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18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in presurgical assessment in patients with drug-resistant focal epilepsy (DRE) if magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) do not localize the seizure onset zone or are discordant.In this multicenter, retrospective observational cohort study, we included consecutive patients with DRE who had undergone FDG-PET as part of their presurgical workup. We assessed the utility of FDG-PET, which was defined as contributing to the decision-making process to refer for resection or intracranial EEG (iEEG) or to conclude surgery was not feasible.We included 951 patients in this study; 479 had temporal lobe epilepsy (TLE), 219 extratemporal epilepsy (ETLE), and 253 epilepsy of uncertain lobar origin. FDG-PET showed a distinct hypometabolism in 62% and was concordant with ictal EEG in 74% in TLE and in 56% in ETLE (p .001). FDG-PET was useful in presurgical decision-making in 396 patients (47%) and most beneficial in TLE compared to ETLE (58% vs. 44%, p = .001). Overall, FDG-PET contributed to recommending resection in 78 cases (20%) and iEEG in 187 cases (47%); in 131 patients (33%), FDG-PET resulted in a conclusion that resection was not feasible. In TLE, seizure-freedom 1 year after surgery did not differ significantly (p = .48) between patients with negative MRI and EEG-PET concordance (n = 30, 65%) and those with positive MRI and concordant EEG (n = 46, 68%). In ETLE, half of patients with negative MRI and EEG-PET concordance and three quarters with positive MRI and concordant EEG were seizure-free postsurgery (n = 5 vs. n = 6, p = .28).This is the largest reported cohort of patients with DRE who received presurgical FDG-PET, showing that FDG-PET is a useful diagnostic tool. MRI-negative and MRI-positive cases with concordant FDG-PET results (with either EEG or MRI) had a comparable outcome after surgery. These findings confirm the significance of FDG-PET in presurgical epilepsy diagnostics.

Objective: To compare the expression of CD-10 in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Study Design: Comparative cross-sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from Jun 2016 to Jun 2017. Methodology: After taking ethics approval from the ethical review committee AFIP, previously diagnosed, thirty-eight cases of each basal cell carcinoma and squamous cell carcinoma were taken from the histopathology department of Armed Forces Institute of Pathology, Rawalpindi. CD-10 was applied according to standard protocol. The intensity of the CD-10 expression is assessed and categorized into three groups. CD-10 expression less than 10% in the tumour cell was taken as negative (-), 10 to 50% staining was taken as positive (+) and greater than 50% staining in tumour cells was taken as strong positive (++). Results: Out of the total 76 cases included in the study, 9 (24%) were strongly positive (++) whereas 20 (52.6%) were positive (+) and 9 (23.7%) were negative (-) for CD-10 expression. Out of the total 38 cases of SCC 4 (11%) cases showed positive CD-10 expression and 34 (89%) showed negative (-) results. A significant association (p-value

Aim: To observe energy drink induced ovarian cytotoxicity and possible protective effects of co-administration of omega 3 fatty acids. Methods: The experimental study comprised of 36 adult female albino rats was conducted at anatomy department, PGMI, Lahore. Animals were divided into 3 groups. Group A was control. Groups B received energy drink. Group C received omega 3 along with energy drinks once daily orally for 30 consecutive days. Rats were sacrificed under deep anesthesia on 30th day. Ovaries were extracted and sections were stained with H&E stains. Results were analyzed using SPSS. A p-value < 0.05 was considered statistically significant. Results: Animals administered with energy drink showed marked pyknosis of graafian follicular cells and oocyte nuclei when compared with control and energy dink plus omega 3 treated animals. Vacuolization of the follicular cells was also more pronounced in energy drinks treated group (p

