Health expenditure and catastrophic spending among older adults living with HIV

Introduction: The burden of HIV is increasing among adults aged over 50, who generally experience increased risk of cormorbid illnesses and poorer financial protection. We compared patterns of health utilisation and expenditure among HIV-positive and HIV-negative adults over 50. Methods: Data were drawn from the Study on global AGEing and adult health in South Africa with analysis focusing on individual and household-level data of 147 HIV-positive and 2725 HIV-negative respondents. Results: HIV-positive respondents reported lower utilisation of private health-care facilities (11.8%) than HIV-negative respondents (25.0%) (p?=?.03) and generally had more negative attitudes towards health system responsiveness than HIV-negative counterparts. Less than 10% of HIV-positive and HIV-negative respondents experienced catastrophic health expenditure (CHE). Women (OR 1.8; p?p?Conclusions: These findings suggest that although HIV-positive and HIV-negative older adults in South Africa are protected to some extent from CHE, inequalities still exist in access to and quality of care available at health-care services – which can inform South Africa’s development of a national health insurance scheme.     

Ellagic acid inhibits RANKL-induced osteoclast differentiation by suppressing the p38 MAP kinase pathway

Bone undergoes continuous remodeling by a coupled action between osteoblasts and osteoclasts. During osteoporosis, osteoclast activity is often elevated leading to increased bone destruction. Hence, osteoclasts are deemed as potential therapeutic targets to alleviate bone loss. Ellagic acid (EA) is a polyphenol reported to possess anticancer, antioxidant and anti-inflammatory properties. However, its effects on osteoclast formation and function have not yet been examined. Here, we explored the effects of EA on RANKL-induced osteoclast differentiation in RAW264.7 murine macrophages (in vitro) and human CD14⁺monocytes (ex vivo). EA dose-dependently attenuated RANKL-induced TRAP⁺ osteoclast formation in osteoclast progenitors with maximal inhibition seen at 1 µM concentration without cytotoxicity. Moreover, owing to perturbed osteoclastogenesis, EA disrupted actin ring formation and bone resorptive function of osteoclasts. Analysis of the underlying molecular mechanisms revealed that EA suppressed the phosphorylation and activation of the p38 MAP kinase pathway which subsequently impaired the RANKL-induced differentiation of osteoclast progenitors. Taken together, these novel results indicate that EA alleviates osteoclastogenesis by suppressing the p38 signaling pathway downstream of RANKL and exerts inhibitory effects on bone resorption and actin ring formation.     

The BMI1 inhibitor PTC-209 is a potential compound to halt cellular growth in biliary tract cancer cells

BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and is up-regulated in biliary tract cancer (BTC), contributing to aggressive clinical features. In this study we investigated the cytotoxic effects of PTC-209, a recently developed inhibitor of BMI1, in BTC cells. PTC-209 reduced overall viability in BTC cell lines in a dose-dependent fashion (0.04 - 20 μM). Treatment with PTC-209 led to slightly enhanced caspase activity and stop of cell proliferation. Cell cycle analysis revealed that PTC-209 caused cell cycle arrest at the G1/S checkpoint. A comprehensive investigation of expression changes of cell cycle-related genes showed that PTC-209 caused significant down-regulation of cell cycle-promoting genes as well as of genes that contribute to DNA synthesis initiation and DNA repair, respectively. This was accompanied by significantly elevated mRNA levels of cell cycle inhibitors. In addition, PTC-209 reduced sphere formation and, in a cell line-dependent manner, aldehyde dehydrogease-1 positive cells. We conclude that PTC-209 might be a promising drug for future in vitro and in vivo studies in BTC.     

Is ERAS in laparoscopic surgery for colorectal cancer changing risk factors for delayed recovery?

There is evidence that implementation of enhanced recovery after surgery (ERAS) protocols into colorectal surgery reduces complication rate and improves postoperative recovery. However, most published papers on ERAS outcomes and length of stay in hospital (LOS) include patients undergoing open resections. The aim of this pilot study was to determine the factors affecting recovery and LOS in patients after laparoscopic colorectal surgery for cancer combined with ERAS protocol. One hundred and forty-three consecutive patients undergoing elective laparoscopic resection were prospectively evaluated. They were divided into two subgroups depending on their reaching the targeted length of stay—LOS (75 patients in group 1—≤4 days, 68 patients in group 2—>4 days). A univariate and multivariate logistic regression analysis was performed to assess for factors (demographics, perioperative parameters, complications and compliance with the ERAS protocol) independently associated with LOS of 4 days or longer. The median LOS in the entire group was 4 days. The postoperative complication rate was higher (18.7 vs. 36.7 %), and the compliance with ERAS protocol was lower (91.2 vs. 76.7 %) in group 2. There was an association between the pre- and postoperative compliance and the subsequent complications. In uni- and multivariate analysis, the lack of balanced fluid therapy (OR 3.87), lack of early mobilization (OR 20.74), prolonged urinary catheterization (OR 4.58) and use of drainage (OR 2.86) were significantly associated with prolonged LOS. Neither traditional patient risk factors nor the stage of the cancer was predictive of the duration of hospital stay. Instead, compliance with the ERAS protocol seems to influence recovery and LOS when applied to laparoscopic colorectal cancer surgery.     

