PSORIASIS PATHOGENESIS: INSIGHTS FROM TRANSCRIPTOMICS AND PROTEOMICS STUDIES OF KERATINOCYTES.

Complex inflammatory skin disease with autoimmune roots is psoriasis. This disease affects various cell types, and the underlying signaling processes are complicated yet not fully understood. Extensive psoriatic lesions' proteome and transcriptome of several researches were combined to understand disease's underlying biological mechanisms. According to a network-based study, both transcriptomics and proteomics control were comparable. They discovered many pathways of signaling previously undiscovered and possibly involved in overexpression of psoriasis genes. They also found a collection of transcription factors in charge of this process. The functional overlap between the results of transcriptomics and proteomics was also examined. There created a network-based method for combining the analysis of many high-throughput data sources. Proteomic and transcriptome studies of psoriasis data sets demonstrated regulatory flexibility apparatus underpinning disease and complementary relationships within two cellular organizations.

Total laparoscopic hysterectomy (TLH) with endosuturing compared with conventional technique using energy sources.

BACKGROUND: The aim of the study was to demonstrate the technique of total laparoscopic hysterectomy (TLH) with intra-corporeal endosuturing using simple sutures and basic surgical instruments and compare with TLH using electric coagulation equipment i.e. energy sources with regard to operative time, blood loss, postoperative stay and pain scores. METHODS: A retrospective study was undertaken, in Max Super Specialty Hospital Saket, from June 2015 to May 2018, which included 586 cases of TLH (for benign gynecological conditions), of which 287 were performed using intra-corporeal endosuturing (Group 1) and 299 were performed using energy sources (Group 2). To avoid bias, baseline matching was done for body mass index (BMI), indications for surgery, size of uterus, previous abdominal surgeries and comorbidities like diabetes and hypertension after which there were 172 patients in each group. RESULTS: The mean age of patients was 48.24 ± 6.76 years. All operative outcomes including operative time (104.1 ± 22.6 vs 107.6 ± 32.6 mins, p=0.25), blood loss (78.9 ± 101.6 vs 99.7 ± 177.6 ml, p=0.19), pain score (2.5 ± 1.3 vs 2.7 ± 1.2, p=0.13) and post-operative stay (2.05 ± 0.2 vs 2.07 ± 0.3 days, p=0.36) were similar between the two groups. Uterine size was the major determinant of operative time and operative blood loss. CONCLUSION: TLH with intracorporeal endosuturing can be performed safely and gives results comparable with TLH performed using energy sources. Advancement in suturing devices can decrease operative time further and potentially make it easier and more acceptable.

Global Collaborations for Cervical Cancer: Can the East-West Alliance Facilitate Treatment for all?

Despite the advances in the primary prevention of cervical cancer, there is an absolute increase in the incidence of cervical cancer as a result of an increase in world population. A vast majority of patients in low and low-middle income countries continue to present at a locally advanced stage, necessitating treatment with chemoradiation and brachytherapy. There is a dearth of equipment and trained professionals for the treatment of cervical cancer, especially in low and low-middle income countries. There is an urgent need to improve treatment availability and develop better treatments. Worldwide trends, however, reveal a low number of therapeutic and innovative research trials in cervical cancer. The present article elucidates the existing challenges and provides solutions to improve outcomes. The proposed strategies hinge on strengthening collaborations for global advocacy.

Dietary supplementation of vitamin C: an effective measure for protection against UV-B irradiation using fish as a model organism.