ZusammenfassungWährend zwei Drittel der PatientInnen mit Epilepsie durch Medikamente anfallsfrei werden, ist die Erkrankung bei 30 % pharmakoresistent. Bei pharmakoresistenter fokaler Epilepsie bietet die Epilepsiechirurgie eine etwa 65 %ige Chance auf Anfallsfreiheit. Vorab muss der Anfallsfokus exakt eingegrenzt werden, wofür bildgebende Methoden unverzichtbar sind. In den letzten Jahren hat sich in der Prächirurgie der Anteil von PatientInnen mit unauffälliger konventioneller Magnetresonanztomographie (MRT) erhöht. Allerdings konnte die Sensitivität der MRT durch spezielle Aufnahmesequenzen und Techniken der Postprozessierung gesteigert werden. Die Quellenlokalisation des Signals von Elektro- und Magnetenzephalographie (EEG und MEG) verortet den Ursprung iktaler und interiktaler epileptischer Aktivität im Gehirn. Nuklearmedizinische Untersuchungen wie die interiktale Positronen-Emissions-Tomographie (PET) und die iktale Einzelphotonen-Emissionscomputertomographie (SPECT) detektieren chronische oder akute anfallsbezogene Veränderungen des Hirnmetabolismus und können auch bei nichtlokalisierendem MRT auf den epileptogenen Fokus hinweisen. Alle Befunde zusammengenommen werden zur Planung eventueller invasiver EEG-Ableitungen und letztlich der chirurgischen Operation eingesetzt. Konkordante Befunde sind mit besseren chirurgischen Ergebnissen assoziiert und zeigen auch im Langzeitverlauf signifikant höhere Anfallsfreiheitsraten.

Objectives: To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. Methods: A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Results: Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Conclusion: Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role. doi: https://doi.org/10.12669/pjms.39.1.6034 How to cite this: Ilyas M, Noor M, Khan HS, Haroon S, Farhat K, Ali S. Cardio protective effect of nicorandil in reperfusion injury among patients undergoing primary percutaneous coronary intervention. Pak J Med Sci. 2023;39(1):---------. doi: https://doi.org/10.12669/pjms.39.1.6034 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective Overexpression of the drug transporter P‐glycoprotein (P‐gp) is thought to be involved in drug‐resistance in epilepsy by extrusion of antiepileptic drugs (AEDs). We used positron emission tomography (PET) and the P‐gp substrate radiotracer (R)‐[11C]verapamil (VPM) together with the third‐generation P‐gp inhibitor tariquidar (TQD) to evaluate P‐gp function in individuals with drug‐resistant epileptogenic developmental lesions. Methods Twelve healthy controls (7 male, median age 45, range 35‐55 years), and two patients with epileptogenic developmental lesions (2 male, aged 24 and 62 years) underwent VPM‐PET scans before and 60 minutes after a 30‐minute infusion of 2 and 3 mg/kg TQD. The influx rate constant, VPM‐K1, was estimated from the first 10 minutes of dynamic data using a single‐tissue compartment model with a VPM plasma input function. Statistical parametric mapping (SPM) analysis was used to compare individual patients with the healthy controls. Results At baseline, SPM voxel‐based analysis revealed significantly lower uptake of VPM corresponding to the area of the epileptogenic developmental lesion compared to 12 healthy controls (P < .048). This was accentuated following P‐gp inhibition with TQD. After TQD, the uptake of VPM was significantly lower in the area of the epileptogenic developmental lesion compared to controls (P < .002). Significance This study provides further evidence of P‐gp overactivity in patients with drug‐resistant epilepsy, irrespective of the type of lesion. Identifying P‐gp overactivity as an underlying contributor to drug‐resistance in individual patients will enable novel treatment strategies aimed at overcoming or reversing P‐gp overactivity.

Background Patients with ESRD comprise less than 1% of the Medicare population, however they are responsible for 7% of all Medicare spending. Hemodialysis (HD) and peritoneal dialysis (PD) have equivalent clinical outcomes; however, PD is more cost-effective. Undocumented immigrants, when given access to dialysis, are suspected to have lower PD utilization. Objectives Establish baseline PD utilization rates amongst patients stratified by funding status, design an intervention to improve PD utilization, and assess impacts of interventions on utilization rates. Methods The intervention was designed by using interview data to identify patient and provider barriers to selection of PD and stratifying the top failure causes through failure modes and effects analysis (figure 1). PD utilization rates before and after the intervention were determined through a retrospective chart review. The impact of the intervention on patient understanding was assessed with patient surveys. Results The chosen intervention was to revise educational materials to address common misconceptions. Prior to the class update, the utilization rate for PD was 14.3% in the non-traditionally funded group, primarily containing undocumented immigrants, compared to a 21.0% utilization rate in the traditionally funded group. After the updated class was implemented, PD utilization in increased to 26.1% and 22.9% in the non-traditionally and traditionally funded groups, respectively (figure 2–4). Preliminary data from post-class patient surveys suggests that patients with a better understanding of class material are more likely to make an earlier selection of a dialysis modality. Conclusions Addressing patient misconceptions about peritoneal dialysis by updating educational materials is an intervention that can increase the utilization rates of PD in patients with non-traditional funding. External factors could have played a role in increased PD utilization and additional data is needed to establish a more robust correlation.

