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Neonatal septicemia is a major cause of infection and mortality in neonates. Neonatal sepsis is a type of neonatal infection, particularly bacteremia, diagnosed by the presence of microorganisms in blood via microbiological culture tests during the first 4 weeks of birth. Neonatal sepsis is classified into early bacterial neonatal septicemia (less than 72 h) and late bacterial neonatal septicemia (>72 h–28 d) according to age. Isolation of septicemia-causing bacteria from the blood of neonates and investigation of their antibiotic susceptibility pattern for disease management. This study was a retrospective analysis of blood cultures from neonates admitted to the NICU with symptoms of septicemia from June to December, 2019. All samples were processed according to standard microbiological procedures using the BACTEC 9050 automated culture system. Results were reported on the basis of microbial appearance on the culture media and microscopic examination using the Gram staining method, and authentication was performed using standard biochemical reactions. Of the 228 patients, 32.89% were positive for blood culture. Early bacteremia was detected in 64% of the patients, and late bacteremia was detected in 36% of the patients. The most effective drugs against the gram-positive bacteria were linezolid, vancomycin, and ciprofloxacin and against the gram-negative bacteria were tigecycline, imipenem, and amikacin. Coagulase-negative staphylococci and gram-negative organisms such as Klebsiella, Acinetobacter, and Staphylococcus aureus were the major cause of neonatal septicemia in this study, and almost all the isolates were resistant to different antibiotics. Overall, antimicrobial drug resistance was observed in all the positive blood culture samples. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory disease believed to be correlated with numerous cardiovascular risk factors including increased blood pressure, elevated blood cholesterol level, diabetes, inactivity, high body mass index (obesity) and dyslipidaemia. The present meta-analysis intends to assess the association between psoriasis and cardiovascular risk factors. Three hundred and fifty articles were primarily screened using NCBI MEDLINE/PubMed and Cochrane library from its inception until June 30, 2018. Of these, 26 observational studies depending upon the inclusion and exclusion criteria were included in the study with 17,672 psoriasis patients and 66,407 non-psoriasis subjects. The psoriasis patients were found to be at significantly increased risk of systolic blood pressure (SBP) [ORs 2.31 (95% CI 1.12, 4.74)], diastolic blood pressure (DBP) [ORs 2.31 (95% CI 1.58, 3.38)], abdominal obesity [ORs 1.90 (95% CI 1.45, 2.50)] and triglycerides [ORs 1.80 (95% CI 1.29, 2.51)] as compared to non-psoriasis subjects. The subgroup analyses of studies based on the continents revealed that psoriasis patients from Middle East are prone to higher risk factors of CVD including increased levels of triglyceride, cholesterol, DBP, SBP, fasting blood sugar, body mass index and decreased HDL levels, whereas psoriasis patients from European population reported increased LDL-C and waist circumference. The present study supports a significant association between psoriasis and incidence of major adverse cardiovascular events. Contrary to the previous literature, our finding suggests that hypertension is a highly associative condition in psoriasis. The findings of this study could be validated amongst well-defined cohorts of patients with psoriasis individually in different regions to confirm the implication of the study. [ABSTRACT FROM AUTHOR]

Introduction: Information is limited about the effectiveness of best practice alerts (BPAs) for potentially inappropriate medications (PIMs) in improving clinical outcomes in older adults. Objective: To assess clinical outcomes of 11 BPAs for PIMs in older adults in the ambulatory setting. Methods: A retrospective cohort study was conducted at an integrated health care delivery system with computerized provider order entry. Patients aged 65 years and older were included if they had a BPA triggered when a prescriber attempted to order a sedating PIM in the ambulatory setting. Patients were categorized into dispensed and nondispensed groups if they did and did not, respectively, have the study PIM for which the BPA was triggered dispensed within 30 days of the alert. Rates of fall, fracture, or other injury and cognitive impairment were measured during 180-day follow-up. Results: A total of 2704 patients were included: 1373 (50.8%) and 1331 (49.2%) in the dispensed and nondispensed groups, respectively. The dispensed group had a lower unadjusted rate of fall/fracture/injury (3.4% vs 5.3%, p = 0.019), but this difference was attenuated with multivariable adjustment (adjusted odds ratio = 0.77, 95% confidence interval = 0.51- 1.13). There was no difference in the rate of cognitive impairment between groups (4.6% vs 4.4%, adjusted odds ratio = 1.40, 95% confidence interval = 0.95-2.05). Conclusion: No association was identified between PIM dispensing after a prescriber was alerted with a BPA and reduced rates of falls/fractures/injuries and cognitive impairment. [ABSTRACT FROM AUTHOR]