The development of UV-B protective mechanisms in aquacultural species is essential for the sustainable production of healthy aqua crop. Freshwater carp Catla catla larvae (13.5 ± 1.12 mg) were fed with a diet containing 0.5% vitamin C (D1) and a control diet (D2) for 40 days. Each group was exposed to two doses of UV-B irradiation: 360 (5 min, D15 min and D25 min) and 720 mJ cm-2 (10 min, D110 min and D210 min) for 15 days. Significantly (p < 0.05) higher survival and average weight were recorded in D1 compared to D2 exposed to the same dose. Also, significantly (p < 0.001) higher nitric oxide synthase and lower thiobarbituric acid reactive substances and heat shock protein 70 levels were recorded in D15 min compared to the other groups. A direct relationship was found between the dose of UV-B and DNA fragmentation in muscles. DNA damage indices such as tail DNA, tail extent moment and olive tail moment were significantly (p < 0.01) lower in D15 min. Thus, supplementation of vitamin C in the diet provides UV-B protection to larvae.

The burden of hepatitis C virus infection in Punjab, India: A population-based serosurvey.

INTRODUCTION: Hepatitis C virus (HCV) infection prevalence is believed to be elevated in Punjab, India; however, state-wide prevalence data are not available. An understanding of HCV prevalence, risk factors and genotype distribution can be used to plan control measures in Punjab. METHODS: A cross-sectional, state-wide, population-based serosurvey using a multi-stage stratified cluster sampling design was conducted October 2013 to April 2014. Children aged ≥5 years and adults were eligible to participate. Demographic and risk behavior data were collected, and serologic specimens were obtained and tested for anti-HCV antibody, HCV Ribonucleic acid (RNA) on anti-HCV positive samples, and HCV genotype. Prevalence estimates and adjusted odds ratios for risk factors were calculated from weighted data and stratified by urban/rural residence. RESULTS: 5,543 individuals participated in the study with an overall weighted anti-HCV prevalence of 3.6% (95% Confidence Interval [CI]: 3.0%-4.2%) and chronic infection (HCV Ribonucleic acid test positive) of 2.6% (95% CI: 2.0%-3.1%). Anti-HCV was associated with being male (adjusted odds ratio 1.52; 95% CI: 1.08-2.14), living in a rural area (adjusted odds ratio 2.53; 95% CI: 1.62-3.95) and was most strongly associated with those aged 40-49 (adjusted odds ratio 40-49 vs. 19-29-year-olds 3.41; 95% CI: 1.90-6.11). Anti-HCV prevalence increased with each blood transfusion received (adjusted odds ratio 1.36; 95% CI: 1.10-1.68) and decreased with increasing education, (adjusted odds ratio 0.37 for graduate-level vs. primary school/no education; 95% CI: 0.16-0.82). Genotype 3 (58%) was most common among infected individuals. DISCUSSION: The study findings, including the overall prevalence of chronic HCV infection, associated risk factors and demographic characteristics, and genotype distribution can guide prevention and control efforts, including treatment provision. In addition to high-risk populations, efforts targeting rural areas and adults aged ≥40 would be the most effective for identifying infected individuals.

Applications of Mass Spectrometry Imaging to Cancer.

Pathologists play an essential role in the diagnosis and prognosis of benign and cancerous tumors. Clinicians provide tissue samples, for example, from a biopsy, which are then processed and thin sections are placed onto glass slides, followed by staining of the tissue with visible dyes. Upon processing and microscopic examination, a pathology report is provided, which relies on the pathologist's interpretation of the phenotypical presentation of the tissue. Targeted analysis of single proteins provide further insight and together with clinical data these results influence clinical decision making. Recent developments in mass spectrometry facilitate the collection of molecular information about such tissue specimens. These relatively new techniques generate label-free mass spectra across tissue sections providing nonbiased, nontargeted molecular information. At each pixel with spatial coordinates (x/y) a mass spectrum is acquired. The acquired mass spectrums can be visualized as intensity maps displaying the distribution of single m/z values of interest. Based on the sample preparation, proteins, peptides, lipids, small molecules, or glycans can be analyzed. The generated intensity maps/images allow new insights into tumor tissues. The technique has the ability to detect and characterize tumor cells and their environment in a spatial context and combined with histological staining, can be used to aid pathologists and clinicians in the diagnosis and management of cancer. Moreover, such data may help classify patients to aid therapy decisions and predict outcomes. The novel complementary mass spectrometry-based methods described in this chapter will contribute to the transformation of pathology services around the world.

