Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternal Nutrition and Offspring Stress Response—Implications for Future Development of Non-Communicable Disease: A Perspective From India

Psychological stress is recognized as a major modifiable risk factor for adult non-communicable disease (NCD) that includes depression, type 2 diabetes mellitus, and cardiovascular disease. Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity resulting in either exaggerated or blunted cortisol responses, and altered autonomic cardiovascular control have been thought to underlie this association. The developmental origins hypothesis proposes that impaired nutrition during fetal and early postnatal growth is associated with a higher NCD risk later in life. Maternal nutrients are vital for fetal growth and development, and both maternal undernutrition and over nutrition as in the case of gestational diabetes are associated with higher NCD risk markers in the offspring. Recent studies suggest that fetal exposure to maternal nutritional imbalances may permanently alter cortisol and cardio-sympathetic stress-responsiveness, which may link early life nutrition with adult disease risk. A few recent studies that examined the association between low birth weight as a marker of fetal undernutrition and stress response in humans showed that lower birth weight was associated with an altered HPA axis and cardiovascular sympathetic nervous system responses to stress in adults as well as in children. In addition, altered stress responses in relation to gestational diabetes have been noted. In this paper, we present available evidence from India for the association between maternal nutrition and offspring stress responsiveness against the backdrop of global evidence, and discuss its role in the escalating NCD rates in this population. We also discuss the scope for future studies in India and other transitioning countries.
Global vs. Network-Specific Regulations as the Source of Intrinsic Coactivations in Resting-State Networks

Spontaneous neural activities are endowed with specific patterning characterized by synchronizations within functionally relevant distant regions that are termed as resting-state networks (RSNs). Although the mechanisms that organize the large-scale neural systems are still largely unknown, recent studies have proposed a hypothesis that network-specific coactivations indeed emerge as the result of globally propagating neural activities with specific paths of transmission. However, the extent to which such a centralized global regulation, rather than network-specific control, contributes to the RSN synchronization remains unknown. In the present study, we investigated the contribution from each mechanism by directly identifying the global as well as local component of resting-state functional MRI (fMRI) data provided by human connectome project, using temporal independent component analysis (ICA). Based on the spatial distribution pattern, each ICA component was classified as global or local. Time lag mapping of each IC revealed several paths of global or semi-global propagations that are partially overlapping yet spatially distinct to each other. Consistent with previous studies, the time lag of global oscillation, although being less spatially homogenous than what was assumed to be, contributed to the RSN synchronization. However, an equivalent contribution was also shown on the part of the more locally confined activities that are independent to each other. While allowing the view that network-specific coactivation occurs as part of the sequences of global neural activities, these results further confirm an equally important role of the network-specific regulation for its coactivation, regardless of whether vascular artifacts contaminate the global component in fMRI measures.
DENTIGEROUS CYST IN THE VENTRAL CONCHAL SINUS OF A HORSE

A 14-year-old Quarter Horse was presented for evaluation of a chronic, intermittent purulent discharge from the left nostril. A radioopaque mass and multiple, air-fluid interfaces in the paranasal sinuses were identified on survey radiographs. The mass was removed and identified as a dentigerous cyst. Substantiated reports of dentigerous cysts in the paranasal sinuses are rare.
Capsaicin-Sensitive Afferent Nerves and the Human Gastrointestinal Tract

