Prevalence of hepatitis G virus in Pakistani children with transfusion dependent beta- thalassemia major

We ought to obtain data on the prevalence of the newly discovered tranfusion transmittable hepatitis G virus in polytransfused b- thalassemia major children. Each individual had received multiple blood transfusions, from 12 to 36 per year. No documentation of prior hepatic infection was available. Serum samples were collected prospectively from the randomly selected subjects and were analyzed for HGV RNA by polymerase chain reaction using primer specific for two different regions of the HGV genome. Among the 100 individuals examined 21 were positive for HGV RNA. Four patients had evidence of dual infection, both HGV RNA and HCV RNA were isolated from their sera. While in one sample presence of both HGV RNA and HBV DNA was established. Only one child was positive for hepatitis E antibodies. The sera of 10 children were reactive for hepatitis B surface antigen whereas 35 individuals were positive for hepatitis C virus antibody. The ALT levels were variable in HGV infected children. Four out of 16 (25%) showed peak ALT levels of 218 IU/I, 8/16 (50%) children demonstrated slightly elevated ALT levels whereas 25% individuals showed normal ALT levels. Alkaline Phosphatase levels were elevated in 90% of the children and 20% patients of this series also had higher GGT levels. The observed AP levels were not statistically different among HGV, HGV/HCV or HGV/HBV groups. Even though the ALT levels were deranged in the children with HGV alone but none of the children had demonstrated symptoms of liver disease, their direct and total bilirubin levels were normal and no complain of jaundice was recorded. In conclusion, our findings suggested that like other blood borne hepatic viruses, HGV is also prevalent in the high risk group of multiple transfused patients in Pakistan but our results support the absence of any causal relationship between HGV and hepatitis.     

Comparing the efficacy of team based learning strategies in a problem based learning curriculum

We introduced two variants of team based learning (TBL) strategies in pathology course to seek their efficacy in a problem based learning (PBL) curriculum. The TBL strategy was adopted in two different sessions. One during regular resource session (RS‐TBL) and other during a weekly review session (RVS‐TBL) of the PBL curriculum. The study involved 104 second year students during their 8 weeks of cardiovascular‐respiratory units and 3 weeks of hematology units. RS‐TBL was adopted for cardiovascular‐respiratory unit and RVS‐TBL for hematology unit. The first 8 weeks of the course were implemented as RS‐TBL and the last 3 weeks as RVS‐TBL. The results showed that the group performance was markedly improved than individual performance in both RS‐TBL and RVS‐TBL (p < 0.001). Comparison between the RS‐TBL and RVS‐TBL revealed that individual student and group performance was better in the RVS‐BL (p < 0.001). The result of the student attitudinal survey indicated an 88% agreement that TBL enhanced their understanding of pathology concepts and critical analysis. Most of the participants (85%) found RVS‐TBL to be more useful. Post‐TBL, end of semester examination results proved beneficial for the students in risk. The study demonstrated that RVS‐TBL may be preferably adopted to enhance the philosophy of TBL in a PBL curriculum.     

Protein crystallization facilitated by molecularly imprinted polymers

We present a previously undescribed initiative and its application, namely the design of molecularly imprinted polymers (MIPs) for producing protein crystals that are essential for determining high-resolution 3D structures of proteins. MIPs, also referred to as "smart materials," are made to contain cavities capable of rebinding protein; thus the fingerprint of the protein created on the polymer allows it to serve as an ideal template for crystal formation. We have shown that six different MIPs induced crystallization of nine proteins, yielding crystals in conditions that do not give crystals otherwise. The incorporation of MIPs in screening experiments gave rise to crystalline hits in 8-10% of the trials for three target proteins. These hits would have been missed using other known nucleants. MIPs also facilitated the formation of large single crystals at metastable conditions for seven proteins. Moreover, the presence of MIPs has led to faster formation of crystals in all cases where crystals would appear eventually and to major improvement in diffraction in some cases. The MIPs were effective for their cognate proteins and also for other proteins, with size compatibility being a likely criterion for efficacy. Atomic force microscopy (AFM) measurements demonstrated specific affinity between the MIP cavities and a protein-functionalized AFM tip, corroborating our hypothesis that due to the recognition of proteins by the cavities, MIPs can act as nucleation-inducing substrates (nucleants) by harnessing the proteins themselves as templates.     

