Silver - Russell syndrome is a clinically and genetically heterogenous condition characterized by severe intrauterine and postnatal growth retardation, craniofacial disproportion and normal intelligence downward curvature of the corner of the mouth, syndactyly and webbed fingers. Diagnosis of Silver - Russell syndrome remains clinical; no definite etiology or specific tests have been established. In the recent years, it has been shown that more than 38% of patients have hypomethylation in the imprinting control region 1 of 11p15 and one-tenth of patients carry a maternal uniparental disomy of chromosome seven. The pathophysiological mechanisms resulting in the Silver - Russell phenotype remain unknown despite the recent progress in deciphering the molecular defects associated with this condition. This case report describes the clinical features of Silver - Russell syndrome in a father and daughter.
Postnatal growth retardation; Silver - Russell syndrome; short stature
Post Graduate Institute (PGI) Chandigarh is a premier institute of North India. There are approximately 70,000 admissions per year. The adult clinical hematology department sees more than 2000 new patients per year. A preliminary analysis of 299 chronic myeloid leukemia patients registered from January 2001 until December 2007 was done. Out of these, 256 (86%) patients were in chronic phase (CP). The median age at presentation was 40 years. At 6 months of follow-up 95% of patients who were started on Imatinib mesylate based therapy remained in CP. Partial cytogenetic remission was seen in 69% of patients while complete cytogenetic response was seen in only 20% of patients at 6 months on Imatinib mesylate.
Chronic myeloid leukemia; chronic phase; Post Graduate Institute
Primary extra nodal lymphomas (EN-NHL) are different from primary nodal non-Hodgkin’s lymphoma (N-NHL) and are comparatively less common. Hemogram findings and bone marrow involvement is less studied and very few reports are available in the literature. The present study is a retrospective analysis of bone marrow samples evaluated for staging of non-Hodgkin’s lymphoma. The age, sex distribution, clinical features, and site of presentation, hemogram findings, pattern of bone marrow involvement and grade of reticulin fibrosis was noted. These findings were compared with the type of non-Hodgkin’s lymphoma and prognostic information was determined. A total of 647 cases of NHL, which underwent bone marrow examination for staging, over a seven year period, were retrieved and analyzed for all hematological parameters. Prevalence of EN-NHL was 23.5% (152/647), while nodal NHL comprised 76.5% (495/647) of all NHL cases. 90.1% (137/152) cases of EN-NHL were adult patients, out of which 15.3% (21/137) cases showed bone marrow infiltration as compared to 89% (441/495) adult primary nodal NHL cases, of which 39% (175/441) showed bone marrow infiltration. 9.9% (15/152) cases of EN-NHL were pediatric patients, out of which 40% (6/15) showed bone marrow infiltration, while 10.9% (54/495) of nodal NHL cases were pediatric, of which 20.3% (11/54) showed bone marrow infiltration. Hemogram findings were not found useful in predicting bone marrow infiltration in both nodal as well as EN-NHL. 100% (6/6) of pediatric patients had high grade lymphoma as compared to 48% (9/21) of adult patients, showing bone marrow infiltration in EN-NHL group. Reticulin fibrosis also did not reveal relation with grading of NHL. Prognostically EN-NHL of stomach and central nervous system were found to be better than EN-NHL of other sites, as none of these cases showed bone marrow infiltration. EN-NHL can involve various sites and the prognosis depends upon the sites of disease as well as the type of NHL. Moreover, pediatric EN-NHL cases are likely to have poorer prognosis, due to increased risk of bone marrow involvement as compared to their counterparts having primary nodal NHL. Bone marrow infiltration at times cannot be assessed reliably from hemogram findings only and a bone marrow biopsy for staging is mandatory.
Bone marrow; Extranodal non-Hodgkin’s lymphoma; Hemogram; Reticulin
Background & objectives:
Chronic myelogenous leukaemia (CML) is the commonest leukaemia in Asia. There is a paucity data on cytogenetic and molecular analyses of Indian CML patients. This apparently reflects the low availability of cytogenetic and molecular techniques in our country. This study aimed to document various types of BCR-ABL fusion transcripts in different phases of CML and to compare the Ph chromosome positivity/negativity vis-a-vis BCR-ABL fusion transcripts in adult CML patients.
