The role of beat-by-beat cardiac features in machine learning classification of ischemic heart disease (IHD) in magnetocardiogram (MCG).

Cardiac electrical changes associated with ischemic heart disease (IHD) are subtle and could be detected even in rest condition in magnetocardiography (MCG) which measures weak cardiac magnetic fields. Cardiac features that are derived from MCG recorded from multiple locations on the chest of subjects and some conventional time domain indices are widely used in Machine learning (ML) classifiers to objectively distinguish IHD and control subjects. Most of the earlier studies have employed features that are derived from signal-averaged cardiac beats and have ignored inter-beat information. The present study demonstrates the utility of beat-by-beat features to be useful in classifying IHD subjects (n = 23) and healthy controls (n = 75) in 37-channel MCG data taken under rest condition of subjects. The study reveals the importance of three features (out of eight measured features) namely, the field map angle (FMA) computed from magnetic field map, beat-by-beat variations of alpha angle in the ST-T region and T wave magnitude variations in yielding a better classification accuracy (92.7 %) against that achieved by conventional features (81 %). Further, beat-by-beat features are also found to augment the accuracy in classifying myocardial infarction (MI) Versus control subjects in two public ECG databases (92 % from 88 % and 94 % from 77 %). These demonstrations summarily suggest the importance of beat-by-beat features in clinical diagnosis of ischemia.

Effects of Eurycoma longifolia Jack standardised water extract (Physta) on well-being of perimenopausal and postmenopausal women: protocol for a randomised, double-blinded, placebo-controlled, parallel group study.

INTRODUCTION: Eurycoma longifolia Jack (EL), profoundly recognised as 'Tongkat Ali', is a medicinal herb originating from Southeast Asia. It is commonly used in traditional 'antiageing' treatments to address decreased energy, mood, libido and hormonal imbalances. While the benefits of EL have been extensively studied among the male population, less attention has been given to its effects on women. Menopause can impact the overall well-being of middle-aged women and incorporation of herbal supplements can aid them in managing the menopausal symptoms. METHODS AND ANALYSIS: This 12-week randomised double-blind, placebo-controlled, parallel-group study aims to evaluate the efficacy of the standardised water extract of EL known as Physta in increasing the quality of life of perimenopausal and postmenopausal women. The study involves 150 women aged 40-55 years who score more than 61 on the Menopause-Specific Quality of Life (MENQOL) assessment. These participants will be randomised into three groups, receiving Physta at either 50 mg or 100 mg or a placebo. The outcomes measures include mood state, quality of life, fatigue, sleep quality, sexual function and pain score assessed using Profile of Mood State, MENQOL, Chalder Fatigue Scale, Pittsburgh Sleep Quality Index, Female Sexual Function Index and the Brief Pain Inventory questionnaires, respectively. The secondary outcome of the study includes full blood analysis, urine analysis, female reproductive hormone profiling, inflammatory and oxidative stress biomarkers analysis. ETHICS AND DISSEMINATION: The research protocol of the study was reviewed and approved by the Research Ethics Committee of Universiti Kebangsaan Malaysia (UKM/PPI/111/8/JEP-2021-898). The findings will be disseminated to participants, healthcare professionals and researchers via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12622001341718.

A method for noninvasive beat-by-beat visualization of His bundle signals.

BACKGROUND: Invasive recording of His bundle signals (HBS) in electrophysiological study (EPS) is important in determining HV interval, the time taken to activate the ventricles from the His bundle. Noninvasive surface measurements of HBS are attempted by averaging typically 100-200 cardiac cycles of ECG time series in body surface potential mapping (BSPM) and in magnetocardiography (MCG) which records weak cardiac magnetic fields by highly sensitive detectors. However, noninvasive beat-by-beat extraction of HBS is challenged by ramp-like atrial signals and noise in PR segment of the cardiac cycle. METHODS: By making use of a signal-averaged trace showing prominent HBS as a guide trace, we developed a method combining interval-dependent wavelet thresholding (IDWT) and signal space projection (SSP) technique to eliminate artifacts from single beats. The method was applied on MCG recorded on 21 subjects with known HV intervals based on EPS and noninvasive signal-averaging, including five subjects with BSPM recorded subsequently. The method was also applied on stress-MCG of a subject featuring autonomic dynamics. RESULTS: HBS could be extracted from 19 out of 21 subjects by signal-averaging whose timing differed from EPS between -8 and 11 ms as tested by 2 observers. HBS in single beats were seen as aligned patterns in inter-beat contours and were appreciable in stress-MCG and conspicuous than BSPM. The performance of the method was evaluated on simulated and measured MCG to be adequate if the signal-to-noise ratio was at least 20 dB. CONCLUSIONS: These results suggest the use of this method for noninvasive assessments on HBS.

