Global benchmarks in primary robotic bariatric surgery redefine quality standards for Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND: Whether the benefits of the robotic platform in bariatric surgery translate into superior surgical outcomes remains unclear. The aim of this retrospective study was to establish the 'best possible' outcomes for robotic bariatric surgery and compare them with the established laparoscopic benchmarks. METHODS: Benchmark cut-offs were established for consecutive primary robotic bariatric surgery patients of 17 centres across four continents (13 expert centres and 4 learning phase centres) using the 75th percentile of the median outcome values until 90 days after surgery. The benchmark patients had no previous laparotomy, diabetes, sleep apnoea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI greater than 50 kg/m2, or age greater than 65 years. RESULTS: A total of 9097 patients were included, who were mainly female (75.5%) and who had a mean(s.d.) age of 44.7(11.5) years and a mean(s.d.) baseline BMI of 44.6(7.7) kg/m2. In expert centres, 13.74% of the 3020 patients who underwent primary robotic Roux-en-Y gastric bypass and 5.9% of the 4078 patients who underwent primary robotic sleeve gastrectomy presented with greater than or equal to one complication within 90 postoperative days. No patient died and 1.1% of patients had adverse events related to the robotic platform. When compared with laparoscopic benchmarks, robotic Roux-en-Y gastric bypass had lower benchmark cut-offs for hospital stay, postoperative bleeding, and marginal ulceration, but the duration of the operation was 42 min longer. For most surgical outcomes, robotic sleeve gastrectomy outperformed laparoscopic sleeve gastrectomy with a comparable duration of the operation. In robotic learning phase centres, outcomes were within the established benchmarks only for low-risk robotic Roux-en-Y gastric bypass. CONCLUSION: The newly established benchmarks suggest that robotic bariatric surgery may enhance surgical safety compared with laparoscopic bariatric surgery; however, the duration of the operation for robotic Roux-en-Y gastric bypass is longer.

UP-regulated levels of sHLA-G in women with a history of RPL in mid-gestation presumably to achieve ongoing pregnancy.

PROBLEM: Recurrent Pregnancy Loss (RPL) is a disorder characterized by two or more pregnancy losses within 20th week of gestation. Globally 1-5% of the couples are affected, 50% of these cases are with unknown etiology. HLA-G, an Immuno-modulatory molecule is a non-classical MHC-1 protein, expressed abundantly on extravillous trophoblastic cells, responsible for spiral artery remodeling, maintaining maternal immune tolerance and fetal growth by adjusting pro and anti-inflammatory milieu during different gestational phases. METHOD OF STUDY: In the present case-control study CD4+HLA-G+ tTreg cells were enumerated by flow cytometry and estimation of the circulating levels of sHLA-G in the blood samples of 300 mid-gestation pregnant women with (iRPL) and without history of RPL (nRPL) by Enzyme-linked Immunosorbent assay was done. The cases included 92 primary and 58 secondary RPL cases RESULTS: A significant reduction in number of tTregs and elevated levels of circulating sHLA-G in iRPL (.03, 200.9) versus nRPL (.09, 90.32) was observed. Further, the primary cases showed higher circulating sHLA-G and no difference in relation to CD4+HLA-G+ tTregs compared to the secondary cases. Receiver operating curve (ROC) characteristics of sHLA-G (AUC = .8) was superior to CD4+HLA-G+ (AUC = .7) for iRPL patients over nRPL group. CONCLUSIONS: Our results are suggestive of the over-expression of sHLA-G which may be caused due to its shedding from surface of trophoblast as a compensatory mechanism to save the on-going pregnancy. To realize the present outcome, studies are required on on-going pregnancy follow-up cases with favorable and unfavorable pregnancy outcome.

Increased expression of HPV-E7 oncoprotein correlates with a reduced level of pRb proteins via high viral load in cervical cancer.

