cm) and controls (AFI: 6 to 24 cm). AFI measured using Phelan's four quadrant method. Detailed history, a clinical assessment and obstetric examination done for participants. Labour onset, amniotic fluid type, reason for LSCS, mode of delivery, birth weight, APGAR score, NICU admission, and delivery outcome were the outcome measures studied. Results: Mean age for case group was 24.36±4.23 years and 25.82±3.45 years for control group. For case group 36% and 30% of control group were induced. In case group liquor in 26% was significantly meconium soiled, compared to 7.3% of control group. Case group had 38% Caesarean procedures due to foetal distress. For case group 38% births were vaginal, while 62% in control group. In case group 30% of newborns were under 2.5 kilogram, compared to 16% in control group. In case group 17.33% participants had APGAR scores <7 compared to 2% in the control group. Case group lost 3.33% of infants, whereas the control group lost 1 (0.70%). Conclusions: Oligohydramnios is a high-risk pregnancy and that patients with this condition require appropriate antepartum care, intensive foetal monitoring, and intrapartum care