The surgical management of penile oleogranuloma: case series.

Oleogranuloma of the penis is a complex set of pathological processes caused by the injection of a foreign substance (gel, balls, rods, etc.) into the penis with the purpose of penile augmentation. In this case series, we investigated a variety of clinical presentations of oleogranuloma and described our experience in managing the complications. We analyzed data on 18 patients with penile self-injections admitted to the hospitals of Astana City, Kazakhstan, during an 11-year period. The mean age of patients at admittance was 37.4 ± 6.4 years. The most common substance of injection was Vaseline (n = 16, 88.9%). The mean interval between the time of injection and the first presentation to the hospital was 10.8 ± 6.5 years. Complications included necrosis (n = 13, 72.2%), pain or swelling (n = 6, 33.3%) and cosmetic dissatisfaction (n = 5, 27.8%). All patients received surgical treatment (n = 18, 100%): simple excision with primary closure was performed for one-half of the patients (n = 9, 50%), while another half of patients underwent the two-stage scrotum skin flap surgery (n = 9, 50%). The findings of this study should raise the awareness about the diverse clinical presentations of penile self-injections among physicians for early diagnosis and timely management.

Origin and evolution of subtype B variants in the former Soviet Union countries.

Contrary to the global trend, between 2010 and 2020, an increase of 43% new HIV infections was recorded in Eastern Europe and Central Asia. Analyses of phylogenetic relationship, and routes and modes of transmission of the HIV-1 subtype B across the former Soviet Union (FSU) region are currently lacking. The objective of this analysis was to investigate the origin and transmission routes of HIV subtype B in FSU countries. We performed phylogenetic and phylodynamic analyses using 21,007 publicly available subtype B sequences from Europe and Asia, including thirteen FSU countries. Our study suggests that BFSU strain evolved more recently in FSU countries (Russia, Kyrgyzstan, Uzbekistan, Tajikistan, Belarus, Ukraine, Lithuania, Latvia, Georgia, Armenia, Azerbaijan) compared to the Western B variant in Western Europe (Austria, Belgium, Germany, Luxembourg, Netherlands, Switzerland). The primary high-risk group responsible for the transmission of subtype B was found to be MSM/homosexual. Intermixing of phylogenetic clusters among high-risk groups and bridging with the general population indicated that the HIV epidemic is no longer confined to distinct key populations - emphasizing an urgent need to improve the HIV harm-reduction efforts among high risk as well as general populations.

Antiretroviral therapy resistance mutations among HIV infected people in Kazakhstan.

In Kazakhstan, the number of people living with HIV (PLHIV) has increased steadily by 39% since 2010. Development of antiretroviral therapy (ART) resistance mutations (ARTRM) is a major hurdle in achieving effective treatment and prevention against HIV. Using HIV pol sequences from 602 PLHIV from Kazakhstan, we analyzed ARTRMs for their association with factors that may promote development of ARTRMs. 56% PLHIV were infected with HIV subtype A6 and 42% with CRF02_AG. The ARTRM Q174K was associated with increased viral load and decreased CD4+ cell count, while infection with CRF02_AG was associated with a lower likelihood of Q174K. Interestingly, CRF02_AG was positively associated with the ARTRM L10V that, in turn, was observed frequently with darunavir administration. Infection with CRF02_AG was positively associated with the ARTRM S162A that, in turn, was frequently observed with the administration of nevirapine, also associated with lower CD4 counts. Zidovudine or Nevirapine receipt was associated with the development of the ARTRM E138A, that, in turn, was associated with lower CD4 counts. Determination of a patient's HIV variant can help guide ART choice in Kazakhstan. For example, PLHIV infected with CRF02_AG will benefit less from darunavir and nevirapine, and emtricitabine should replace zidovudine.

Hepatitis B, Hepatitis C, tuberculosis and sexually-transmitted infections among HIV positive patients in Kazakhstan.

In contrast with global trends, HIV prevalence in Kazakhstan and other Central Asian countries has been rising in recent years. In this study, we analyzed hepatitis B (HBV), hepatitis C (HCV), tuberculosis (TB) and sexually-transmitted (STI) co-infections among 500 HIV positive study participants recruited from all regions of Kazakhstan. Among our study participants, 27%, 8%, 2%, and 5% were coinfected with, respectively, HCV, TB, HBV, and STI. A considerable proportion of the study participants was also found with triple or quadruple infections of HCV/TB (12%), TB/STI (0.8%), HCV/STI (2%), HCV/HBV (1%), HBV/TB (0.4%), HBV/STI (0.2%), HBV/HCV/TB (0.4%), HBV/HCV/STI (0.2%), or HCV/TB/STI (0.2%). Strong associations were found of certain age groups, duration of HIV infection, and practices of injection drug use and sexual contact with PLWH, with co-infections of HIV/HCV and HIV/TB. The odds of having death was 4.07 times higher with TB/HIV as compared to other co-infections. Co-occurrence of HIV with HCV, HBV, and TB infections among participants of this study highlights the necessity of regular screening for HCV infection among HIV infected patients, together with implementation of vigilant vaccination protocols against HBV and TB. Additionally, persons who inject drugs especially need to be focused for harm reduction efforts that include opiate substitution therapy, needle or syringe exchange programs, regular screening, and increased availability of ART and direct acting antivirals.

Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance.

BACKGROUND: Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. METHOD: We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. RESULTS: We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. CONCLUSION: Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy.

Nuclear matrix metalloproteinases: functions resemble the evolution from the intracellular to the extracellular compartment.

Matrix metalloproteinase (MMP) is defined as an endopeptidase in the extracellular matrix (ECM), which plays essential roles in physiological processes such as organogenesis, wound healing, angiogenesis, apoptosis and motility. MMPs are produced and assembled in the cytoplasm as proenzymes with a cytoplasmic domain and require extracellular activation. MMPs can degrade receptors, extracellular matrix proteins, PARPs and release apoptotic substances. MMPs have been found in the cytosol, organelles and extracellular compartments and recently many types of MMPs have been found in the nucleus. However, the mechanisms and roles of MMPs inside the cell nucleus are still poorly understood. Here we summarized the nuclear localization mechanisms of MMPs and their functions in the nucleus such as apoptosis, tissue remodeling upon injury and cancer progression. Most importantly, we found that nuclear MMPs have evolved to translocate to membrane and target ECM possibly through evolution of nuclear localization signal (NLS), natural selection and anti-apoptotic survival. Thus, the knowledge about the evolution and regulation of nuclear MMPs appears to be essential in understanding a variety of cellular processes along with the development of MMP-targeted therapeutic drugs against the progression of certain diseases.