These studies were carried out as propective, randomized and multiclinical studies of human healthy subjects and in patients with various gastrointestinal disorders including gastric mucosal damage produced by application of NSAIDs or H. pylori infection. The aims this review are: (1) to give a short summary on the actions of capsaicin on the human gastrointestinal tract (dominantly on the stomach), (2) to indicate some details of gastroprotective actions of capsaicin in human healthy subjects; (3) to demonstrate the capsaicin-induced gastric protective effects against the NSAID-(selective and non-selective COX inhibitor) induced gastric microbleedings in human healthy subjects; (4) to prove the independency of TRPV1 and CGRP expression from the presence of the H. pylori positive or negative chronic gastritis, the efficacy of successfully carried out eradication treatment in patients with H. pylori positive gastritis in patients; 5. to indicate the clinical pharmacological problems of plant origin capsaicin in humans (in term of drug processing); (6). to point out that the gastroprotective effects of capsaicin (given orally in stimulatory doses of capsaicin on afferent nerves) to human healthy subjects, and as treatment to patients who are under chronic NSAID use (like patients with myocardial stroke, thrombo‐ phylia, rheumatic diseases, etc.). out in 198 healthy human subjects years (40± years) patients with various GI disorders (gastritis, erosion, ulcer, polyps, cancer and chronic bowel diseases, polyps, precancerous states, colorectal cancer), ranged 25-75 years (45±10), 69 patients with chronic gastritis 39-68 years (mean: years) healthy persons GI
Delayed evoked potentials in zebra finch (Taeniopygia guttata) under midazolam-butorphanol-isoflurane anesthesia

Avian animals are visually inclined, which has caused them to attract increasing attention for visual neurophysiology or electrophysiology studies, including the study of the visual evoked potential (VEP). VEP has developed into an investigative tool for understanding the physiology and the pathology of the visual pathway. Chemical restraint is a common method to minimize motion artifacts in animals when acquiring VEP data, but little is known about its influence on the signal in an avian animal. In addition, it is difficult to make comparisons between conscious state data when the animals are ultimately under anesthesia. Therefore, finding drugs and developing protocols that have an acceptable effect is valuable. We compared the local field potentials of physically and chemically restrained zebra finches (Taeniopygia guttata), a small avian species, to simulate a relatively challenging recording condition. Finches were sedated with midazolam-butorphanol, and anesthesia was maintained by isoflurane. Electrodes were implanted into the left nucleus rotundus, which is a visual nucleus in birds. The VEPs of the control group (N = 3) were recorded after they fully recovered and were restrained by towels. The other birds (N = 3) were recorded under anesthesia. The results show that without the visual stimuli, anesthesia generally suppressed the overall power of field potentials. However, by focusing on the spectra during VEPs, visual stimuli still triggered significant VEPs in frequencies below 30.8 Hz, which were even stronger than towel-restrained birds. The drugs also prolonged the latency of the VEP, increased the duration of the VEP when compared to towel-restrained birds. As regard to towel-restrained zebra finches, the field potentials were less synchronized and may need data preprocessing to have clear VEPs. In conclusion, the current study presents evidence of basic VEP for zebra finch under midazolam-butorphanol-isoflurane anesthesia with a protocol that is a safe and feasible anesthetic combination for chemical restraint, which is particularly useful for small animals when obtaining evoked potentials.
Cost and Efficacy of Therapies for Advanced Parkinson's Disease

The economic burden of Parkinson’s disease (PD) has become a very important health topic. From the perspective of a general neurologist, health economics can appear as not prioritary; however, it is a growing topic in most modern healthcare systems; consequently health professionals should have at least a minimal understanding of how health economic information is derived. It has become important that payers and providers consider the significant impact the disease has on quality of life and how resource utilisation is directed to improve PD related clinical problems. Such measures are determinant in assessing the value of drug therapy, particularly for chronic conditions such as PD, and in determining the appropriate placement of medications on plan formularies. In the past, a comprehensive examination of a clinical condition would focus almost exclusively on areas considered relevant to patient management, such as diagnosis, etiology, treatment, and prognosis. Now, however, additional demands are being made by health policy decision makers, who can influence medical decisions through coverage and reimbursement policies. Physicians and other professional caregivers increasingly must consider the economic implications of their decisions, which has led to increased demand for disease-specific cost information.
Opening the black box: Understanding cross-media effects

