Peripheral arterial disease (PAD) is a common complication of Diabetes Mellitus (DM) and often culminates in amputation of the affected foot. Pseudomonas aeruginosa infections associated with PAD are difficult to treat due to their multi-drug resistance. Herein we report a 38 year old male who reported with DM, chronic kidney disease (CKD) and rest pain of the right second toe in October 2011. He underwent percutaneous transluminal angioplasty (PTA) which was unsuccessful. The gangrene of the toes worsened and amputation of the right second toe was done. Bacteriological examination showed presence of P. aeruginosa which during the course of antibiotic therapy became multi-drug resistant. Gangrene and abscess of the foot worsened and amputation of the right third toe was performed. Then autologous peripheral blood mononuclear cell (PBMNC) therapy was performed but as infection control could not still be achieved, the fourth toe was amputated. A protocol of foot bath using carbonic water, local usage of antibiotics (Polymyxin-B), and basic fibroblast growth factor (b-FGF) spray was then employed after which the infection could be controlled and improvement in vascularity of the right foot could be observed in angiography. This combined approach after proper validation could be considered for similar cases.
Abscess ; Amputation ; Angiography ; Angioplasty ; Anti-Bacterial Agents ; Baths ; Carbon ; Cell- and Tissue-Based Therapy ; Diabetes Mellitus ; Drug Resistance, Multiple ; Fibroblast Growth Factor 2 ; Fibroblast Growth Factors* ; Foot ; Gangrene* ; Humans ; Infection Control* ; Kidney Failure, Chronic* ; Limb Salvage* ; Male ; Peripheral Arterial Disease ; Pseudomonas aeruginosa ; Renal Insufficiency, Chronic ; Toes* ; Water

The purpose of this study was to investigate the actual conditions of nosocomial infection control in Kathmandu City, Nepal as a basis for the possible contribution to its improvement. The survey was conducted at 17 hospitals and the methods included a questionnaire, site visits and interviews. Nine hospitals had manuals on nosocomial infection control, and seven had an infection control committee (ICC). The number of hospitals that met the required amount of personal protective equipment preparation was as follows: gowns (13), gloves (13), surgical masks (12). Six hospitals had carried out in-service training over the past one year, but seven hospitals responded that no staff had been trained. Eight hospitals were conducting surveillance based on the results of bacteriological testing. The major problems included inadequate management of ICC, insufficient training opportunities for hospital staff, and lack of essential equipment. Moreover, increasing bacterial resistance to antibiotics was recognized as a growing issue. In comparison with the results conducted in 2003 targeting five governmental hospitals, a steady improvement was observed, but further improvements are needed in terms of the provision of high quality medical care. Particularly, dissemination of appropriate manuals, enhancement of basic techniques, and strengthening of the infection control system should be given priority.

STUDY DESIGN: We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. PURPOSE: We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. OVERVIEW OF LITERATURE: SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues. METHODS: Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology. RESULTS: We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology. CONCLUSIONS: We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.
Cells, Cultured ; Ethics ; Fibroblasts ; Humans ; Induced Pluripotent Stem Cells* ; Infant, Newborn* ; Meningomyelocele ; Plasmids ; Pluripotent Stem Cells ; Regenerative Medicine ; Skin ; Spina Bifida Cystica* ; Spinal Cord ; Spinal Dysraphism* ; Stem Cell Transplantation ; Stem Cells

Introduction Zinc,an essential trace element in the human body,is known to serve as the active center of approxi-mately 300 enzymes.Zinc deficiency causes various pathological conditions such as growth retardation,immunodeficiency,and neurological degeneration.Zinc deficiency is typically the result of inadequate dietary intake of zinc,the recommended dietary allow-ance for zinc has been presented for healthy individ-uals in the“Dietary Reference Intakes for Japanese,2005”by the Japanese Ministry of Health,Labor,and Welfare. However,we have recently reported that zinc deficiency is common in elderly bedridden patients receiving long- termenteral nutrition based on the recommended dietary allowance,and that zinc deficiency may be associated with increased suscepti-bility to infections in those patients.On the basis of the findings,we have proposed that zinc preparations should be added to the standard enteral formulas to prevent infectious diseases in elderly bedridden patients.Ordinarily,zinc preparations used for zinc therapy are inorganic salts(e.g.,zinc sulphate,zinc picolinate,or zinc chloride)and organic compounds(e.g.,polaprezinc or zinc gluconate).Previous studies have revealed the different activities for zinc therapy between inorganic salts and organic compoundsWe carried out a randomized crossover study to compare organic zinc compounds with inorganic zinc salts,looking at whether there was a difference in their effects on serum zinc and cupper concentrations in elderly bedridden patients receiving long-term stan-dard enteral nutrition.We used zinc chloride as an inorganic salt and polaprezinc as an organic com-pound.Polaprezinc［N-(3- aminopropionyl)-Lhistidinato zinc］,a chelating compound of zinc ion and L- carnosine,is commonly used in the treatment of gastric ulcers in Japan.7 In addition,we carried out a pilot study to examine the therapeutic effects of polapr- ezinc on pressure ulcer healing in elderly bedridden patients receiving long-term standard enteral nutrition because zinc is essential for the wound-healing process.

Objective. Molecular chaperone 78 kDa glucose-regulated protein (GRP78) is a residential protein in the endoplasmic reticulum (ER) that is induced by an unfolded- protein response triggered under many kinds of stress against a cell. GRP78 is also known to act as an anti-apoptotic factor by protecting ER-stress- induced cell death. In this study, we examined the significance of GRP78 expression in endometrial cancer. Methods. Tissue samples obtained from patients with a diagnosis of enodometrial cancer were subjected to immunohistochemistry and RT-PCR to determine protein and mRNA expression levels of GRP78 and estro- gen receptor α. We used Western blot and RT-PCR to examine whether estrogen induced GRP78 expression in cancer cell lines. Western blots and MTT assays of GRP78 siRNA transfected Ishikawa and HHUA cells were used to demonstrate whether GRP78 is involved in chemoresistence. Results. GRP78 was highly expressed in well and moderately differentiated endometrial carcinoma. Estrogen induced GRP78 expression, which was correlated with cell viability and resistance to paclitaxel and cisplatin. Western blot analysis indicated that active caspase-3 and the 85-kDa protein poly (ADPribose) polymerase (PARP) were increased by incubation with either paclitaxel or cisplatin, suggesting that the apoptotic pathway was involved in cancer-drug-induced cell death. Conclusions. These results may open up a novel therapeutic strategy for endometrial cancer: namely, the targeting of GRP78 to sensitize the tumor cell to chemotherapy.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.