Case series of aspergillus spondylodiscitis from a tertiary care centre in India.

Aspergillus spondylodiscitis is a rare entity reported in the literature. In tuberculosis endemic regions like India, more often it could be misdiagnosed as tuberculous spondylodiscitis. Herein we report a case series of three patients with Aspergillus spondylodiscitis presenting with chronic low backpain and clinically diagnosed as tuberculosis spine. Culture and histopathological examination of the debrided tissue provided a definite diagnosis. Interestingly, one of the cases had coexisting tuberculosis spine. All three patients underwent surgical intervention-debridement, decompression and fusion of spine and combined medical management with voriconazole with successful outcome.

Conservative management of staghorn stones.

INTRODUCTION: Since the seminal works by Singh and Blandy in the 1970s, the management of staghorn stones has almost exclusively involved surgical intervention. In contrast, a more recent study found that conservative management was not as unsafe as previously believed. The present review sought to examine the available literature to understand the implications of a conservative strategy. METHODS: A systematic search of the literature was carried out using MEDLINE®, Embase™ and the Cochrane Central Register of Controlled Trials. All papers looking at management of staghorn calculi were reviewed and studies with a conservative management arm were identified. Outcomes of interest were recurrent or severe urinary tract infections, progressive renal deterioration, dialysis requirements, morbidity and disease specific mortality. Owing to the lack of relevant data, a descriptive review was carried out. RESULTS: Our literature search yielded 10 suitable studies involving a total of 304 patients with staghorn stones managed conservatively. Progressive renal deterioration occurred in 0-100% of cases (mean 27.5%) with a higher rate among bilateral staghorn sufferers (44% vs 9%). Dialysis was required in 9% of patients (20% bilateral, 6% unilateral). The mean rate of severe infection was 8.7% and recurrent urinary tract infections occurred in as high as 50% of cases (80% bilateral, 41% unilateral). Disease specific mortality ranged from 0% to 67% (mean 20.5%). CONCLUSIONS: It appears that conservative management of staghorn calculi is not as unsafe as previously thought and selection of patients with unilateral asymptomatic stones with minimal infection should be considered.

In Silico Docking of Vitamin E Isomers on Transport Proteins.

BACKGROUND: Vitamin E is comprised of α, ß, γ and δ-tocopherols (Ts) and α, ß, γ and δ- tocotrienols (T3s). Vitamin E has neuroprotective antioxidant, anti-cancer, and cholesterol-lowering effects. Intracellular trafficking of these isomers remains largely unknown, except for αT which is selectively transported by αT transfer protein (αTTP). OBJECTIVE: This study aimed to determine the binding of vitamin E isomers on transport proteins using in silico docking. METHODS: Transport proteins were selected using AmiGo Gene Ontology tool based on the same molecular function annotation as αTTP. Protein structures were obtained from the Protein Data Bank. Ligands structures were obtained from ZINC database. In silico docking was performed using SwissDock. RESULTS AND DISCUSSION: A total of 6 transport proteins were found: SEC14-like protein 2, glycolipid transfer protein (GLTP), pleckstrin homology domain-containing family A member 8, collagen type IV alpha-3-binding protein, ceramide-1-phosphate transfer protein and afamin. Compared with other transport proteins, αTTP had the highest affinities for all isomers except ßT3. Binding order of vitamin E isomers toward αTTP was γT > ßT > αT > δT > αT3 > γT3 > δT3 > ßT3. GLTP had a higher affinity for tocotrienols than tocopherols. ßT3 bound stronger to GLTP than αTTP. CONCLUSION: αTTP remained as the most preferred transport protein for most of the isomers. The binding affinity of αT toward αTTP was not the highest than other isomers suggested that other intracellular trafficking mechanisms of these isomers may exist. GLTP may mediate the intracellular transport of tocotrienols, especially ßT3. Improving the bioavailability of these isomers may enhance their beneficial effects to human.

Screening of health-care workers for latent tuberculosis infection in a Tertiary Care Hospital.

