Mitral valve replacement in systemic lupus erythematosus associated Libman–Sacks endocarditis

Libman–Sacks endocarditis, first discovered in 1924, is a cardiac manifestation of systemic lupus erythematosus (SLE). Valvular involvement has been associated with SLE and antiphospholipid syndrome (APS). Mitral valve, especially its posterior leaflet, is most commonly involved.We report a case of a 34 year old woman with antiphospholipid antibody syndrome and SLE, who presented with mitral valve regurgitation. The patient underwent a prosthetic mitral valve replacement, with no followup complications.We suggest mechanical valve replacement employment in the management of mitral regurgitation in Libman–Sacks endocarditis, in view of the recent medical literature and our own case report.     

Hepatitis C therapy—the future looks bright

Hepatitis C virus (HCV) infections affect about 170 million individuals worldwide and can be life-threatening if left untreated. Over the past three decades, ribavirin and interferon-α have remained the only available medicines for treating hepatitis C sufferers. Given that this combination therapy is partially effective at best and is associated with severe side-effects, there is an unmet need for new molecular entities which inhibit HCV replication. By employing a combination of structure-based drug design together with high-throughput screening approaches, several pharmaceutical companies have been successful in identifying potentially useful compounds for treating HCV infections. This article provides an overview of some of the small-molecule inhibitors that have shown promise so far in clinical trials and which could reach the clinic within the next three years.     

A mixed Th1/Th2 response elicited by a liposomal formulation of Leishmania vaccine instructs Th1 responses and resistance to Leishmania donovani in susceptible BALB/c mice

In this study, we have developed a vaccine with Leishmania donovani promastigote membrane antigens (leishmanial antigens (LAg)) encapsulated in a liposome carrier formulated with distearyol (DSPC, transition temperature (Tc) = 54 degrees C) derivative of l-alpha-phosphatidyl choline, for immunizing BALB/c mice against progressive visceral leishmaniasis. This formulation could limit hepatosplenomegaly to almost normal levels and conferred strong levels of protection in both liver and spleen against challenge infection. Immunization with liposomal LAg activated peritoneal macrophages for enhanced leishmanicidal activity in association with NO production, and induced antibody as well as T-cell mediated immune responses. Production of both IFN-gamma and IL-4 by splenic T cells, and serum IgG1 and IgG2a, suggest induction of a mixed Th1/Th2 response following immunization. Experimental challenge corresponded with elevated DTH, and mitogen and antigen specific cellular responses. Increased production of NO and IFN-gamma by spleen cells, and down regulation of IL-4, demonstrate that an initial stimulation of a mixed Th1/Th2 response by vaccination instructs Th1 responses and resistance against a progressive infection by L. donovani.     

Survival from oral cancer in Mumbai (Bombay), India

OBJECTIVE: Cancer survival information is available for only few populations in developing countries. Data on survival of oral cancer patients registered by the Bombay population-based cancer registry, India, during 1992-1994 is presented in this paper. METHODS: Vital status of the patients was established by matching against death certificates, reply paid postal enquiries, telephone enquiries, scrutiny of hospital records and house visits. Of the 1808 eligible cases for analysis, 1204 (66.6%) were dead; and 604 (33.4%) were alive at last follow-up, of whom 136 were lost to follow-up during the first 5-years after diagnosis. Observed and relative survival rates are presented and hazard ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazard model. RESULTS: The overall 5-year observed and relative survival rates were 30.5% and 39.7%, respectively. Survival steadily declined with advancing age and advanced clinical stages. Five-year observed survival was 59.1% for localised cancer, 15.7% for cancers with regional extension and 1.6% for those with distant metastasis. Those with tongue, buccal mucosa and retromolar trigone cancers had poor survival rates. CONCLUSIONS: Our study shows that detecting oral cancer in early stages, when these are amenable to single modality therapies, offers the best chance of long-term survival. However, primary prevention by tobacco/alcohol control measures is important in the long-term perspective.     