Purpose. Leadership experiences taught within the Kaiser Permanente Colorado (KPCO) postgraduate year 2 (PGY2) ambulatory care pharmacy residency program were evaluated. Methods. KPCO leadership training incorporated 6 mandatory leadership sessions and offered a 6-week elective rotation. In this qualitative study, an 18-item semistructured interview guide was developed, tested, and administered telephonically to former KPCO PGY2 residents who had been in clinical practice for a minimum of 1 year. The primary outcome was the perceived value of the leadership experiences, and perceived gaps was the secondary outcome. Qualitative analysis was performed for openended questions. Responses were coded and key phrases were highlighted to illustrate major concepts and themes. Results. Of 34 former residents, 29 (85%) completed the interview. Ninety-seven percent of participants reported that the leadership experiences provided value in their professional career; 89% reported value in their personal development. The 3 most common themes of perceived value that emerged from the interviews were exposure to leadership, managing and leading self and others, and clinical service development. Identified gaps included further exposure to senior leadership within the organization and a better understanding of the national pharmacy landscape. Conclusion. Leadership experiences during the PGY2 ambulatory care pharmacy residency at KPCO were perceived positively by former residents on a professional and a personal level. [ABSTRACT FROM AUTHOR]

Objective: We sought to define the intrinsic stem cell capacity in pediatric heart lesions, and the effects of diagnosis and of age, in order to inform evidence-based use of potential autologous stem cell sources for regenerative medicine therapy. Methods: Ventricular explants derived from patients with hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TF), dilated cardiomyopathy (DCM) and ventricular septal defect (VSD) were analyzed following standard in vitro culture conditions, which yielded cardiospheres (C-spheres), indicative of endogenous stem cell capacity. C-sphere counts generated per 5 mm3 tissue explant and the presence of cardiac progenitor cells were correlated to patient age, diagnosis and echocardiographic function. Results: Cardiac explants from patients less than one year of age with TF and DCM robustly generated c-kit- and/or vimentin-positive cardiac mesenchymal cells (CMCs), populating spontaneously forming C-spheres. Beyond one year of age, there was a marked reduction or absence of cardiac explant-derivable cardiac stem cell content in patients with TF, VSD and DCM. Stem cell content in HLHS and DCM strongly correlated to the echocardiographic function in the corresponding ventricular chamber, with better echocardiographic function correlating to a more robust regenerative cellular content. Conclusions: We conclude that autologous cardiomyogenic potential in pediatric heart lesions is robust during the first year of life and uniformly declines thereafter. Depletion of stem cell content occurs at an earlier age in HLHS with the onset of ventricular failure in a chamber-specific pattern that correlates directly to ventricular dysfunction. These data suggest that regenerative therapies using autologous cellular sources should be implemented in the neonatal period before the potentially rapid onset of single ventricle failure in HLHS or the evolution of biventricular failure in DCM. [ABSTRACT FROM AUTHOR]

The article discusses the integration of leadership development into the revised American Society of Health-System Pharmacists (ASHP) postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) pharmacy residency accreditation standards. The PGY2 ambulatory care pharmacy residency program of Kaiser Permanente Colorado (KPCO) is described. The key components of a leadership-driven residency training are discussed.

This study aims to examine the inter-district and inter-village variation of utilization of health services for institutional births in EAG states in presence of rural health program and availability of infrastructures. District Level Household Survey-III (2007–08) data on delivery care and facility information was used for the purpose. Bivariate results examined the utilization pattern by states in presence of correlates of women related while a three-level hierarchical multilevel model illustrates the effect of accessibility, availability of health facility and community health program variables on the utilization of health services for institutional births. The study found a satisfactory improvement in state Rajasthan, Madhya Pradesh and Orissa, importantly, in Bihar and Uttaranchal. The study showed that increasing distance from health facility discouraged institutional births and there was a rapid decline of more than 50% for institutional delivery as the distance to public health facility exceeded 10 km. Additionally, skilled female health worker (ANM) and observed improved public health facility led to significantly increase the probability of utilization as compared to non-skilled ANM and not-improved health centers. Adequacy of essential equipment/laboratory services required for maternal care significantly encouraged deliveries at public health facility. District/village variables neighborhood poverty was negatively related to institutional delivery while higher education levels in the village and women’s residing in more urbanized districts increased the utilization. “Inter-district” variation was 14 percent whereas “between-villages” variation for the utilization was 11 percent variation once controlled for all the three-level variables in the model. This study suggests that the mere availability of health facilities is necessary but not sufficient condition to promote utilization until the quality of service is inadequate and inaccessible considering the inter-districts variation for the program implementation. [ABSTRACT FROM AUTHOR]

Concurrent activation of RAS/ERK and PI3K/AKT pathways is implicated in prostate cancer progression. The negative regulators of these pathways, including sprouty2 (SPRY2), protein phosphatase 2A (PP2A), and phosphatase and tensin homolog (PTEN), are commonly inactivated in prostate cancer. The molecular basis of cooperation between these genetic alterations is unknown. Here, we show that SPRY2 deficiency alone triggers activation of AKT and ERK, but this is insufficient to drive tumorigenesis. In addition to AKT and ERK activation, SPRY2 loss also activates a PP2A-dependent tumor suppressor checkpoint. Mechanistically, the PP2A-mediated growth arrest depends on GSK3ß and is ultimately mediated by nuclear PTEN. In murine prostate cancer models, Pten haploinsufficiency synergized with Spry2 deficiency to drive tumorigenesis, including metastasis. Together, these results show that loss of Pten cooperates with Spry2 deficiency by bypassing a novel tumor suppressor checkpoint. Furthermore, loss of SPRY2 expression correlates strongly with loss of PTEN and/or PP2A subunits in human prostate cancer. This underlines the cooperation between SPRY2 deficiency and PTEN or PP2A inactivation in promoting tumorigenesis. Overall, we propose SPRY2, PTEN, and PP2A status as an important determinant of prostate cancer progression. Characterization of this trio may facilitate patient stratification for targeted therapies and chemopreventive interventions. [ABSTRACT FROM AUTHOR]