BACKGROUND: Health-care workers (HCWs) are at increased risk of acquiring tuberculosis (TB) than the general population. While national-level data on the burden of TB in general population is available from reliable sources, nationally representative data on latent tuberculosis infection (LTBI) burden in HCWs in the high burden countries is lacking. METHODS: A prospective study was carried out to assess the risk of TB infection among HCWs who directly engage in medical duties. HCWs were recruited between January 2014 and December 2015. A structured questionnaire was used for risk assessment of TB infection among HCWs, including sociodemographic characteristics (e.g., age, gender, period of professional work, and employed position), knowledge of TB prevention and control, and history of professional work. A single-step tuberculin skin test (TST) using 5 international units (IU; 0.1 ml) of tuberculin (purified protein derivative from Mycobacterium bovis Bacillus Calmette-Guérin [BCG]). TB infection was determined using a TST induration ≥10 mm as a cutoff point for TST positivity. TST-positive participants were further subjected to detailed clinical evaluation and chest radiography to rule out active TB. The associations between TB infection and the sociodemographic characteristics, duration of possible exposure to TB while on medical duties, BCG vaccination, and knowledge about TB were estimated using Chi-square test. A two-sided P < 0.05 indicated statistical significance. RESULTS: A total of 206 eligible HCWs signed the informed consent and completed the questionnaires between January 2014 and December 2015. The age of the participants ranged from 18 to 71 years, with a mean age of 27.13 years. TST induration size (mean 6.37 mm) the TST results suggested that 36.8% (76/206) were infected with TB using a TST induration ≥10 mm as a cut-off point. All 76 TST-positive HCWs showed no evidence of active TB in clinical evaluation and chest radiography. However, during the study, two HCWs developed pulmonary TB (both TST baseline test negative). Statistical analysis suggested that age, duration of employment as a health-care professional, literacy status, and working in medical wards/OP/Intensive Care Unit were significantly associated with TB infection. CONCLUSIONS: Many studies propose serial tests of LTBI as effective occupational protection strategies. However, practically, it is not feasible because it has to be done at frequent intervals, but how frequently to be done is not clear. Another concern is even if found to have LTBI, there are no clear consensus guidelines about the treatment in high prevalence settings. The prevalence of LTBI is so high in countries like India that affected HCWs could not be exempted from working in high-risk areas. The depth of knowledge of TB prevention and control among HCWs should be improved by regular infection control training.

Structural Behavior of SFRC Beams strengthened with GFRP Laminates: An Experimental and Analytical Investigation

ABSTRACT This paper presents the experimental results of a reinforced concrete beams (RC) strengthened with internal steel fibers (SF) and external glass fiber reinforced polymer laminates (GFRP). The research work studied the load carrying capacity, deformation, crack width and ductility of the reinforced concrete beams strengthened with different steel fiber ratios and steel fiber reinforced concrete beams strengthened with three different glass fiber reinforced polymer laminates of two different thickness. The experimental results clearly shows that incorporating steel fibers in to the reinforced concrete beams reduced the crack width and distribute the crack evenly and also increases the bonding between tension face of the beam with glass fiber reinforced polymer laminates. The results also shows that glass fiber reinforced polymer laminates strengthened steel fiber reinforced concrete beams increases the flexural strength and ductility as compared with unstrengthened counterpart. In addition to this experimental work, theoretical calculations were done to find the ultimate load carrying capacity of the beam tested, and also compared with the experimental results.

Field evaluation on the effectiveness of a modified approach of chemical fogging against the conventional fogging in controlling dengue outbreak.

A field evaluation on the effectiveness of a modified approach of chemical fogging of insecticides against the conventional method was carried out in the Seremban district within the state of Negeri Sembilan, Malaysia from 7th February 2003 to 7th September 2003. In the 3 months period, November 2002 to January 2003, prior to institution of modified approach of chemical fogging, 27 of 42 (64.3%) dengue outbreaks were successfully controlled within the stipulated time frame of 14 days by the conventional approach of thermal chemical fogging. However, during the period when the modified approach of chemical fogging was instituted, 25 of 27 (92.6%) dengue outbreaks within the same district were successfully controlled within the 14-days time-line. Statistically, the modified approach of chemical fogging significantly improved the success rate of achieving dengue outbreak control within the stipulated time frame (chi2 = 5.65, p = 0.01745). The modified approach of chemical fogging also appeared to reduce the number of dengue cases recorded in the same district. This small pilot study shows that the modified approach of chemical fogging reduced cost in carrying out each fogging activity to control dengue outbreak. It also substantially reduced the required time taken to complete each fogging activity in comparison to the conventional approach. Thus, it enabled similar number of workers to cover more localities simultaneously affected by the outbreaks. In addition, the modified approach reduced the exposure time to hazardous insecticides for each worker doing hand-held thermal fogging.

