Metabolic syndrome in patients with chronic plaque psoriatic disease: a case-control study from western Uttar Pradesh, India

Background: Various studies on psoriasis and metabolic syndrome have shown a large variation in their results. An increasing frequency is imposing a substantial burden on the overall health of psoriasis patients that needs to be appropriately foreseen and addressed. Aim of this study was to study various aspects of metabolic syndrome in patients with chronic plaque psoriatic disease in northern Indian region.Methods: A cohort of patients registering for treatment of chronic plaque psoriasis at Dermatology outpatients’ department formed the study population. Detailed history was captured. General physical examination was carried out. A thorough cutaneous examination was undertaken which captured details on type, distribution and arrangement of primary lesions and secondary changes in patients. After overnight fasting, venous blood samples were collected from the subjects and were analysed for serum glucose, triglyceride and HDL-cholesterol. Results: Metabolic syndrome in psoriasis was associated with higher age. Gender wise male preponderance was observed. Among the psoriasis cases, 64% had metabolic syndrome whereas among the control subjects 48% had the condition (p-value 0.158). The mean for serum triglyceride level for psoriasis patients (159.42 mg/dL) was higher than controls (144.25 mg/dL). Forty six percent of cases fulfilled elevated triglycerides ≥150 mg/dl as a criterion of metabolic syndrome, compared to 40% of controls. Conclusions: We observed a higher frequency of metabolic syndrome among psoriasis cases in a northern Indian population. An association of dyslipidemia with psoriasis was also noted. Routine screening of the condition to facilitate early diagnosis and treatment should be undertaken

Comparative Analysis of MIT Rule and Lyapunov Rule in Model Reference Adaptive Control Scheme

Adaptive control involves modifying the control law used by the controller to cope with the fact that the parameters of the system being controlled change drastically due to change in environmental conditions or change in system itself. This technique is based on the fundamental characteristic of adaptation of living organism. The adaptive control process is one that continuously and automatically measures the dynamic behavior of plant, compares it with the desired output and uses the difference to vary adjustable system parameters or to generate an actuating signal in such a way so that optimal performance can be maintained regardless of system changes. This paper deals with application of model reference adaptive control scheme and the system performance is compared with Lyapunov rule and MIT rule. The plant which is taken for the controlling purpose is the first order system for simplicity. The comparison is done for different values of adaptation gain between MIT rule and Lyapunov rule. Simulation is done in MATLAB and simulink and the results are compared for varying adaptation mechanism due to variation in adaptation gain

Clinico-pathological study of skin appendageal tumours from northern India

Background: The skin appendageal tumours (ATs) encompass a wide variety of tumours clinically presenting as papules and nodules and with histologically distinct features. Early recognition of skin adnexal tumours is very important aspect as far as patient management and prognosis is concerned. The main of the study was to analyse and ascertain clinico-pathological study of skin appendageal tumours in a tertiary care centre.Methods: Retrospective cohort of patients with confirmed diagnosis of AT during 1st January 2013 to 31st December 2015 formed the study population. Study tools were records of the patients such as information from MRD (Medical Record Department) and records from histopathological section i.e. histopathological requisition forms and clinical case sheets. Cases clinically diagnosed as appendageal tumours, but not histologically, were excluded from the study. Results: Finally a total of 48 cases were included in this study. Mean age of onset was 22.7±6.4 years and the duration of complaints 5.34 ± 4.5 years. Benign follicular, benign eccrine, benign sebaceous and benign apocrine tumours were observed to be 48.89%, 42.22%, 2.22% and 6.67% respectively. Regarding distribution of benign and malignant tumours, among the all types of skin appendageal tumours diagnosed, 93.75% (N=45) were benign and 6.25% (N=3) were malignant. Pilomatricoma (54.54%), eccrine acrospiroma (26.31%) and syringocystadenoma papilliferum (67%) were observed as most commonly distributed histopathological types of diagnosed benign follicular, benign eccrine and benign apocrine tumours. Number of benign skin appendageal tumours was found maximum (n=25) in the age group of 26-50 years in both the sexes whereas malignant skin appendageal tumours were observed only (n=3) in the age group of 51-75 years in both the sexes.Conclusions: Findings of this study can be utilized to suspect type of AT thus helping in diagnosis. Profile, pattern and clinical appearance can serve as vital clue though histological confirmation is mandatory to confirm