Human Papillomavirus (HPV) is the most common cause of sexually transmitted diseases and causes a wide range of pathologies including cervical carcinoma. Integration of the HR-HPV DNA into the host genome plays a crucial role in cervical carcinoma. An alteration of the pRb pathways by the E7 proteins is one of the mechanisms that's account for the transforming capacity of high-risk papillomavirus. For the proper understanding of the underline mechanism of the progression of the disease, the present study investigate the correlation of concentration of host pRb protein, viral E7 oncoprotein and viral load in early and advanced stages of cervical carcinoma. It was found that the viral load in early stages (stage I and II) was less (log10 transformed mean value 2.6 and 3.0) compared to advanced stages (stage III and IV) (Log10 transformed value 5.0 and 5.8) having high expression of HPV E7 onco-protein and reduced level of pRb protein, signifying the role of viral load and expression level of E7 oncoprotein in the progression of cervical cancer.

Incidence of anemia and red blood cell (RBC) transfusion requirement in breast cancer.

Background: Cancer-related anaemia is one of the main burdens in oncology, although the available data on its prevalence and treatment options such as blood transfusion are often contradictory. This study aimed to evaluate the prevalence of anaemia and the requirement for packed red blood cell (PRBC) transfusion among women with breast cancer (BC) and to determine the associated factors for chemotherapy-induced anaemia (CIA). Methods: This cross-sectional retrospective study conducted in Kelantan involved 104 newly diagnosed female BC patients from 2015 to 2016 who underwent chemotherapy. For statistical analysis, chi-square was used to compare between CIA and non-CIA groups. In addition, simple and multiple logistic regression were used to determine the association of the CIA. Results: Our study revealed that 34.6% (n=36) of patients had mild anaemia, and 59.6% (n=62) had normal haemoglobin at pre-chemotherapy. The prevalence of anaemia increased from 40.4% to 77% at the end of our study. About 30.8% of patients received PRBC transfusion during chemotherapy with mean haemoglobin before the first transfusion of 7.9 g/dl. CIA was observed in 54.8% of cases. There was no significant association between CIA concerning the patient characteristic, cancer characteristic, or cancer treatment. Conclusion: We concluded that a significant proportion (40.4%) of BC patients was anaemic even before chemotherapy, with the red blood cell requirements up to 30.8% throughout chemotherapy. A larger prospective study is needed to determine the predictors for the CIA and subsequently improve patient management.

Wildlife habitat mapping using Sentinel-2 imagery of Mehao Wildlife Sanctuary, Arunachal Pradesh, India.

Mehao Wildlife Sanctuary, situated in the state of Arunachal Pradesh, is part of an important biodiversity hotspot in the north-eastern part of India in the Himalayas. The current study deals with the identification of important wildlife habitats in the sanctuary. We used a supervised classification technique to delineate these habitats in the sanctuary, which are used by several mammals and bird species encountered during camera trap and sign surveys conducted between November 2017 and May 2020. Satellite images from Sentinel - 2A were used to classify the land use land cover (LULC) of the sanctuary. The LULC information was generated by using a maximum likelihood classifier. We classified a total of thirteen LULC classes, i.e., water, built-up, agriculture, orchard, grassland, bamboo forest, bamboo-mixed forest, riverbed, barren land, snow, wild banana, riverine forest and mixed forest. LULC classification reveals a high percentage of mixed forest, about 69.9%, followed by wild bananas at 7.2%. The commission and omission error rates, however, are high for riverbed and agriculture (0.5) and bamboo forest (0.5), respectively. The accuracy assessment showed an overall classification accuracy of 88.5% with a Kappa coefficient of 0.87. The abundance of mammals was high in the mixed forest, but Ivlev's electivity index shows that species generally avoided this habitat and preferred specialized forest habitats, such as bamboo forest, bamboo-mixed forest, grassland, riverbed and riverine forest. Our LULC map will provide a baseline for potential planning and monitoring changes of wildlife habitats in Mehao WLS.

