Increased promoter diversity reveals a complex phylogeny of human immunodeficiency virus type 1 subtype C in India

OBJECTIVE: To evaluate human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) sequence diversity among distinct populations within India and to determine the prevalent subtype. STUDY DESIGN/METHODS: Analysis of the 3'LTR was conducted from 28 HIV-1-positive samples: 1992-1993 (Pune, New Delhi) and 1995-1996 (Pune, Mumbai and Vellore). Genomic DNA was extracted from cocultivated peripheral blood mononuclear cells (PBMCs) and used for polymerase chain reaction (PCR) amplification and sequencing using dye terminator chemistry. Sequences were edited, aligned, and analyzed phylogenetically utilizing gap-stripped and bootstrapping parameters. Mobility shift assays were used to confirm binding activity. RESULTS: All nucleotide sequences were HWV-1 subtype C based on phylogenetic analysis. The isolates from Pune/Delhi formed subclusters when analyzed separately, irrespective of time or sample source. However, no significant subclustering was observed with isolates from Mumbai or Vellore or with the entire sample set when analyzed collectively. Subtype-specific enhancer analysis revealed an expected third NF-kappaB site but also revealed six isolates with insertions and deletions not previously described, one of which resembles an AP-1 binding site. CONCLUSIONS: The results confirm the prevalence of HIV-1C and suggest increasingly complex phylogeny of HIV-1C within India, such that the previously observed subclustering may no longer adequately reflect the diversity of isolates currently circulating throughout India.     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Cervical squamous intra-epithelial changes and human papillomavirus infection in women infected with human immunodeficiency virus in Pune, India

In view of the dual burden of HIV infection and cervical cancers in India, this study was undertaken to estimate the prevalence of Pap smear abnormalities and human papillomavirus infection among HIV-infected women. Consecutive HIV-infected women attending voluntary counseling testing clinics were enrolled. Written informed consent, demographic information, Pap smears, cervical swabs for HPV typing and a blood sample for CD4+ cell count were collected. Treatment for opportunistic and sexually transmitted infections and reproductive tract infections was provided. Women with Pap smear abnormality were referred for further intervention. Between January 2003 and May 2004, 287 HIV-infected women were enrolled. Pap smear abnormalities were seen in 6.3% women and were more common among women aged 30 and above (P=0.042) and those who had suffered from opportunistic infections (P=0.004). In multivariate analysis, Pap smear abnormalities were associated independently with opportunistic infections (P=0.02, AOR 3.8, 95% CI 1.2--11.5). Of the 100 random cervical specimens screened for HPV 16 and 18 genotypes, 33% (95 CI 23.9--43.1) were positive for HPV 16/18. Of the 122 patients who returned for a follow-up visit, 5 patients (4.1%) who did not have Pap smear abnormality at baseline, had developed Pap smear abnormality. The incidence of Pap smear abnormalities was 5.5 per 100 person year of follow-up. In order to prevent thousands of deaths due to cervical cancer in India, there is a need for strengthening the Pap smear screening program and HPV vaccine development.     

Thirty-day mortality of patients with hip fracture during COVID-19 pandemic and pre-pandemic periods: A systematic review and meta-analysis

BACKGROUNDTimely intervention in hip fracture is essential to decrease the risks of perioperative morbidity and mortality. However, limitations of the resources, risk of disease transmission and redirection of medical attention to a more severe infective health problem during coronavirus disease 2019 (COVID-19) pandemic period have affected the quality of care even in a surgical emergency.AIMTo compare the 30-d mortality rate and complications of hip fracture patients treated during COVID-19 pandemic and pre-pandemic times.METHODSThe search of electronic databases on 1^st August 2020 revealed 45 studies related to mortality of hip fracture during the COVID-19 pandemic and pre-pandemic times. After careful screening, eight studies were eligible for quantitative and qualitative analysis of data.RESULTSThe pooled data of eight studies (n = 1586) revealed no significant difference in 30-d mortality rate between the hip fracture patients treated during the pandemic and pre-pandemic periods [9.63% vs 6.33%; odds ratio (OR), 0.62; 95%CI, 0.33, 1.17; P = 0.14]. Even the 30-d mortality rate was not different between COVID-19 non-infected patients who were treated during the pandemic time, and all hip fracture patients treated during the pre-pandemic period (OR, 1.03; 95%CI, 0.61, 1.75; P = 0.91). A significant difference in mortality rate was observed between COVID-19 positive and COVID-19 negative patients (OR, 6.99; 95%CI, 3.45, 14.16; P < 0.00001). There was no difference in the duration of hospital stay (OR, -1.52, 95%CI, -3.85, 0.81; P = 0.20), overall complications (OR, 1.62; P = 0.15) and incidence of pulmonary complications (OR, 1.46; P = 0.38) in these two-time frames. Nevertheless, the preoperative morbidity was more severe, and there was less use of general anesthesia during the pandemic time.CONCLUSIONThere was no difference in 30-d mortality rate between hip fracture patients treated during the pandemic and pre-pandemic periods. However, the mortality risk was higher in COVID-19 positive patients compared to COVID-19 negative patients. There was no difference in time to surgery, complications and hospitalization time between these two time periods.     

