Topical Micro-Emulsion of 5-Fluorouracil by a Twin Screw Processor-Based Novel Continuous Manufacturing Process for the Treatment of Skin Cancer: Preparation and In Vitro and In Vivo Evaluations.

5-Fluorouracil (5-FU), a BCS class III drug, has low oral bioavailability and is cytotoxic in nature causing severe systemic side effects when administered through the intravenous route. Topical drug delivery could potentially mitigate the systemic side-effects. Microemulsions (MEs) would be an apt solution due to enhanced partitioning of the drug to the skin. However, conventional methods for preparing MEs are inefficient since they are not continuous and are very tedious and time-consuming processes hence revealing the need for the development of continuous manufacturing technology. In our study, 5-FU MEs were prepared using a continuous manufacturing Twin Screw Process (TSP) and its efficiency in the treatment of skin cancer was evaluated. Water-in-oil MEs were prepared using isopropyl myristate as the oil phase and Aerosol OT and Tween 80 as the surfactants. The average particle size was observed to be 178 nm. Transmission electron microscopy was employed to confirm the size and shape of the MEs. FTIR study proved no physical or chemical interaction between the excipients and the drug. In vitro drug release using vertical diffusion cells and ex vivo skin permeation studies showed that the drug was released sustainably and permeated across the skin, respectively. In in vitro cytotoxicity studies, 5-FU MEs were accessed in HaCat and A431 cell lines to determine percentage cell viability and IC50. Skin irritation and histopathological examination implied that the 5-FU MEs did not cause any significant irritation to the skin. In vivo pharmacodynamics studies in rats suggested that the optimised formulation was effective in treating squamous cell carcinoma (SCC). Therefore, 5-FU MEs efficiently overcame the various drawbacks faced during oral and intravenous drug delivery. Also, TSP proved to be a technique that overcomes the various problems associated with the conventional methods of preparing MEs.

Perceptions and experiences of diploma nursing students on clinical learning. A descriptive qualitative study in Tanzania.

BACKGROUND: The quality of nursing education depends largely on the experience student receive in the clinical environment. The learning environment is complex with factors that may positively or negatively influence students learning. The current study aimed to explore the experiences and perceptions of diploma nursing students toward their clinical learning in Dodoma-Tanzania. METHODS: A qualitative descriptive study design was employed. The study was conducted in four nursing schools involving 32 nursing students who were purposively selected. Data was collected using focus-group discussions and analyzed using thematic analysis. RESULTS: Three main themes emerged during the discussions: experience on personal and technical support for clinical learning, the importance of the clinical environment in clinical learning, and insufficient clinical educational planning. The majority of students had negative experiences including poor clinical supervision, lack of equipment, congestion of students, and inability to meet clinical objectives. Few students had positive experiences related to exposure to a real clinical environment and great support from staff nurses. CONCLUSION: Students had mixed experiences, both positive and negative on their clinical learning. The majority of students had negative experiences. This may have a serious impact on the student completing their education, the services they will offer to patients when employed, and nursing professional development.

Integrating baseline MR imaging biomarkers into BCLC and CLIP improves overall survival prediction of patients with hepatocellular carcinoma (HCC).

OBJECTIVES: We aimed to evaluate the independent predictive role of baseline imaging biomarkers for overall survival (OS) and transplant-free survival (TFS) in patients with HCC and assess the incremental value of these biomarkers to current staging systems. METHODS: In this retrospective IRB approved study, the clinical, laboratory, and imaging parameters of 304 HCC patients were collected. Cox regression model was utilized to identify the potential predictors of survival. Recursive partitioning test was utilized to identify the optimal ADC cutoff for stratifying patients' OS. Patients were stratified based on Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Binary ADC value (above vs. below the cutoff) and tumor margin (well- vs. ill-defined) were integrated into BCLC and CLIP. OS and TFS was compared for patients based on standard criteria with and without imaging biomarkers. RESULTS: At baseline, patients with low tumor ADC and well-defined tumor margin (favorable imaging biomarkers) had longer survival, as compared to those with high ADC and ill-defined tumor margin (unfavorable imaging biomarkers) (median OS of 43 months vs. 7 months, respectively) (p < 0.001). Tumor ADC and tumor margin remained strong independent predictors of survival after adjustment for demographics, BCLC and CLIP staging, and tumor burden. Incorporating ADC and tumor margin improved performance of OS prediction by 9% in BCLC group and 6% in CLIP group. CONCLUSION: Incorporating ADC and tumor margin to current staging systems for HCC significantly improve prediction of OS and TFS of these criteria. KEY POINTS: • ADC and tumor margin are predictors of overall survival in HCC patients, independent of clinical, laboratory, and other imaging variables. • Adding ADC and tumor margin improved the prognostic value of BCLC and CLIP criteria by 9% and 6%, respectively. • High ADC and ill-defined tumor margin at baseline predicted poor survival, regardless of patient's liver function and general health status.