Recent Advances in Anticancer Activity of Novel Plant Extracts and Compounds from Curcuma longa in Hepatocellular Carcinoma.

PURPOSE: Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. METHODS: A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent. RESULTS: This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it's postulated molecular targets of curcumin when used against liver cancers. CONCLUSIONS: This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers.

Mortality among healthcare workers in Indonesia during 18 months of COVID-19

The impact of SARS-CoV-2 infections upon Indonesian health care workers (HCWs) remains unclear, as mortality data specific to HCWs is not systematically collected or analyzed in this setting. This report describes findings from a systematic collation, abstraction and analysis of HCW fatalities during the first 18 months of COVID-19 in Indonesia. HCW who died during the period of March 2020 to July 2021 across Indonesia were identified on Pusara Digital, a community web-based digital cemetery database dedicated to HCW. We calculated mortality rates and death risk ratio among HCWs and the general population. Qualitative methods explored concerns regarding mortality among HCWs. The analysis suggests that at least 1,545 HCWs died during the study period. The death of males and females HCWs were almost equally distributed (51% vs. 49%). Most were medical doctors and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Deaths most frequently occurred in the age group of 40 to 59 years old with the median age of 50 years (IQR: 39-59). At least 322 (21%) deaths occurred with pre-existing conditions, including 45 who were pregnant. We estimated a minimal HCW mortality rate in Indonesia at 1.707 deaths per 1000 HCW during the first 18 months of COVID-19. Provincial HCW mortality rates ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1000 HCWs (East Java). HCW had a significantly higher mortality rate than the general population (RR = 4.92, 95% CI 4.67 - 5.17). The COVID-19 event in Indonesia resulted in the loss of many hundreds of HCWs, most of them being senior physicians, nurses, and midwives. The HCW death rates is 5-times higher than everyone else. The sheer sparseness of the workforce requires more protective steps and a national systematic surveillance of occupational mortality is urgently needed in this setting.

Using Brain-Breaks® as a Technology Tool to Increase Attitude towards Physical Activity among Students in Singapore.

The purpose of this study was to investigate the effects of classroom-based Brain Breaks® Physical Activity Solution in Southeast Asia Singaporean primary school students and their attitude towards physical activity (PA) over a ten-week intervention. A total of 113 participants (8-11 years old) were randomly assigned to either an experimental (EG) or a control group (CG), with six classes to each group; the Brain Breaks® group (EG: six classes) and the Control group (CG: six classes). All EG members participated in a Brain Breaks® video intervention (three-five min) during academic classes and the CG continued their lessons as per normal. The student's attitudes towards PA in both research conditions were evaluated using the self-reported Attitudes toward Physical Activity Scale (APAS), applied before and after intervention. The effects of the intervention on APAS scores were analysed using a mixed model analysis of variance with Time as within-subject and Group as between-subject factors. The analysis revealed evidence in support of the positive effect of classroom video interventions such as Brain Breaks® on student's attitudes toward benefits, importance, learning, self-efficacy, fun, fitness, and trying to do their personal best in PA. The Brain Breaks® intervention provided a positive significant impact on students in Singapore. This study also revealed that interactive technology tools implemented into the school curriculum benefit students in terms of health and education.

Improving the documentation quality of point-of-care ultrasound scans in the emergency department.