MUC1, CK20, and CDX2 immunohistochemical markers can sub-classify periampullary carcinomas into pancreaticobiliary, intestinal, and mixed subtypes.

INTRODUCTION: Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype. We assessed the potential of cytokeratins and mucin markers to classify the sub-types of periampullary tumors and compared them with the survival data to identify markers that may predict prognosis. METHODOLOGY: PAC tumor tissues were obtained from 94 patients undergoing Whipples Pancreaticoduodenectomy. Paraffin-embedded tissues were immunostained with cytokeratins CK7, CK20), mucins (MUC1, MUC2, MUC5Ac), and CDX2 antibodies. The survival status of patients was obtained as follow-up up to 5-years of surgery. The Receiver Operating Character Curve (ROC) analysis was used for detecting sensitivity and specificity. The survival data were analyzed using the Kaplan-Meier survival curve. RESULTS: Tumors were initially categorized on the basis of histological classification as pancreaticobiliary (n = 46), intestinal (n = 35) and indeterminate (n = 13). Further, using immunohistochemical markers (MUC1, CK20, and CDX2), we gave systematic classification of IHC-PB (n = 51), IHC-Int (n = 30) and IHC-Mixed (n = 13). The interobserver analysis showed good agreement between histologic and IHC type with a kappa value of 0.554. Combined expression of CK20, MUC1 and CDX2 accurately classify the mixed type of tumor. Overall survival rate and duration were 74.4% and 44.95 ± 2.29 months. Survival analysis for subtypes reveal, pancreaticobiliary tumors have low survival (27.9 ± 1.63 months) than mixed type (35.5 ± 0.45 months) and intestinal-type (52.92 ± 2.18 months). Among these, intestinal-type have better survival. Only TNM Stage III (tumor staging as per American Joint Committee on Cancer classification) and perineural invasion have been associated with predicting poor survival in PAC patients. CONCLUSION: Our results suggest that the combined expression of MUC1, CK20 and CDX2 could serve as markers to diagnose histological inconclusive specimens as mixed subtype tumors.

Effect of Eurycoma longifolia standardised aqueous root extract-Physta® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study.

BACKGROUND: Low testosterone levels cause physiological changes that compromise the quality of life in ageing men. A standardised water extract from the root of Eurycoma longifolia (EL), known as Physta®, is known to increase testosterone levels. OBJECTIVE: To evaluate the safety and efficacy of Physta® in improving the testosterone levels and quality of life in ageing male subjects. DESIGN: This randomised, double-blind, placebo-controlled study enrolled 105 male subjects aged 50-70 years with a testosterone level <300 ng/dL, BMI ≥ 18 and ≤30.0 kg/m2. The subjects were given either Physta® 100 mg, 200 mg or placebo daily for 12 weeks. The primary endpoints were changes in serum total and free testosterone levels. The secondary endpoints included changes in the level of sex hormone-binding globulin (SHBG), dihydroepiandrosterone (DHEA), glycated haemoglobin (HbA1c), insulin-like growth factor-1 (IGF-1), thyroid function tests (T3, T4, TSH and Free T3) and cortisol. Changes in Ageing Male Symptoms (AMS) score, Fatigue Severity Scale (FSS) score and muscle strength are other secondary endpoints. The safety of the intervention products was measured by complete blood count, lipid profile, liver and renal function tests. RESULTS: There was a significant increase in the total testosterone levels at week 12 (P < 0.05) in the Physta® 100 mg group and at weeks 4 (P < 0.05), 8 (P < 0.01) and 12 (P < 0.001) in the Physta® 200 mg group compared to placebo. No significant between-group differences in free testosterone levels were observed but a significant within-group increase occurred at weeks 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta®100 mg group and at weeks 2 (P < 0.01), 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta® 200 mg group. The AMS and FSS showed significant reduction (P < 0.001) in total scores at all time-points within- and between-group in both Physta® groups. DHEA levels significantly increased (P < 0.05) within-group in both Physta® groups from week 2 onwards. Cortisol levels significantly (P < 0.01) decreased in the Physta® 200 mg group, while muscle strength significantly (P < 0.001) increased in both Physta® groups at week 12 in the within-group comparison. There were no significant changes in SHBG. No safety related clinically relevant changes were observed. CONCLUSION: Supplementation of Physta® at 200 mg was able to increase the serum total testosterone, reduce fatigue and improve the quality of life in ageing men within 2 weeks' time. TRIAL REGISTRATION: This clinical study has been registered in ctri.nic.in (CTRI/2019/03/017959).