While two thirds of patients with epilepsy become seizure-free with antiseizure medications, 30% remain drug-resistant. In drug-resistant focal epilepsy, epilepsy surgery offers an approximately 65% chance of becoming seizure-free; however, for a successful outcome of surgery a seizure focus must be precisely located, for which imaging techniques are essential. In recent years, the proportion of patients with apparently inconspicuous findings in magnetic resonance imaging (MRI) in the presurgical evaluation has increased. The sensitivity of MRI can be increased using special MRI sequences and MRI postprocessing techniques. Ictal and interictal source localization based on electroencephalography (EEG) and magnetencephalography (MEG) aim at determining the onset of interictal discharges and seizures. Nuclear medicine imaging techniques such as interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) can detect chronic or acute seizure-related changes in brain metabolism and can indicate an epileptogenic focus even if MRI is inconspicuous. The results of these techniques are used to plan invasive EEG recordings and subsequently surgery. Concordant findings are associated with better surgical outcomes and show significantly higher rates of seizure freedom in the long-term seizure outcome.Während zwei Drittel der PatientInnen mit Epilepsie durch Medikamente anfallsfrei werden, ist die Erkrankung bei 30 % pharmakoresistent. Bei pharmakoresistenter fokaler Epilepsie bietet die Epilepsiechirurgie eine etwa 65 %ige Chance auf Anfallsfreiheit. Vorab muss der Anfallsfokus exakt eingegrenzt werden, wofür bildgebende Methoden unverzichtbar sind. In den letzten Jahren hat sich in der Prächirurgie der Anteil von PatientInnen mit unauffälliger konventioneller Magnetresonanztomographie (MRT) erhöht. Allerdings konnte die Sensitivität der MRT durch spezielle Aufnahmesequenzen und Techniken der Postprozessierung gesteigert werden. Die Quellenlokalisation des Signals von Elektro- und Magnetenzephalographie (EEG und MEG) verortet den Ursprung iktaler und interiktaler epileptischer Aktivität im Gehirn. Nuklearmedizinische Untersuchungen wie die interiktale Positronen-Emissions-Tomographie (PET) und die iktale Einzelphotonen-Emissionscomputertomographie (SPECT) detektieren chronische oder akute anfallsbezogene Veränderungen des Hirnmetabolismus und können auch bei nichtlokalisierendem MRT auf den epileptogenen Fokus hinweisen. Alle Befunde zusammengenommen werden zur Planung eventueller invasiver EEG-Ableitungen und letztlich der chirurgischen Operation eingesetzt. Konkordante Befunde sind mit besseren chirurgischen Ergebnissen assoziiert und zeigen auch im Langzeitverlauf signifikant höhere Anfallsfreiheitsraten.

Background: The use of mosquito coils has increased exponentially, especially in the under developed countries. Many researches have been conducted over the past few years to advocate both the possible risks and potential benefits. These coils and the inhalation of their smoke have been proved to cause upper and lower airway tract infections. But still the possible side effects of inhalation of these coil smoke on other organ systems of the body were unclear. Methods: Adult male Wistar rats were divided into two groups each containing eight rats. Group A was control group while group B was allowed to inhale mosquito coil smoke for four week. The experimental group was exposed to MCS for 8 hours / day. Histopathological analysis of testis was carried out. Results: Histopathological studies of rats exposed to MCS revealed changes in parenchyma of testis. Decrease in the height of germinal epithelium and diameter of seminiferous tubules and increase in and vascular congestion was observed. Conclusion: The results of present study suggest that allethrin based mosquito coil smoke has harmful effects on testis