A point-of-care ultrasound scan (POCUS) is a core element of the Royal College of Emergency Medicine (RCEM) specialty training curriculum. However, POCUS documentation quality can be poor, especially in the time-pressured environment of the emergency department (ED). A survey of 10 junior ED clinicians at the Princess Royal University Hospital (PRUH) found that total POCUS documentation was as low as 38% in some examinations.This quality improvement project aimed to increase the coverage and quality of POCUS documentation in the ED. This was done by using a plan-do-study-act (PDSA) regime to improve the quality of POCUS documentation from the original baseline to 80%. There were three discreet PDSA cycles and the interventions included improving education and training about POCUS documentation and the introduction of an original proforma, which incorporated six minimum requirements for POCUS documentation as per the joint RCEM and Royal College of Radiologists (RCR) guidelines for POCUS documentation (patient details, indications, findings, conclusions, signature and date).The project team audited the quality of all documented scans in the resuscitation department of the PRUH against the RCEM/RCR guidelines at baseline and following three discrete PDSA cycles. This was done over an 8-week period, spanning 696 attendances to the resuscitation area of the ED and 42 documented POCUS examinations.Quality recording of the six RCEM/RCR elements of POCUS documentation was poor at baseline but improved following three successful PDSA cycles. There was a demonstrated improvement in five of six documentation elements: patient details on POCUS documentation increased from 53.3% to the 66.7%, indication from 60.0% to 66.7%, conclusion from 13.0% to 83.0%, signature from 86.7% to 100.0% and date from 46.7% to 66.7%.These results suggest that the introduction of a proforma and a vigorous education strategy are effective ways to improve the quality of documentation of ED POCUS.

Prevalence of Dumping Syndrome After Laparoscopic Sleeve Gastrectomy and Comparison with Laparoscopic Roux-en-Y Gastric Bypass.

BACKGROUND: Dumping syndrome is a well-known side effect of laparoscopic gastric bypass (LRYGB), and it is commonly believed that dumping syndrome is less likely to occur after laparoscopic sleeve gastrectomy (LSG), due to the preservation of the pyloric sphincter. However, it is not uncommon for patients undergoing LSG at our center to report symptoms suggestive of dumping syndrome. OBJECTIVE: To assess the prevalence of symptoms of dumping syndrome after LSG compared with LRYGB. SETTING: A single surgical group at a high-volume (700 cases per year) Bariatric and Metabolic Surgery Center of Excellence. METHODS: One thousand four hundred seventy-one LRYGB (366) and LSG (1105) patients received a questionnaire to assess symptoms of dumping syndrome, utilizing a modified version of the Sigstad scoring system. Dumping syndrome was considered to be present when the questionnaire score exceeded a threshold value. RESULTS: A total of 360 responses were received (249 LSG, 111 LRYGB). 26.5% (66) LSG and 41.4% (46) LRYGB exceeded the threshold for dumping syndrome (p < 0.01). 84.8% (56) LSG and 84.7% (39) LRYGB reported early dumping syndrome (p > 0.05). Thirty-six percent (24) LSG and 28% (13) LRYGB reported late dumping syndrome (p > 0.05). Twenty-seven percent (62) LSG and 44.4% (44) LRYGB reported at least one symptom of dumping syndrome with sweets (p < 0.05). 34.3% (85) LSG and 35.5% (39) LRYGB reported symptoms when drinking with or within 30 min of a meal (p > 0.05). 14.5% (36) LSG and 17.3% (19) LRYGB reported symptoms after alcohol consumption (p > 0.05). CONCLUSION: Dumping syndrome after LSG is prevalent but has not been widely reported. This finding may impact clinicians and patients in their choice of procedure and has relevance in post-operative education and care.

Association of Red Blood Cell Transfusion with Mortality and Morbidity in Post Cardiac Surgery Patients

@#Introduction: CAD accounts for 25% of mortality in Malaysia public hospitals. CABG is one of treatment for patients with CAD, but requires RBC transfusion, which is associated with morbidity and mortality. This study was to evaluate the association between RBC transfusion and morbidity and mortality in CABG patients at the National Heart Centre, Malaysia (IJN). Methods: Retrospective cross-sectional study performed using data from 434 patients who underwent CABG in 2013 and 2014. Subjects had systematic random sampling every fifth subject of the patients in the sequence of dates of the year. Data related to the relationship between RBC transfusion with mortality and morbidity, and the predicting factors captured. Results: 64.3% of CABG patients (n = 279) received RBC transfusion perioperatively. Age, gender, BMI, and EF, were factors that contributed for RBC transfusion. RBC transfusion was a contributor to longer intensive care unit length of stay (ICULOS) and hospital length of stay (HLOS). Multiple logistic regression revealed, for every 1 year increase of age, there is 3.5% higher chance of transfusion. Whereas an increase of 1 kg/m2 of BMI and 1% of EF reduced the odds of RBC transfusion by 13.0% and 3.0% respectively. Conclusions: Age, gender, BMI, and EF determine the probability of needing RBC transfusion during CABG, and RBC transfusion will result in longer ICULOS, and HLOS. Probability of RBC transfusion will be higher in older patients and reduced in those with higher BMI and EF.