InFlo: a novel systems biology framework identifies cAMP-CREB1 axis as a key modulator of platinum resistance in ovarian cancer.

Characterizing the complex interplay of cellular processes in cancer would enable the discovery of key mechanisms underlying its development and progression. Published approaches to decipher driver mechanisms do not explicitly model tissue-specific changes in pathway networks and the regulatory disruptions related to genomic aberrations in cancers. We therefore developed InFlo, a novel systems biology approach for characterizing complex biological processes using a unique multidimensional framework integrating transcriptomic, genomic and/or epigenomic profiles for any given cancer sample. We show that InFlo robustly characterizes tissue-specific differences in activities of signalling networks on a genome scale using unique probabilistic models of molecular interactions on a per-sample basis. Using large-scale multi-omics cancer datasets, we show that InFlo exhibits higher sensitivity and specificity in detecting pathway networks associated with specific disease states when compared to published pathway network modelling approaches. Furthermore, InFlo's ability to infer the activity of unmeasured signalling network components was also validated using orthogonal gene expression signatures. We then evaluated multi-omics profiles of primary high-grade serous ovarian cancer tumours (N=357) to delineate mechanisms underlying resistance to frontline platinum-based chemotherapy. InFlo was the only algorithm to identify hyperactivation of the cAMP-CREB1 axis as a key mechanism associated with resistance to platinum-based therapy, a finding that we subsequently experimentally validated. We confirmed that inhibition of CREB1 phosphorylation potently sensitized resistant cells to platinum therapy and was effective in killing ovarian cancer stem cells that contribute to both platinum-resistance and tumour recurrence. Thus, we propose InFlo to be a scalable and widely applicable and robust integrative network modelling framework for the discovery of evidence-based biomarkers and therapeutic targets.

Piriformis fossa - an anatomical and orthopedics consideration.

INTRODUCTION: Piriformis fossa is an important anatomical landmark having significant clinical value in orthopedic surgery; but its location and anatomical relationship with surrounding structures are not clearly defined. Hence it is necessary to clearly describe it in respect to anatomical and orthopedic aspect. MATERIALS AND METHODS: Fifty Cadaveric dry femoral bones and Dissection of the four hip specimens were used to study the Piriformis fossa in respect to location and its relationship with surrounding structures. Clinical importance of piriformis fossa was determined in reference to antegrade femoral nail insertion. OBSERVATIONS: Piriformis muscle and so called piriformis fossa are unrelated entities. Piriformis fossa is anatomical site of insertion of obturator externus. In dry cadaveric femora; fossa was not always located in the direction of femoral shaft. It was located in the direction of femoral shaft in 24% cases only. In 68% cases femoral canal was aligned lateral and in 8% cases, it lies medial to the fossa. CONCLUSION: Piriformis fossa should be named as Trorchanteric fossa or Obturator fossa for better anatomical description. So called Piriformis fossa does not found to be universally corresponding to femoral shaft hence selection of entry site should be based on variable proximal femur and area on femur which corresponds to femoral shaft.

Morphology of the bicipital aponeurosis: a cadaveric study.

The bicipital aponeurosis (BA) is a fascial expansion which arises from the tendon of biceps brachii and dissipates some of the force away from its enthesis. It helps in dual action of biceps brachii as supinator and flexor of forearm. The aim of the present work was to study the morphology of BA. Thirty cadavericupper limbs (16 right and 14 left side limbs) were dissected and dimensions ofthe BA were noted. The average width of aponeurosis at its commencement on the right was 15.74 mm while on the left it was 17.57 mm. The average angle between tendon and aponeurosis on the right was 21.16° and on the left it was 21.78°. The fibres from the short head of the biceps brachii contributed to the formation of proximal part of aponeurosis. Fascial sheath over the tendon oflong head of biceps brachii was seen to form the distal part of the aponeurosis. In 5 cases, large fat globules were present between the sheath and the tendon. Histologically: The aponeurosis showed presence of thick collagen bundles. Fascials heath covering the tendon of long head extended towards the aponeurosis and passed superficial to the tendon of biceps. Blood vessels and adipose tissue were found to be present between fascial sheath and the tendon. This morphological description of BA may be helpful 1) in elucidating the dynamic role that BA plays in normal functioning and 2) to the surgeons in the repair of ruptured biceps brachii tendon.