IMPORTANCE OF DONOR SELECTION IN RENAL TRANSPLANTATION

Renal transplantation has become a treatment of choice for patients with end stage renal disease. A successful transplant is the result of a combination of several factors acting synergistically, such as the degree of HLA compatibility between donor and the recipient, pretransplant blood transfusions, the recipient''s state of immunoreactivity and sensitization, immunosuppressive therapy given in post operative period etc. Donor selection appears to be the most critical factor for the long term success of the organ graft. In this brief review, some of the important parameters of donor selection in renal transplantation are highlighted.KEY WORDS: Histocompatibility (HLA) matching, Cross match, Sensitization     

Detecting collinear dots in noise

We estimated the sensitivity for detecting a row of collinear target elements (usually dots) by measuring the maximum density of randomly positioned noise elements that allowed 75% correct detection of the orientation of alignment (binary choice: horizontal versus vertical) of the target elements. We varied the number of target elements, their mode of generation, and their accuracy of positioning. As reported previously (Moulden (1994) Higher-order processing in the visual system. Ciba Foundation Symposium 184. Chichester: Wiley), target detection improved rapidly until the number of target elements reached about seven, and then improved more slowly beyond this point. However, this break was reduced (and often removed entirely) when the target array was formed by repositioning pre-existing noise elements lying close to the target location, rather than by superimposition of additional target elements onto the noise array. This almost linear slope of improvement, coupled with the observation that target detection was disrupted more by random jitter of target elements at right angles to their axis of alignment than by jittering along this axis, argues against a two-stage process of perceptual grouping (Moulden, 1994) and supports instead an explanation based on the operation of a single mechanism. This single mechanism explanation is further supported by the observation that intrinsic positional uncertainty (estimated from the results of jitter experiments) was independent of target element number. Additional experiments showed that target detection is facilitated by aperiodic noise dots that fall close to the target axis. The results are discussed in relation to alternative explanations of perceptual grouping.     

Proteus syndrome

Abstract: This female Asian (Malay) baby had clinical features of Proteus syndrome. She had a large right facial lipolymphangioma with hyperpigmentation of the overlying skin. There was a smaller lymphangioma over the left side of her neck with excess nuchal folds, macrodactyly and bilateral talipes equinovarus. Despite the extensive hemifacial swelling, there was no evidence of upper respiratory tract obstruction. Generalized seizures developed on the sixth day of life which were controlled with phenobarbital. The lymphangiomas were excised without recurrence.     

ANTIBIOTIC RESISTANCE PATTERN OF ISOLATES FROM WOUND AND SOFT TISSUE INFECTIONS

Two-hundred and eighty bacterial isolates from wound and soft tissue infections were studied for species identification and antibiotic resistance pattern. Amongst them 122 isolates were from community acquired infection and 158 were from nosocomial infections. The common community acquired pathogens were Staphylococcus aureus (67.8%) and Streptococcus pyogenes (10.7%), whereas Staphylococcus aureus (60.1%) and E. Coli (8.9%) were common in nosocomial infection. Only two anaerobes (Cl perfringens) were isolated. Penicillin resistance was found to be 87% and 92% for Staphylococccus aureus in community acquired and noscomial infections respectively. 85% of Proteus isolates were resistant to ampicillin. There was relatively lower level of resistance by all isolates to cefotaxime. Gentamicin showed higher rate of resistance than netilmicin and amikacin. Resistance of E. coli isolates to fluoroquinolones being 79% for norfloxacin, 81% for ciprofloxacin and 60% for ofloxacin. The study showed a higher resistance of methicillin resistant Staphylococcus aureus (MRSA) to other antibiotics. Amikacin and ofloxacin were the best recommended drugs for empirical therapy for all organisms, the susceptibility rate being 80.7% and 80.4%.KEY WORDS: Antibiotic resistance, Soft tissue infections, Wound infections