Despite their popularity, the reasons why cross-media campaigns are more successful than single medium campaigns are still unknown. Therefore, the aim of this study is (a) to investigate which psychological processes are present when people are exposed to cross-media campaigns, and (b) to examine to what extent these processes contribute to campaign results. Three psychological processes are investigated to gain insight into the effectiveness of cross-media campaigns: forward encoding (i.e., the ad in the first medium primes interest in the ad in the second medium); image transfer (i.e., mentally replaying the ad previously viewed during exposure to the ad in the second medium); and multiple source perception (i.e., believing the brand is good and popular because of the amount of advertising). To identify the role of these processes, 219 participants were exposed to one of four media conditions (two cross-media conditions and two repeated media conditions). The results showed that two processes were present when participants were exposed to the cross-media combinations: forward encoding and multiple source perception. We also found support for the hypothesis that these two processes contributed to campaign results. However, the third process, image transfer, was present in all conditions and did not add to the explanation of cross-media effects.
1562. Safety and Efficacy of High-Dose Cefazolin Therapy in Obesity

Abstract Background Obesity leads to altered pharmacokinetics through changes in volume of distribution and clearance, which can impact antimicrobial dosing. Although there is data to support higher cefazolin pre-operative dosing for surgical prophylaxis, data evaluating treatment doses of cefazolin in obese patients is lacking. This study was designed to assess the safety and efficacy of high-dose (HD) cefazolin compared with traditional-dose (TD) cefazolin in obesity. Methods This was a multicenter, retrospective, cohort study of patients admitted from September 1, 2013 to August 31, 2018. Obese adults, defined as a BMI > 30 kg/m2, receiving cefazolin for at least 48 hours for bacteremia or skin and soft-tissue infection were eligible for inclusion. Patients with creatinine clearances <30 mL/minute or positive MRSA cultures were excluded. TD cefazolin was defined as 1–2 g IV every 8 hours and HD cefazolin was defined as 2 g every 4–6 hours. Patients were matched 1:1 based on indication, severity of illness, and BMI. Primary objective was to compare rates of treatment-emergent adverse events (TEAE). Secondary outcomes included comparison of treatment failure rates and 30-day readmission. Results A total of 332 patients (166 matched pairs) were included in this analysis. Baseline demographics were similar between groups with the exception of higher age in the TD group (61.8 TD vs 55.1 HD; P < 0.001) and more males in the HD group (39.2% TD vs. 65.6% HD; P < 0.001). Median Charlson comorbidity index was also higher in the TD group [4 (2–6) TD vs. 3 (1–4) HD; P < 0.001]. There were no differences in TEAE between groups (24.1% TD vs. 16.9% HD; P = 0.103). Treatment failure occurred more frequently in the TD group (24.7% TD vs. 15.1% HD; P = 0.028), driven primarily by rates of readmission secondary to recurrence or relapse of the index infection (18.7% vs. 11.5%; P = 0.07). Conclusion There were no differences in TEAE in patients who received TD cefazolin vs. HD cefazolin therapy. Obese patients receiving TD therapy experienced higher treatment failure than those receiving HD therapy. Dose-optimization strategies with cefazolin in obese patients should be further explored. Disclosures All authors: No reported disclosures.
Outcomes of Empirical Antimicrobial Therapy for Pediatric Community-onset Febrile Urinary Tract Infection in the Era of Increasing Antimicrobial Resistance