Field evaluation of Icon®Life, a long-lasting insecticidal net (LLIN) against Anopheles culicifacies and transmission of malaria in District Gautam Budh Nagar (Uttar Pradesh), India.

BACKGROUND & OBJECTIVES: In the present study, Icon®Life net, a long-lasting polyethylene net, 100 denier and bursting strength of minimum 280 kpa incorporated with deltamethrin @ 65 mg/m2 was evaluated for its efficacy in reducing the density of malaria vector Anopheles culicifacies and impact on malaria prevalence in a malaria endemic area of District Gautam Budh Nagar, India. METHODS: Wash resistance of Icon®Life LLIN was determined up to 20 serial washings using An. culicifacies in cone bioassays under field conditions. Efficacy of Icon®Life LLIN was determined in the field in three sets of villages in District Gautam Budh Nagar (Uttar Pradesh), India, selected randomly for the intervention with Icon®Life LLIN, untreated nets and a control without any intervention for the period of August 2008-July 2009. Entomological and malariometric indices in all the three villages were compared during pre- and post-intervention periods for one year against An. culicifacies. A survey was also conducted in the village provided with Icon®Life LLIN to assessing the perception of community regarding acceptance of these nets by the community. RESULTS: In cone bioassays on Icon®Life LLIN with An. culicifacies, >95% knockdown within 1 h and 100% mortality after 24 h exposure were reported even after 20× serial washings under field conditions. Results of the field study revealed reduced entry rate, resting density and parity rate of An. culicifacies in the village with Icon®Life LLIN when compared to no net and untreated net villages. Number of malaria cases reported were less in the Icon®Life LLIN used villages when compared to other two villages. The community compliance and acceptance was high and no adverse health events were reported by the households using these nets. CONCLUSIONS: Icon®Life LLIN is an effective intervention for the control of An. culicifacies transmitted malaria in India. Long-term studies are indicated for the duration of effectiveness and to ascertain the epidemiological impact of the use of Icon®Life nets.

Insecticide susceptibility status of Phlebotomus argentipes, a vector of visceral leishmaniasis in different foci in three states of India.

BACKGROUND & OBJECTIVES: Phlebotomus argentipes is the vector for visceral leishmaniasis in India. The development of resistance in kala-azar vector to DDT has been reported from various parts of India. The main objective of this study was to generate information on insecticides susceptibility status of P. argentipes to DDT, malathion and deltamethrin in different parts in three states of India. METHODS: Phlebotomus argentipes were collected from different villages, identified and used to investigate the susceptibility status against DDT, malathion and deltamethrin as per the WHO standard methods. RESULTS: Phlebotomus argentipes was resistant to DDT in different areas, viz. PHCs Murumgaon in Maharashtra; Ramgarh in Jharkhand; Kodah, Falka, Mahua and Lalganj in Bihar. In Phulwari Shareef PHC of Patna district in Bihar, DDT produced 89% mortality in P. argentipes, indicating resistant/tolerance (verification required) to DDT. The corrected percent mortality to malathion (5%) in different areas ranged between 98 and 100%; and to deltamethrin (0.05%) between 98.4 and 100%. The results showed that the tested P. argentipes are susceptible to malathion and deltamethrin. CONCLUSION: Phlebotomus argentipes are still susceptible to malathion and deltamethrin, but resistant to DDT. The susceptibility status of P. argentipes should be monitored regularly in diversified situations to ascertain the judicious use of insecticides being used for indoor residual spraying in the programme for rational use of appropriate insecticide.