Between June 2004 and February 2009, 208 patients were diagnosed as CML in chronic phase (CP), accelerated phase (AP) and blast crisis (BC), according to standard criteria. Cytogenetic and molecular genetic analyses were performed in all patients. Various types of BCR-ABL hybrid transcripts were compared with phases of CML and cytogenetic abnormalities.
Among 208 CML patients, b3a2 BCR-ABL transcripts were most commonly detected (66.82%) followed by b2a2 (28.84%), b3a2 + b2a2 (3.36%), b3a2 + e19a2 (0.48%) and b2a2 + e19a2 (0.48%). b3a2 transcripts were more frequently detected than b2a2 transcripts, in the whole group of 208 as well as in 183 CML-CP patients (P<0.0001). Ph chromosome was positive in 135 of 139 patients with b3a2 transcripts and 56 of 60 patients with b2a2 transcripts, difference not being significant. Additional cytogenetic abnormalities detected in 3.8 per cent patients in CML-CP and 44 per cent patients in CML-AP/BC, did not show predilection for any BCR-ABL transcript type.
Interpretation & conclusions:
This study documents higher Ph positivity (96.15%) by cytogenetic analysis among CML patients, as confirmed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in a large patient group from north India. Both the techniques contribute towards understanding the disease biology, and have important implications for diagnosis and management of CML patients.
BCR-ABL fusion transcripts; chronic myelogenous leukaemia; cytogenetic analysis; polymerase chain reaction; reverse transcriptase
The MPAL comprise 2–5% of all acute leukemia. The present WHO 2008 classification has separated two groups in MPAL based on t(9;22) positivity and MLL rearrangement.
Aims & Objectives:
The aim of the present pilot study is to note the frequency of BCR-ABL transcript in MPAL cases using the RT-PCR assay and to correlate the status with hematological remission post induction.
Materials & Methods:
A total of 10 MPAL cases classified on Flow-cytometry based on the current WHO 2008 criteria were enrolled. In all the cases Bone marrow or peripheral blood sample in EDTA was processed for molecular studies and the RT-PCR reaction carried out using primers specific to the t (9;22) and t(4;11) translocation. The post induction check marrow slides were also reviewed.
Out of the total 10 MPAL cases, 7/10 (70%) were adult and 3/10 (30%) pediatric cases. A total of 4/10 (40%) cases showed positivity for the t(9;22) transcript and none for t (4;11). Of the 4 positive cases, 3/10(30%) were adult cases and 1/10(10%) pediatric case. The BCR-ABL transcript type in adult cases was b3a2 (p210) in 2/3 (66%) and e1a2 (p190) in 1/3 (33.3%) case. The single pediatric case was positive for b3a2 transcript.
Discussion & Conclusion:
All the 4 positive MPAL cases presented with high TLC and low platelet count (p<0.05). The positive cases also showed hematological remission at post induction check marrow (blasts<5%). This could partly be explained due to good response to the imatinib added to the treatment protocol.
The incidence of common fusion transcripts in AML is 40–45%, but data from Indian sub-continent is limited.
Aims & Objectives
The aim of the present study is to note the incidence of common fusion transcripts of AML1-ETO, PML-RARA and CBFβ-MYH11 in adult and pediatric AML cases.
Materials & Methods
A total of 116 AML cases diagnosed on bone marrow, cytochemistry and Flow-cytometry over a period of 2 year were enrolled and bone marrow samples in EDTA were processed by multiplex RT-PCR assay.
Of 116 cases, 96 (83%) were adult and 20 (17%) pediatric cases. A total of 39/116 (33.6%) cases showed positivity for fusion transcripts of which 28/96 (29.16%) were adult and 11/20 (55%) pediatric cases. Of the 28 positive adult cases, 14/96 (14.58%) were positive for AML1-ETO, 12/96 (12.5%) for PML-RARA and 2/96 (2.08%) for CBFβ-MYH11. In the 11 positive pediatric cases, 6/20 (30%) were positive for AML1-ETO, 3/20 (15%) for PML-RARA and 2/20 (10%) for CBFβ-MYH11.