Prostate cancer (CaP) is the most common cancer among adult men in the Western world. Better insight into its tumor-activating pathways may facilitate the development of targeted therapies. In this study, we show that patients who develop prostate tumors with low levels of PTEN and high levels of HER2/3 have a poor prognosis. This is functionally relevant, as targeting Her2 activation to the murine prostate cooperates with Pten loss and drives CaP progression. Mechanistically, this is associated with activation of the MAPK pathway and abrogation of the Pten loss-induced cellular senescence program. Importantly, inhibition of MEK function strongly suppressed proliferation within these tumors by restoring the Pten loss-induced cellular senescence program. Taken together, these data suggest that stratification of CaP patients for HER2/3 and PTEN status could identify patients with aggressive CaP who may respond favorably to MEK inhibition. [ABSTRACT FROM AUTHOR]

Abstract: Among tea polyphenols, the anti-initiating properties of polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, are poorly elucidated. Hence, this study was undertaken to investigate the effects of PBP extract on the induction of phase II enzymes. PBP extract induced transcriptional up-regulation of phase II enzymes in liver and lungs by increasing Nrf2-mediated antioxidant-responsive element (ARE) binding. PBP extract did not alter Nrf2 or Keap1 at the transcriptional level but may have increased their levels by posttranslational modifications such as phosphorylation and decreased ubiquitination. PKC and PI3-kinase-mediated phosphorylation of Nrf2 seems to be critical for the release of Nrf2 from Keap1 and its subsequent nuclear translocation. mafK was found to be the heterodimeric partner of Nrf2 for binding to ARE sequences in liver upon PBP extract pretreatment. Differences in phosphorylation, activation of cellular kinases, and speculated heterodimeric binding partners of Nrf2 by PBP extract in hepatic and pulmonary tissues suggested the possibility of tissue-specific differences in the activation of Nrf2. Thus, we conclude that the pathway of PBP extract-induced ARE activity involves the activation of Nrf2 through phosphorylation by PKC and PI3-kinases in hepatic cells, which is critical for the increased stability of Nrf2 upon release from Keap1 and nuclear translocation, respectively. [Copyright &y& Elsevier]

Abstract: Tea polyphenols like epigallocatechin gallate and theaflavins are established chemopreventive agents for colorectal carcinogenesis. However, studies on evaluating similar chemopreventive properties of thearubigins or polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, are limited. Hence, in the present study we aim to investigate chemopreventive effects along with probable mechanisms of action of PBP extract employing 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in Sprague–Dawley rats as experimental model. The present study suggests that PBPs, like other tea polyphenols, also inhibit DMH-induced colorectal tumorigenesis by decreasing tumor volume and multiplicity. This study also shows that although the pretreatment with PBP extract could induce detoxifying enzymes in hepatic and colorectal tissue, it did not show any additional chemopreventive effects when compared to treatments with PBP extract after initiation with DMH. Mechanistically, PBP extract may inhibit colorectal carcinogenesis by decreasing DMH-induced cell proliferation via Wnt/β-catenin pathway. Treatments with PBP extract showed decreased levels of COX-2, c-MYC and cyclin D1 proteins which aid cell proliferation probably by regulating β-catenin by maintaining expression of APC and decreasing inactivation of GSK3β. DMH-induced activation of MAP kinases such as ERK and JNK was also found to be inhibited by treatments with PBP extract. In conclusion, the protective effects of PBP extract could be attributed to inhibition of DMH-induced cellular proliferation probably through β-catenin regulation. [Copyright &y& Elsevier]

The article reports on the use of personal digital assistants for documenting primary care clinical pharmacy services in a health maintenance organization in the U.S. The medical community has recognized the significance of developing a standardized electronic documentation system to facilitate data collection, compilation, and analysis to assess the value of clinical pharmacy staff in a primary care setting.