Job satisfaction of rural medical interns: A qualitative study.

OBJECTIVE: To study reasons for job satisfaction and dissatisfaction among interns. DESIGN: Using a qualitative methodology, one-to-one interviews were conducted with interns. SETTING: The study was based at a Victorian Rural Intern Training program. PARTICIPANTS: Twelve interns from the program were interviewed during their final rotation. MAIN OUTCOME MEASURES: Reasons for job satisfaction and dissatisfaction among rural interns. RESULTS: Reasons for job satisfaction included feeling supported in the workplace as well as getting quality supervision, teaching and clinical exposure. Reasons for job dissatisfaction included poor access to administration, unduly stressful working situations, lack of support for mental health and well-being, and poorly organised teaching sessions. CONCLUSION: The internship experience, together with the people they are influenced by, can determine a doctor's future career pathway. It is therefore vital for internship coordinators and hospital managers to facilitate a positive internship experience. The findings have implications for human resource management policy and practice in rural hospitals.

Increased Incidence of Villitis in Placentas Exposed to Chemotherapy During Pregnancy: Is There a Correlation?

We have identified 9 pregnant patients who were diagnosed with malignancy and initiated chemotherapy during their second trimester (cervical cancer [n = 3], leukemia [n = 3], breast cancer [n = 2], and Hodgkin's lymphoma [n = 1]). Five of the patients' placentas were small for gestational age (SGA). Pathologic examination revealed inflammatory changes in 4 of the placentas: 2 from the SGA placentas and 2 from non-SGA placentas. Examination revealed 3 placentas with villitis of unknown etiology (VUE) and 1 with intervillositis; all were negative for bacterial and viral cultures and by immunohistochemical (IHC) stains. In the VUE cases, IHC stains showed positivity of CD25+/FOXP3+ with focal positivity and CD3 and CD4 IHC were focally to strongly positive. Literature suggests that the use of chemotherapy during pregnancy can be detrimental to both the mother and the fetus; however, there has been limited focus on the effects of chemotherapy on the placenta. We suggest that the inflammatory process noted in the placentas is due to chemotherapy-induced toxic effects.

Correlation between quantitative liver and spleen volumes and disease severity in primary sclerosing cholangitis as determined by Mayo risk score.

OBJECTIVES: To correlate total and lobar liver and spleen volume with disease severity in primary sclerosing cholangitis (PSC) as determined by Mayo risk score. METHODS: This HIPAA-compliant single center retrospective study included 147 PSC patients with available imaging studies (MRCP/CT) and laboratory data between January 2003 and January 2018. Total and lobar (right, left and caudate) liver volume and spleen volume were measured. ANOVA test was performed to assess the differences in volumes between low, intermediate and high-risk groups (Mayo risk score <0, >0 and <2, >2, respectively). Correlations between volumes and Mayo risk score were calculated. ROC analysis was performed to assess the accuracy of the variable with the strongest correlation to PSC severity to predict Mayo risk score. P value <0.05 was considered statistically significant. RESULTS: The mean age of this cohort was 45 ± 17 years; 58% were men. Absolute volumes of left lobe, caudate and spleen and volume ratios of left lobe and caudate to total liver volume of the high-risk group were significantly higher compared to those of low and intermediate risk groups (p < 0.05). Left lobe to total liver volume ratio had the highest correlation to Mayo risk score (Pearson correlation coefficient 0.61, p < 0.05) and on ROC analysis it had 84.4% accuracy in detecting high-risk PSC. CONCLUSIONS: In this single institution large cohort study, the left lobe to total liver volume ratio was the best quantifiable volumetric biomarker to correlate with severity of PSC as identified by Mayo risk score.