Discussion & Conclusion
The incidence of the common fusion transcripts in our pilot study is in accordance with that described in western studies. It is important to identify these transcripts as they provide useful prognostic information to the treating clinician.
Bone marrow aspiration and biopsy still remains as one of the vital tests for confirmation of diagnosis of visceral Leishmaniasis. The aim of the present study is to assess the relative frequency of common, uncommon and atypical hematological findings in cases of Visceral Leishmaniasis.
Materials & Methods:
A total of 16 cases of Leishmaniasis diagnosed on Bone marrow examination over a period of two years (2008–2010), were retrieved from the archives and the peripheral blood smear, bone marrow aspiration smears and trephine biopsies were examined for the common, uncommon and atypical features as described in the literature.
Out of the total of 16 cases, 10 were pediatric and 6 adult cases. The common findings like pancytopenia, peripheral blood monocytosis, increased histiocytes on aspirate smears and granulomas on biopsies were noted in 12/16 (75%), 9/16 (56.25%), 13/16 (81.2%) and 11/16 (69%) cases respectively. Amongst the uncommon findings, hemophagocytosis was noted in 12/16 (75%) cases, plasma cells with inclusions in 6/16 (37.5%) and LD bodies in cells other than histiocytes in 4/16 (25%) cases. The atypical findings included organism aggregates noted in 9/16 (56%) cases, Pelger-Heut cells seen in 4/16 (25%) cases and increased focal vascularity on biopsies in 10/16 (62.5%) cases. The average parasite density (APD) on smears was 3+ and the range of positivity was 1+ to 5+.
The knowledge of these morphological clues can assist us in searching for LD bodies and correctly diagnosing the condition without excessive dependence on unnecessary and sophisticated tests.
The prevalence rate and spectrum of fungi infecting deep tissues of diabetic lower-limb wounds (DLWs) have not been previously studied. Five hundred eighteen (382 male and 136 female) consecutive patients with type 2 diabetes hospitalized due to infected lower-limb wounds were enlisted in this study. Deep tissue (approximately 0.5- × 0.5-cm size) taken perioperatively from the wound bed was cultured for fungi. Fungi was found in 27.2% (141/518) of the study population. Candida parapsilosis (25.5%), Candida tropicalis (22.7%), Trichosporon asahii (12.8%), Candida albicans (10.6%), and Aspergillus species (5.0%) were the most predominant fungal isolates. Of the fungal isolates, 17.7% were resistant to itraconazole, 6.9% were resistant to amphotericin B, 6.9% were resistant to voriconazole, 3.9% were resistant to fluconazole, and 1.5% were resistant to flucytosine. Of the population, 79.7% (413/518) had bacterial infection in deep tissue. The predominant isolates were Enterococcus faecalis (14.1%), Staphylococcus aureus (12.2%), and Pseudomonas aeruginosa (10.8%). Mixed fungal and bacterial infections were seen in 21.4% of patients, while 5.8% had only fungal infection and 58.3% had only bacterial infections. Another 14.5% had neither bacteria nor fungi in the deep tissue. Patients with higher glycosylated hemoglobin levels had significantly more fungal infections. Our study reveals that deep-seated fungal infections are high in DLWs. In the context of delayed wound healing and amputation rates due to DLWs, it is important to study the pathogenicity of fungi in deep tissues of DLWs and their possible contribution to delayed wound healing. The role of antifungal agents in wound management needs to be evaluated further.
High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35–134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.
amplification; array CGH; breast cancer; deletion; radiation
Mutated spliceosome components are recurrently being associated with perturbed tissue development and disease pathogenesis. Cephalophŏnus (cph), is a zebrafish mutant carrying an early premature STOP codon in the spliceosome component Prpf8 (pre-mRNA processing factor 8). Cph initially develops normally, but then develops widespread cell death, especially in neurons, and is embryonic lethal. Cph mutants accumulate aberrantly spliced transcripts retaining both U2- and U12-type introns. Within early haematopoeisis, myeloid differentiation is impaired suggesting Prpf8 is required for haematopoietic development. Cph provides an animal model for zygotic PRPF8 dysfunction diseases and for evaluating therapeutic interventions.