Supplemental Digital Content is available in the text. Background: Urinary tract infection (UTI) is a common cause of fever in children. Despite the increasing numbers of extended-spectrum beta-lactamase-producing organisms in the community, the empirical therapy of choice is still third-generation cephalosporins. This study was performed to investigate whether inappropriate empirical therapy (IAT) of community-onset UTI results in adverse clinical outcomes. Methods: We retrospectively studied a cohort of pediatric patients with first-episode community-onset UTI caused by Escherichia coli, Klebsiella pneumoniae and Proteus spp. at Ramathibodi Hospital from 2011 to 2017. The patients were classified into IAT and appropriate empirical therapy (AT) groups. Medical records were reviewed to assess clinical outcomes. Results: One hundred fifty-one eligible patients were enrolled in this study. The most common causative organism was E. coli (88.8% and 96.2% in the AT and IAT groups, respectively). Among the causative organisms, 19.8% were extended-spectrum beta-lactamase-producing organisms. There was no significant difference in clinical failure, microbiologic failure, relapse or time to defervescence between the 2 groups. No patients in either group developed sepsis after receiving empirical therapy. However, the length of hospital stay was significantly longer in the IAT than AT group [4.00 (4.50–6.00) vs. 7.00 (5.00–11.25) days, respectively; P = 0.000]. Conclusions: No significant difference in treatment outcomes was found between pediatric patients receiving AT and IAT for the treatment of UTI. In the era of increasing antimicrobial resistance, third-generation cephalosporins may still be a good choice as an empirical antimicrobial for children diagnosed with community-onset UTI.
Volunteer safer than replacement donor blood: a myth revealed by evidence

The dogma that volunteer non‐remunerated blood donors (VNRD) are safer has been a cornerstone of world transfusion, including developing countries, for WHO and other major transfusion organizations although the data supporting this dogma has never been convincing. It was supported by data collected without regard for the basic rule of epidemiology, which is to compare what is comparable. In this case, first‐time and repeat VNRD were amalgamated, and genuine replacement/family donors (R/F) were mixed with paid donors. In sub‐Saharan Africa (SSA), VNRD and R/F donors have a median age of < 20 and around 30, respectively. In VNRD, the proportion of females is considerably higher than in R/F donors further distorting the comparisons. In epidemiological terms, only first‐time VNRD can be validly compared to R/F donors.
An interesting case of HSV pneumonia and PCP co-infection in a patient with AIDS: A diagnostic and management challenge

The advent of HIV and AIDS has brought about many diagnostic and management challenges regarding multiple opportunistic infections. Pneumocystis jirovecii pneumonia (PCP) is a common presentation in patients with AIDS who are not on prophylaxis or highly active antiretroviral therapy (HAART). Herpes simplex 1 virus (HSV-1) is a ubiquitous virus that mainly causes benign disease during primary infection. However, it is known to cause severe pneumonia and disseminated disease in the immunocompromised.1 We present a case of HSV-1 pneumonitis and PCP co-infection in an HIV-positive patient with respiratory failure. To the best of our knowledge, based on Pubmed and Google Scholar searches, this is the first case to be reported in the English language literature.
LB20. Valacyclovir to Prevent Vertical Transmission of Cytomegalovirus After Maternal Primary Infection During Pregnancy

Abstract Background Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. The highest risk of fetal injury follows a maternal primary infection early in pregnancy. Despite the potential for severe fetal injury, to date there are no proven means to prevent viral transmission. Valacyclovir is an antiviral drug proven effective in decreasing the risk for CMV infection among transplant recipients. Valacyclovir is safe for use in pregnancy, and concentrates in the amniotic fluid without accumulating. A dose of 8 g/day creates therapeutic drug levels in the amniotic fluid and fetal blood. Methods This is a randomized, double-blind, placebo-controlled study comprising pregnant women with serologic evidence of primary CMV infection during the periconceptional period and first trimester. After informed consent, patients were randomly assigned to a treatment group (8 g/day of Valacyclovir) or control group (placebo). Treatment was initiated at the time of serological detection, and continued until amniocentesis. The primary endpoint was the rate of vertical transmission of CMV—determined by amniotic fluid CMV PCR. Secondary endpoints included evidence of symptomatic congenital CMV infection—in utero or postnatally. Results One hundred women were recruited, 90 were included in the data analysis; 45 patients received Valacyclovir and 45 placebo. There were 2 twin pregnancies, and therefore 92 amniocentesis Amongst the Valacyclovir group, 5 (11.1%) amniocentesis were positive for CMV, compared with 14 (29.8%) in the placebo group (P GLMM = 0.03), corresponding with an odds ratio of 0.29 (95% CI: 0.09–0.90) for vertical CMV transmission. Amongst patients infected during the first trimester, a positive amniocentesis for CMV was significantly (P = 0.02) less likely in the Valacyclovir arm (2/19) compared with placebo (11/23). No significant differences (P = 0.91) in CMV-positive amniocentesis were observed between study arms amongst patients infected periconceptionally. Conclusion Valacyclovir at a dose of 8 g/day is effective in reducing the rate of fetal CMV infection following early maternal primary infection during pregnancy. The drug reduces the rate of fetal infection by 71%. Disclosures All authors: No reported disclosures.
Chronic and Low Dose Exposure to Nonlyphenol or Di(2-Ethylhexyl) Phthalate Alters Cell Proliferation and the Localization of Steroid Hormone Receptors in Uterine Endometria in Mice

