Prevalence of PALB2 Germline Mutations in Early-onset and Familial Breast/Ovarian Cancer Patients from Pakistan / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan. MATERIALS AND METHODS: PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations. RESULTS: A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated. CONCLUSION: Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.

Silymarin-Laden PVP-Nanocontainers Prepared Via the Electrospraying Technique for Improved Aqueous Solubility and Dissolution Rate

Abstract The aim of the present research was to develop a silymarin-laden PVP-nanocontainer providing ameliorated aqueous solubility and dissolution of the drug. Several silymarin-laden formulations were formed with varying quantities of PVP and SDS via the solvent evaporation method using the electrospraying technique. The influence of the hydrophilic carriers on solubility and dissolution was explored. The solid-state characterization was carried out by particle-size analysis, PXRD, DSC, FTIR and SEM. All of the formulations demonstrated better solubility and dissolution than did silymarin plain powder. Both the SDS and PVP had positive effects on solubility and dissolution of silymarin in the aqueous media. An increased solubility was attained as the drug/PVP ratio was 1/4; however, further increase in PVP did not provide significant improvement. In particular, a nanocontainer formulation prepared with silymarin, PVP and SDS (1/4/0.5, w/w/w) exhibited the best solubility (26432.76 ± 1749.00 μg/mL) and an excellent dissolution (~92 % in 20 min) than did silymarin plain powder. Also, it demonstrated similar dissolution profiles compared to a commercial product; therefore, might be bioequivalent to the commercial product (f 1 = 3 and f 2 = 69). Moreover, cumulative undersize distribution values as represented by X10, X50 and X90 were 201 ± 21.01 nm, 488 ± 36.05 nm and 392 ± 48.10 nm, respectively. The drug existed in the amorphous state in the PVP-nanocontainers with no strong chemical bonding with other excipients. Thus, this formulation might be used for more effective administration of silymarin via the oral route.

Fibrodysplasia ossificans progressiva

Fibrodysplasia Ossificans Progressiva [FOP] is a rare autosomal dominant disorder characterized by postnatal progressive heterotopic ossification of connective tissue and congenital malformation of big toes. We report a 3-year male toddler with clinical and radiological features of FOP. He was born with bilateral hallux valgus and at the age of 3 years presented with hard swellings over back, scapular region and forehead that were initially inflammatory and then became bony hard. There is also tilting of neck towards the left due to calcification in neck region. The radiographs showed heterotopic ossification in thoracic region, neck, spine and region of hip joint

Impact of psychosocial rehabilitation on patients with schizophrenia

The current work was conducted to asses the impact of psychosocial rehabilitation program on symptoms and quality of life of patients with schizophrenia. The study was carried out on 24 male patients with an age range of 21-70 years [M=38, SD=11] admitted in a residential rehabilitation centre with the diagnosis of schizophrenia. The study consisted of three phases: assessment, therapeutic, and re-assessment. Patients were assessed in both assessment phases by the following instruments: Positive and Negative Syndrome Scale [PANSS] and WHO Quality of Life Bref scale [WHOQOL BREF. The therapeutic phase consisted of involvement in daily activities and Psychoeducation Teaching Module, especially designed for this study. Two-way repeated-measures ANOVA was conducted to investigate the effect of rehabilitation program on symptoms of schizophrenia and quality of life. The results showed significant main and interactional effects with a significant decrease in symptoms of disorder and increase in quality of life as a result of rehabilitation program. Apart from conventional treatment of psychosis, the findings of this study suggest, psychosocial rehabilitation programs structured according to behavioral paradigms should be initiated in psychiatric units for improving the clinical profile as well as overall functioning of the patients with schizophrenia

Expressed emotions and schizophrenia in Pakistan

To investigate the differences in expressed emotion among families of patients with Schizophrenia and develop an instrument for expressed emotion. A sample of 35 families was selected by using non-probability sampling technique. It was hypothesized that there would be significant difference in expressed emotion among families of patients with schizophrenia and families of normal subjects. A questionnaire based on Likert Scale technique was used to measure expressed emotion of the families. Those members were selected who have spent at least 35 hours with the patient. Independent t-test was performed to see the difference in their expressed emotion on criticism, hostility, positive remarks, warmth and emotional overinvolvement. Descriptive statistics was used to find out the relationship between demographic variables. The research finding showed a significant difference in expressed emotion between parents of schizophrenics and parents of normal subjects. This is the first study on expressed emotions in Pakistani perspective and provides guidelines for future management in schizophrenia