The synergic effect of HPV infection and epigenetic anomaly of the p16 gene in the development of cervical cancer.

BACKGROUND: Cervical cancer is the most common cancer in Indian women. Infection with a high-risk human papillomavirus (HR-HPV) is the greatest risk factor for developing cervical cancer. The genetic and epigenetic changes in the tumor suppressor p16 gene is play an important role in the development of cervical cancer. OBJECTIVE: To evaluate the expression and promoter methylation of p16 gene in HR-HPV infected squamous cell carcinoma of the uterine cervix. METHODS: To find out p16INK4a expression and methylation status 105 squamous cell carcinoma of the uterine cervix were investigated by using immunohistochemistry and Methylation Specific PCR techniques. RESULTS: HPV16/18 was amplified in 83.8% cases of the cervix. 80% of them were positive for HPV type 16, while only 3.8% were positive for HPV type 18. Promoter CpG island hypermethylation of p16 gene was detected in 20.9% tissue samples of cervical carcinoma. Of these hypermethylated samples 90.9% cases showed nil/very low p16INK4a expression (P= 0.001). Overexpression of p16INK4a was observed in 73.3% cases of HR-HPV infected squamous cell carcinoma of the cervix. CONCLUSION: An association between p16 methylation, expression, and HR-HPV infection suggested the compliance of HPV infection and aberration of p16 gene have a synergic effect on initiation and progression of cervical carcinoma.

Robotic surgery: current perceptions and the clinical evidence.

BACKGROUND: It appears that a discrepancy exists between the perception of robotic-assisted surgery (RAS) and the current clinical evidence regarding robotic-assisted surgery among patients, healthcare providers, and hospital administrators. The purpose of this study was to assess whether or not such a discrepancy exists. METHODS: We administered survey questionnaires via face-to-face interviews with surgical patients (n = 101), healthcare providers (n = 58), and senior members of hospital administration (n = 6) at a community hospital that performs robotic surgery. The respondents were asked about their perception regarding the infection rate, operative time, operative blood loss, incision size, cost, length of hospital stay (LOS), risk of complications, precision and accuracy, tactile sensation, and technique of robotic-assisted surgery as compared with conventional laparoscopic surgery. We then performed a comprehensive literature review to assess whether or not these perceptions could be corroborated with clinical evidence. RESULTS: The majority of survey respondents perceived RAS as modality to decrease infection rate, increase operative time, decrease operative blood loss, smaller incision size, a shorter LOS, and a lower risk of complications, while increasing the cost. Respondents also believed that robotic surgery provides greater precision, accuracy, and tactile sensation, while improving intra-operative access to organs. A comprehensive literature review found little-to-no clinical evidence that supported the respondent's favorable perceptions of robotic surgery except for the increased costs, and precision and accuracy of the robotic-assisted technique. CONCLUSIONS: There is a discrepancy between the perceptions of robotic surgery and the clinical evidence among patients, healthcare providers, and hospital administrators surveyed.

Study of IL4-590C/T and IL6-174G/C Gene Polymorphisms in Type 2 Diabetic Patients With Chronic Kidney Disease in North Indian Population.

