RNA-seq analysis of the rat placentation site reveals maternal obesity-associated changes in placental and offspring thyroid hormone signaling.

INTRODUCTION: In animal models, maternal obesity (OB) leads to augmented risk of offspring OB. While placental function is influenced by maternal habitus, the effect of maternal obesity on the interacting zones of the placenta [the labyrinth (LZ), junctional (JZ) and metrial gland (MG)] remains unknown. METHODS: Using a rat maternal obesity model, we conducted transcriptomic profiling of the utero-placental compartments and fetal liver (FL) at dpc 18.5, in conjunction with analyses of mRNA expression of key thyroid hormone (TH) signaling genes in the placenta, fetus and weanling offspring. RESULTS AND DISCUSSION: Gene expression analysis of placenta and offspring revealed that each utero-placental compartment responds distinctly to maternal OB with changes in inflammatory signaling, lipid metabolism and hormone stimulus being the predominant effects. OB-induced alterations in 17 genes were confirmed by qPCR, including reductions in thyrotropin-releasing hormone (Trh) in JZ. We further characterized mRNA and protein expression of TH signaling regulators including deiodinases (Dio), TH receptors (Tr), and downstream targets (uncoupling proteins (Ucp)). A concerted down-regulation of multiple facets of thyroid hormone signaling in the JZ and FL was observed. JZ expression of thyroid hormone signaling components Trh, Dio2, Trα, and Ucp2 were negatively associated with maternal leptin. mRNA expression of TRH, TRß and UCP1 were also decreased in term placenta from OB women. Finally, our studies identified persistent impairments in expression of TH related genes in tissues from offspring of obese dams. CONCLUSIONS: The role of lower placental thyroid expression is worthy of further study as a possible pathway that leads to low energy metabolism and obesity in animals born to obese mothers.

Maternal obesity is associated with a lipotoxic placental environment.

Maternal obesity is associated with placental lipotoxicity, oxidative stress, and inflammation, where MAPK activity may play a central role. Accordingly, we have previously shown that placenta from obese women have increased activation of MAPK-JNK. Here, we performed RNA-sequencing on term placenta from twenty-two subjects who were dichotomized based on pre-pregnancy BMI into lean (BMI 19-24 kg/m(2); n = 12) and obese groups (BMI, 32-43 kg/m(2); n = 12). RNA-seq revealed 288 genes to be significantly different in placenta from obese women by ≥ 1.4-fold. GO analysis identified genes related to lipid metabolism, angiogenesis, hormone activity, and cytokine activity to be altered in placenta from obese women. Indicative of a lipotoxic environment, increased placental lipid and CIDEA protein were associated with decreased AMPK and increased activation of NF-κB (p65) in placenta from obese women. Furthermore, we observed a 25% decrease in total antioxidant capacity and increased nuclear FOXO4 localization in placenta from obese women that was significantly associated with JNK activation, suggesting that maternal obesity may also be associated with increased oxidative stress in placenta. Maternal obesity was also associated with decreased HIF-1α protein expression, suggesting a potential link between increased inflammation/oxidative stress and decreased angiogenic factors. Together, these findings indicate that maternal obesity leads to a lipotoxic placental environment that is associated with decreased regulators of angiogenesis and increased markers of inflammation and oxidative stress.

Pattern of breast cancer in a tertiary care center.

INTRODUCTION: Breast Cancer is the second commonest cause of cancer death in women. Almost all women survive breast cancer if it is detected before it starts to spread. The aim of the study is to analyze the demographical profile, stage of presentation, histological type, and treatment modalities of breast cancer in a tertiary care setting. METHODS: Total 1141 cases of breast cancer had been followed retrospectively from 1999 to 2006 A.D. in a tertiary care center and their patterns were analyzed. RESULTS: The mean age of presentation of breast cancer was 47.30 +/- 11.57 years in female and 59.03 +/- 14.63 in male, 31 (2.1%) cases of breast cancer were male. There were 123 (10.78%) stage I, 281 (24.62%) stage II, 466 (40.84%) stage III, and 271 (23.75%) stage IV patients. Infiltrating ductal carcinoma was the commonest variety 610 (53.5%). Chemotherapy was the mainstay for treatment of breast cancer 341 (29.9%) followed by surgery 287 (25.2%). CONCLUSIONS: Breast cancer trend is rising with more in late and advanced stages, mostly due to lack of awareness. Infiltrating ductal carcinoma is the commonest variety. Chemotherapy is the most commonly used modality of treatment. Male breast cancer present late and is not so uncommon.