An evaluation of quality of life of skin cancer patients after surgery using dermatology life quality index tool

Background: Quality of life (QOL) has been identified as an important outcome in cancer researches yet the most common malignancy among humans, non-melanoma skin cancer (NMSC), but poorly studied. Aim of the study was to analyze the quality of life of non-melanoma skin cancer patients after surgery using dermatology life quality index inventory (DLQI).Methods: Retrospective cohort of patients operated for non-melanoma skin cancer in last 2 years and paid postoperative 4-month visit formed the study population. Inclusion criteria consisted of subjects operated for non-melanoma skin cancer and paid follow up visits having sufficient physical and mental capacity. Fifty-six subjects fulfilled the selection criteria laid down thus included in this study. Study tools were records of patients, which were obtained from medical records section. If any more information was required, study subjects were contacted.Results: Out of total 56 study subjects, Basal cell carcinomas were found in 91.1% (n=51); squamous cell carcinomas were detected in 7.2% (n=4). Single location wise more lesions were located on the nose 22.1% (n=15) and forehead 17.6% (12). For most patients (75%), the lesion had not been previously treated. 58.9% subjects did not have any other associated co-morbid condition. Lower mean values were observed post-operative i.e. lower DLQI scores were recorded 4 months after surgery in our study which indicates that adverse effects were not very prominent thus preserving quality of life post operatively. Paired sample t-tests revealed a significant effect on DLQI item 1 (p=0.008), item 2 (p=0.043), and item 4 (p=0.003), with scores decreasing (improving QOL) after treatment. The change in total DLQI score demonstrated a trend toward significance, with overall QOL improving after treatment (p=0.024).Conclusions: Previously commonly employed dermatological Quality of life tools demonstrated minimal handicap at initial diagnosis and little change after treatment of nonmelanoma skin cancer. Development of disease-specific instrument is warranted to explore the disease process.

A UNIQUE CASE OF BILATERAL VOCAL FOLD PARALYSIS FOLLOWING SPINAL ANAESTHESIA

Cranial nerve palsies are potential but rare complications of spinal anaesthesia. Most of the literatures support upper cranial nerve palsies like VI, IV and III cranial nerve palsies. Intrathecal hypotension resulting in tractional injury of the cranial nerves is the likely mechanism of injury. As on date, some cases of unilateral vocal fold paralysis and very little bilateral vocal fold paralysis have been described in case reports. We have described a patient who developed hoarseness and dysphagia 7 days after receiving spinal anaesthesia for fixation of inter-trochanteric fracture femur. The patient was diagnosed with bilateral vocal fold paralysis. He was managed conservatively and exhibited complete spontaneous recovery as has been described in the previously reported cases. Any patient presenting with idiopathic vocal fold paralysis should be enquired about the history of spinal or epidural anaesthesia. If the history is affirmative, then it points towards transient intrathecal hypotension as a potential etiology of the cranial nerve palsy

Usage of Low-dose Glimepiride (0.5 mg) and Metformin Combination in the Management of Type 2 Diabetes Continuum in Indian Setting

Background: To understand the approach of clinicians about the treatment pattern, dosage, efficacy and safety of the combination of low-dose glimepiride (0.5 mg) and metformin fixed-dose combination (FDC) in the management of type 2 diabetes mellitus (T2DM) continuum in Indian settings. Methods: This case-based questionnaire survey included health care professionals (n = 112) across India, who were prescribing glimepiride and metformin FDC. Data were collected from the medical records and analyzed. Results: The data of 1,403 patients with T2DM were included. The mean age was 49.1 years and 68.4% of patients were males. The median duration of T2DM was 36 months. A total of 86.7% of patients received glimepiride and metformin FDC as first-line therapy. The most commonly prescribed (71.5%) dosage of glimepiride and metformin was 0.5 mg/500 mg. The titration of the dose was performed in 231 patients, of which 82.7% required up-titration and 17.3% required down-titration. The mean glycated hemoglobin (HbA1c), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels reduced significantly (mean change: 1.2%, 36.5 mg/dL and 50.2 mg/dL,respectively) post-treatment. The hypoglycemic event and weight gain were reported in 7.7% and 9.5% of patients, respectively. Overall physician’s global evaluation of efficacy and tolerability was rated good to excellent in the majority of patients (>85%). Conclusion: Results demonstrate low-dose (0.5 mg) glimepiride and metformin FDC is effective in achieving glycemic control through lowering HbA1c, FPG and PPG levels with acceptable safety outcomes

