Primary malignant melanoma: a rare cause of mediastinal mass

A case of primary malignant melanoma in the mediastinum presenting as recurrent laryngeal nerve palsy is reported. Tissue biopsy at mediastinotomy yielded a diagnosis of malignant melanoma. The mass was fixed to the left aspect of the trachea and to the upper border of the left main bronchus and could not be removed surgically. Further extensive clinical and radiological investigations revealed no evidence of tumor elsewhere in the body.     

All-inside meniscal repair surgery: factors affecting the outcome

BackgroundMeniscal injury is currently a well-recognized source of knee dysfunction. While it would be ideal to repair all meniscus tears, the failure rate is significantly high, although it may be reduced by careful selection of the patients. Our objective was to assess the outcome of meniscal repair surgery and the role of simultaneous reconstruction of the anterior cruciate ligament (ACL).Results136 Meniscal repairs were performed in 122 patients with a mean age of 26.8 years. Mean follow-up duration was 9 months. 63 % of the patients underwent medial and 37 % underwent lateral meniscal repair, with failure rates of 19 % for medial and 12 % for lateral menisci. Ligament injuries were found in 61 % of the patients (n = 83). Failure of meniscal repair occurred in 14.5 % (n = 12) of the patients who had early ACL reconstruction and in 27 % (n = 22) of the patients who had delayed ACL reconstruction (p = 0.0006). The failure rate was found to be 13 % in patients who were younger than 25 years (61 %) and 15 % in patients who were older than 25 years (39 %).ConclusionThe success rate of meniscal repair was found to be significantly better when ACL reconstruction was performed simultaneously with meniscal repair.

Level of evidence

Level IV.     

Heart failure in people with type 2 diabetes vs. those without diabetes: A retrospective observational study from South India

Background and aimDespite diabetes being an independent risk for HF, only some DM patients develop HF and hence our aim was to compare the clinical features of DM with and without HF and non-DM with and without HF.MethodsA retrospective observational study was conducted among 397 individuals who visited two tertiary care centres. They were classified into 4 groups – DM with HF(DM-HF), DM without HF, non-DM with HF(non-DM-HF) and non-DM without HF. We assessed and compared the clinical profile of DM with HF vs. DM without HF and non-DM with HF groups respectively.ResultsThe parameters such as age, BMI, BP, eGFR showed significant difference between the groups. People with DM-HF were older compared to DM without HF group(58.9 ± 9.2vs.49.5 ± 9.3; p < 0.001). An increasing trend was observed in HF prevalence with increasing duration of DM among the DM-HF group. DM-HF showed a higher prevalence of hypertension and coronary artery disease(CAD) by history than DM without HF group. DM-HF group(91.2%) had HF with preserved left ventricular ejection fraction(HFpEF) whereas a high proportion(43.5%) of non-DM-HF group had HF with reduced LV ejection fraction(HFrEF).ConclusionsThe DM-HF group differed from other groups significantly in age, diabetes duration, HbA1c level, prevalence of hypertension, CAD and HFpEF.     

β-Asarone Exhibits Antifungal Activity by Inhibiting Ergosterol Biosynthesis in Aspergillus niger ATCC 16888

Fungi play an important role in the degradation of leather goods. Economics often influence the choice of fungicide, thus, search for highly effective and low cost fungicides is immensely important. The authors have screened antifungal activity of ten Indian traditional medicinal plants viz Acalypha fruticosa, Acalypha indica, Aegle marmelos, Adathoda vasika, Calotropis gigantea, Erythrina indica, Morinda citrifolia, Nerium oleander, Pithecellobium dulce, and Acorus calamus based upon their traditional knowledge and usage. Various solvent extracts and essential oils were screened for antifungal activity against Aspergillus niger. The antifungal potency was compared to untreated control and standard antifungal drugs itraconazole and voriconazole. The bioactive principle from highly active fragment was isolated and chemically characterized. The mode of action was determined by a range of studies that include the lesion of plasma membrane, ergosterol content in the plasma membrane, acidification of external medium, and mitochondrial dehydrogenase activity in A. niger ATCC 16888. Among the ten plants studied, A. calamus exhibited greater antifungal potency in comparison to untreated control and standard drugs itraconazole and voriconazole. The minimum inhibitory concentration of both methanolic extract and essential oil of A. calamus against A. niger ATCC 16888 is around 5 µg/ml. The authors identified β-Asarone as the bioactive principle of A. calamus using spectral studies viz ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy and gas chromatography coupled mass spectroscopy. The results indicate that β-Asarone interfere and reduces the ergosterol content in the plasma membrane of A. niger ATCC 16888 thus exert their antifungal activity.