Treatment of ovarian cancer cells with nutlin-3 and resveratrol combination leads to apoptosis via caspase activation

The current study was focused on the induction of apoptotic effects of resveratrol along with the combination treatments of nutlin-3 and transforming growth factor-β (TGF-β) against the human ovarian cancer cell line A2780/CP70. To determine the extent of apoptosis following the above-mentioned treatments, we assessed the execution of apoptotic events that proceed via caspase activation and cytochrome c release. We estimated the caspase-3 and -9 activities using a direct enzymatic assay that measures the cleavage of synthetic peptide substrate (N-acetyl-Asp-Glu-Val-Asp-p-nitroanilide). Our experiments showed an increase in caspase-3 and -9 activities in the cells that were treated with the combination of resveratrol (5?μM) with nutlin-3 (5?μM) or TGF-β (1?μg/mL). Since activation of procaspase-3 by caspase-9 requires the release of cytochrome c into the cytoplasm, we measured the levels of cytochrome c in the cytoplasm by western blot experiments. The data indicated a considerable increase in caspase-3 and cytochrome c levels when cells were treated with drugs for 24 hours. Experiments with 4,6'-diamino-2-phenylindole dihydrochloride (DAPI) staining also confirmed the induction of apoptosis in all the above-mentioned treatments done at 24 and 48 hours. These results support our hypothesis that resveratrol combination can induce programmed cell death at doses that are less than half of what is typically needed for nutlin-3 and TGF-β to induce apoptosis.     

Patterns of recognition of Arabic consonants by non-native children with cochlear implants and normal hearing

Objective: This study examined the patterns of recognition of Arabic consonants, via information transmission analysis for phonological features, in a group of Malay children with normal hearing (NH) and cochlear implants (CI).

Method: A total of 336 and 616 acoustic tokens were collected from six CI and 11 NH Malay children, respectively. The groups were matched for hearing age and duration of exposure to Arabic sounds. All the 28 Arabic consonants in the form of consonant–vowel /a/ were presented randomly twice via a loudspeaker at approximately 65?dB SPL. The participants were asked to repeat verbally the stimulus heard in each presentation.

Results: Within the native Malay perceptual space, the two groups responded differently to the Arabic consonants. The dispersed uncategorized assimilation in the CI group was distinct in the confusion matrix (CM), as compared to the NH children. Consonants /?/, /t?/, /s?/ and /?/ were difficult for the CI children, while the most accurate item was /k/ (84%). The CI group transmitted significantly reduced information, especially for place feature transmission, then the NH group (p?Conclusion: CI and NH Malay children may be using different acoustic cues to recognize Arabic sounds, which contribute to the different assimilation categories’ patterns within the Malay perceptual space.     

Immune Checkpoint Inhibitors in Older Adults

Cancer is primarily a disease of older adults. The treatment of advanced stage tumors usually involves the use of systemic agents that may be associated with significant risk of toxicity, especially in older patients. Immune checkpoint inhibitors are newcomers to the oncology world with improved efficacy and better safety profiles when compared to traditional cytotoxic drugs. This makes them an attractive treatment option. While there are no elderly specific trials, this review attempts to look at the current available data from a geriatric oncology perspective. We reviewed data from phase III studies that led to newly approved indications of checkpoint inhibitors in non-small cell lung cancer, melanoma, and renal cell cancer. Data were reviewed with respect to response, survival, and toxicity according to three groups: <65 years, 65–75 years, and >75 years. Current literature does not allow one to draw definitive conclusions regarding the role of immune checkpoint inhibitors in older adults. However, they may offer a potentially less toxic but equally efficacious treatment option for the senior adult oncology patient.