Thiamine antivitamins – an opportunity of therapy of fungal infections caused by Malassezia pachydermatis and Candida albicans

Severe skin diseases and systemic fungaemia are caused by Malassezia pachydermatis and Candida albicans respectively. Antifungal therapies are less effective because of chronic character of infections and high percentage of relapses. Therefore, there is a great need to develop new strategies of antifungal therapies. We previously found that oxythiamine decreases proliferation of yeast (Saccharomyces cerevisiae), therefore we suggest that thiamine antivitamins can be considered as antifungal agents. The aim of this study was the comparison of thiamine antivitamins (oxythiamine, amprolium, thiochrome, tetrahydrothiamine and tetrahydrooxythiamine) inhibitory effect on the growth rate and energetic metabolism efficiency in non‐pathogenic S. cerevisiae and two potentially pathogenic species M. pachydermatis and C. albicans. Investigated species were cultured on a Sabouraud medium supplemented with trace elements in the presence (40 mg l^?1) or absence of each tested antivitamins to estimate their influence on growth rate, enzyme activity and kinetic parameters of pyruvate decarboxylase and malate dehydrogenase of each tested species. Oxythiamine was the only antivitamin with antifungal potential. M. pachydermatis and S. cerevisiae were the most sensitive, whereas C. albicans was the least sensitive to oxythiamine action. Oxythiamine can be considered as supportive agent in superficial mycoses treatment, especially those caused by species from the genus Malassezia.     

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation

The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/?) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100?% penetrance, as compared to 16?% in the local GEM model, with an average survival time of 66?±?55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.     

Detection of dermatophytes in human nail and skin dust produced during podiatric treatments in people without typical clinical signs of mycoses

Pedicures are the most common cosmetic foot treatment. Many pedicurists and podiatrists suffer from respiratory infections and diseases such as asthma, sinusitis, chronic cough and bronchitis. Skin and nail dust may play an important role in the development of occupational diseases and the transmission of mycosis to other clients. To examine the presence of dermatophytes in nail and skin dust produced during podiatric treatments of people without typical symptoms of mycosis and to assess the epidemiological hazards of tinea pedis for podiatrists as well as other clients. Seventy‐seven samples underwent direct microscopy and culture. The results of direct microscopy were positive in 28/77 samples (36.36%) and doubtful in 3/77 (3.9%). Fungi were cultured from 36/77 samples (46.75%), including 8/77 (10.3%) positive for dermatophytes (Trichophyton rubrum‐6 isolates and Trichophyton mentagrophytes‐2). Material collected during podiatric treatments is potentially infected by pathogenic fungi; thus, there is a need to protect both workers who perform such treatments, as well as other clients, to prevent the transmission of pathogens in the Salon environment. Exposure to this occupational hazard may increase not only the risk of respiratory infections but also increase asthmatic or allergic reactions to Trichophyton.     

Marian Zierski (1906-1998): world-famous Polish phtysiatrist

Marian Zierski was born in Lviv on May 1, 1906. He studied medicine at the Jan Kazimierz University in Lviv and the Charles University in Prague, where he received his medical degree. Before and during Second World War (until 1942) he worked in Lviv and then he moved to Warsaw. He experienced the tragedy of the Warsaw Uprising (1944) and the total destruction of the city. After the war he settled in Lód?. He held numerous managerial posts in medical care institutions in Lód?. There he also established a tuberculosis outpatient clinic for students. At the same time, Zierski carried out phtysiatric research publishing numerous works (approx. 300) and participating in conventions and scientific conferences both in the country and abroad. Apart from many awards and offices, Prof. Marian Zierski was a holder of an honorary doctorate of universities in Great Britain, Brazil, Germany, France, the USA and Hungary.     

Dissociated production of perforin, granzyme B, and IFN-gamma by HIV-specific CD8(+) cells in HIV infection

CD8(+) T cells play a crucial role in the control of viral infections such as HIV. The functional characterization of HIV-specific CD8(+) T cells has so far been largely restricted to studies of IFN-gamma. The TCR-triggered release of the effector molecules perforin (PFN) and granzyme B (GzB), however, is thought to be a central pathway for the destruction of virus-infected target cells by CD8(+) effector T cells. Here we would like to address two major findings. On the one hand we propose that ex vivo measurements of PFN and GzB secretion via ELISPOT may permit the distinction between in vivo resting versus activated CD8(+) memory T cells in healthy and HIV-infected individuals. Therefore, extending the present standard of IFN-gamma measurements to the analysis of PFN and GzB release in functional T cell assays will provide new insights into CD8(+) effector T cell functions. It should enable the evaluation of therapeutic vaccination efficacy by its ability to reactivate and convert IFN-gamma-positive, but GzB- and PFN-negative memory CD8(+) T cells into PFN/GzB-secreting effector cells. On the other hand, we report on a frequent ex vivo dissociation of the HIV peptide-induced secretion of PFN and GzB in chronic HIV infection underlining CD8(+) effector T cell diversity in this disease--an aspect that also has to be accounted for in immune monitoring approaches.