Background: Prostate cancer is highly prevalent worldwide. Androgen deprivation therapy (ADT) remains the treatment of choice for incurable prostate cancer, but majority of patients develop disease recurrence following ADT. There is therefore an urgent need for early detection of treatment resistance. Methods: Isogenic androgen-responsive (CWR22Res) and castration-resistant (22Rv1) human prostate cancer cells were implanted into the anterior lobes of the prostate in CD-1 Nu mice to generate prostate orthografts. Castrated mice bearing CWR22Res and 22Rv1 orthografts mimic clinical prostate cancer following acute and chronic ADT, respectively. 18F-Fluciclovine (1-amino-3-fluorocyclobutane-1-carboxylic acid) with a radiochemical purity of > 99% was produced on a FASTlab synthesiser. Ki67 staining in endpoint orthografts was studied. Western blot, quantitative RT-PCR and next-generation sequencing transcriptomic analyses were performed to assess the expression levels of amino acid transporters (including LAT1 and ASCT2, which have been implicated for Fluciclovine uptake). Longitudinal metabolic imaging with 18F-Fluciclovine-based positron emission tomography (PET) was performed to study tumour response following acute and chronic ADT. Results: Both immunohistochemistry analysis of endpoint prostate tumours and longitudinal 18F-Fluciclovine imaging revealed tumour heterogeneity, particularly following ADT, with in vivo 18F-Fluciclovine uptake correlating to viable cancer cells in both androgen-proficient and castrated environment. Highlighting tumour subpopulation following ADT, both SUVpeak and coefficient of variation (CoV) values of 18F-Fluciclovine uptake are consistent with tumour heterogeneity revealed by immunohistochemistry. We studied the expression of amino acid transporters (AATs) for 18F-Fluciclovine, namely LAT1 (SLC7A5 and SLC3A2) and ASCT2 (SLC1A5). SLC7A5 and SLC3A2 were expressed at relatively high levels in 22Rv1 castration-resistant orthografts following chronic ADT (modelling clinical castration-resistant disease), while SLC1A5 was preferentially expression in CWR22Res tumours following acute ADT. Additional AATs such as SLC43A2 (LAT4) were shown to be upregulated following chronic ADT by transcriptomic analysis; their role in Fluciclovine uptake warrants investigation. Conclusion: We studied in vivo 18F-Fluciclovine uptake in human prostate cancer orthograft models following acute and chronic ADT. 18F-Fluciclovine uptakes highlight tumour heterogeneity that may explain castration resistance and can be exploited as a clinical biomarker. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus is responsible for causing a variety of human infections, which may range from minor skin diseases to life-threatening infections. It colonizes healthy individuals and causes severe infection in hospitalized patients. Staphylococcus aureus infections used to respond to ß-lactam and related group of antibiotics but the emergence of Methicillin-resistant S. aureus (MRSA) has posed a serious therapeutic challenge. The present study aimed to determine prevalence of Methicillin-resistant Staphylococcus aureus in Dhiraj General Hospital, Gujarat and to determine antibiotic sensitivity pattern of Methicillin resistant Staphylococcus aureus in various samples and to determine inducible clindamycin resistance strains out of Methicillin resistant Staphylococcus aureus at Dhiraj General Hospital. Materials and methods: The present study was conducted in Microbiology Department of SBKS MI and RC during January 2022 to December 2022. The study comprised of 114 coagulase-positive staphylococci (COPS), isolated from a total of 1470 clinical specimens (like pus, blood, urine, high vaginal swab, sputum, etc.) of patients admitted in Dhiraj General hospital attached to SBKS MI and RC, Hospital, Waghodia, Gujarat. All the isolates were identified by standard procedures. Antimicrobial susceptibility test was carried out on each bacterial isolate using the disc diffusion method on Muller Hinton agar (MHA). Data were entered and analyzed statistically. Results: During one year of study period, a total of 1470 positive culture samples were there. Out of that, 114 positive samples of Staphylococcus aureus were isolated. Out of total Staphylococcus aureus positive samples, 24 strains of Methicillin resistant Staphylococcus aureus (MRSA) were detected. Out of total MRSA, 10 inducible clindamycin resistant Staphylococcus aureus were detected. Conclusion: To conclude, we can say that Vancomycin and Teicoplanin is the drug of choice in MRSA patients. As MRSA is an alarming issue for the health system, one should always think about drug sensitivity test before starting treatment. [ABSTRACT FROM AUTHOR]

• Nine polycyclic aromatic hydrocarbons and cotinine were found in the cord blood, confirming its transfer to the fetus. • Machine learning approach used in the study provides an insight to distinguish between low and normal birth weight babies. • Proposed pLBW webserver predicts the state of the baby with a maximum accuracy of 82.42% using SVM algorithm. Prenatal exposure to organic pollutants increases the risk of low birth weight (LBW) offspring. Women involved in the plucking of tea leaves can be exposed to polycyclic aromatic hydrocarbons (PAHs) during pregnancy through inhalation and diet. Therefore, the aim of the study was to investigate the association of maternal socio-demographic features and blood PAH concentration with LBW; also to develop a model for predicting LBW risk. The study was performed by recruiting 55 women who delivered LBW and 120 women with NBW (normal birth weight) babies from Assam Medical College. The placental tissue, maternal and cord blood samples were collected. A total of sixteen PAHs and cotinine were analysed by HPLC and GC-MS. Association of PAH concentration with weight was determined using correlation and multiple logistic regression analyses. Predictive model was developed using SVM light and Weka software. Maternal features such as age, education, food habits, occupation, etc. were found to be associated with LBW deliveries (p-value<0.05). Overall, 9 PAHs and cotinine were detected in the samples. A multiple logistic regression depicted an increased likelihood of LBW by exposure to PAHs (pyrene, di-benzo (a,h) anthracene, fluorene and fluoranthene) and cotinine. Models based on the features and PAHs/ cotinine predicted LBW offspring with 84.35% sensitivity and 74% specificity. LBW prediction models are available at http://dev.icmr.org.in/plbw/ webserver. With machine learning gaining more importance in medical science; our webserver could be instrumental for researchers and clinicians to predict the state of the fetus. [ABSTRACT FROM AUTHOR]