ABSTRACT Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In 133 μg/L and 1,330 μg/L di(2-ethylhexyl) phthalate (DEHP) and 50 μg/L nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in 500 μg/L NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in 1,330 μg/L DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.
18F-FDG Is a Surrogate Marker of Therapy Response and Tumor Recovery after Drug Withdrawal during Treatment with a Dual PI3K/mTOR Inhibitor in a Preclinical Model of Cisplatin-Resistant Ovarian Cancer

Abstract AIM: Targeting the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is a potential means of overcoming chemoresistance in ovarian cancer. We investigated the capability of 18 F-fluororodeoxyglucose ( 18 F-FDG) small-animal positron emission tomography (SA-PET) to predict the effects of a dual PI3K/mTOR inhibitor (BEZ-235) in a cisplatin-resistant ovarian cancer model. METHODS: In a first experiment, nude rats bearing subcutaneous SKOV3 tumors received BEZ-235 for 3 days given alone or after paclitaxel and were compared to controls (either untreated or that were given the excipients of paclitaxel and BEZ-235). SA-PET was performed at baseline, on day 3, and day 7. In a second experiment aiming at further exploring the kinetics of 18 F-FDG tumor uptake during the first 48 hours following drug cessation, untreated controls were compared to rats receiving BEZ-235, which were imaged at baseline, on day 3, on day 4, and on day 5. SA-PET results were compared to cell proliferation assessment (Ki-67), PI3K/mTOR downstream target expression studies (pAKT and phospho-eukaryotic translation initiation factor 4E-binding protein 1), and apoptosis evaluation (cleaved caspase-3). RESULTS: In the first experiment, BEZ-235, compared to untreated controls, induced a marked decrease in 18 F-FDG uptake on day 3, which was correlated to a significant decrease in cell proliferation and to a significant PI3K/mTOR pathway inhibition. No tumor necrosis or apoptosis occurred. Four days following treatment cessation, tumor recovery (in terms of PI3K/mTOR inhibition and cell proliferation) occurred and was identified by 18 F-FDG SA-PET. Paclitaxel plus BEZ-235 showed results similar to BEZ-235 alone. In the second experiment, PI3K/mTOR pathways exhibited partial recovery as early as 24 hours following treatment cessation, but both 18 F-FDG SA-PET and cell proliferation remained unchanged. CONCLUSIONS: 18 F-FDG SA-PET is a surrogate marker of target inhibition during treatment with BEZ-235 and predicts tumor recovery 4 days after drug withdrawal, but not during the first 48 hours following drug cessation, when a lag between PI3K/mTOR pathway recovery and metabolic recovery is observed. 18 F-FDG SA-PET could be used for therapy monitoring of PI3K/mTOR inhibitors, but our results also raise questions regarding the potential impact of the delay between PET imaging and the last drug intake on the accuracy of FDG imaging.