The value of CD23 expression as an additional marker in distinguishing mediastinal (thymic) large B-cell lymphoma from Hodgkin lymphoma.

Mediastinal diffuse large B-cell lymphoma (Med-DLBCL) is a subtype of DLBCL that has morphologic and clinical similarities and phenotypic overlaps with classical Hodgkin lymphoma (CHL) involving the mediastinum. CD23 is a marker that has been previously reported in Med-DLBCI and is proposed in the differential diagnosis of M-DLBCL and CHL. A panel of immunostains, including CD45, CD20, CD3, CD30, CD15, CD21, and CD23 as well as Eber was performed on Med-DLBCL and 20CHL. 23/27 Med-DLBCL (85%) were positive for CD23 (membranous) CD30 was negative in 6 and positive in 21 cases. 18 CHL cases were negative for CD23 and only 2 showed rare scattered Reed-Sternberg cells with weak cytoplasmic CD23 staining. CD23 showed a sensitivity of 85% and positive predictive value of 92%. In conclusion CD23 is a useful marker in distinguishing Med-DLBCL and CHL in mediastinal biopsies and may be helpful as an adjunct to histomorphology and other markers in the diagnosis and appropriate clinical management of these lesions.

A comparative analysis of lymphatic vessel density in ovarian serous tumors of low malignant potential (borderline tumors) with and without lymph node involvement.

Lymph node involvement is seen in approximately one quarter of women with surgically staged ovarian serous tumors of low malignant potential (serous borderline tumors), and this finding apparently does not adversely impact their overall survival. To help illuminate some of the pathomechanisms underlying this novel phenomenon, in which a largely noninvasive epithelial neoplasm is able to exit its primary site and be transported to lymph nodes with such a substantial frequency, we investigated whether significant differences in lymphatic vessel density exist between ovarian serous borderline tumors that show lymph node involvement and those that do not. The lymphatic vessel density of 13 conventional ovarian serous borderline tumors (i.e. tumors without stromal microinvasion, micropapillary/cribriform areas, or invasive implants) with at least 1 positive lymph node (study group) was compared with the lymphatic vessel density of an age- and disease extent-matched control group of 13 similarly selected lymph node-negative ovarian serous borderline tumors. Lymphatic vessel density was determined by counting the total number of vascular spaces immunohistochemically stained by the lymphatic endothelium marker D2-40 in 5 consecutive microscopic fields (x20 objective, field area of 1 microscopic field, 0.95 mm) in the most vessel-dense areas and calculating the average value per microscopic field. The peritumoral lymphatic vessel density was significantly higher than the intratumoral lymphatic vessel density in both groups. However, no statistically significant differences were found between the study and control groups regarding intratumoral lymphatic vessel density (8.0 vs. 7.61; P=0.77), peritumoral lymphatic vessel density (20.33 vs. 21.0; P=0.79), or combined, that is, peritumoral plus intratumoral lymphatic vessel density (27.81 vs. 28.62; P=0.83). Our findings, in conjunction with others in the medical literature, do not support a role for tumor lymphatics in nodal metastasis in this neoplasm. We discuss the possibility that nodal deposits may represent metastatic disease from secondary tumor implants.

Novel mechanisms of protein synthesis in diabetic nephropathy--role of mRNA translation.

Ambient protein levels are affected by both synthesis and degradation. Synthesis of a protein is regulated by transcription and messenger RNA (mRNA) translation. Translation has emerged as an important site of regulation of protein expression during development and disease. It is under the control of distinct factors that regulate initiation, elongation and termination phases. Regulation of translation occurs via signaling reactions, guanosine diphosphate-guanosine triphosphate binding and by participation of non-coding RNA species such as microRNA. Recent work has revealed an important role for translation in hypertrophy, matrix protein synthesis, elaboration of growth factors in in vivo and in vitro models of diabetic nephropathy. Studies of translation dysregulation in diabetic nephropathy have enabled identification of novel therapeutic targets. Translation of mRNA is a fertile field for exploration in investigation of kidney disease.

