Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiologic Function of Oxytocin After Birth: Influence on Postpartum Blood Loss and Lactation

The purpose of this program of research is to examine the physiologic role of the neuropeptide and hormone, oxytocin, and the use of pharmaceutical oxytocin administration during childbirth, on outcomes relevant to childbearing women. These outcomes include postpartum hemorrhage and breastfeeding/ lactation, both of which involve oxytocin function. Through a series of studies and manuscripts, the aims of this work are to 1) investigate the premise for clinical oxytocin use in postpartum hemorrhage prevention, specifically in lower-risk populations, and 2) assess downstream effects of oxytocin use during labor and birth on lactation hormones and breastfeeding outcomes. Four chapters, including one literature review paper and three data-based analyses are included in this body of work. The aims were addressed using variety of methodological and statistical techniques with original prospective, longitudinal as well as cross-sectional data. This work is informed by the conceptual care model of Normal Physiologic Childbirth as well as life-history (evolutionary) theory. Collectively, this dissertation demonstrates that interventions performed with the goal of risk reduction may be in the best interest of some, but not all birthing women. The findings challenge the routine practice of oxytocin administration after birth and active management of third stage labor for women undergoing low-risk physiologically stimulated birth as it may be ineffective or potentially harmful. Additionally, this work highlights the possible role of oxytocin administration during the birthing process to influence the physiology of lactation (e.g. prolactin response). Implications of this work are discussed in terms of advancing personalized risk reduction strategies in maternity care, a need for knowledge development in the physiology of nonpathologic childbirth, in addition to the use of statistical techniques in research to provide clinically meaningful findings. PHYSIOLOGIC FUNCTION OF OXYTOCIN AFTER BIRTH iv
Acarbose versus Metformin in the Treatment of Metabolic Syndrome

Background: Prevalence of excess weight is increasing after the age of 50 years with a high cost on health in society. Method: Consecutive patients with excess weight desiring weight loss at and above the age of 50 years were divided into two subgroups according to wishes of patients as to whether they preferred medication or just a diet. Acarbose 100 mg three times daily was initiated in the medication group, orally. Results: The study included 451 patients, and 81.8% of them were overweight or obese, 71.3% of them had white coat hypertension or hypertension, 57.2% of them had impaired glucose tolerance or diabetes mellitus, and 71.1% of them had dyslipidemia. Initially, 179 patients preferred acarbose. Only 10.6% of patients stopped the acarbose therapy due to excessive flatulence or loose stool. The mean weight loss was 8.3 ± 4.1 kg (0-23) in the acarbose group, whereas it was 0.8 ± 1.3 kg (0-7) in the diet group (p<0.001). Although body mass index, low density lipoprotein cholesterol, triglyceride, high density lipoprotein cholesterol, fasting plasma glucose, and systolic and diastolic blood pressure at home decreased with acarbose, significantly (p<0.001 for all), none of them decreased with diet, significantly (p>0.05 for all). Conclusion: Due to the high prevalence of excess weight and its consequences after the age of 50 years, acarbose should be initiated in patients with excess weight after the age of 50 years. It should be preferred to metformin due to high prevalence of excessive anorexia induced metformin intolerance in the society.
O,O'-diethyl-(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochloride enhances influx of effective NK and NKT cells in murine breast cancer