To explore the associations between potential functional promoter polymorphisms in pro-inflammatory and anti-inflammatory (IL-4(-590C/T) and IL-6(-174G/C) cytokine genes, and kidney dysfunction in North Indian type 2 diabetic subjects with chronic kidney disease. A total of 150 subjects aged 25-75 year were included in this study. The glomerular filtration rate (GFR) and serum creatinine were estimated. PCR was performed to analyse genotype distribution in IL-4 (-590T/C) and IL-6 (-174G/C) among healthy, type 2 diabetic patients with or without CKD. The genotype distributions were determined by Hardy-Weinberg equilibrium. CKD patients showed lower GFR (59.36 ± 1.33 ml/min/1.73 m2 ) and higher serum creatinine (1.93 ± 0.99% mg) level in comparison to diabetic patients without CKD and healthy subjects. Genotypic distribution of the different genotypes among the study groups in IL-4 gene was genotype CC = 30, TC = 12, and TT = 8 in CKD patients. In type 2 diabetic patients without CKD, genotype distribution was CC = 38, TC = 10, and TT = 2. In healthy subjects, distribution of genotype was CC = 35, TC = 14, and TT = 1. The distribution of different genotype among the study groups for IL-6 gene was GG = 27, GC = 20, and CC = 3 in healthy subjects; GG = 28, GC = 19, and CC = 3 in diabetic patients without CKD and GG = 38, GC = 11, and CC = 1 in diabetic patients with CKD. There was no significant difference in the distribution of genotype frequencies between healthy subjects and diabetic patients without CKD but a significant difference was found in diabetic patients with CKD. The functional promoter polymorphisms IL4-590C/T and IL6-174G/C, which affect the IL-4 and IL-6 levels in north Indian subjects, were associated with kidney dysfunction and CKD. J. Cell. Biochem. 118: 1803-1809, 2017. © 2016 Wiley Periodicals, Inc.

A percutaneous technique of liver retraction in laparoscopic bariatric & upper abdominal surgery.

BACKGROUND: Laparoscopic bariatric surgery requires retraction of the left lobe of the liver to provide adequate exposure of the hiatus and the stomach. Currently used approaches utilize retractors that require additional incisions and prolong operative time. OBJECTIVES: A retrospective evaluation of the efficacy and safety of a percutaneous liver retractor in a large series of patients undergoing laparoscopic bariatric surgery. SETTING: Private practice, United States. METHODS: A retrospective chart review was performed on 2601 patients undergoing bariatric surgery from January 2011 to September 2015. A percutaneously introduced grasper (Teleflex MiniLap Percutaneous Surgical System, Morrisville, NC) was used to retract the left lobe of the liver in all cases. The retractor could be repositioned as necessary by releasing and regrasping the diaphragm at different locations. RESULTS: This technique was used in 2601 patients from January 2011 until September 2015. The average body mass index was 43.1 (range: 20.6-80.3). In all patients, this new method was found to be satisfactory to complete the bariatric procedure. The majority of procedures included laparoscopic Roux-en-Y gastric bypass, sleeve gastrectomy, and gastric band placement. No intraoperative liver injuries occurred with use of the Teleflex retractor. CONCLUSION: Percutaneous retraction of the liver using the Teleflex MiniLap Percutaneous Surgical System was found to be safe and effective in this large series of morbidly obese patients. The rate of complications involving this technique is extremely low. This novel method provides safe and effective retraction with less trauma and better cosmesis than conventional technique.

Laparoscopic versus robotic-assisted Roux-en-Y gastric bypass: a retrospective, single-center study of early perioperative outcomes at a community hospital.