Association of Paternal Individual Deprivation Measure with General Anthropometric Data and Dental Caries among 12 to 15 year old school going children, in Tiruvallur District - A cross sectional study.

AIM: To determine General anthropometric data and dental caries and their association of paternal Individual Deprivation Measure among 12- to 15-year-old school going children in Tiruvallur District. METHODS AND MATERIAL: The Anthropometric data such as Body mass index, Skin fold thickness and mid arm circumference was assessed. The study was also conducted to assess children's paternal deprivation using individual deprivation index (IDM). Paternal deprivation was calculated using Individual deprivation index which comprises of 15 dimensions. Pilot study was done to calculate sample size which is found to be 800. RESULTS: Dimension of paternal individual deprivation measure in parent Education, Housing, toileting, family planning, problem in visiting doctor between Government and Private School children was significant with P value of 0.0005. Interpretation of Paternal individual deprivation measure was found to be significant among Government and private school children. There was no association of individual deprivation measure with dental caries, but there was an association of Individual paternal deprivation measure with one of the anthropometric measure was mid arm circumference. In paternal deprivation index 21.8% of the children's parent were not deprived, 45.8% were somewhat deprived, 22.6% were deprived, 7.3% were very deprived, 2.6 were extremely deprived among school children.

An epoch based methodology to denoise magnetocardiogram (MCG) signals and its application to measurements on subjects with implanted devices.

Magnetocardiograms (MCG) provide clinically useful diagnostic information in a variety of cardiac dysfunctions. Low frequency baseline drifts and high frequency noise are inevitably present in routine MCG even for those measured inside magnetically shielded rooms. These interferences sometimes exceed subtle cardiac features in MCG recorded on subjects with implanted devices like cardiac pacemakers; this makes interpretation of cardiac magnetic fields difficult. The present study proposes a correlation-based beat-by-beat approach and principal component analysis to eliminate drifts and high frequency noise respectively; the approach is suitable for denoising both single and multi-channel MCG data. The methodology is critically evaluated on simulated noisy measurements using a 37 channel MCG system, when objects such as implantable permanent pacemaker and stainless-steel wire are sequentially kept externally on the chests of five healthy subjects. By characterizing the noise introduced by each of these objects, the deterioration in the quality of MCG and its subsequent restoration by using the proposed method is assessed. The performance of the proposed method is also compared with other conventional denoising techniques namely, bandpass filters, wavelets and ensemble empirical mode decomposition. The proposed method not only exhibits least distortion, but also preserves the beat-by-beat dynamics of cardiac time series. The method has also been illustrated on actual MCG measurements on two subjects with implanted pacemaker which highlight the ability of the proposed method for denoising MCG in general and during extremely noisy measurement situations.

Electrospun freestanding hydrophobic fabric as a potential polymer semi-permeable membrane for islet encapsulation.

One of the significant problems associated with islet encapsulation for type 1 diabetes treatment is the loss of islet functionality or cell death after transplantation because of the unfavorable environment for the cells. In this work, we propose a simple strategy to fabricate electrospun membranes that will provide a favorable environment for proper islet function and also a desirable pore size to cease cellular infiltration, protecting the encapsulated islet from immune cells. By electrospinning the wettability of three different biocompatible polymers: cellulose acetate (CA), polyethersulfone (PES), and polytetrafluoroethylene (PTFE) was greatly modified. The contact angle of electrospun CA, PES, and PTFE increased to 136°, 126°, and 155° as compared to 55°, 71°, and 128° respectively as a thin film, making the electrospun membranes hydrophobic. Commercial porous membranes of PES and PTFE show a contact angle of 30° and 118°, respectively, confirming the hydrophobicity of electrospun membranes is due to the surface morphology induced by electrospinning. In- vivo results confirm that the induced hydrophobicity and surface morphology of electrospun membranes impede cell attachment, which would help in maintaining the 3D circular morphology of islet cell. More importantly, the pore size of 0.3-0.6 µm obtained due to the densely packed structure of nanofibers, will be able to restrict immune cells but would allow free movement of molecules like insulin and glucose. Therefore, electrospun polymer fibrous membranes as fabricated in this work, with hydrophobic and porous properties, make a strong case for successful islet encapsulation.

Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study.

BACKGROUND: Interest in herbal medicines and non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy. Vasomotor symptoms are the most characteristic and notable symptoms of menopause. OBJECTIVE: To investigate the changes in the frequency and severity of hot flush and associated vasomotor symptoms experienced by peri-menopausal and menopausal women supplemented with the herbal formulation (Nu-femme™) comprising Labisia pumila (SLP+®) and Eurycoma longifolia (Physta®) or placebo. DESIGN: Randomised, double-blind, placebo-controlled, 24-week study enrolled 119 healthy women aged 41-55 years experiencing peri-menopausal or menopausal symptoms and supplemented with Nu-femme™ or placebo. The primary endpoint was comparative changes between treatment groups in the change in the frequency and severity of hot flushes. The secondary objectives were to assess the changes in the frequency and severity of joint pain, Menopause Rating Scale (MRS) and Menopause-Specific Quality of Life (MENQOL) questionnaire domain scores. Concentrations of serum hormone, lipid profile, bone markers, sleep quality and vitality were also studied as secondary objectives. RESULTS: At week 12, significant (P < 0.01) improvements in hot flush symptoms were observed in Nu-femme™ and placebo groups. Even though there was no significant difference between groups, higher percentage of improvement, 65%, was seen in Nu-femme™ compared to 60% in placebo. Significant improvements (P < 0.001) in MRS and MENQOL scores at weeks 12 and 24 were observed in both groups, respectively. Luteinising hormone and follicle-stimulating hormone levels were significantly reduced (P < 0.05) at weeks 12 and 24, respectively, compared to baseline in the Nu-femme™ group, with no significant changes observed in the placebo group. There were significant (P < 0.05) reductions in serum low-density lipid and triglycerides levels at week 12 in Nu-femme™ group, but no changes seen in placebo group. At the end of week 24, changes in haematology and clinical chemistry parameters remained within normal clinical ranges in both groups. CONCLUSION: Herbal formulation consists of L. pumila and E. longifolia (Nu-femme™) may support reduction in hot flushes and improvements in hormone and lipid profile in healthy peri-menopausal and menopausal women.

Reduced pancreatic polypeptide response is associated with early alteration of glycemic control in chronic pancreatitis.

AIM: To study the incidence of glucose intolerance in CP patients without diabetes by performing oral glucose tolerance test (OGTT). METHODS: We screened consecutive Indian CP patients without diabetes over 6 months by performing OGTT and correlated with physical characteristics and glycated hemoglobin (HbA1c). We also compared c-peptide and pancreatic polypeptide response in different groups based on OGTT. Relevant statistical tests were performed. P < 0.05 was considered significant. RESULTS: Total of 171 patients were screened. Mean duration of CP was 5.03 ± 4.32 years. 55 were detected to have prediabetes and 40 DM on OGTT. CP patients with diabetes and prediabetes had significantly dilated pancreatic duct compared to non-diabetic CP (4.2 ± 2.7 mm, 3.6 ± 2.7 mm, 2.84 ± 2.25 mm; p = 0.018). Fasting blood glucose (FBS) and 2-hour OGTT were 109.35 ± 19.06, 97.47 ± 11.94, 85.24 ± 9.95 and 236.13 ± 31.42, 154.65 ± 19.53, 112.89 ± 16.32 in patients with DM, prediabetes and CP patients without diabetes (p < 0.0001). There was a good c-peptide response (p = 0.001) and reduced pancreatic polypeptide response (p = 0.003) in CP patients compared to controls. CONCLUSION: Early in the course of disease reduced pancreatic polypeptide response in the presence of good c-peptide response may result in development of DM.

Corrigendum to "Nephroprotective Effect of Herbal Extract Eurycoma longifolia on Paracetamol-Induced Nephrotoxicity in Rats".