Background/Aim. O,O'-diethyl-(S,S)-ethylenediamine- N,N'-di-2-(3-cyclohexyl)propanoate dihydrochloride (DEEDCP) has been found to possess promising cytotoxic activity against various tumor cell lines. Also, DE-EDCP reduces tumor progression by several mechanisms such as triggering tumor cell death and inhibition of cell proliferation. The aim of present study was to further evaluate antitumor activity of DE-EDCP by investigating effects on migratory potential of tumor cells and anti-tumor immune response. Methods. Migratory potential of DE-EDCP was evaluated by scratch wound assay. Female BALB/c mice were inoculated with 4T1 breast cancer cells and treatment with DE-EDCP started five days following orthotopic tumor implantation. The frequency and phenotype of tumorinfiltrating natural killer (NK) and natural killer T (NKT) cells were analyzed by flow cytometry. Results. DE-EDCP inhibited migratory potential of highly metastatic 4T1 cells. DE-EDCP facilitated accumulation of CD3+CD49+ NKT cells and CD3-CD49+ NK cells in tumor microenvironment. DE-EDCP treatment led to significant decrement of tumor infiltrating anergic NKT cells expressing cytotoxic Tlymphocyte- associated protein 4 (CTLA-4), killer cell lectin like receptor G1 (KLRG-1) and programmed cell death protein- 1 (PD-1). Mice given DE-EDCP had significantly increased percentages of tumoricidal fas ligand (FasL) positive NK cells. Conclusion. DE-EDCP inhibits murine breast cancer progression through direct effects on tumor cells and by facilitating anti-tumor immunity. DE-EDCP enhances accumulation, promotes tumoricidal phenotype and maintenances responsiveness of NK and NKT cells in 4T1 murine breast cancer.
Characteristics Associated with Negative Interferon-γ Release Assay Results in Culture-Confirmed Tuberculosis Patients, Texas, USA, 2013–2015

Interferon-γ release assays (IGRAs) are the preferred diagnostic test for tuberculosis (TB) infection in at-risk populations in developed countries. However, IGRAs have high false-negative rates in patients with TB disease. Population-based studies assessing the factors associated with negative IGRA results in TB patients have not been performed. Using statewide TB surveillance data of culture-confirmed TB patients in Texas, USA, during 2013–2015, we describe the patient characteristics and treatment outcomes associated with false-negative IGRA results. Among 2,854 TB patients, 1,527 (53.5%) had an IGRA result; 97.4% (1,487/1,527) of those had a positive (87.7%) or negative (12.3%) result. Older age, HIV co-infection, non-Hispanic white race/ethnicity, and being tested with T-SPOT.TB were associated with negative IGRA results. TB patients with negative IGRA results had a higher mortality, potentially due to delayed treatment. Healthcare providers should consider these risk factors when making decisions for patients with suspected TB and negative IGRA results and potentially provide treatment.
Brief Reviews Human Renin Inhibitor Peptides

The discovery of angiotensin I converting enzyme inhibitors (ACEI) and of their efficiency in the treatment of high blood pressure and cardiac insufficiency constitutes one of the major advances in medicinal chemistry and therapeutics of the last decade. The design of captopril and its congeners resulted from a rational and systematic study of the interactions of carboxypeptidase A and angiotensin converting enzyme (ACE) with their substrates and inhibitors. Not only were ACEI found to be effective for treating high renindependent forms of hypertension, but unexpectedly, they were also active in normal and low renin hypertension. Very productive research on the ways of blocking the renin-angiotensin system has been undertaken by several academic and drug company laboratories with the aim of finding drugs that could be at least as potent but more selective. Indeed, long-term treatment by ACEI seems not to completely suppress the circulating renin-angiotensin system as plasma angiotensin II (Ang II) and aldosterone levels tend to return toward pretreatment values. In addition, ACE is not a specific enzyme in that it can hydrolyze substrates other than angiotensin I (Ang I), such as bradykinin, substance P, and enkephalins. The side effects observed with all ACEI, such as the rare cases of angioneurotic edema and the more frequent occurrence of cough, may be related to this lack of selectivity. It could be anticipated that potent and specific renin inhibitors would constitute an interesting alternative to ACEI for two reasons: 1) the first step in the renin-angiotensin system, the hydrolysis of angiotensinogen by renin, is rate limiting; and 2) renin has a unique specificity for angiotensinogen as there is no other known substrate for this enzyme. Research on renin inhibitors has been facilitated by the recent progress made on the molecular structures of renin and angiotensinogen and by the elucidation of the molecular mechanisms of action of aspartyl proteases and their inhibitors. Several other factors were apparently promising for the rapid design of a renin inhibitor: the discovery of pepstatin, a lead compound inhibiting the class of aspartyl proteases to which renin belongs; the use of simple biochemical assays for testing renin blockade; and the knowledge
Some Explanations From INTERSALT