Characterization of immunoglobulin G and its subclass response to Indian kala-azar infection before and after chemotherapy

Serologic parameters of kala-azar were evaluated by Western blot analysis. Sera from kala-azar patients with confirmed diagnoses were screened for immunoglobulin G (IgG) and IgG subclass-specific reactivity against Leishmania donovani membrane antigen (LAg). Heterogeneous LAg-specific IgG reactivity with numerous proteins with molecular masses ranging from 18 to 190 kDa was observed. Though the individual band patterns were varied, seven polypeptides of approximately 31, 34, 51, 63, 72, 91, and 120 kDa were immunoreactive with all the sera tested from kala-azar patients. The band patterns of the immunoblots of sera from patients after treatment and clinical cure with sodium antimony gluconate revealed a decrease in the frequency of the bands. Still, recognition of the 63- and 120-kDa bands was 100%, and the 55- and 91-kDa fractions were recognized in 93% of the sera from cured individuals. Among the IgG subclasses, IgG1 reacted with the greatest number of polypeptides. The 63-kDa protein was again detected by all of the IgG subclasses of all the sera tested. Other fractions recognized by the subclasses of more than 70% of the serum samples included those of 47, 51, 55, and 78 kDa. Following treatment, 63- and 51-kDa bands were the most reactive with the IgG subclasses. LAg-associated cross-reaction with other reference human antisera revealed a mild reactivity of the 63-kDa polypeptide with some of the serum samples from leprosy, malaria, typhoid, tuberculosis, and healthy controls. Western blot analysis of LAg entrapped in liposomes, strong vaccine candidates against experimental visceral leishmaniasis, revealed a more restricted band pattern. The 63-kDa fraction revealed by all pre- and posttreatment sera showed almost negligible levels of cross-reaction with sera from patients with other diseases or from healthy controls. These observations provide insight into induced immunity during kala-azar infection for future application.     

Characterization of Leishmania donovani antigens encapsulated in liposomes that induce protective immunity in BALB/c mice

Leishmania donovani promastigote membrane antigens (LAg) encapsulated in positively charged liposomes have been found to induce very significant levels of protection against experimental visceral leishmaniasis. The protectively immunized animals exhibited profound delayed-type hypersensitivity and antibody responses. The extent of protection induced by the same antigens, however, varied depending on the charge of the vesicles, with maximum induction by positively charged liposomes, followed by neutral liposomes and last negatively charged liposomes. Characterization of LAg and LAg entrapped in liposomes of different charges by Western blot analysis revealed the immunodominance of gp63 in all three vaccine preparations. The strong reactivity of antigens in a restricted antigen profile that included, in addition to gp63, 72-, 52-, 48-, 45-, 39-, and 20-kDa components in neutral and positively charged liposomes contrasted with the reactivity of a greater number of LAg components in negatively charged liposomes. Resistance to visceral leishmaniasis appears to depend on the immunity induced by gp63 and a few select antigens in association with the right liposomes. A striking similarity between the immunogenic profile of partially purified soluble antigens and that of LAg in neutral and positively charged liposomes suggests the potentiality of these antigens in future vaccine studies of L. donovani.     

Correction: Efficient biomass saccharification using a novel cellobiohydrolase from Clostridium clariflavum for utilization in biofuel industry

Correction for ‘Efficient biomass saccharification using a novel cellobiohydrolase from Clostridium clariflavum for utilization in biofuel industry’ by Asma Zafar et al., RSC Adv., 2021, 11, 9246–9261, DOI: 10.1039/D1RA00545F.