Evaluation of indoor residual spray and insecticide treated bed nets in a malaria endemic area of Santhal Pargana, Dumka district (Jharkhand).

The study was carried out for evaluation of various activities of malaria control programme in five different tribal and malaria endemic Primary Health Centres of Dumka district (Jharkhand) during 2007-08. A total of 321 houses of 18 villages were surveyed on use of indoor residual spray (IRS) and insecticide-treated bed nets (ITN) and other activities as tool for vector control and interrupting the transmission of malaria. Out of 690 living rooms and 343 verandahs examined, IRS with Dichlorodiphenyl-trichloro-ethane (DDT) was done only in 16.23% living rooms and 64.72% verandahs. Refusal rate of IRS in living rooms was 81.93% due to lack of knowledge regarding the importance of IRS, no prior information to villagers, houses locked, reluctance to remove domestic articles, dislike of smell of DDT spray. Compliance rate of ITN uses was 71.66% during the night, which might be a factor for decline in malaria cases in the study area. Various important components of the programme, viz. surveillance and compliance to treatment activities, use of rapid diagnostic test kits (RDKs), involvement of accredited social health activist (ASHA's) and fever treatment depots (FTDs), laboratory activities, adult mosquito collection, other activities like constitution of village health sanitation committee, information education and communication activities, capacity building, use of larvivorous fishes, supervision of IRS etc. require much strengthening. However, 100% community acceptance was recorded for ITN in the villages surveyed. In addition, an entomological study was carried out for information on prevalence of mosquito species in this area to find out effectiveness of IRS activities. Eleven anopheline species, including three malaria vectors i.e., An. culicifacies, An. stephensi, An. fluviatilis, An. annularis, An. subpictus, An. nigerrimus, An. pallidus, An. aconitus, An. vagus, An. jamsii and An. splendidus were collected from cattle and human dwellings.

Evaluation of the impact of ZeroFly®, an insecticide incorporated plastic sheeting on malaria incidence in two temporary labour shelters in India.

BACKGROUND & OBJECTIVES: Prevention of malaria is a major technical and operational problem in displaced and mobile populations such as refugee camps and temporary labour settlements. Insecticide incorporated plastic sheeting is a new technology to control mosquitoes in emergency shelters and also temporary habitations at different locations. In view of this, efficacy of ZeroFly® , an insecticide incorporated plastic sheeting (factory treated with deltamethrin 2.0 g/kg or 265 mg/m2 ) was evaluated for its efficacy against malaria vectors and its impact on malaria incidence in temporary labour settlements in two urban areas in India. METHODS: This trial was conducted in two labour settlements in two urban areas, Delhi and Noida (U.P.), India with ~ 250 populations. In an area, two localities were selected for intervention with ZeroFly and untreated plastic sheets (control). Entomological and epidemiological data were collected using standard methods for one year. RESULTS: Baseline studies on the susceptibility of mosquitoes in Delhi and Noida areas revealed 100% susceptibility of the malaria vector species Anopheles culicifacies and An. stephensi to deltamethrin. Cone bioassay tests performed against An. culicifacies and An. stephensi to determine the efficacy of ZeroFly sheets showed 100% mortality against An. culicifacies and An. stephensi with 3 min exposure and after 24 h recovery period. Against Culex quinquefasciatus and housefly 100% mortality was obtained after 30 min of exposure period. Intervention with the ZeroFly plastic sheets resulted in almost complete reduction in the resting density of An. culicifacies and An. stephensi, the two major malaria vectors and also in the reduction of malaria cases in ZeroFly camps as compared to control camps. The ZeroFly plastic sheeting was found to be safe for human. Barring some complaints of skin irritation and itching, which were temporary in nature, no adverse health effects were reported by the users. The community acceptance was high. CONCLUSION: Results of the present study revealed that ZeroFly® plastic sheeting is highly effective in reducing the indoor resting density of mosquitoes, man -vector contact and malaria incidences in labour populations living in temporary shelters.