Introduction The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown. Methods We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 (N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance. Results Among 8591 cancer patients, 215 unique patients submitted a total of 478 successful PAP requests for cancer drugs. 40% of PAP-utilizing patients were uninsured, 23% had Medicaid coverage, 20% had Medicare coverage, 2% were dual Medicare/Medicaid eligible, and 14% were commercially insured. Among all cancer patients who received medical treatment, 6.0% required PAP assistance, whereas 10.6% receiving an oral agent required PAP assistance. The proportion receiving PAP assistance varied substantially by drug, ranging from <1% of patients (e.g. carboplatin, methotrexate) to 50% of patients (e.g. ponatinib, temsirolimus). The majority of the retail value obtained was for oral agents, including $1,556,575 of imatinib and $1,449,633 of dasatinib, which were the two drugs with the highest aggregate retail value. Conclusions A substantial proportion of cancer patients receive private charitable assistance to obtain standard-of-care treatments. This includes patients with federal and private insurance, suggesting an inability of patients to meet cost-sharing requirements. [ABSTRACT FROM AUTHOR]

[Display omitted] The purpose of this study aimed to evaluate the impact of the surface area per volume (SA/V) ratio on drug transport from two supersaturated solutions (SSs) of ketoconazole with and without hydroxypropyl methylcellulose (HPMC), used as a precipitation inhibitor. In vitro dissolution, membrane permeation with two SA/V ratios, and in vivo absorption profiles for both SSs were determined. For the SS without HPMC, a two-step precipitation process due to the liquid–liquid phase separation was observed; the constant concentration with approximately 80 % of the dissolved amount was maintained for the first 5 min and subsequently decreased between 5 and 30 min. For the SS with HPMC, a parachute effect was observed; the constant concentration with approximately 80 % dissolved amount was maintained for more than 30 min and decreased very slowly thereafter. Assessment of the SA/V ratio using in vitro and in vivo models demonstrated that when the SA/V ratio was small, the SS with HPMC resulted in a significantly higher permeated amount than the SS without HPMC. In contrast, when the SA/V ratio was large, the HPMC-mediated parachute effect on drug transport from SSs was attenuated, both in vitro and in vivo. The parachute effect by HPMC decreased as the SA/V ratio increased, and the performance of supersaturating formulations would be overestimated by in vitro studies with small SA/V ratios. [ABSTRACT FROM AUTHOR]

Which factors impact on clinical pregnancy rate (CPR) and live birth rates (LBR) in euploid frozen embryo transfer (eFET) cycles? Retrospective observational study including 1660 eFET cycles with 2439 euploid blastocysts, from November 2016 to December 2020. The impact of clinical and laboratory parameters on CPR, biochemical miscarriage rate (BMR), clinical miscarriage rate (CMR) and LBR was evaluated. CPR per transfer was 63.4%, LBR per transfer 51.6%. CPR and LBR were significantly higher when double embryo transfer (DET) was performed (71.6% versus 57.7%, P < 0.001; 55.2% versus 49.1%, P = 0.016, respectively). However, pregnancy loss was significantly higher in the DET group (28.8% versus 22.8%, P = 0.02). When patients were classified by body mass index (BMI), no differences were observed for CPR, but CMR was lower (P < 0.001) and LBR higher (p = 0.031) for the normal BMI group. The natural cycle protocol revealed lower CMR (P < 0.001) and lower pregnancy loss (P < 0.001); subsequently, higher LBR (57.6%, 48.8%, 45.0%, P = 0.001) compared with hormonal replacement protocol and stimulated cycle. Day of trophectoderm biopsy affected CPR (P < 0.001) and LBR (P < 0.001), yet no differences were observed for BMR, CMR or pregnancy loss. The multivariate analysis showed that day 6/7 embryos had lower probabilities for pregnancy; overweight and obesity had a negative impact on LBR, and natural cycle improved LBR (adjusted odds ratio 1.445, 95% confidence interval 0.519–0.806). Day of biopsy affected CPR, while BMI and endometrial preparation protocol were associated with LBR in eFET. DET should be discouraged as it will increase the risk of pregnancy loss. Women with higher BMI should be aware of the higher risk of pregnancy loss and lower LBR even though a euploid blastocyst is transferred. [ABSTRACT FROM AUTHOR]