An inverse association between social class and disease has frequently been reported; education, an indicator of social class, was negatively related to blood pressure in several studies. Reasons are not clear. INTERSALT, an international study on electrolytes and blood pressure, obtained data on years of education for 10,079 adults in 52 centers in 32 countries. Data presented here are for 47 centers, omitting five where the population in the sample had no education or no differences in educational level. Regression coefficients were calculated for the education-blood pressure association in each center. An inverse association was found for men in 28 centers and for women in 38. Center coefficients were combined to give a studywide estimate of that association. When adjusted only for age, systolic pressure in men was 1.3 mm Hg higher for 10 fewer years of education (/><0.05) and for women 4.5 mm Hg higher (p<0.001). However, when adjusted also for five lifestyle factors (24-hour sodium and potassium excretion, body mass index, alcohol intake, and smoking), these estimates were reduced by about one half, and the inverse association was no longer significant for men. Similar findings were obtained for diastolic pressure. Those with less education had on average higher sodium excretion, lower potassium excretion, greater body mass, and higher alcohol intake, all factors tending to increase blood pressure. Improvement of these factors, which help explain the differences in blood pressure related to years of education, has the potential to reduce the blood pressure disadvantage associated with lower socioeconomic status. (Hypertension 1992;19:237-241)
Diagnostic Reference Levels for Computed Tomography Examinations in Iran: A Nationwide Radiation Dose Survey

Introduction: International Commission on Radiological Protection introduced three basic principles of radiation protection, namely justification, optimization, and dose limit. Medical exposure has no dose limits, and generally, diagnostic reference levels are used as a tool for optimization of patient protection. Material and Methods: Dosimetry was performed on 20 CT scanners located in 14 cities in 12 provinces of Iran. A calibrated pencil-shaped ionization chamber, standard head and body CT dosimetry phantoms and a radiation monitor were used to determine and calculate Computed Tomography Dose Index (CTDI) and Dose Length Product (DLP). The DLP-based estimates of effective dose were derived using effective dose conversion coefficients. Results: The nCTDIw values for head phantoms fell within the range of 22.05-168.38 and 43.77-426.69 µGy/mAs for 5 and 10mm slice thicknesses, respectively. These values for body phantom were 4.65-146.39 and 9.43-308.92 µGy/mAs for 5 and 10mm slice thicknesses, respectively. The third quartile of CTDIvol and DLP values for head CT examinations were 49.85 mGy and 1161.00 mGy-cm, respectively. The body CT examinations had the values of 8.89 mGy and 370.97 mGy-cm, respectively. The findings of this study revealed that the above-mentioned values can be considered as national diagnostic reference levels for head and body CT examinations in Iran. Conclusion: The results of the current study suggested that there is a need to re-assess DRLs for CT examinations at regular time intervals by the appropriate regulatory authority which can improve the continuous performance of CT scanners in Iran.
A Pilot Study to Evaluate the Efficacy and Safety of Treatment with Botulinum Toxin in Patients with Recalcitrant and Persistent Erythematotelangiectatic Rosacea

Background There are few pharmacologic options to reduce erythema and flushing in patients with recalcitrant erythematotelangiectatic rosacea (ETR). We previously reported two cases of refractory flushing and erythema of rosacea that were successfully treated with intradermal botulinum toxin injection, and additional research is needed to prove the efficacy and safety of this treatment. Objective To report the efficacy and safety of botulinum toxin injection as an aid in persistent erythema of rosacea patients. Methods A total of 20 Korean patients with recalcitrant ETR were enrolled to receive treatment by injection of botulinum toxin. Patients received one treatment of intradermal botulinum toxin injection and were assessed 1, 2, 4, and 8 weeks after treatment. The severity of erythema and telangiectasia was investigated by a non-treating physician, and the Erythema Index (EI) was assessed by mexameter at each visit. Patient satisfaction and any adverse events were also assessed at each visit. Results 17 patients completed all follow-up visits and were included in the analysis. Intradermal injection of botulinum toxin significantly reduced erythema severity and EI in ETR patients. Patients reported a satisfaction score of 2.94±0.56 at 8 weeks after treatment. Except for three patients who discontinued the study early due to inconvenience of facial muscle paralysis, 17 patients participating in the final analysis did not report side effects except injection pain at the time of the procedure. Conclusion Intradermal injection of botulinum toxin can be used as an effective and relatively safe adjuvant agent for recalcitrant and persistent erythema of ETR patients.
New Insights Into Mechanisms