     

HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman,India

A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during July–August 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT‐PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA‐DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA‐DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide‐binding pockets of HLA‐DQB1 molecules were investigated. The frequencies of HLA‐DRB1 alleles were not significantly different, whereas lower frequency of HLA‐DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0·001, corrected P = 0·024; odds ratio (OR)  = 0, 95% confidence interval (95% CI) 0·0–0·331; Peto's OR = 0·1317, 95% CI 0·0428–0·405). Significantly lower frequency of glutamic acid at position 86 of peptide‐binding pocket 1 coding HLA‐DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0·004, OR = 0·307, 95% CI 0·125–0·707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA‐DQ molecules are known to bind more CHIKV peptides than HLA‐DRB1 molecules. The results suggest that HLA‐DQB1 alleles and critical amino acid differences in the peptide‐binding pockets of HLA‐DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV.     

Induction of inflammation by West Nile virus capsid through the caspase-9 apoptotic pathway

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade.     

Both products of the mouse Ink4a/Arf locus suppress melanoma formation in vivo

Deletion of the INK4a/ARF locus at 9p21 is detected with high frequency in human melanoma. Within a short genomic distance, this locus encodes several proteins with established tumor-suppressor roles in a broad spectrum of cancer types. Several lines of evidence support the view that p16INK4a and p19ARF exert the tumor-suppressor activities of this locus, although their relative importance in specific cancer types such as melanoma has been less rigorously documented on the genetic level. Here, we exploit a well-defined mouse model of RAS-induced melanomas to examine the impact of germline p16INK4a or p19ARF nullizygosity on melanoma formation. We demonstrate that loss of either Ink4a/Arf product can cooperate with RAS activation to produce clinically indistinguishable melanomas. In line with the common phenotypic end point, we further show that RAS+ p16INK4a-/- melanomas sustain somatic inactivation of p19ARF-p53 and, correspondingly, that RAS+ p19ARF-/- melanomas experience high-frequency loss of p16INK4a. These genetic studies provide definitive proof that p16INK4a and p19ARF cooperate to suppress the development of melanoma in vivo.     

Psychometric Properties of Osteoporosis Knowledge Tool and Self-Management Behaviours Among Malaysian Type 2 Diabetic Patients

Osteoporosis is a major growing public health problem and it is clear that much needs to be done to bridge the gap between patients and practitioners. However, the educator must have a valid and reliable tool to evaluate the effectiveness of the teaching and learning that are done. Osteoporosis Knowledge Tool (OKT) provides an important strategy for healthcare professionals to start early intervention for patients who are at risk of osteoporosis. The aims of this study were to translate and examine the psychometric properties of the Malaysian version of the Osteoporosis Knowledge Tool (OKT-M) among 250 type 2 diabetes patients and to assess factors that affect diabetic patients’ osteoporosis knowledge. The OKT English version was translated and validated using the internationally accepted and recommended methodology. The sensitivity and specificity of OKT-M was calculated using receiver operating characteristic curve analysis. The face and content validity showed acceptable results. Internal consistency, test–retest reliability, mean difficulty factor and discriminatory power values were 0.72, 0.83, 0.47 ± 0.16 and 0.96, respectively. The cut-off point of the OKT-M to predict osteoporosis/osteopenia was 14 with optimal sensitivity (84.1 %) and specificity (85.5 %). Regression analysis revealed that health belief, self-efficacy and some demographic data had an impact on the OKT-M. The findings of this validation study indicate that the OKT-M is a reliable and valid tool with good psychometric properties in the Malaysian setting. The OKT-M is an appropriate tool for application in clinical setting to identify patients need for a bone health-promoting intervention regarding lifestyle behaviour changes.