Objective: To evaluate the effects of the mosquito coil smoke (MCS) inhalation on histology of proximal (PCT) and distal (DCT) convoluted tubules of kidney in Wistar Albino rats. Methods: This study was approved by the Ethical Committee of PGMI, Lahore. 24 Wistar rats were selected and randomly divided into 3 groups, each containing eight animals. Group A was control; Group B and C were experimental groups and were exposed to mosquito coil smoke inhalation for 8 hours/day for two and four weeks respectively. Kidney tissue of albino rats was dissected, examined and analyzed histologically. Results: The results of MCS inhalation in histological sections of group B and C showed marked cellular necrosis and vacuolization in PCT (proximal convoluted tubule) of the kidney as compared to the group A. protein cast was absent in PCT of all groups. DCT (distal convoluted tubules) in group B and C showed marked necrosis, vacuolization and protein cast. Necrosis was more marked in group C treated with mosquito coil smoke for 4 weeks. Conclusion: The results indicate that pyrethroids in mosquito coil smoke though considered least toxic pesticides, are very harmful. Exposure of pyrethroids can induce adverse changes in tubules of kidney. Key Words: MCS Mosquito Coil Smoke, Pyrethroids, PCT Proximal convoluted tubules, DCT Distal convoluted tubules. How to Cite: Siddique N, Ahmed M, Ilyas M, Jabeen R, Jawad A.H, Iqbal Z. histological changes in proximal and distal convoluted tubules of kidney of albino rats after exposure to mosquito coil smoke inhalation. Esculapio.2020;16(04):87-91.

Background: Energy drinks (EDs) are commonly used to prevent fatigue, enhance physical, and cognitive performance. Its administration induces toxic effects in body. Omega-3 is an antioxidant and anti-inflammatory agent that helps in proper functioning of immune system. Objectives of this study were to evaluate the morphological effects of fish oil omega 3 fatty acids (Eicosapentaenoic acid / Docosahexaenoic acid) on energy drink induced ovarian cytotoxicity in adult female albino rats. Methods: The study was conducted at animal house, Anatomy department, Postgraduate Medical Institute, Lahore from January to march 2019. ARRIVE guidelines were followed for conduct of animal study. Ethical approval was obtained from PGMI, Lahore and Advanced Studies and Research Board of University of Health Sciences, Lahore. The study comprised 36 adult female albino rats divided into 3 groups i.e., control, energy drink and omega 3 treated. Rats were sacrificed, ovaries extracted, and sections were stained with H&E and PAS. SPSS version 21.0 were used. Results: Statistically significant difference was present in gross parameters between the control and experimental groups. Energy drink administration caused a decrease in diameter of mature graafian follicle and diameter of the oocyte. Disruption in basement membrane was more pronounced in Energy drink treated group. Conclusion: Energy drinks were found to cause cytotoxic effects on ovarian and oocyte morphology, ultimately leading to infertility. Omega 3 reduces the extent of damage caused by the intake of energy drinks.

To determine long-term seizure outcome, use of antiseizure medication (ASM) and seizure recurrence risk after its withdrawal in patients with autoimmune encephalitis (AE) due to neuronal surface and GAD antibodies.In patients from a specialized AE outpatient clinic, we assessed seizure manifestation, ASM and immunotherapy at onset of AE as well as seizure occurrence, development of autoimmune-associated epilepsy (AAE) and use of ASM in the long-term. Data were collected from patients via telephone interviews and medical records.Out of 94 AE patients, 75 were analyzed; 47 patients had NMDAR, 17 LGI1, 7 GAD, 3 CASPR2 and 1 mGluR5 antibodies. Fifty-three of the 75 patients (71 %) experienced seizures, all of which for the first time occurred at AE onset. After a median follow-up of 6 years (range, 1-15), 47 of the 53 AE patients had 1-year terminal seizure remission, median duration of terminal seizure freedom was 5 years. Rate of 1-year terminal seizure remission was significantly higher in patients with neuronal surface antibodies (NMDAR 97 %, LGI1 93 %, CASPR2 100 %) compared to patients with GAD antibodies (20 %, p < 0.001). In seizure-free patients, ASM was withdrawn after 13 months (median) without any relapse seizures.Seizures are common in most forms of AE manifesting at disease onset in all cases. However, the development of AAE is rare and typically occurs in patients with GAD antibodies. Thus, in most AE cases with neuronal surface antibodies, ASM can be withdrawn after the acute phase of AE with low risk of seizure relapse.