[This corrects the article DOI: 10.1155/2019/4916519.].

Prevalence of haemoprotozoan diseases in cattle of Cauvery delta region of Tamil Nadu.

A study was carried out to determine the prevalence of haemoparasites in cattle in Cauvery delta region over a period of one year. A total of 228 giemsa stained blood smears were screened for the presence of haemoprotozoa, out of which 34 animals were found to be positive. An overall prevalence of haemoparasites in the sampled cattle were 14.9%, among this Anaplasma sp (8.3%), Babesia sp (3.95%), Theileria sp (2.19%) and Trypanosoma sp (0.44%) as single or mixed blood parasitic infections. In this study Anaplasmosis (14%) was highly prevalent during the winter season and Babesiosis (13.73%) was highly prevalent during summer months followed by Anaplasmosis (9.8%) and Theileriosis (7.8%), the lowest prevalence of Trypanosomiasis was observed during the rainy season. The seasonal variation in prevalence of haemoprotozoan disease might be due to influence of climatic factors on density of vector population in that geographical area. Haemogram revealed decreased level of haemoglobulin, packed cell volume and total erythrocyte count. The serum biochemistry revealed elevated level of liver enzyme Asparate transaminase enzyme. All haemoparasitaemic animals were treated with specific drugs and recovered successfully.

Nephroprotective Effect of Herbal Extract Eurycoma longifolia on Paracetamol-Induced Nephrotoxicity in Rats.

Paracetamol (PCM) is a well-known drug widely used for its analgesic and antipyretic properties. PCM is generally considered as safe but overdose of PCM can cause nephrotoxicity. Traditionally, herbs have been used for the treatment of drug or toxin-induced renal disorders and numerous medicinal plants were tested for nephroprotection effect in PCM-induced nephrotoxicity model. The aim of the present study was to evaluate the protective effect of the herbal extract Eurycoma longifolia (EL) against PCM-induced nephrotoxicity rat model. Forty Wistar rats were randomly divided into five groups of eight rats each: control (vehicle 10 ml/kg), PCM alone (200 mg/kg PCM), EL 100 (EL 100 mg/kg+200 mg/kg PCM), EL 200 (EL 200 mg/kg+200 mg/kg PCM), and EL 400 (EL 400 mg/kg+200 mg/kg PCM). All animals from control group received vehicle daily and animals from groups PCM alone, EL 100, EL 200, and EL 400 received repeated dose of PCM and the assigned treatment of EL daily for a period of 14 days. On the 15th day, serum creatinine, blood urea nitrogen, protein, and albumin were measured in blood and creatinine clearance was measured in urine collected over 24 hours. Kidney sections of all experimental groups underwent histopathological analysis. There was a significant (p<0.05) increase in serum creatinine and blood urea levels in the PCM alone group compared to the treatment groups due to nephrotoxicity. In the treatment groups, there was a dose-dependent protection against PCM-induced changes observed in serum total protein, albumin, urea, and creatinine. Significant (p<0.05) drop was seen in serum creatinine and blood urea content in EL 200 and EL 400 groups. Creatinine clearance significantly increased for EL 200 (p<0.01) and EL 400 (p < 0.001) groups. Serum total protein and serum albumin content were significantly increased (p<0.05) in EL 200 and EL 400 groups compared to PCM alone group. Histopathological examination (H&E staining) of the rat kidneys revealed severe degeneration in the PCM alone group, while there was evidence of significant dose-dependent protection in the treatment groups against PCM-induced changes. The serum and urine biochemical results and histopathology analysis of the kidney indicate the nephroprotective potential of EL extract against PCM-induced nephrotoxicity.

Aqueous leaf extract of Clinacanthus nutans improved metabolic indices and sorbitol-related complications in type II diabetic rats (T2D).