PRPF8; haematopoiesis; splicing; zebrafish; myelopoiesis; spliceosome; snRNP
We report the complete genome sequence of a Newcastle disease virus (NDV) isolate, NDV-D1/1998, from an apparently healthy village chicken in South India. This class II, genotype II virus is 15,186 nucleotides in length with unique amino acid variations and was found to be a velogenic pathotype by standard pathogenicity tests.
Prior injury to the knee, particularly anterior cruciate ligament (ACL) injury, is known to predispose one to premature osteoarthritis (OA). The study sought to explore if there was a biomechanical rationale for this process by investigating changes in external knee moments between people with a history of ACL injury and uninjured participants during walking: (1) on different surface inclines and (2) at different speeds. In addition we assessed functional differences between the groups.
12 participants who had undergone ACL reconstruction (ACLR) and 12 volunteers with no history of knee trauma or injury were recruited into this study. Peak knee flexion and adduction moments were assessed during flat (normal and slow speed), uphill and downhill walking using an inclined walkway with an embedded Kistler Force plate, and a ten-camera Vicon motion capture system. Knee injury and Osteoarthritis Outcome Score (KOOS) was used to assess function. Multivariate analysis of variance (MANOVA) was used to examine statistical differences in gait and KOOS outcomes.
No significant difference was observed in the peak knee adduction moment between ACLR and control participants, however, in further analysis, MANOVA revealed that ACLR participants with an additional meniscal tear or collateral ligament damage (7 participants) had a significantly higher adduction moment (0.33±0.12 Nm/kg m) when compared with those with isolated ACLR (5 participants, 0.1±0.057 Nm/kg m) during gait at their normal speed (p<0.05). A similar (non-significant) trend was seen during slow, uphill and downhill gait.
Participants with an isolated ACLR had a reduced adductor moment rather an increased moment, thus questioning prior theories on OA development. In contrast, those participants who had sustained associated trauma to other key knee structures were observed to have an increased adduction moment. Additional injury concurrent with an ACL rupture may lead to a higher predisposition to osteoarthritis than isolated ACL deficiency alone.
Central retinal artery occlusion (CRAO) is an ophthalmic emergency and the ocular analogue of cerebral stroke. Best evidence reflects that over three-quarters of patients suffer profound acute visual loss with a visual acuity of 20/400 or worse. This results in a reduced functional capacity and quality of life. There is also an increased risk of subsequent cerebral stroke and ischaemic heart disease. There are no current guideline-endorsed therapies, although the use of tissue plasminogen activator (tPA) has been investigated in two randomized controlled trials. This review will describe the pathophysiology, epidemiology, and clinical features of CRAO, and discuss current and future treatments, including the use of tPA in further clinical trials.
central retinal artery occlusion; management; thrombolysis
Pulmonary vein isolation (PVI) for atrial fibrillation (AF) is associated with a transient increased risk of thromboembolic and hemorrhagic events. We hypothesized that dabigatran can be safely used as an alternative to continuous warfarin for the peri-procedural anticoagulation in PVI.
Methods and Results
999 consecutive patients undergoing PVI were included; 376 patients were on dabigatran (150 mg) and 623 were on warfarin with therapeutic INR. Dabigatran was held 1 to 2 doses prior to PVI and restarted at the conclusion of the procedure or as soon as patients were transferred to the nursing floor. Propensity score matching was applied to generate a cohort of 344 patients in each group with balanced baseline data. Total hemorrhagic and thromboembolic complications were similar in both groups, before (3.2% vs 3.9%; p = 0.59), and after (3.2% vs 4.1%; p = 0.53) matching. Major hemorrhage occurred in 1.1% vs 1.6% (p = 0.48) before, and 1.2% vs 1.5% (p = 0.74) after matching in the dabigatran vs warfarin group respectively. A single thromboembolic event occurred in each of the dabigatran and warfarin groups. Despite higher doses of intra-procedural heparin, the mean ACT was significantly lower in patients who held dabigatran for 1 or 2 doses than those on warfarin.