OBJECTIVES: To observe the possible curative effects of whole-ground flax seeds meal versus flax oil for pesticide residue-induced nephrotoxicity. METHODS: In this experimental study, 24 male Wistar rats were divided into four equal groups: control group (A) and experimental groups (B, C & D), as approved by ethical committee, Postgraduate Medical Institute, Lahore, Pakistan. Subchronic dose of triazophos-8.2 mg/kg body weight (1/10th of LD50) was given to the group B, C & D via oral gavage, as 1:100 dilution solution for 21 consecutive days. In addition, group C was given flax seeds oil (1.86 g/kg/day) while group D was given whole ground flax seeds meal (800 mg/kg/day). Biochemical analysis of serum creatinine on day 1, 7, 14 and 21 was done. Hematoxylin and Eosin and Periodic Acid Schiff staining was used for histological examination. The mean diameter of renal corpuscle (RCD), proximal convoluted tubule (PCT) and distal convoluted tubule (DCT) in all groups were calculated by micrometry. RESULTS: Micrometric measurement in group A were as follows: RCD-89.43±3.43µm, PCT diameter-38.90±2.72µm, DCT diameter-34.48±2.58µm). Group B, C & D slides showed RCD-70.12±2.76µm, 80.67±3.34µm, 87.49±4.66µm), PCT diameters (50.35±2.61µm, 43.70±2.35µm, 38.45±2.57µm) and DCT diameters (48.03±3.42µm, 38.65±2.55µm, 35.33±3.02µm) respectively. Biochemical analysis showed raised serum creatinine in group B (2.183±0.367mg/dL), near normal levels in group C (0.698±0.013mg/dL) & comparable with control group, in group D (0.718±0.051mg/dL). CONCLUSION: Renal tissue when exposed to pesticides, showed disturbed biochemical and histological architecture. Whole-ground flax seeds ameliorate the histopathological and biochemical renal damage better than flax seeds oil against pesticides-residues exposure.

Several members of the Protoparvovirus genus, capable of infecting humans, have been recently discovered, including cutavirus (CuV) and tusavirus (TuV). To begin the characterization of these viruses, we have used cryo-electron microscopy and image reconstruction to determine their capsid structures to ~2.9 &Aring, resolution, and glycan array and cell-based assays to identify glycans utilized for cellular entry. Structural comparisons show that the CuV and TuV capsids share common features with other parvoviruses, including an eight-stranded anti-parallel &beta, barrel, depressions at the icosahedral 2-fold and surrounding the 5-fold axes, and a channel at the 5-fold axes. However, the viruses exhibit significant topological differences in their viral protein surface loops. These result in three separated 3-fold protrusions, similar to the bufaviruses also infecting humans, suggesting a host-driven structure evolution. The surface loops contain residues involved in receptor binding, cellular trafficking, and antigenic reactivity in other parvoviruses. In addition, terminal sialic acid was identified as the glycan potentially utilized by both CuV and TuV for cellular entry, with TuV showing additional recognition of poly-sialic acid and sialylated Lewis X (sLeXLeXLeX) motifs reported to be upregulated in neurotropic and cancer cells, respectively. These structures provide a platform for annotating the cellular interactions of these human pathogens.

Nuklearmedizinische Untersuchungen wie PET und SPECT werden v. a. bei nichtlasionellen Epilepsien in der prachirurgischen Epilepsiediagnostik eingesetzt. Auch bei unauffalliger MRT ist ein Hypometabolismus in der FDG-PET indikativ fur den epileptogenen Fokus, zudem kann sie bei Patienten mit limbischer Enzephalitis einen meist temporalen Hypermetabolismus darstellen. Iktales SPECT hat eine besonders hohe lokalisatorische Wertigkeit, wenn die Anfalle komplex-fokal sind und langer als 15 s dauern. Allerdings ist der Aufwand fur diese Diagnostik mit mehreren Tagen Video-EEG-Monitoring hoch. Sie wird daher bei nichtlasionellen oder diskordanten Fallen angewendet. Die iktale SPECT sollte mittels „post-processing“ vom interiktalen SPECT subtrahiert und auf das MRT koregistriert werden (z. B. SISCOM).