The authors regret that in the original article, the name and affiliation for one of the co-authors (Hasan Ufak Celebioglu) were incorrectly given. The correct name and affiliation are shown here.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Are there gender differences in objective and subjective sleep measures? A study of insomniacs and healthy controls

It is well known that insomnia is more frequent in women than in men throughout all age groups. In this respect insomnia resembles other psychiatric disorders that occur more frequently in women such as anxiety and depressive disorders. Since insomnia is frequently a symptom of anxiety and depression, it remains an open question whether the comorbidity with psychiatric disorders fully explains the gender differences in the prevalence of insomnia or whether gender influences sleep independently from psychiatric conditions. We analyzed sleep measures of patients diagnosed with a primary insomnia (n=86) and of an age- and sex-matched healthy control group (n=86) by polysomnography; additionally, subjective rating scales were available for 70 patients and 54 controls matched for mean age and sex ratio. Surprisingly, none of the sleep continuity measures (sleep duration, sleep efficiency, arousal index, and wake%), nor slow wave or REM sleep % showed significant gender differences in both insomniacs and healthy controls. Also, subjective estimates of sleep quality were comparable in both sexes. As expected, insomniacs strongly differed from the control group in all subjective measures of sleep. Polysomnography showed significantly reduced sleep duration and efficiency, increased arousal index, and slightly, but significantly, less REM sleep in the insomniacs as compared to the healthy controls. These studies indicate that gender seems to have, if any, relatively little influence on sleep per se. We hypothesize that the clear gender differences in the prevalence of insomnia are caused predominantly by gender differences in the prevalence of anxiety and depression. Primary insomnia may be, at least in a part of the cases, a subclinical or subthreshold form of anxiety or depression.     

Exploring the impact of cancer registry completeness on international cancer survival differences: a simulation study

Background Data from population-based cancer registries are often used to compare cancer survival between countries or regions. The ICBP SURVMARK-2 study is an international partnership aiming to quantify and explore the reasons behind survival differences across high-income countries. However, the magnitude and relevance of differences in cancer survival between countries have been questioned, as it is argued that observed survival variations may be explained, at least in part, by differences in cancer registration practice, completeness and the availability and quality of the respective data sources.Methods As part of the ICBP SURVMARK-2 study, we used a simulation approach to better understand how differences in completeness, the characteristics of those missed and inclusion of cases found from death certificates can impact on cancer survival estimates.Results Bias in 1- and 5-year net survival estimates for 216 simulated scenarios is presented. Out of the investigated factors, the proportion of cases not registered through sources other than death certificates, had the largest impact on survival estimates.Conclusion Our results show that the differences in registration practice between participating countries could in our most extreme scenarios explain only a part of the largest observed differences in cancer survival.Subject terms: Epidemiology, Cancer epidemiology     

Methylation of viral and host genes and severity of cervical lesions associated with human papillomavirus type 16

Methylation of human papillomavirus (HPV) and host genes may predict cervical cancer risk. We examined the methylation status of selected sites in HPV16 and human genes in DNA extracted from exfoliated cervical cell samples of 244 women harboring HPV16‐positive cancer or cervical intraepithelial neoplasia (CIN) or negative for intraepithelial lesions or malignancy (NILM). We quantified the methylation of CpG sites in the HPV16 L1 gene (CpG 6367 and 6389) and in the human genes EPB41L3 (CpG 438, 427, 425) and LMX1 (CpG 260, 262, 266, 274) following bisulfite treatment and pyrosequencing. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic utility of methylation level for the different sites and for a joint predictor score. Methylation in all sites significantly increased with lesion severity (p < 0.0001). Area under the curve (AUC) was highest among the CIN2/3 vs. cancer ranging from 0.786 to 0.853 among the different sites. Site‐specific methylation levels strongly discriminated CIN2/3 from NILM/CIN1 and cancer from CIN2/3 (range of odds ratios [OR]: 3.69–12.76, range of lower 95% confidence bounds: 1.03–4.01). When methylation levels were mutually adjusted for each other EPB41L3 was the only independent predictor of CIN2/3 vs. NILM/CIN1 contrasts (OR = 9.94, 95%CI: 2.46–40.27). High methylation levels of viral and host genes are common among precancerous and cancer lesions and can serve as independent risk biomarkers. Methylation of host genes LMX1 and EPB41L3 and of the viral HPV16 L1 sites has the potential to distinguish among precancerous lesions and to distinguish the latter from invasive disease.