Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system resulting from the productive infection of oligodendrocytes by the opportunistic polyomavirus JC virus (JCV). Apoptosis is a host defense mechanism to dispose of damaged cells; however, certain viruses have the ability to deregulate apoptotic pathways to complete their life cycles. One such pathway involves survivin, a member of the inhibitor of apoptosis family, which is abundantly expressed during development in proliferating tissues but should be absent in normal, terminally differentiated cells. Immunohistochemistry performed in 20 cases of PML revealed the presence of survivin in JCV-infected oligodendrocytes and bizarre astrocytes within demyelinated plaques. Survivin up-regulation was also found in oligodendroglial and astrocytic cultures infected with JCV. Cell cycle analysis and DNA laddering demonstrated a significantly lower number of cells undergoing apoptosis on JCV infection compared with noninfected cultures; small interfering RNA inhibition of survivin resulted in a dramatic increase in apoptotic cells in JCV-infected cultures. This is the first report describing the activation of survivin by JCV infection in vitro and in PML clinical cases. These observations provide new insights into the anti-apoptotic mechanisms used by JCV to complete its lytic cycle and may suggest new therapeutic targets for PML. 相似文献
The objective of this review is to identify enabling and inhibiting factors for mHealth adoption in low resource settings, by giving emphasis on the stakeholders representing the caregiving side. Another objective of this study is to support implementation agencies (governmental and non-governmental) in designing scalable mHealth interventions.
Methods
A PEO (Population, Exposure, Outcome) approach was used to formulate the review question. A pre-defined search strategy was implemented; Google Scholar, PubMed and gray literature were searched using alternate terms for “mHealth”, “adoption” and “developing countries”. CASP [7] tools were used to assess the quality of selected evidence. After applying inclusion and exclusion criteria on search results and critical appraisal of the selected evidence, twelve studies were selected for the review.
Results
Adoption factors operated at the levels of organization, facility-based service provider and frontline health worker. Engagement of end users during design phase, informed clinical decision making, utilization of mHealth evidence, employers’ tolerance of some personal use of devices, automation of tasks and user-friendliness of application are key enabling factors for mHealth adoption in developing countries. On the contrary, absence of national policy on mHealth, poor knowledge base on mHealth, using two systems in parallel, duplication of efforts, poor Internet connectivity and shortage of electricity are important inhibiting factors for mHealth adoption.
Conclusions
The review provides an insight about the challenges and opportunities related to mHealth adoption in developing countries. Implementation agencies should give careful consideration to these factors before designing and deploying any mHealth-enabled intervention. It is also important to understand the concept of incremental innovation so that resources spent on pilot interventions are optimized and full potential is achieved. 相似文献
Despite being a potent anticancer drug, nephrotoxicity is an adverse effect which renders the clinical use of cisplatin (Cis) limited. The protective role of diallyl sulfide (DAS); a naturally occurring organo‐sulfide, present in garlic, in cisplatin‐induced nephrotoxicity has been reported earlier. However, the mechanism through which DAS exerts its nephroprotective activity remains elusive. The aim of the current study was to elucidate the possible mechanisms underlying the reno‐protective effect of DAS in cisplatin‐induced nephrotoxicity in rats. DAS was given at 2 dose levels; 50 and 100 mg/kg, orally for 4 consecutive days, starting 1 hour after administration of single dose of cisplatin (3.5 mg/kg, intraperitoneally [i.p.]). The Cis‐induced elevation in serum urea and creatinine, degree of histopathological alterations was significantly ameliorated in cisplatin groups co‐treated with DAS. In addition, DAS significantly restored Cis‐depleted glutathione (GSH) content and superoxide dismutase (SOD) activity and attenuated Cis‐elevated Malondialdehyde (MDA) level. Also, DAS significantly reduced Cis‐increased renal expression of nuclear factor kappa B (NF‐κB) and subsequent pro‐inflammatory mediators; tumour necrosis factor alpha (TNF‐α), interleukin‐1β (IL‐1β), intercellular adhesion molecule‐1 (ICAM‐1) and inducible nitric oxide synthase (iNOS) in kidney tissues. Moreover, co‐treatment with DAS significantly inhibited Cis‐increased caspase‐8 and ‐9 levels. Additionally, DAS significantly mitigated Cis‐induced protein expression of p53, Puma, and Bax while, it significantly restored Cis‐reduced protein expression of Bcl‐xL compared to the Cis group. In conclusion, these results demonstrate that DAS ameliorates cisplatin‐induced nephrotoxicity in rats through enhancement of antioxidant defense, reduction of inflammatory cytokine tissue levels as well as inhibition of apoptosis via p53/Puma signalling pathway. 相似文献
The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy. 相似文献
Benign prostatic hypertrophy or hyperplasia (BPH) is a frequent urological complain particularly in old-aged individuals. Those patients usually have other risk factors (such as ischemic cardiovascular diseases) for which they might be treated with anti-thrombotic agents chronically. These medicines may induce blood thinning and raise the incidence of hemorrhage. Thus, if those patients needed operative treatment for BPH, they may be at high risk of hemorrhage or its related adverse effects with the usage of anti-thrombotic drugs during the peri-operative time. On the other hand, dis-continuation of these agents can lead to ischemic events in susceptible individuals.