A Paper-Based Multiplexed Transaminase Test for Low-Cost, Point-of-Care Liver Function Testing

In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout “bins” [5× ULN, corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings.Chemistry and Chemical Biolog

Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells

Mucin 4 (MUC4) is a high molecular weight glycoprotein that is differentially overexpressed in pancreatic cancer (PC), functionally contributes to disease progression, and correlates with poor survival. Further, due to its aberrant glycosylation and extensive splicing, MUC4 is a potential target for cancer immunotherapy. Our previous studies have demonstrated the utility of amphiphilic polyanhydride nanoparticles as a useful platform for the development of protein-based prophylactic and therapeutic vaccines. In the present study, we encapsulated purified recombinant human MUC4-beta (MUC4β) protein in polyanhydride (20:80 CPTEG:CPH) nanoparticles (MUC4β-nanovaccine) and evaluated its ability to activate dendritic cells and induce adaptive immunity. Immature dendritic cells when pulsed with MUC4β-nanovaccine exhibited significant increase in the surface expressions of MHC I and MHC II and costimulatory molecules (CD80 and CD86), as well as, secretion of pro-inflammatory cytokines (IFN-γ, IL-6, and IL-12) as compared to cells exposed to MUC4β alone or MUC4β mixed with blank nanoparticles (MUC4β+NP). Following immunization, as compared to the other formulations, MUC4β-nanovaccine elicited higher IgG2b to IgG1 ratio of anti-MUC4β-antibodies suggesting a predominantly Th1-like class switching. Thus, our findings demonstrate MUC4β-nanovaccine as a novel platform for PC immunotherapy

From the Bench to the Field in Low-Cost Diagnostics: Two Case Studies

Despite the growth of research in universities on point-of-care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field—the processes intended to evaluate operation and performance under realistic conditions—are more complicated than they might seem. Two case studies illustrate this process: the development of a paper-based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource-limited environments.Chemistry and Chemical Biolog

Disruption of FDPS/Rac1 Axis Radiosensitizes Pancreatic Ductal Adenocarcinoma by Attenuating DNA Damage Response and Immunosuppressive Signalling

BACKGROUND: Radiation therapy (RT) has a suboptimal effect in patients with pancreatic ductal adenocarcinoma (PDAC) due to intrinsic and acquired radioresistance (RR). Comprehensive bioinformatics and microarray analysis revealed that cholesterol biosynthesis (CBS) is involved in the RR of PDAC. We now tested the inhibition of the CBS pathway enzyme, farnesyl diphosphate synthase (FDPS), by zoledronic acid (Zol) to enhance radiation and activate immune cells. METHODS: We investigated the role of FDPS in PDAC RR using the following methods: in vitro cell-based assay, immunohistochemistry, immunofluorescence, immunoblot, cell-based cholesterol assay, RNA sequencing, tumouroids (KPC-murine and PDAC patient-derived), orthotopic models, and PDAC patient\u27s clinical study. FINDINGS: FDPS overexpression in PDAC tissues and cells (P \u3c 0.01 and P \u3c 0.05) is associated with poor RT response and survival (P = 0.024). CRISPR/Cas9 and pharmacological inhibition (Zol) of FDPS in human and mouse syngeneic PDAC cells in conjunction with RT conferred higher PDAC radiosensitivity in vitro (P \u3c 0.05, P \u3c 0.01, and P \u3c 0.001) and in vivo (P \u3c 0.05). Interestingly, murine (P = 0.01) and human (P = 0.0159) tumouroids treated with Zol+RT showed a significant growth reduction. Mechanistically, RNA-Seq analysis of the PDAC xenografts and patients-PBMCs revealed that Zol exerts radiosensitization by affecting Rac1 and Rho prenylation, thereby modulating DNA damage and radiation response signalling along with improved systemic immune cells activation. An ongoing phase I/II trial (NCT03073785) showed improved failure-free survival (FFS), enhanced immune cell activation, and decreased microenvironment-related genes upon Zol+RT treatment. INTERPRETATION: Our findings suggest that FDPS is a novel radiosensitization target for PDAC therapy. This study also provides a rationale to utilize Zol as a potential radiosensitizer and as an immunomodulator in PDAC and other cancers. FUNDING: National Institutes of Health (P50, P01, and R01)