Consanguineous marriage is defined as marriage between first or second-degree cousins, with high prevalence in many cultures and societies. Descendants from consanguineous unions have an increased risk for genetic diseases. Additionally, in consanguineous couples, chromosomal disjunction during embryogenesis could also be affected, increasing the risk of chromosomal errors. Nowadays, genomic testing allows to identify new genetic syndromes and variants related to copy-number variations (CNV), including whole chromosome, segmental and micro-segmental errors. This is the first study evaluating chromosomal ploidy status on blastocysts formed from consanguineous couples during IVF/ICSI treatments with Preimplantation Genetic Testing for Aneuploidies (PGT-A), compared to non-consanguineous couples. Although consanguine couples were significantly younger, no differences were observed between groups for fertilisation rate, blastulation rate and euploidy rate, once adjusted by age. Nevertheless, the number of blastocysts biopsied on day 5 was lower for consanguine couples. Segmental errors, and aneuploidies of chromosomes 13 and 14 were the most prominent abnormalities in relation to consanguinity, together with errors in chromosome 16 and sex chromosomes when the female partner was younger than 35. Once euploid blastocysts were considered for subsequent frozen embryo transfer, pregnancy outcomes were similar in both groups. The current findings point toward the fact that in consanguine unions, not only the risk of having a child with genetic disorders is increased, but also the risk of specific chromosomal abnormalities seems to be increased. Premarital counselling and tailored reproductive treatments should be offered to these couples. [ABSTRACT FROM AUTHOR]

ARF GTPases are central regulators of membrane trafficking that control local membrane identity and remodeling facilitating vesicle formation. Unraveling their function is complicated by the overlapping association of ARFs with guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and numerous interactors. Through a functional genomic screen of three-dimensional (3D) prostate cancer cell behavior, we explore the contribution of ARF GTPases, GEFs, GAPs, and interactors to collective invasion. This revealed that ARF3 GTPase regulates the modality of invasion, acting as a switch between leader cell-led chains of invasion or collective sheet movement. Functionally, the ability of ARF3 to control invasion modality is dependent on association and subsequent control of turnover of N-cadherin. In vivo, ARF3 levels acted as a rheostat for metastasis from intraprostatic tumor transplants and ARF3/N-cadherin expression can be used to identify prostate cancer patients with metastatic, poor-outcome disease. Our analysis defines a unique function for the ARF3 GTPase in controlling how cells collectively organize during invasion and metastasis. [ABSTRACT FROM AUTHOR]

Objectives: To test for evidence of statin‐mediated effects in patients with castration‐resistant prostate cancer (CRPC) as post‐diagnosis use of statins in patients with prostate cancer is associated with favourable survival outcome. Patients and Methods: The SPECTRE trial was a 6‐weeks‐long proof‐of‐concept single‐arm Phase II treatment trial, combining atorvastatin and androgen deprivation therapy in patients with CRPC (regardless of metastatic status), designed to test for evidence of statin‐mediated effects in patients with CRPC. The primary study endpoint was the proportion of patients achieving a ≥50% drop from baseline in prostate‐specific antigen (PSA) levels at any time over the 6‐week period of atorvastatin medication (PSA response). Exploratory endpoints include PSA velocity and serum metabolites identified by mass spectrometry. Results: At the scheduled interim analysis, one of 12 patients experienced a ≥50% drop in PSA levels (primary endpoint), with ≥2 patients satisfying the primary endpoint required for further recruitment. All 12 patients experienced substantial falls in serum cholesterol levels following statin treatment. While all patients had comparable pre‐study PSA velocities, six of 12 patients showed decreased PSA velocities after statin treatment, suggestive of disease stabilization. Unbiased metabolomics analysis on serial weekly blood samples identified tryptophan to be the dominant metabolite associated with patient response to statin. Conclusions: Data from the SPECTRE study provide the first evidence of statin‐mediated effects on CRPC and early sign of disease stabilization. Our data also highlight the possibility of altered tryptophan metabolism being associated with tumour response. [ABSTRACT FROM AUTHOR]

Background: While increase in the number of women delivering in health facilities has been rapid, the quality of obstetric and neonatal care continues to be poor in India, contributing to high maternal and neonatal mortality.Methods: The USAID ASSIST Project supported health workers in 125 public health facilities (delivering approximately 180,000 babies per year) across six states to use quality improvement (QI) approaches to provide better care to women and babies before, during and immediately after delivery. As part of this intervention, each month, health workers recorded data related to nine elements of routine care alongside data on perinatal mortality. We aggregated facility level data and conducted segmented regression to analyse the effect of the intervention over time.Results: Care improved to 90-99% significantly (p < 0.001) for eight of the nine process elements. A significant (p < 0.001) positive change of 30-70% points was observed during post intervention for all the indicators and 3-17% points month-to-month progress shown from the segmented results. Perinatal mortality declined from 26.7 to 22.9 deaths/1000 live births (p < 0.01) over time, however, it is not clear that the intervention had any significant effect on it.Conclusion: These results demonstrate the effectiveness of QI approaches in improving provision of routine care, yet these approaches are underused in the Indian health system. We discuss the implications of this for policy makers. [ABSTRACT FROM AUTHOR]