Our study found no evidence to suggest a higher risk of thromboembolic or hemorrhagic complications with use of dabigatran for peri-procedural anticoagulation in patients undergoing PVI compared to uninterrupted warfarin therapy.
anticoagulants; fibrillation; ablation; catheter ablation; stroke
Osteocare, a herbal formulation, has been found to be very effective in bone mineralization and support of the microstructure of bone tissue. The water-soluble components of Osteocare (WSCO) induced osteogenic activity in human osteoblast-like SaOS-2 cells. The addition of WSCO (100 μg/ml) to SaOS-2 cells was effective in increasing the cell proliferation by 41.49% and DNA content by 1.9-fold. WSCO increased matrix mineralization in SaOS-2 cells by increased alkaline phosphatase levels and calcium-rich deposits as observed by Alizarin red staining. WSCO markedly increased mRNA expression for osteopontin (OPN), osteocalcin (OCN), type I collagen (Col I) in SaOS-2 cells, and it down-regulated IL-6 mRNA levels in SaOS-2 cells. The present study showed that WSCO plays an important role in osteoblastic bone formation through enhanced activities of ALP, Col I, bone matrix proteins such as OPN and OCN, down-regulation of cytokines like IL-6, as well as promoting mineralization in SaOS-2 cells.
Osteocare; Cell proliferation; ALP activity; OCN; OPN; Col-I; IL-6; Mineralization
We present a series of 50 patients with tuberculous cord compression who were offered systematic non-surgical treatment, and thereby, the author proposes that clinico-radiological soft tissue cord compression is not an emergency indication for surgery.
Overview of Literature
Spinal cord compression whether clinical or radiological has usually been believed to be an indication for emergency surgery in spinal tuberculosis.
Fifty adults were prospectively studied at our clinic for spinal cord compression due to tuberculous spondylitis, between May 1993 and July 2002. The inclusion criteria were cases with clinical and/or radiological evidence of cord compression (documented soft tissue effacement of the cord with complete obliteration of the thecal sac at that level on magnetic resonance imaging scan). Exclusion criteria were lesions below the conus level, presence of bony compression, severe or progressive neurological deficit (
At the time of presentation, 10 patients had a motor deficit, 18 had clinically detectable hyper-reflexia and 22 had normal neurology. Forty-seven of the 50 patients responded completely to non-operative treatment and healed with no residual neurological deficit. Three patients with progressive neurological deficit while on treatment were operated on with eventual excellent recovery.
Radiological evidence of cord compression and early neurological signs need not be an emergency surgical indication in the management of spinal tuberculosis.
Non-surgical management; Spinal tuberculosis; Spinal cord compression
The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations.
To characterize the transcriptional changes of early breast neoplasia, we sequenced 3′- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns.
This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer.
Marr famously decomposed cognitive theories into three levels. Newell, Pylyshyn, and Anderson offered parallel decompositions of cognitive architectures, which are psychologically plausible computational formalisms for expressing computational models of cognition. These analyses focused on the objective meaning of each level – how it supports computational models that correspond to cognitive phenomena. This paper develops a complementary analysis of the subjective meaning of each level – how it helps cognitive scientists understand cognition. It then argues against calls to eliminatively reduce higher levels to lower levels, for example, in the name of parsimony. Finally, it argues that the failure to attend to the multiple meanings and levels of cognitive architecture contributes to the current, disunified state of theoretical cognitive science.
cognitive architecture; unified theories of cognition; computational models; reduction; parsimony; identifiability
The National Cancer Institute’s NCI-60 cell line panel, the most extensively characterized set of cells in existence and a public resource, is frequently used as a screening tool for drug discovery. Since many laboratories around the world rely on data from the NCI-60 cells, confirmation of their genetic identities represents an essential step in validating results from them. Given the consequences of cell line contamination or misidentification, quality control measures should routinely include DNA fingerprinting. We have, therefore, used standard DNA microsatellite short tandem repeats to profile the NCI-60, and the resulting DNA fingerprints are provided here as a reference. Consistent with previous reports, the fingerprints suggest that several NCI-60 lines have common origins: the melanoma lines MDA-MB-435, MDA-N, and M14; the central nervous system lines U251 and SNB-19; the ovarian lines OVCAR-8 and OVCAR-8/ADR (also called NCI/ADR); and the prostate lines DU-145, DU-145 (ATCC), and RC0.1. Those lines also demonstrate that the ability to connect two fingerprints to the same origin is not affected by stable transfection or by the development of multidrug resistance. As expected, DNA fingerprints were not able to distinguish different tissues-of-origin. The fingerprints serve principally as a barcodes.