Clinacanthus nutans (Burm. f.) Lindau (C. nutans) has been reported to lower blood glucose level; however, evidence on its efficacy in lowering diabetic complications is limited. The antidiabetic properties of C. nutans aqueous leaf extract on serum metabolic indices, sorbitol production, and aldose reductase enzyme activities in the kidneys, lens, and sciatic nerve of type II diabetic (T2D) rats were evaluated. All rats except normal control rats were fed with a high-fat diet for 8 weeks to induce obesity and subsequently injected with 35 mg/kg streptozotocin to induce type II diabetes. Aqueous leaf extract of C. nutans (100 and 200 mg kg-1 day-1) and quercetin (10 mg kg-1 day-1) were fed orally for 4 weeks. Diabetic rats administered with C. nutans at 100, 200 mg kg-1 day-1 and quercetin had significantly (p < 0.05) lower fasting blood glucose levels post-intervention: 14.2, 14.0, and 19.9 mm, respectively, compared with the untreated group (22.1 mm). Total cholesterol was significantly (p < 0.05) lower in the C. nutans groups in comparison with the diabetic control group. Levels of F2-isoprostane, a marker of oxidative stress, were attenuated in the presence of the extract. Aldose reductase enzyme activity increased by 64, 99, and 0% and total antioxidant activities by 22, 29, and 126%, respectively. Sorbitol levels in the kidney, lens, and nerve were reduced in diabetic rats administered with C. nutans and quercetin group (by 8, 16, and 3%, respectively). The protective effect of the extract to the liver and kidney was confirmed through liver and kidney enzyme markers and histological analyses. The C. nutans has the potential to attenuate T2D-induced metabolic perturbations and complications related to sorbitol accumulation.

Automatic Anisotropic Diffusion Filtering and Graph-search Segmentation of Macular Spectral-domain Optical Coherence Tomographic (SD-OCT) Images.

BACKGROUND: Optical Coherence Tomography (OCT) is a non-invasive medical imaging technique that provides high-resolution cross-sectional images of the retina. There is a need to develop algorithms for obtaining quantitative and qualitative information about the retina which are essential for assessing and managing eye conditions. METHODS: This work emphasizes on an automated image processing algorithm for segmenting retinal layers. It involves preprocessing of the acquired retinal SD-OCT image (B-scan) using the proposed automatic Anisotropic diffusion filter, followed with contrast stretching to suppress intrinsic speckle noise without blurring structural edges. Graph search segmentation using Dijkstra algorithm with a combination of threshold and axial gradient as the cost function is used to segment the retinal layer boundaries. RESULTS: The algorithm was performed and the average thickness of the segmented retina was computed for the 3D retinal scan (128 B-scans) of 8 subjects (4 normal and 4 abnormal) using Early Treatment Diabetic Retinopathy Screening (ETDRS) chart. CONCLUSION: Segmentation was evaluated using manually segmented B-scan by an Ophthalmologist as ground truth and accuracy was found to be 99.14 ± 0.27%.

Distal pancreatectomy with autologous islet transplantation in chronic pancreatitis patients: First case series from India.

Pancreatectomy and autologous islet transplantation (AIT) are performed in highly specialized centers to alleviate abdominal pain and preserve endocrine function in patients with chronic pancreatitis. We aimed at initiating AIT studies in India for the first time in patients undergoing distal pancreatectomy (DP) to prevent development of diabetes. Four out of 14 chronic pancreatitis patients screened underwent DP with AIT. Pancreatectomy specimen preserved in Wisconsin solution was subjected to islet isolation employing standard protocol using collagenase V. Isolated islets were infused into the liver through portal vein after quality assessment and the four patients were followed for 1 year. During the study period, blood glucose, fasting insulin, and C-peptide were analyzed and glucose tolerance was assessed. Three patients could be infused with islets (4363 Islet equivalents, IEQ/kg, 3860 IEQ/kg, 3600 IEQ/kg) into liver without any infusion-related complications. Two of these patients maintained glucose tolerance and glycemic control (HbA1c: 6.0%) and one became diabetic at the end of 1 year (HbA1c: 7.5%). Circulating fasting insulin increased (2.7-24.4 µU/mL and 4.0-21.2 µU/mL) and C-peptide levels increased (2.2 to 3.6, 3.4-5.6 ng/mL) in these two patients. Circulating insulin was 2.7 µU/mL and C-peptide was 2.4 ng/mL in the patient who became diabetic at the end of 1 year, while insulin was 2.3 µU/mL and C-peptide was 1.2 ng/mL in the patient who could not be infused with islets after DP. Safety and feasibility of autologous islet transplantation is established in India for the first time.

Bach2 repression mediates Th17 cell induced inflammation and associates with clinical features of advanced disease in chronic pancreatitis.