Obesity is strongly associated with hypertension and cardiovascular disease. Several central and peripheral abnormalities that can explain the development or maintenance of high arterial pressure in obesity have been identified. These include activation of the sympathetic nervous system and the renin-angiotensin–aldosterone system. Obesity is also associated with endothelial dysfunction and renal functional abnormalities that may play a role in the development of hypertension. The continuing discovery of mechanisms regulating appetite and metabolism is likely to lead to new therapies for obesity-induced hypertension. Better understanding of leptin signaling in the hypothalamus and the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. Other hunger and satiety signals such as ghrelin and peptide YY are potentially attractive therapeutic strategies for treatment of obesity and its complications. These recent discoveries should lead to novel strategies for treatment of obesity and hypertension. (Hypertension. 2005;45:9-14.)
Chemical Renal Medullectomy

We have studied the possible vasodepressor role of the renal medulla by chemical medullectomy. Bromoethylamine hydrobromide (200 mg/kg) was injected to induce selective renal medullary necrosis in rats. The acute effects on sodium balance and long-term effects on blood pressure, plasma renin concentration (PRC) and urinary prostaglandin E2 (PGE2) were studied and compared with saline injected controls. There was an immediate and sustained increase in urine volume of low osmolality. Direct blood pressure in conscious free-moving animals was higher at 2 and 10 weeks after injection in medullary-damaged rats, although this was only significant at 10 weeks (136 ± 3.3 vs 118 ± 4.5 mm Hg, p < 0.01). An initial negative sodium balance returned to normal by 7 days and rats with established medullary damage tolerated a wide range of sodium intakes. Although there was no evidence of sodium retention on the normal diet, with very high sodium loads some sodium retention was apparent since PRC was suppressed and body weight increased. Plasma creatinine and creatinine clearance were normal. PRC in rats with medullary damage was unchanged on normal diet and rose to similar levels as in control rats on low sodium intake. Urinary PGE2 was markedly reduced (148 ± 54 vs 536 ± 71 ng/day, p < 0.01) in medullary damaged rats, consistent with the renal medulla being the major source of urinary PGE2. High salt intake increased urinary PGE2 in normal and proportionally in medullary damaged rats, whereas on a low sodium intake, urinary PGE2 was not different from that on the normal diet in either group. Direct blood pressure was positively correlated with urine volume (r = 0.60) and negatively with urinary PGE2 (r = — 0.43). Higher blood pressures were not related to PRC or the presence of renal cortical damage. These results are consistent with the theory that higher blood pressure in medullary-damaged rats is due to a reduction in renal medullary interstitial cell function. Chemical renal medullectomy induced by bromoethylamine hydrobromide may provide a useful model for unraveling the role of the renal medulla in blood pressure control. (Hypertension 5: 951-957, 1983)
An In Situ Hybridization Study

The angiotensin II type 1 (AT,) receptor in murine species exists as two isoforms (AT,A and AT1B) encoded by two different genes. Both subtypes have a 9/10 homology in the coding sequence of their mRNA. We examined organs of adult rats (liver, pituitary gland, adrenal gland, kidney, heart, and lung) to study the differential expression of these two genes in target tissues for angiotensin II. AT1A and AT1B mRNAs were detected by in situ hybridization using specific riboprobes for the 3' noncoding region of the mRNAs that have the lowest homology (approximately 6/10). Only AT1A was expressed in the liver, heart, and lung, and only AT,B was expressed in the anterior pituitary, where most cells were positive. In the adrenal gland, AT1A mRNA was detected in the zona glomerulosa and medulla and AT,B in the glomerulosa. In the kidney, Angiotensin II (Ang II) receptors establish the connection between the extracellular hormonal message and the cascade of intracellular events triggered by the peptidic hormone corresponding to various effects in different target cells. Among other effects, Ang II induces aldosterone secretion in adrenal glomerulosa cells, vasoconstriction in vascular smooth muscle cells, and salt reabsorption in proximal tubule cells of the kidney as well as upregulates angiotensinogen secretion in hepatocytes. These effects, which all contribute at various levels to the regulation of blood pressure and hydromineral homeostasis, underscore the broad range of Ang II functions.
Controversies in IBD

