Missense mutations in the perforin (PRF1) gene as a cause of hereditary cancer predisposition

Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies. Herein we report a family in which a wide range of systemic inflammatory and neoplastic manifestations have occurred across three generations. We found that disease was linked to two missense perforin gene mutations (encoding A91V, R410W) that cause protein misfolding and partial loss of activity. These cases link the partial loss of perforin function with some solid tumours that are known to be controlled by the immune system, as well as haematological cancers. Our findings also demonstrate that perforin gene mutations can contribute to hereditary cancer predisposition

Biotoxic effects of the herbicides on growth, seed yield, and grain protein of greengram

We studied the effects of atrazine, isoproturon, metribuzin and sulfosulfuron on plant vigour, nodulation, chlorophyll content, seed yield and protein content in seeds, in greengram inoculated with Bradyrhizobium sp. (vigna). The pre-emergence application of the four herbicides at 400 µg kg-1 of soil adversely affected the measured parameters. The average maximum increase of 10 % in seed yield occurred at 200 µg kg-1 of sulfosulfuron, while atrazine at 200 and 400 µg kg-1 of soil decreased the seed yield by 25 % and 40%, respectively. The average maximum chlorophyll content of 1.2 mg g-1 was obtained at 200 µg kg-1 of sulfosulfuron which declined consistently for all herbicides and increasing dose rates. Sulfosulfuron at 200 µg kg-1 increased the number of nodules found per plant by 7 % at 45 days after seeding the greengram. In contrast, the tested dose rates of atrazine, isoproturon and metribuzin significantly reduced the nodulation (nodule number and dry mass). The average maximum grain protein of 182 mg g-1 was obtained for sulfosulfuron at 400 µg kg-1, while minimum grain protein was obtained at 400 µg kg-1- of isoproturon (124 mg g-1) and atrazine (125 mg g-1) application. Among the herbicides tested, atrazine and metribuzin showed a large degree of phytotoxicity to the crop, inhibiting its vegetative growth and was thus incompatible with greengram. Journal of Applied Sciences and Environmental Management Vol. 10(3) 2006: 141-14

Impact of Study Anxiety Sources on the Grade Achievements of University Students

Anxiety is a common phenomenon among all kind of learners and university students. Study anxiety has been recognized by students of all educational institutes as they face new atmosphere and people in the campus. The objective of this study is to recognize the sources of study anxiety and then determine the impact of these sources on the grade achievements among university students. The results showed that exam anxiety, subject anxiety, language anxiety, library anxiety, social anxiety and presentation anxiety are sources of study anxiety. All of the sources have a great impact on grade achievements except presentation anxiety. The results proved that anxiety put a high impact on the grade achievements of students and those students who had more anxiety get low marks

The Recognition of Cavitary Retinoblastoma Tumors: Implications for Management and Genetic Analysis

PURPOSE: To assess the role of consolidating adjuvant therapy for cavitary retinoblastoma and to understand if there is any phenotype-genotype correlation. METHODS: Patients with retinoblastomas having ophthalmoscopically visible cavities between 2004 and 2014 in whom 4 to 6 cycles of systemic chemotherapy were given. RESULTS: Eighteen eyes of 17 patients displayed cavitary retinoblastomas. This represented 6.8% of 250 patients. Mean age at diagnosis was 13 months; 5 unilateral (29%) and 12 bilateral (71%). The mean (median, range) number of retinoblastoma tumors per eye was 2 (2; 1-6). The number of cavities per tumor was 3 (2, 1-6). Intratumoral cavities were seen in the superficial portion of the tumor in 10 eyes (55%). The cavities became visible in eight eyes (44%) and collapsed in eight eyes (44%). Two eyes required enucleation because of relapse in noncavitary tumors. Germline mutations were detected in 14 patients (82%) of whom four demonstrated mosaicism (29%); only one had a low penetrant mutation. The mean follow-up period was 40 (35, 6-120) months. CONCLUSION: Cavitary retinoblastomas can be detected after systemic chemotherapy with cavities becoming visible after mean two cycles of chemotherapy (secondary cavitary retinoblastoma). The etiology is uncertain. They remain stable and do not require aggressive adjuvant therapy. There was no evident phenotype-genotype correlation with mosaicism noted in 29%