DNA fingerprinting; NCI-60; cell contamination
There is considerable interest in translating laboratory advances in neuronal regeneration following spinal cord injury (SCI). A multimodality approach has been advocated for successful functional neuronal regeneration. With this goal in mind several biomaterials have been employed as neuronal bridges either to support cellular transplants, to release neurotrophic factors, or to do both. A systematic review of this literature is lacking. Such a review may provide insight to strategies with a high potential for further investigation and potential clinical application.
To systematically review the design strategies and outcomes after biomaterial-based multimodal interventions for neuronal regeneration in rodent SCI model. To analyse functional outcomes after implantation of biomaterial-based multimodal interventions and to identify predictors of functional outcomes.
A broad PubMed, CINHAL, and a manual search of relevant literature databases yielded data from 24 publications; 14 of these articles included functional outcome information. Studies reporting behavioral data in rat model of SCI and employing biodegradable polymer-based multimodal intervention were included. For behavioral recovery, studies using severe injury models (transection or severe clip compression (>16.9 g) or contusion (50 g/cm)) were categorized separately from those investigating partial injury models (hemisection or moderate-to-severe clip compression or contusion).
The cumulative mean improvements in Basso, Beattie, and Bresnahan scores after biomaterial-based interventions are 5.93 (95% CI = 2.41 − 9.45) and 4.44 (95% CI = 2.65 – 6.24) for transection and hemisection models, respectively. Factors associated with improved outcomes include the type of polymer used and a follow-up period greater than 6 weeks.
The functional improvement after implantation of biopolymer-based multimodal implants is modest. The relationship with neuronal regeneration and functional outcome, the effects of inflammation at the site of injury, the prolonged survival of supporting cells, the differentiation of stem cells, the effective delivery of neurotrophic factors, and longer follow-up periods are all topics for future elucidation. Future investigations should strive to further define specific factors associated with improved functional outcomes in clinically relevant models.
Spinal cord injuries; Axonal regeneration; Neuronal bridge; Biomaterials; Functional recovery; Translational research
Background: Genetic factors cause about 15% of male infertility. Azoospermia factors (AZFa, AZFb, and AZFc) present on Yq are most important for spermatogenesis. We have made an attempt to evaluate the frequencies of microdeletions of AZFa, AZFb, AZFc in idiopathic cases of azoospermia and oligozoospermia from central Indian population.
Materials and Methods: We have analyzed a total of 156 subjects (95 oligozoospermia and 61 azoospermia) & 50 control subjects. DNA samples were analyzed for microdeletions of Y chromosome by PCR-screening of 18 sequences-tagged-site (STS) markers from different region of the AZF on Yq and SRY on Yp.
Results: Out of 156 cases analyzed, 13 (8.33%) subjects (8 azoospermia and 5 oligozoospermia) showed partial deletion of AZF regions, of which deletion in AZFc region was the most common (84.6%) followed by AZFb (15.4%) and AZFa (15.4%). The sites and sizes of deletions varied among patients. Histological study of the testicular tissue of the available subjects, who showed microdeletions of Y chromosome, showed spermatogenic arrest at different stages. The frequency of Y chromosome microdeletion in our subjects was 8.33%.
Conclusion: Some Indian studies reported low frequencies of microdeletions than that of our result. We suggest that the frequency of deletions may be affected by the involvement of different genetic factors, ethnic population and different geographical regions. PCR based Y chromosome screening for microdeletions will be useful and great help to infertility clinics for genetic counselling and assisted reproduction.