Need for improvement of medical records.

INTRODUCTION: A medical record is a systematic documentation of a patient's medical history and care for legal and future use. A poor quality medical record can negatively affect patient care and safety. The study aims to assess the adequacy of medical records in Bir Hospital, a central hospital. METHODS: A cross-sectional study was conducted by analyzing consecutive discharge summaries of patients admitted during a 6 month period in a single unit of a tertiary care center. The discharge summary format of the hospital was taken as the standard and evaluation for adequacy of data entered was assessed. Descriptive statistics were used to analyze various statistical discrepancies. RESULTS: Patient's condition at discharge was missing in 86 (66.15%). Patient's address was missing in 21 (16.1%) cases. Almost all the discharge sheets lacked mailing address. Total 96 (73.8%) had use of abbreviations diagnosis. Age and sex were missing in 1 (0.76%). Doctor's signature was illegible in 103 (79.3%) and missing in 2 (1.5%) summaries. Doctor's name and their level/position were missing in 118 (90.76%) and 125 (96.1%) respectively. Total 126 patients (96.9%) were not given any instructions on discharge. CONCLUSIONS: The discharge summaries analyzed were seen to be inadequate especially in documenting course during the hospital stay, condition at discharge, appropriate instructions and the treating physician's details. These can probably be addressed by introducing electronic medical records if feasible. Otherwise, the discharge summary should be standardized and doctors should be trained to write legible, complete discharge summaries.

A scenario of cervical carcinoma in a cancer hospital.

INTRODUCTION: Cervical carcinoma is an important women's health problem throughout the world. There are very few published data on this disease in Nepal. We wanted to study the pattern of cervical carcinoma based on hospital data. METHODS: A 10 years retrospective study of scenario of cervical carcinoma was conducted. The data have been analyzed according to age, occurrence of other cancers, histological type, religion, risk factors and district wise. RESULTS: The number of cervical carcinoma showed a rising pattern over the 10 year period. The median age of the patients was 45 years and maximum frequency (33%) of cases were found in the age group 40 to 49 years. Squamous cell carcinoma comprised 40% of cases, Adenocarcinoma 4% and 1.1% cases were of mixed variety. 92% of cases were Hindu by religion. 43% of patients were smoker in our study, 5% had positive family history. Chitwan with 7.35% had the maximum number of cases followed by Rupandehi with 6.40% and Nawalparasi with 5.41%. CONCLUSIONS: The cancer pattern revealed by the present study provides valuable leads to cervical cancer epidemiology in Nepal. Routine cytological screening of the population for cervical cancer is highly necessary for its early detection and treatment.

HIV/AIDS and STI related knowledge, attitude and practice among high school students in Kathmandu valley.

OBJECTIVE: To assess the knowledge, attitude and practice of high school students regarding HIV/ AIDS and STI and to determine if a school education programme would bring about statistically significant positive change in the knowledge, attitude and practice regarding HIV/AIDS and STI. METHODS: The study was conducted among 1012 students of various schools in Kathmandu Valley (Kathmandu, Bhaktapur and Lalitpur). The tool for assessment was confidentially administered closed questionnaire both before and after the education programme of 45 minutes single class, standardized education package. RESULTS: Knowledge on some aspect of the disease was quite low in the study group. 45.8% had prior knowledge of HIV, 65.2% knew that HIV/AIDS could be transmitted by sharing same needle, 46.2% knew that vaccine is not yet available for HIV/AIDS. Knowledge about STI was also quite low, 41.5% knew that pus in the urine is a symptom of STI and 41.7% knew that STI is curable. 4.2% of the study group had previous sexual intercourse, 64.2% had sexual intercourse with friend and 35.17% had sexual intercourse with commercial sex workers. 1.8% would commit suicide if they contracted HIV/AIDS. According to sex wise distribution of the sample, female's knowledge about HIV was low 43.2% as compared to male 48%, male's knowledge about transmission of HIV/AIDS from pregnant mother to child was low; 89.7% as compared to female's knowledge 94.2%. Female's knowledge about commercial sex worker as high risk group was low (87.8%) as compared to male's knowledge 90.6%.