Background: Digital learning tools have proliferated among healthcare workers in India. Evidence of their effectiveness is however minimal. We sought to examine the impact of the Safe Delivery App (SDA) on knowledge and confidence among frontline health workers (HW) in India. We also studied whether facilitation to address technical challenges enhanced self-learning. Methods: Staff nurses and nurse-midwives from 30 facilities in two states were divided into control and intervention groups through randomization. Knowledge and confidence were assessed at baseline and after 6 months. Three rounds of facilitation addressing technical challenges in downloading and usage along with reminders about the next phase of learning were conducted in the intervention group. A user satisfaction scale along with qualitative interviews was conducted in the intervention group at the endline along with qualitative interviews on facilitation. Results: The knowledge and confidence of the healthcare workers significantly increased from the baseline to endline by 4 percentage points (P < 0.001). The participants who received facilitation had a higher mean score difference in knowledge and confidence compared to those who did not receive facilitation (P < 0.001). The participants were highly satisfied with the app and video was the most-watched feature. They reported a positive experience of the facilitation process. Conclusion: The effectiveness and acceptability of the SDA indicate the applicability of mHealth learning tools at the primary healthcare level. In a time of rapid digitalization of training, facilitation or supportive supervision needs further focus while on-ground digital training could be invested in to overcome digital illiteracy among healthcare workers. [ABSTRACT FROM AUTHOR]

Objectives: To address pneumonia, a major killer of under-5 children in India, a multimodal pulse oximeter was implemented in Health and Wellness Centers. Given the evidence of pulse oximetry in effective pneumonia management and taking into account the inadequate skills of front-line healthcare workers in case management, the device was introduced to help them readily diagnose and treat a child and to examine usability of the device. Design: The implementation was integrated with the routine OPD of primary health centers for 15 months after healthcare workers were provided with an abridged IMNCI training. Monthly facility data was collected to examine case management with the diagnostic device. Feedback on usefulness of the device was obtained. Setting: Health and Wellness Centers (19) of 7 states were selected in consultation with state National Health Mission based on patient footfall. Participants: Under-5 children presenting with ARI symptoms at the OPD. Results: Of 4846 children, 0.1% were diagnosed with severe pneumonia and 23% were diagnosed with pneumonia. As per device readings, correct referrals were made of 77.6% of cases of severe pneumonia, and 81% of pneumonia cases were correctly given antibiotics. The Pulse oximeter was highly acceptable among health workers as it helped in timely classification and treatment of pneumonia. It had no maintenance issue and battery was long-lasting. Conclusion: Pulse oximeter implementation was doable and acceptable among health workers. Together with IMNCI training, PO in primary care settings is a feasible approach to provide equitable care to under-5 children. [ABSTRACT FROM AUTHOR]

Objectives: To address pneumonia, a major killer of under-5 children in India, a multimodal pulse oximeter was implemented in Health and Wellness Centers. Given the evidence of pulse oximetry in effective pneumonia management and taking into account the inadequate skills of front-line healthcare workers in case management, the device was introduced to help them readily diagnose and treat a child and to examine usability of the device. Design: The implementation was integrated with the routine OPD of primary health centers for 15 months after healthcare workers were provided with an abridged IMNCI training. Monthly facility data was collected to examine case management with the diagnostic device. Feedback on usefulness of the device was obtained. Setting: Health and Wellness Centers (19) of 7 states were selected in consultation with state National Health Mission based on patient footfall. Participants: Under-5 children presenting with ARI symptoms at the OPD. Results: Of 4846 children, 0.1% were diagnosed with severe pneumonia and 23% were diagnosed with pneumonia. As per device readings, correct referrals were made of 77.6% of cases of severe pneumonia, and 81% of pneumonia cases were correctly given antibiotics. The Pulse oximeter was highly acceptable among health workers as it helped in timely classification and treatment of pneumonia. It had no maintenance issue and battery was long-lasting. Conclusion: Pulse oximeter implementation was doable and acceptable among health workers. Together with IMNCI training, PO in primary care settings is a feasible approach to provide equitable care to under-5 children. [ABSTRACT FROM AUTHOR]

Background: Docetaxel chemotherapy in prostate cancer has a modest impact on survival. To date, efforts to develop combination therapies have not translated into new treatments. We sought to develop a novel therapeutic strategy to tackle chemoresistant prostate cancer by enhancing the efficacy of docetaxel.Methods: We performed a drug-repurposing screen by using murine-derived prostate cancer cell lines driven by clinically relevant genotypes. Cells were treated with docetaxel alone, or in combination with drugs (n = 857) from repurposing libraries, with cytotoxicity quantified using High Content Imaging Analysis.Results: Mebendazole (an anthelmintic drug that inhibits microtubule assembly) was selected as the lead drug and shown to potently synergise docetaxel-mediated cell killing in vitro and in vivo. Dual targeting of the microtubule structure was associated with increased G2/M mitotic block and enhanced cell death. Strikingly, following combined docetaxel and mebendazole treatment, no cells divided correctly, forming multipolar spindles that resulted in aneuploid daughter cells. Liposomes entrapping docetaxel and mebendazole suppressed in vivo prostate tumour growth and extended progression-free survival.Conclusions: Docetaxel and mebendazole target distinct aspects of the microtubule dynamics, leading to increased apoptosis and reduced tumour growth. Our data support a new concept of combined mebendazole/docetaxel treatment that warrants further clinical evaluation. [ABSTRACT FROM AUTHOR]