Male Infertility; Y microdeletions; AZF factor
Reassortment between different species or strains plays a key role in the evolution of multipartite plant viruses and can have important epidemiological implications. Identifying geographic locations where reassortant lineages are most likely to emerge could be a valuable strategy for informing disease management and surveillance efforts. We developed a predictive framework to identify potential geographic hot spots of reassortment based upon spatially explicit analyses of genome constellation diversity. To demonstrate the utility of this approach, we examined spatial variation in the potential for reassortment among Cardamom bushy dwarf virus (CBDV; Nanoviridae, Babuvirus) isolates in Northeast India. Using sequence data corresponding to six discrete genome components for 163 CBDV isolates, a quantitative measure of genome constellation diversity was obtained for locations across the sampling region. Two key areas were identified where viruses with highly distinct genome constellations cocirculate, and these locations were designated as possible geographic hot spots of reassortment, where novel reassortant lineages could emerge. Our study demonstrates that the potential for reassortment can be spatially dependent in multipartite plant viruses and highlights the use of evolutionary analyses to identify locations which could be actively managed to facilitate the prevention of outbreaks involving novel reassortant strains.
disease emergence; geographic hot spot; multipartite virus; reassortment
The aim of this ex vivo study was to compare the antibacterial activity of total-etch and self-etch adhesive systems against Streptococcus mutans, Lactobacillus acidophilus, and Actinomyces viscosus through disk diffusion method.
Materials and Methods:
The antibacterial effects of Single Bond (SB) and Adper Prompt (AP) and aqueous solution of chlorhexidine 0.2% (positive control) were tested against standard strain of S. mutans, L. acidophilus, and A. viscosus using the disk diffusion method. The diameters of inhibition zones were measured in millimeters. Data was analyzed using Kruskal-Wallis test. Mann-Whitney U test was used for pairwise comparison.
Of all the materials tested, AP showed the maximum inhibitory action against S. mutans and L. acidophilus. Aqueous solution of chlorhexidine 0.2% showed the maximum inhibitory action against A. viscosus. Very minimal antibacterial effect was noted for SB.
The antibacterial effects observed for the tested different dentin bonding systems may be related to the acidic nature of the materials.
Antibacterial activity; actinomyces viscosus; dentin bonding systems; lactobacillus acidophilus; streptococcus mutans
Although advances in genomics during the last decade have opened new avenues for translational research and allowed the direct evaluation of clinical samples, there is still a need for reliable preclinical models to test therapeutic strategies. Human cancer-derived cell lines are the most widely used models to study the biology of cancer and to test hypotheses to improve the efficacy of cancer treatment. Since the development of the first cancer cell line, the clinical relevance of these models has been continuously questioned. Based upon recent studies that have fueled the debate, we review the major events in the development of the in vitro models and the emergence of new technologies that have revealed important issues and limitations concerning human cancer cell lines as models. All cancer cell lines do not have equal value as tumor models. Some have been successful, whereas others have failed. However, the success stories should not obscure the growing body of data that motivates us to develop new in vitro preclinical models that would substantially increase the success rate of new in vitro–assessed cancer treatments.
There are limited data comparing imaging modalities in the diagnosis of pancreas divisum. We aimed to: 1. Evaluate the sensitivity of endoscopic ultrasound (EUS), magnetic resonance cholangiopancreatography (MRCP) and multi-detector computed tomography (MDCT) for pancreas divisum. 2. Assess interobserver agreement (IOA) among expert radiologists for detecting pancreas divisum on MDCT and MRCP.
For this retrospective cohort study, we identified 45 consecutive patients with pancreaticobiliary symptoms and pancreas divisum established by endoscopic retrograde pancreatography (ERP) who underwent EUS and cross-sectional imaging. The control group was composed of patients without pancreas divisum who underwent ERP and cross-sectional imaging.
The sensitivity of EUS for pancreas divisum was 86.7%, significantly higher than sensitivity reported in the medical records for MDCT (15.5%) or MRCP (60%) [p<0.001 for each]. On review by expert radiologists the sensitivity of MDCT increased to 83.3% in cases where the pancreatic duct was visualized, with fair IOA (қ=0.34). Expert review of MRCPs did not identify any additional cases of pancreas divisum; IOA was moderate (қ=0.43).
EUS is a sensitive test for diagnosing pancreas divisum and is superior to MDCT and MRCP. Review of MDCT studies by expert radiologists substantially raises its sensitivity for pancreas divisum.
Pancreas Divisum; Pancreatitis; Endoscopic Ultrasound; Magnetic Resonance Cholangiopancreatography; Endoscopic retrograde Cholangiopancreatography; Computer Tomography
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