Microsatellite instability and mismatch repair protein defects in ovarian epithelial neoplasms in patients 50 years of age and younger.

Ovarian malignancies occurring in the setting of hereditary nonpolyposis colorectal carcinoma syndrome typically present in young women, often as the first or "sentinel" cancer, but the frequency of microsatellite instability (MSI) and mismatch repair (MMR) defects in ovarian surface epithelial malignancies in women

Mucocele-like tumor and columnar cell hyperplasia of the breast occurring in a morphologic continuum.

INTRODUCTION: Mucocele-like tumor was originally described in 1986 as a benign breast proliferation consisting of multiple dilated cysts lined by cytologically bland, flat to cuboidal cells. Subsequent reports described the coexistence of, including the morphologic inter-transitions between, mucocele-like tumor and a variety of other breast proliferations, including intraductal carcinoma, invasive carcinoma, atypical ductal hyperplasia, and hyperplasia of the usual type. The spectrum of breast alterations characterized by variably enlarged terminal-ductal lobular units lined by variably hyperplastic and variably atypical columnar cells has been the subject of significant discussion in the recent literature. In one scheme, these lesions may be classified into four groups, that is, columnar cell change with and without atypia and columnar cell hyperplasia with and without atypia. Morphologic and molecular observations suggest an association, perhaps in a nonobligate precursor role, between some columnar cell lesions and a variety of other neoplastic lesions. CASE PRESENTATION: We describe the case of a 43-year-old woman whose breast tumor contained areas diagnostic of mucocele-like tumor and columnar cell hyperplasia, with morphologic transitions in between. CONCLUSION: Our case represents the second broadly similar case that has been reported, and suggests a potential relationship between these two enigmatic lesions.

''Minor'' BCL2 breakpoints in follicular lymphoma: frequency and correlation with grade and disease presentation in 236 cases.

Follicular lymphomas are frequently associated with the t(14;18)(q32;q21). This translocation can be detected by karyotype, polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH). In addition to the breakpoints currently used for diagnosis located in the major breakpoint region (MBR) and the minor cluster region (mcr), recent studies have reported the existence of other breakpoints (3' BCL2, 5'mcr, and icr). In this study, we examined the frequency of all five breakpoints in 236 cases of follicular lymphomas by real-time PCR analysis. The distribution of breakpoint sites consisted of MBR in 118 cases (50%), mcr in 11 (5%), icr in 32 (13%), 3' BCL2 in 13 (6%), and 5' mcr in three cases (1%). These findings illustrate significantly higher frequency of the icr breakpoint as compared with the more frequently studied mcr. Correlation of breakpoints with histology showed that MBR breakpoints occur more frequently in grade 2 lymphomas (P = 0.042). A majority of the PCR-negative cases (75%) contained an IGH/BCL2 translocation with FISH methods, suggesting the presence of other BCL2 breakpoints. Correlation of breakpoints with survival did not reveal significant differences. Diagnostic laboratories should consider expanding their PCR methods to include other BCL2 breakpoints and correlating with FISH methods when appropriate.

Non-Hodgkin lymphoma of the breast.

BACKGROUND: Primary lymphoma of the breast has been reported to have a high local and central nervous system recurrence (CNS) rate, suggesting the need for consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to evaluate the institutional experience in this patient population. METHODS: In all, 37 patients with lymphoma involving the breast at initial diagnosis and managed at Stanford University from 1981-2005 were included. Diagnostic tissue biopsies were obtained either from the breast mass or an involved lymph node. Treatment and response data, patterns of recurrence, and outcomes were reviewed. RESULTS: Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes were seen in 38%. Most patients presented with an incidental breast mass in stage I(E) or II(E). Four (11%) patients presented with bilateral breast involvement, with only 1 patient presenting with CNS disease. DLBCL patients received doxorubicin-based chemotherapy, with 70% receiving involved field radiotherapy and a single patient receiving intrathecal therapy. No recurrences occurred in the involved breast and a single parenchymal CNS recurrence was recorded. Among the DLBCL patients, the 5-year progression-free survival (PFS) was 61%, with a median follow-up of 3.8 years (range, 5 months to 19 years) and the 5-year overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had an estimated 5-year PFS of 76% and an OS of 92%. CONCLUSIONS: DLBCL of the breast was successfully treated with doxorubicin-based chemotherapy alone or with involved field radiotherapy in an estimated 61% of patients at 5 years. A single CNS recurrence was observed in our series of patients, most of whom presented with limited disease.