Therefore, this research aims to assess the safety of the continuation of using anti-thrombotic agents throughout the peri-operative duration in patients with prostate surgery in form of Transurethral Resection of Prostate (TURP) only for Benign Prostatic Hypertrophy (BPH).
Methods
Patients’ notes were reviewed retrospectively. The entire participants were categorized into two categories. First category was on clopidogrel therapy (CTC) for prolong time and the usage of these agents was carried on throughout the peri-operative period. The second category was not on clopidogrel therapy at all (NCTC). Both of these categories had Transurethral Resection of Prostate (TURP) for Benign Prostatic Hypertrophy (BPH). A comparison had been conducted between the two categories with regards to: (i) the amount of blood lost intra-operatively (ii) the duration of operation (iii) hematocrit concentration per-operatively (iv) transfused packed red blood cells (PRBC) if needed (v) clearance of hematuria postoperatively (vi) secondary hemorrhage and clot retention after discharge. Pearson Chi-square test, Independent sample t test and test for numeric variables were used as appropriate.
Results
The study identified 329 patients. One hundred and sixty five participants in the CTC (clopidogrel therapy category) and 164 in the NCTC (non-clopidogrel therapy category). It had been revealed that there was no statistically significant difference between the CTC and NCTC regarding: (i) the amount of blood lost intra-operatively (ii) the duration of operation (iii) hematocrit concentration per-operatively (iv) transfused packed red blood cells (packed RBC) if needed (v) clearance of hematuria postoperatively (vi) secondary hemorrhage and clot retention after discharge (P?>?0.65).
Conclusion
The continuation of usage of anti-thrombotic therapy (clopidogrel) during peri-operative period in patients with TURP for BPH is a safe practice. It is not associated with high probability of hemorrhage or PRBC transfusion or other adverse effects.
Aim: Catheter associated urinary tract infections (CAUTI) are the most common hospital-acquired infection in ICUs. The aim of this study was to estimate the effectiveness of an intervention program by implementing urinary catheter bundle elements to reduce the CAUTI frequency in an ICU. Methods: The intervention study was conducted over a period of 6 months. During a pre-intervention phase, the base line catheter associated CAUTI incidence rates were determined and compared with the incidence rates during the post-intervention phase. The compliance of health care staff with urinary catheter bundle elements was also measured. The implemented CAUTI prevention bundle consisted of hand hygiene, wearing personal protective equipment, use of disposable gloves, cleansing of urethral meatus prior to catheter insertion using sterile saline, assessment of catheter need, aseptic urine sampling technique, and correct draining bag positioning.Results: During the study period, 55 out of 77 patients were diagnosed with a CAUTI. The mean CAUTI incidence rate for the pre-intervention period was 90.12/1,000 catheter days and for the post intervention phase 65.69/1,000 catheter days. The CAUTIs rate was inversely proportional to insertion bundle elements and maintenance bundle elements compliance rate. This negative relationship was statistically significant only with maintenance bundle elements (p=0.042) (rs=–0.828). The compliance rate of the ICU nurses to the bundle elements was raised to 100% during the last 2 months of the post intervention phase.Conclusion: Increased compliance to recommended catheter associated urinary tract infections preventive practices reduced the incidence of CAUTI in an ICU unit. It is simple and effective and is recommended as a part of patient safety culture. 相似文献