Fulminant colitis is an ill-defined entity that is usually viewed as the most severe form of uncomplicated acute colitis, with intense symptoms, high fever, and sometimes colectasia. However, the term “fulminant colitis” is also used synonymously with that of acute severe colitis (ASC) (1,2). It occurs usually in the course of ulcerative colitis (UC) or Crohn’s colitis, but can also be seen in infectious, amebic, and ischemic colitis. In this paper, the terms “fulminant colitis” and “acute severe colitis” will be used interchangeably. The first priority of any therapeutic strategy for ASC is to avoid mortality. This aim was achieved almost 50 years ago, when Truelove et al. proposed a simple threestep strategy: 1) selection of patients with severe UC on the basis of clinicobiologic criteria; 2) intensive medical treatment including high-dose intravenous and rectal steroids for 5–7 days; and 3) colectomy for patients who fail to respond or deteriorate (3,4). In true fulminant colitis, the previous therapeutic scheme is basically the same, but should be shortened: 2 to 3 days of intense steroid therapy followed by surgery, in case of resistance. ASC mortality decreased dramatically from 30% to less than 2%, with a colectomy rate of about 30% within 6 weeks of treatment onset (3,4). Any further improvement in ASC management will thus aim at reducing the need for colectomy while keeping mortality at a low rate. The introduction of endoscopy and more recently the use of cyclosporine A (CsA) in the management of ASC are advances that, although still controversial, may help to progress toward this goal; they will be the focus of this paper. ASC clinical evaluation and management recently have been reviewed in depth in this journal and elsewhere (2,5).
The outflow history of two Herbig-Haro jets in RCW 36: HH 1042 and HH 1043 ?

Jets around low- and intermediate-mass young stellar objects (YSOs) contain a fossil record of the recent accretion and outflow activity of their parent star-forming systems. We aim to understand whether the accretion/ejection process is similar across the entire stellar mass range of the parent YSOs. To this end we have obtained optical to near-infrared spectra of HH 1042 and HH 1043, two newly discovered jets in the massive star-forming region RCW 36, using X-shooter on the ESO Very Large Telescope. HH 1042 is associated with the intermediate-mass YSO 08576nr292. Over 90 emission lines are detected in the spectra of both targets. Highvelocity (up to 220 km s 1 ) blue- and redshifted emission from a bipolar flow is observed in typical shock tracers. Low-velocity emission from the background cloud is detected in nebular tracers, including lines from high ionization species. We applied combined optical and infrared spectral diagnostic tools in order to derive the physical conditions (density, temperature, and ionization) in the jets. The measured mass outflow rates are ˙ Mjet 10 7 M yr 1 . It is not possible to determine a reliable estimate for the accretion rate of the driving source of HH 1043 using optical tracers. We measure a high accretion rate for the driving source of HH 1042 ( ˙ Macc 10 6 M yr 1 ). For this system the ratio ˙ Mjet= ˙ Macc 0:1, which is comparable to low-mass sources and consistent with models for magneto-centrifugal jet launching. The knotted structure and velocity spread in both jets are interpreted as fossil signatures of a variable outflow rate. While the mean velocities in both lobes of the jets are comparable, the variations in mass outflow rate and velocity in the two lobes are not symmetric. This asymmetry suggests that the launching mechanism on either side of the accretion disk is not synchronized. For the HH 1042 jet, we have constructed an interpretative physical model with a stochastic or periodic outflow rate and a description of a ballistic flow as its constituents. We have simulated the flow and the resulting emission in position velocity space, which is then compared to the observed kinematic structure. The knotted structure and velocity spread can be reproduced qualitatively with the model. The results of the simulation indicate that the outflow velocity varies on timescales on the order of 100 yr.
The Salt Conundrum

For millennia, salt has had an intimate history with human social, economic, and political relationships. In earlier times man’s work value was paid in salt as gauged by body weight, social stature was dictated by assigned position at the table nearest to the salt, and its etymological root still remains in common parlance.1 Early last century, however, the relationship between salt intake and health was recognized.2 Initially, this relationship was made with the association between magnitude of salt intake and hypertension; but more recently two achievements make a major impact on this subject, the quantitative measurement of dietary sodium intake and repeated recognition that the greater the daily sodium intake, the higher the prevalence of hypertension in populations.