Overexpression of the drug transporter P-glycoprotein (P-gp) is thought to be involved in drug-resistance in epilepsy by extrusion of antiepileptic drugs (AEDs). We used positron emission tomography (PET) and the P-gp substrate radiotracer (R)-[Twelve healthy controls (7 male, median age 45, range 35-55 years), and two patients with epileptogenic developmental lesions (2 male, aged 24 and 62 years) underwent VPM-PET scans before and 60 minutes after a 30-minute infusion of 2 and 3 mg/kg TQD. The influx rate constant, VPM-KAt baseline, SPM voxel-based analysis revealed significantly lower uptake of VPM corresponding to the area of the epileptogenic developmental lesion compared to 12 healthy controls (P .048). This was accentuated following P-gp inhibition with TQD. After TQD, the uptake of VPM was significantly lower in the area of the epileptogenic developmental lesion compared to controls (P .002).This study provides further evidence of P-gp overactivity in patients with drug-resistant epilepsy, irrespective of the type of lesion. Identifying P-gp overactivity as an underlying contributor to drug-resistance in individual patients will enable novel treatment strategies aimed at overcoming or reversing P-gp overactivity.

Background: Tobacco is obtained from a plant of genus nicotiana and Solanaceae family, it contains alkaloid nicotine. It is consumed in smoking and smokeless forms amongst these water-pipe smoking(wps) is found to be second highest in gaining popularity mainly because it seems appealing to youth and is trending. The objective of this study is to assess knowledge, attitude and practices of water-pipe smoking among health professionals and its harmful oral effects.Methods: A cross-sectional study was conducted among health professionals in Baqai Medical University Karachi for the duration of six months from April 2018 to October 2018. Simple random technique was used and the inclusion criteria was students from first year to final year BDS, house officers and faculty members from Baqai dental college. 350 participants were included in this study and were informed about the questionnaire. Ethical approval was taken from the research department of Baqai medical university. The obtained data was analyzed using SPSS version 21.0.Results: Total 294 from 350 participants submitted the questionnaire after a review. In our analysis, 203 individuals were aware of the term water pipe smoking whereas 91 were unaware regarding WPS. In 226 participants, They have never consumed shisha; sixty-eight (68) health professionals were currently using it in which (16.0%)Of them were male and (7.1%) of them were female. About 4.1 % of the participants mentioned that they Started shisha Smoking at the age of 18 years. Majority (21.4%) of the members reported that they consumed WPS for just trend, and 10.9% because of stress.Conclusions: water-pipe smoking is common and teenagers use it more frequently as a trend, very less participants were aware about the health hazards and effects of water pipe smoking on oral cavity therefore health professionals should know and awareness should be spread to condemn the use of wps. Keywords: water pipe smoking, health professionals, oral health hazards

Ribonucleic acid (RNA) silencing, RNA interference (RNAi) or post-transcriptional gene silencing takes place in a variety of eukaryotes and it was discovered firstly in the plants. The RNA silencing process is activated by a trigger from dsRNA predecessor. A very important step in the silencing pathways the conversion of dsRNA into small duplexes of RNA of the representative length and arrangement. Then these small dsRNA monitor RNA silencing by different mechanisms. Post transcriptional gene silencing mechanisms were initially identified as an anti-viral process that give protection to the organisms from the viruses or which inhibit the unsystematic incorporation of transposable components. The basic aim of this review article is to study the mechanism of gene silencing by dsRNA and the roles of certain proteins in cellular post transcriptional RNA silencing machinery and finally we also discuss the RNA silencing as an anti-viral defense mechanism in the plants.

Bufavirus strain 1 (BuV1), a member of the Protoparvovirus genus of the Parvoviridae, was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by cryo-electron microscopy and image reconstruction to 2.84, 3.79, and 3.25 angstrom, respectively. The BuVs, 65-73% identical in amino acid sequence, conserve the major viral protein, VP2, structure and general capsid surface features of parvoviruses. These include a core -barrel (B-I), -helix A, and large surface loops inserted between these elements in VP2. The capsid contains depressions at the icosahedral 2-fold and around the 5-fold axes, and has three separated protrusions surrounding the 3-fold axes. Structure comparison among the BuVs and to available parvovirus structures revealed capsid surface variations and capsid 3-fold protrusions that depart from the single pinwheel arrangement of the animal protoparvoviruses. These structures provide a platform to begin the molecular characterization of these potentially pathogenic viruses.