Efficacy of Advanced Odomos repellent cream (N, N-diethyl-benzamide) against mosquito vectors.

BACKGROUND & OBJECTIVES: Repellents are commonly used personal protection measures to avoid mosquito bites. In the present study, Advanced Odomos cream (12% N, N-diethyl-benzamide) was tested for its efficacy against mosquitoes in comparison to DEET (N,N-diethyl-3-methyl benzamide). METHODS: Bioassays were conducted to assess the repellency of Advanced Odomos and DEET creams against Anopheles stephensi and Aedes aegypti. Their efficacy was tested on human volunteers applied with different concentrations of test creams ranging from 1 to 12 mg/cm 2 and by exposing them to mosquitoes at hourly intervals. Field evaluation was also carried out to test the duration of protection of the test creams against Anopheles and Aedes mosquitoes during whole night and day time collections, respectively on human volunteers. Mosquito collections were done using torch light and aspirator. RESULTS: Complete (100%) protection was achieved at 10 mg/cm 2 cream formulation of Advanced Odomos (1.2 mg a.i/cm 2 ) dose against An. stephensi and 12 mg/cm 2 (1.44 mg a.i./cm 2 ) against Ae. aegypti on human baits. There was no statistically significant differences in per cent protection against mosquito bites between Advanced Odomos and DEET cream (P>0.05) in respective doses. Complete protection up to 11 h was observed against Anopheles mosquitoes during whole night collections and up to 6 h against Ae. aegypti in day time collections. No adverse reactions such as itching, irritation, vomiting, nausea, etc. were reported by the volunteers. INTERPRETATION & CONCLUSIONS: Advanced Odomos cream applied at 10 mg/cm 2 concentration provided 100% protection from Anopheles mosquitoes up to 11 h whereas about 6 h protection was recorded against Ae. aegypti. The laboratory and field trials indicate that for longer protection against Anopheles mosquitoes 10 mg/cm 2 will be appropriate and in case of Ae. aegypti more than 10 mg/cm 2 application is required for complete protection. In conclusion, the Advanced Odomos cream was comparable to the known repellent cream DEET for prolonged protection against malaria and dengue vectors.

Effect of topical application of methylsulfonylmethane (MSM), EDTA on pitting edema and oxidative stress in a double blind, placebo-controlled study.

No pharmacological treatment exists for lower extremity pitting edema, characterized by inflammation, found in chronic venous insufficiency. Treatment with EDTA, an effective metal chelator, was explored because it can modulate free calcium and iron and prevent further free radical production. However, EDTA may not effectively penetrate the cell membrane, hence methylsulfonylmethane(MSM), reported to facilitate transmembrane transport, was added. The effect of topical application of a lotion containing MSM+EDTA was assessed in two phases of a double blind, placebo controlled clinical trial. In phase 1, patients having swelling in the lower extremities were randomly distributed to receive the MSM+EDTA lotion or a placebo (vehicle) alone. In the second phase, patients were given MSM as placebo followed by MSM+EDTA lotion for 2 weeks. The circumference of calf, ankle and foot for both legs were found to decline significantly after 2 weeks of application of the lotion/ but not placebo, and total antioxidant capacity (FRAP) and lipid peroxidation products (MDA), assayed in blood, showed decline in oxidative stress. Application of MSM alone increased the swelling. Thus EDTA+MSM offers an efficacious treatment for lower extremity pitting edema, through reduction in oxidative stress.

Hemichorea hemiballism syndrome: the first presentation of type 2 diabetes mellitus as a rare cause of chorea.

Hemichorea-hemiballism (HCHB) syndrome, which is most commonly related to non-ketotic hyperglycemia, is a rare type of chorea. Here, we present an unusual case of HCHB syndrome who was not a known case of diabetes. This case highlights the importance of recognising underlying non-ketotic hyperglycemia, as control of hyperglycemia is helpful in the quick relief of symptoms.