BACKGROUND: The purpose of this study was to compare the operative and early perioperative outcomes of laparoscopic versus robotic-assisted Roux-en-Y gastric bypass procedures performed in a community hospital setting. METHODS: The study was a chart review and analysis of the early perioperative outcomes of a total of 345 Roux-en-Y gastric bypass procedures performed by a single surgeon in a community hospital setting from January 2011 to October 2014. Of these, 173 procedures were performed laparoscopically and 172 were performed with robotic assistance utilizing the daVinci(®) surgical platform. Factors such as baseline patient characteristics, operative time, estimated blood loss (EBL), conversions to open procedure, complication rates, adverse events, length of stay (LOS), and return to the operating room for the two groups were retrospectively analyzed from a prospectively maintained database. Student's t test with unequal variances was used for statistical analysis, and a p value <0.05 was used for significance. RESULTS: There were no statistically significant differences in complication rates, EBL, or LOS between the two groups. There was a significant difference between the total operative times (135.30 ± 37.60 min for the laparoscopic procedure versus 154.84 ± 38.44 min for the robotic procedure, p < 0.05). There were no adverse intraoperative events, conversions to open procedures, leaks, strictures, returns to the operating room within 30 days, or mortalities in either group. CONCLUSION: Our study, which is the first of its kind to analyze the operative and early perioperative outcomes between laparoscopic and robotic-assisted Roux-en-Y gastric bypass procedures in the US community hospital setting, indicates that both are comparable in terms of safety, efficacy, and operative and early perioperative outcomes.

Promoter Hypermethylation in Tumor Suppressing Genes p16 and FHIT and Their Relationship with Estrogen Receptor and Progesterone Receptor Status in Breast Cancer Patients from Northern India.

BACKGROUND: Aberrant DNA methylation has been recognized in human breast carcinogenesis as a common molecular alteration associated with the loss of expression of a number of key regulatory genes. The present study was undertaken to determine whether methylation and expression of p16 and FHIT genes would correlate with the estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: Methylation-specific polymerase chain reaction, messenger RNA (mRNA) expression analysis, immunohistochemistry, and Western blot analysis were performed to study the methylation of p16 and FHIT genes in 351 pairs of malignant/normal breast tissues. We examined the expression of ER and PR in those specimens by immunohistochemistry. Mutations of p16 and FHIT genes in tumors were detected by direct sequencing. RESULTS: The frequency of hypermethylation was 31.9% and 36.8% in p16 and FHIT genes, respectively, and showed significant harmony in concordant hypermethylation (P < .0001). In postmenopausal patients, methylation frequency in both genes is significantly higher in poorly and moderately differentiated tumors. Loss of protein expression of p16 and FHIT in 77 and 74 tumors, respectively, is associated with their methylation status in premenopausal women. CONCLUSION: We did not find any significant differences in tumor-related gene methylation patterns relevant to both ER and PR status of breast tumors.

Analysis of the SRY gene in two sex-reversed XY sisters identifies two new novel point mutations in the high mobility group box domain.

OBJECTIVE: To determine mutations in the SRY gene in two sisters with 46, XY karyotype. DESIGN: Case report. SETTING: Jamia Millia Islamia, New Delhi, and CSIRO Human Nutrition, Adelaide, Australia. PATIENT(S): Two sisters aged 23 and 27 years old with primary amenorrhea. INTERVENTION(S): Endocrine, mutations in the SRY gene, and DNA binding ability. MAIN OUTCOME MEASURE(S): LH, FSH, and testosterone levels, DNA sequence findings. RESULT(S): We found a new point mutation in the SRY gene in patient 1 at position +275 (A>T), which results in amino acid change (K92M). In patient 2, we found a double mutation in the SRY gene at two different loci. The first mutation is a substitution of C at +352, resulting in a change of amino acid (A118P), and second is deletion of T, resulting in a frame shift within a highly conserved DNA-binding motif-high mobility group box at +379 (T127IfsX179). Electrophoretic mobility shift assay showed that mutant K92M and A118P show reduced and greatly reduced binding ability, respectively. These mutations have the potential to interfere with protein-DNA binding activity and nuclear localization necessary for interactions of these proteins with DNA. CONCLUSION(S): Our results suggest involvement of the SRY gene in sex reversal, which supports the relationship between SRY alterations, gonadal dysgenesis, and/or primary infertility, and provides further evidence of a high-mobility group box significance in DNA-binding/-bending properties.