We report here the genome sequences of three newly isolated phages that infect Mycobacterium smegmatis mc 2 155. Phages Findley, Hurricane, and TBond007 were discovered in geographically distinct locations and are related to cluster K mycobacteriophages, with Findley being similar to subcluster K2 phages and Hurricane and TBond007 being similar to subcluster K3 phages.

Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to a resolution of 2.8 to 3.0 Å by cryo-electron microscopy and three-dimensional image reconstruction. The bocaparvovirus capsids, which display different tissue tropisms, have features in common with other parvoviruses, such as depressions at the icosahedral 2-fold symmetry axis and surrounding the 5-fold symmetry axis, protrusions surrounding the 3-fold symmetry axis, and a channel at the 5-fold symmetry axis. However, unlike other parvoviruses, densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of a genus-specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring capsid surface topologies different from those of other parvoviruses. Structural comparisons at the strain (HBoV) and genus (bovine parvovirus and HBoV) levels identified differences in surface loops that are functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses and likely play similar roles in these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of antiviral strategies to control human bocavirus infections. IMPORTANCE Human bocaviruses are one of only a few members of the Parvoviridae family pathogenic to humans, especially young children and immunocompromised adults. There are currently no treatments or vaccines for these viruses or the related enteric bocaviruses. This study obtained the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, and HBoV3 and HBoV4 infect the gastrointestinal tract, tissues that are likely targeted by the capsid. Comparison of these viruses provides information on conserved bocaparvovirus-specific features and variable regions resulting in unique surface topologies that can serve as guides to characterize HBoV determinants of tissue tropism and antigenicity in future experiments. Based on the comparison to other existing parvovirus capsid structures, this study suggests capsid regions that likely control successful infection, including determinants of receptor attachment, host cell trafficking, and antigenic reactivity. Overall, these observations could impact efforts to design antiviral strategies and vaccines for HBoVs.

Human bocaviruses (HBoV1 to -4) are emerging pathogens associated with pneumonia and/or diarrhea in young children. Currently, there is no treatment or vaccination, so there is a need to study these pathogens to understand their disease mechanisms on a molecular and structural level for the development of control strategies. Here, we report the structures of six HBoV monoclonal antibody (MAb) fragment complexes, HBoV1-15C6, HBoV2-15C6, HBoV4-15C6, HBoV1-4C2, HBoV1-9G12, and HBoV1-12C1, determined by cryo-electron microscopy and three-dimensional image reconstruction to 18.0- to 8.5-Å resolution. Of these, the 15C6 MAb cross-reacted with HBoV1, HBoV2, and HBoV4, while the 4C2, 12C1, and 9G12 MAbs recognized only HBoV1. Pseudoatomic modeling mapped the 15C6 footprint to the capsid surface DE and HI loops, at the 5-fold axis and the depression surrounding it, respectively, which are conserved motifs in Parvoviridae . The footprints for 4C2, 12C1, and 9G12 span the surface loops that assemble portions of the 2-/5-fold wall (a raised surface feature between the 2-fold and 5-fold axes of symmetry) and the shoulder of the 3-fold protrusions. The MAb footprints, cross reactive and strain specific, coincide with regions with high and low sequence/structural identities, respectively, on the capsid surfaces of the HBoVs and identify potential regions for the development of peptide vaccines for these viruses. IMPORTANCE Human bocaviruses (HBoVs) may cause severe respiratory and gastrointestinal infections in young children. The nonenveloped parvovirus capsid carries determinants of host and tissue tropism, pathogenicity, genome packaging, assembly, and antigenicity important for virus infection. This information is currently unavailable for the HBoVs and other bocaparvoviruses. This study identifies three strain-specific antigenic epitopes on the HBoV1 capsid and a cross-reactive epitope on the HBoV1, HBoV2, and HBoV4 capsids using structures of capsid-antibody complexes determined using cryo-electron microscopy and image reconstruction. This is the first study to report the highly conserved parvovirus DE loop at the 5-fold axis as a determinant of antigenicity. Additionally, knowledge of the strain-specific and conserved antigenic epitopes of the bocaviruses can be instrumental in characterization of the virus life cycle, development of peptide vaccines, and generation of gene delivery vectors for cystic fibrosis given the strict tropism of HBoV1 for human airway epithelial cells.