Padronizaçäo das concentraçöes de esteróides no líquido amniótico: II. Testosterona, sulfato de deidroepiandrosterona e cortisol / Standardization of steroid concentrations in the amniotic fluid: II. Testosteroni, dehydroepiandrosterone sulfate and cortisol

As dosagens de testosterona, sulfato de deidroepiandrosterona (SDHEA) e cortisol no líquido amniótico (LA) permitem avaliar as funçöes das adrenais e das gônadas fetais. Estudamos LAs de 41 gestaçöes, obtidos por amniocentese no segundo trimestre da gestaçäo. Trinta e sete destas gestaçöes (das quais quatro de risco para hiperplasia adrenal congênita por deficiência da 21-hidroxilase) resultaram em fetos normais, três foram anencéfalos e um, portador de deficiência da 21-hidroxilase. Os esteróides foram dosados utilizando-se radioimunoensaio previamente descritos para dosagens séricas. Valores médios (ñ DP) destes esteróides no LA de gestaçöes com fetos normais foram testosterona: 76 ñ 34 ng/del; SDHEA: 22 ñ 9 ng/ml; cortisol 19 ñ 8 ng/ml. LAs de gestaçöes que resultaram em anencéfalos apresentaram concentraçöes de SDGEA e cortisol significativamente mais baixas em relaçäo aos normais. Testosterona foi mais baixa em fetos femininos quando comparados aos masculinos normais e discretamente mais elevada que o normal no feto feminino afetado.Näo houve diferença no valor destes esteróides ao compararmos LAs de fetos de risco para a deficiência da 21-hidroxilase com os normais. Assim, a dosagem destes esteróides näo contribui de modo definitivo para o diagnóstcio de defeitos de síntese adrenal ou de anencefalia. Também näo permitem definir com segurança o sexo fetal

Prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Documentamos uma gravidez de alto risco para Hiperplasia Adrenal Congênita através das determinaçöes dos níveis hormonais de 17-hidroxiprogesterona e androstenodiona em amostras de líquido amniótico colhidas na 16ª e 37ª semanas da gestaçäo. As mesmas determinaçöes foram executadas em amostras de sangue materno e do cordäo umbilical. Foi estabelecido o diagnóstico da Hiperplasia Adrenal Congênita em um feto feminino com cariótipo normal 46,XX. Tal diagnóstico foi confirmado no recém-nascido. A experiência acumulada com este procedimento propedêutico permitirá estabelecer bases sólidas para a conveniente assistência genético-clínica aos casais heterozigotos para o gene da HAC, inclusive com a prevençäo da virilizaçäo de fetos femininos afetados

Padronizaçäo das concentraçöes de esteróides no líquido amniótico: I. 17 alpha-hidroxiprogesterona e androstenediona / Standardization of steroid concentrations in the amniotic fluid: I. 17 alpha-hydroxyprogesterone and androstenedione

A funçäo adrenal fetal pode ser avaliada pelo estudo das concentraçöes de 17alfa-OHP e androstenediona no líquido amniótico (LA). Estudamos LAs de 38 gestaçöes, obtidos por amniocentese no 2§ trimestre. Trinta e três destas gestaçöes resultaram em fetos normais, 3 foram anencéfalos e um portador de hiperplasia adrenal congênita por deficiência de 21-OH. Uma segunda gestaçäo de risco para deficiência da 21-OH, ainda em curso, apresentou valores normais de 17alfa-OHP e androstenediona. Os esteróides foram dosados conforme radioimunoensaio previamente descritos para dosagens séricas. Valores médios + ou - DP no LA de gestaçöes com fetos normais foram semelhantes àqueles previamente obtidos no soro: 17alfa-OHP = 218 + ou - 106ng/dl e androstenediona = 75 + ou - 50ng/dl enquanto que, na gestaçäo com feto portador de HAC, os valores foram extremamente elevados: 2.300ng/dl e 1.300ng/dl, respectivamente. Nos fetos anencéfalos, apenas androstenediona foi significativamente mais baixa (45 + ou - 13ng/dl, p < 0,02). Estes achados tornam possível o diagnóstico intra-útero de defeitos de síntese adrenal, especialmente da deficiência da 21-OH, abrindo a possibilidade de tratamento do nascimento