OBJECTIVES: Altered immune homeostasis and involvement of T cells has been reported in chronic pancreatitis (CP). We evaluated the role of Bach2 (BTB and CNC homology basic leucine zipper transcription factor 2), a key regulator of immune homeostasis in the chronicity of CP. METHODS: Expression of Bach2 and T-cell transcription factors, enumeration of BACH2+/CD4+ T-lymphocytes were performed by qRT-PCR and flow cytometry respectively. Bach2silenced human CD4+ T-lymphocytes were exposed to CP tissue extract to assess T-cell lineage commitment. Aryl hydrocarbon receptor (Ahr) and Deubiquitinase enzyme A (DUBA/OTUD5gene) were evaluated as markers of persistent Th17 cell differentiation. Bach2 gene (exons) was sequenced to identify risk variants and functionally validated. RESULTS: Decrease in Bach2 (p < 0.0001) and increase (p < 0.001) in TBX21, RORC, Ahr, PRDM1, IL23R mRNA were noted in pancreatic tissues, while BACH2+/CD4+ T-lymphocytes were decreased (p < 0.01) in circulation and tissues. Exposure of Bach2 silenced CD4+ T-lymphocytes to CP tissue extract showed increased Ahr, decreased OTUD5, and enhanced Th17 cell differentiation. Sequencing of Bach2 gene revealed association of novel variant (rs9111 in 5'-UTR) with advanced disease and luciferase assay confirmed its role in Bach2 repression. CONCLUSION: Bach2 repression mediates Th17 cell induced inflammation and rs9111-TT in individuals with primary genetic susceptibility to CP is associated with clinical features of advanced disease.

Design of PSIRA with focusing lens concentrating picosecond impulse on biological target.

The Prolate Spheroidal Impulse Radiating Antenna (PSIRA) is used to radiate very fast pulses in a narrow beam with low dispersion and high field amplitude. The PSIRA is suitable to apply fast, intense pulses without direct contact, for skin cancer treatment. In this proposed work, SWB (Slanted Wire Biconical), EPH (Elliptical Profile Horn), TSVS (Tapered Slot Vivaldi Shape) and Tapered Arm Conical Plate (TACP) feed antenna configurations for Prolate Spheroidal Reflector (PSR) are explored to enhance spatial resolution on biological targets. The feed antenna is placed at the first focal point and the target is located at the second focal point of the PSR. Next, the near field focusing lens is designed to enhance the amplitude and the resolution of the wave incident at the second focus. A 10 layer Log periodic lens system is placed before the target to reduce the spot size of the focused field on the target. The delivery of subnanosecond pulses using reflector in conjunction with and without Log periodic lens system on the biological target is compared for all feed antenna configurations. Tapered Arm Conical Plate (TACP) fed PSR with the 10 layer Log periodic lens system greatly reduces the spot size to 0.75 cm along lateral direction and 1.5 cm along axial direction. The enhancement in spatial resolution is very suitable to reduce the damage to healthy tissues during cancer treatment.

Interferon-γ Decreases Nuclear Localization of Pdx-1 and Triggers ß-Cell Dysfunction in Chronic Pancreatitis.

Interferon-gamma (IFN-γ) is shown to play a major role in ß-cell dysfunction in chronic pancreatitis (CP). However, the underlying mechanisms are to be elucidated. The present study was conducted to determine the role of IFN-γ subverting insulin gene expression in CP. Pancreatic tissues from control (n=15) and CP patients (n=30) were analyzed for nuclear localization of pancreatic and duodenal homeobox transcription factor (Pdx-1) after ascertaining their diabetic status. By immunofluorescence and western blot analysis, the influence of IFN-γ, anti-inflammatory cytokine (interleukin-10), and anti-IFN-γ agent epigallocatechin-3-gallate (EGCG) on nuclear localization of Pdx-1was examined in the islets isolated from resected normal pancreatic tissue. Nuclear localization of Pdx-1 was 20.25±2.19 in the islets of diabetic CP patients and 31.44±2.09 in nondiabetic CP patients as compared with controls (60.45±5.11) and the corresponding distribution of Pdx-1 protein in the nuclear compartment was also decreased. Exposure of normal islets to IFN-γ revealed decreased nuclear localization of Pdx-1. Pretreatment with polyphenolic compound EGCG restored the nuclear localization of Pdx-1. These results suggest that IFN-γ induced ß-cell dysfunction is mediated through decreased nuclear localization of Pdx-1.