Purpose. The outcomes of a patient-centered layered learning practice model (LLPM) in which the clinical specialist acted as the attending pharmacist and managed a pharmacy team to provide direct patient care were evaluated. Methods. Two 30-day evaluations were conducted on the acute care malignant hematology and medical oncology services of the University of North Carolina Medical Center in 2011. The primary objective of this study was to design an LLPM that used a team to expand the pharmacist care services offered. The primary outcome was the frequency of pharmacy team encounters at discharge (medication reconciliation and counseling), termed the discharge capture rate. Results. During the study months, 42 and 78 malignant hematology and medical oncology patients were eligible for study inclusion, respectively. The overall discharge capture rate was 51%. Sixty-one patients received discharge medication reconciliation services during patient counseling. Patients included in the malignant hematology group received a mean of 11 prescriptions at discharge, compared with 9.83 in the medical oncology group. Means of 1.26 and 2.1 medication-related problems per patient were identified in the malignant hematology and medical oncology studies, respectively, during discharge medication reconciliation. The overall mean face time spent per patient was 21.3 minutes. Conclusion. Patients in malignant hematology and medical oncology services were counseled and provided discharge medication reconciliation by a pharmacy student or resident whose activities were managed and reviewed by an attending pharmacist using an LLPM, resulting in an improvement in all clinical outcomes and measures. [ABSTRACT FROM AUTHOR]

Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up-regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/ pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition. [ABSTRACT FROM AUTHOR]

Purpose. Investigators report the results of a study to determine the proportion of residency projects presented as abstracts at a regional residency conference that were subsequently published as full-length articles. Summary. Using every third item listed in the abstract booklets from the Western States Conference for the years 1995, 2000, and 2005, a search of MEDLINE and EMBASE for journal citations indicating publication of the corresponding residency projects was conducted; the searches covered a period including and extending five years beyond the year of abstract presentation at the conference. Of the total of 270 abstracts evaluated, 17 were expanded to full-length articles and published within the search time frame. The average time to publication (mean S.D.) was 24 10 months. The publication rates associated with abstracts presented at the 1995, 2000, and 2005 conferences were 4.2%, 5.2%, and 8.2%, respectively. All published articles appeared in peer-reviewed journals, with more than half (54.2%) in pharmacy journals. The majority of residency projects published were retrospective and prospective cohort studies. In most cases (58.8%), the resident was listed as the first author of the published journal article. Conclusion. The overall publication rate of abstracts presented at a regional residency conference in 1995, 2000, and 2005 was 6.3%, with an increase in the rate over those years. [ABSTRACT FROM AUTHOR]

Purpose. Investigators report the results of a study to determine the proportion of residency projects presented as abstracts at a regional residency conference that were subsequently published as full-length articles. Summary. Using every third item listed in the abstract booklets from the Western States Conference for the years 1995, 2000, and 2005, a search of MEDLINE and EMBASE for journal citations indicating publication of the corresponding residency projects was conducted; the searches covered a period including and extending five years beyond the year of abstract presentation at the conference. Of the total of 270 abstracts evaluated, 17 were expanded to full-length articles and published within the search time frame. The average time to publication (mean ± S.D.) was 24 ± 10 months. The publication rates associated with abstracts presented at the 1995, 2000, and 2005 conferences were 4.2%, 5.2%, and 8.2%, respectively. All published articles appeared in peer-reviewed journals, with more than half (54.2%) in pharmacy journals. The majority of residency projects published were retrospective and prospective cohort studies. In most cases (58.8%), the resident was listed as the first author of the published journal article. Conclusion. The overall publication rate of abstracts presented at a regional residency conference in 1995, 2000, and 2005 was 6.3%, with an increase in the rate over those years. [ABSTRACT FROM AUTHOR]

Plakophilin3 is a desmosomal plaque protein whose levels are reduced in poorly differentiated tumors of the oropharyngeal cavity and in invasive colon carcinomas, suggesting that plakophilin3 may function as a tumor suppressor. To test the above hypothesis, plakophilin3 expression was inhibited by short hairpin RNA's in two different epithelial cell lines, HCT116 and FBM. The down regulation of plakophilin3 led to a decreased deposition of the desmosomal cadherins - the desmogleins, at the cell surface but did not affect the deposition of plakoglobin and other desmosomal plaque proteins. The altered desmosomal composition was accompanied by colony formation in soft agar and growth to high density in culture, both properties of transformed cells. Additionally, the induction of skin papillomas in mice was accompanied by plakophilin3 loss. These data indicate that plakophilin3 loss contributes to cellular transformation and that plakophilin3 functions as a tumor suppressor gene. [ABSTRACT FROM AUTHOR]