Assessing the efficacy of a brief universal family skills programme on child behaviour and family functioning in Gilgit-Baltistan, Pakistan: Protocol for a feasibility randomised controlled trial of the Strong Families programme

Purpose The global burden of mental health difficulties among children underscores the importance of early prevention. This study aims to assess the efficacy, feasibility and acceptability of the Strong Families programme in enhancing child behaviour and family functioning in low-resource settings in Gilgit-Baltistan, Pakistan. Methods and analysis This is a two-arm, multisite feasibility randomised controlled trial with an embedded process evaluation in three districts of Gilgit-Baltistan, namely Gilgit, Hunza and Skardu. 90 families living in these challenged settings, comprising a female primary caregiver aged 18 or above, and at least one child aged 8-15 years, will participate. Participants will be randomly assigned to either receive the Strong Families programme or to the waitlist group. Strong Families is a 7-hour family skills group intervention programme attended by children and their primary caregivers over 3 weeks. The waitlist group will be offered the intervention after their outcome assessment. Three raters will conduct blind assessments at baseline, 2 and 6 weeks postintervention. The primary outcome measures include the feasibility of Strong Families, as determined by families' recruitment and attendance rates, and programme completeness (mean number of sessions attended, attrition rates). The secondary outcomes include assessment of child behaviour, parenting practices, parental adjustment and child resilience. Purposefully selected participants, including up to five caregivers from each site, researchers and facilitators delivering the intervention, will be interviewed. Descriptive statistics will be used to analyse primary and secondary outcomes. The process evaluation will be conducted in terms of programme context, reach, fidelity, dose delivered and received, implementation, and recruitment. Ethics and dissemination This study has been approved by the UNODC Drug Prevention and Health Branch in the Headquarters office of Vienna and the National Bioethics Committee of Pakistan. Findings will be disseminated through publication in reputable journals, newsletters and presentations at conferences. Trial registration number NCT05933850

Overwhelming postsplenectomy infection due to Mycoplasma pneumoniae in an asplenic cirrhotic patient: Case report

<p>Abstract</p> <p>Background</p> <p><it>Mycoplasma </it><it>pneumoniae </it>infection is usually self-limited, but some fulminant cases are fatal, even when occurring in previously healthy individuals. It can also be the cause of overwhelming postsplenectomy infection (OPSI).</p> <p>Case presentation</p> <p>We report a case of OPSI in a 41-year-old woman with hypersplenism associated with hepatitis B cirrhosis. We detected a significant <it>Mycoplasma pneumoniae </it>agglutination titer, but no evidence of infection with <it>Chlamydia pneumoniae, Legionnella spp</it>., or any other bacterial or fungal pathogens. She eventually died despite aggressive therapy.</p> <p>Conclusions</p> <p><it>M. pneumoniae </it>could be an underestimated cause of OPSI, and should be suspected in fulminant infectious cases in asplenic patients.</p

Population genetics of benzimidazole-resistant Haemonchus contortus and Haemonchus placei from buffalo and cattle: implications for the emergence and spread of resistance mutations

The population genetics of nematode parasites are poorly understood with practical reference to the selection and spread of anthelmintic resistance mutations. Haemonchus species are important to study the nematode population genetics due to their clinical importance in ruminant livestock, and the availability of genomic resources. In the present study, it has been examined that Haemonchus contortus and Haemonchus placei populations from three buffalo and nine cattle hosts. Seventy-three individual adult worms of H. contortus and 148 of H. placei were analysed using a panel of seven microsatellite markers. The number of alleles per locus in H. contortus and H. placei indicated that all populations were polymorphic for the microsatellites used in the present study. Genetic diversity parameters included high levels of allelic richness and heterozygosity, indicating effective population sizes, high mutation rates and high transmission frequencies in the area. Genetic structure parameters revealed low genetic differentiation between and high levels of genetic variation within H. contortus and H. placei populations. Population dynamic analyses showed an absence of heterozygosity excess in both species, suggesting that there was no deviation from genetic drift equilibrium. Our results provide a proof of concept for better understanding of the consequences of specific control strategies, climatic change or management strategies on the population genetics of anthelmintic resistance alleles in Haemonchus spp. infecting co-managed buffalo and cattle