The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation.

Although a large proportion of patients with polycythemia vera (PV) harbor a valine-to-phenylalanine mutation at amino acid 617 (V617F) in the JAK2 signaling molecule, the stage of hematopoiesis at which the mutation arises is unknown. Here we isolated and characterized hematopoietic stem cells (HSC) and myeloid progenitors from 16 PV patient samples and 14 normal individuals, testing whether the JAK2 mutation could be found at the level of stem or progenitor cells and whether the JAK2 V617F-positive cells had altered differentiation potential. In all PV samples analyzed, there were increased numbers of cells with a HSC phenotype (CD34+CD38-CD90+Lin-) compared with normal samples. Hematopoietic progenitor assays demonstrated that the differentiation potential of PV was already skewed toward the erythroid lineage at the HSC level. The JAK2 V617F mutation was detectable within HSC and their progeny in PV. Moreover, the aberrant erythroid potential of PV HSC was potently inhibited with a JAK2 inhibitor, AG490.

Identification of mislabeled specimen by molecular methods: case report and review.

Specimen misidentification is a common cause of errors in surgical pathology. We report a case where bone-marrow biopsies from patients of different genders were mislabeled and molecular methods were applied to resolve the identity. A short tandem repeat (STR)-polymerase chain reaction-based assay, commonly used in paternity testing, was employed in an attempt to assign the correct identity to the specimens. However, the specimens had been processed by decalcification and the DNA yield was poor. One of the markers in the assay is the non-STR amelogenin locus that distinguishes the X and Y chromosomes. This amelogenin marker results in a product of low molecular weight, enabling unequivocal resolution of identity despite a poor DNA yield. The prevalence of errors in pathology due to specimen misidentifications is reviewed.

Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement".

Dinitrophenol, a chemical currently used as an insecticide, is known to uncouple mitochondrial oxidative phosphorylation. A component of explosives, it has also been used in the past as a food coloring and clothing dye. In the 1930s, physicians prescribed it for weight loss, but this practice was discontinued when reports of cataracts, deaths, and other adverse outcomes came to light. We describe in our report the overdose and fatality of a teenager who purchased the product as a weight loss dietary supplement by mail order. We also describe a laboratory method that allowed postmortem determination of the dinitrophenol concentration in the victim's serum. Her death, despite prompt medical treatment, underscores the danger of dinitrophenol. The easy accessibility and apparent resurgent interest in dinitrophenol as a weight loss agent is extremely timely and troubling.

An endometrial stromal tumor with osteoclast-like giant cells.

Endometrial stromal tumors (ESTs) of the uterine corpus have a striking propensity to display diverse morphological variations, including sex cord-like, smooth muscle, or skeletal muscle differentiation; fibrous change; myxoid change; or bland endometrioid-type glands. They may also contain rhabdoid, foam, clear, or epithelioid/granular cells among others. Recently, we have encountered an EST showing smooth muscle differentiation and osteoclast-like giant cells that were predominantly concentrated in the areas showing smooth muscle differentiation. Osteoclastlike giant cells have not been previously reported in EST to our knowledge; thus, this finding expands the morphological spectrum of these tumors. In addition, although the level of infiltration at the peripheries of the tumor exceeded that allowable under the Tavassoli and Norris criteria for stromal nodules, it did not reach the classic permeative infiltration generally associated with endometrial stromal sarcomas. Historical, prognostic, and diagnostic aspects of margins in EST, especially in those borderline cases such as ours, are also discussed.