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Khat and stroke     
Khat chewing, though a tradition followed majorly in African countries, has of late spread widely across the globe due to faster transport systems and advanced preservation techniques. Many complications such as psychosis, arterial hypertension, angina pectoris, and myocardial infarction have been reported in connection to khat abuse. We present a case of a young man who presented with acute onset left-sided weakness. He was a known khat addict for over three decades. A diagnosis of left hemiplegia due to right middle cerebral artery infarction was established. Detailed evaluation revealed no significant underlying cause for stroke. Since the main central nervous system effects of khat are comparable with those of amphetamines and there are established reports of stroke in amphetamine abuse, the former was assumed to be the etiological factor. The patient was discontinued from taking khat and was managed conservatively. The subject showed significant recovery with no further complications or similar episodes during follow-up. To the best of our knowledge, this is the second case of stroke associated with khat. Since the management is essentially conservative, a vigilant history eliciting of khat abuse in prevalent countries would cut down unnecessary healthcare costs.  相似文献   
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Introduction

Open fractures in the elderly are distinct compared to younger populations. The purpose of this study is to follow a series of open fractures of the lower extremity in the geriatric population to better prognosticate outcomes.

Methods

We performed a retrospective chart review of patients over the age of 65 years old who were treated for an open, lower extremity fracture across two level I trauma medical systems. Patients were included if they had documented wound healing problems in the postoperative period, or 6 months of follow-up, or if they had a definitive radiographic outcome. Sixty-four patients were included of an average age of 76.23, of whom 73.4% were female.

Results

The fracture types were midshaft femur in 3, distal femur in 9, patella in 2, proximal tibia in 3, proximal fibula in 1, midshaft tibia in 14, distil tibia in 8, ankle in 23, and talar neck/calcaneus in 1. Forty-two fractures were the result of low energy mechanism and 22 fractures were from high energy mechanism. Fourteen fractures were type 1, 32 were type 2, 11 were type 3A, 6 were type 3B, and 1 was type 3C. At final follow-up, 13 wounds were well healed, 39 wounds were healed following a delay of more than 6 weeks to achieve healing, 3 were infected, 3 had been treated with amputation, 2 had chronic ulceration, 2 with active draining, and 2 had draining sinuses.

Discussion

Open lower extremity fractures are serious injuries with high rates of morbidity. Such risks are even higher in the geriatric population, particularly with regard to wound healing. This study provides important prognostic information in counseling geriatric patient with an open lower extremity fracture, as well as informs treatment in terms of wound surveillance and care in the postoperative period.

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Research Question:

Is LQAS technique better than cluster sampling technique in terms of resources to evaluate the immunization coverage in an urban area?

Objective:

To assess and compare the lot quality assurance sampling against cluster sampling in the evaluation of primary immunization coverage.

Study Design:

Population-based cross-sectional study.

Study Setting:

Areas under Mathikere Urban Health Center.

Study Subjects:

Children aged 12 months to 23 months.

Sample Size:

220 in cluster sampling, 76 in lot quality assurance sampling.

Statistical Analysis:

Percentages and Proportions, Chi square Test.

Results:

(1) Using cluster sampling, the percentage of completely immunized, partially immunized and unimmunized children were 84.09%, 14.09% and 1.82%, respectively. With lot quality assurance sampling, it was 92.11%, 6.58% and 1.31%, respectively. (2) Immunization coverage levels as evaluated by cluster sampling technique were not statistically different from the coverage value as obtained by lot quality assurance sampling techniques. Considering the time and resources required, it was found that lot quality assurance sampling is a better technique in evaluating the primary immunization coverage in urban area.  相似文献   
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Background

Cancer is a multifactorial disease, which makes it difficult to cure. Since more than one defective cellular component is often involved during oncogenesis, combination therapy is gaining prominence in the field of cancer therapeutics.

Objective

The purpose of this study was to investigate the combinatorial effects of a novel PARP inhibitor, P10, and HDAC inhibitor, SAHA, in leukemic cells.

Methods

Combinatorial effects of P10 and SAHA were tested using propidium iodide staining in different leukemic cells. Further, flowcytometry-based assays such as calcein-AM/ethidium homodimer staining, annexin-FITC/PI staining, and JC-1 staining were carried out to elucidate the mechanism of cell death. In addition, cell-cycle analysis, immunocytochemistry studies, and western blotting analysis were conducted to check the combinatorial effect in Nalm6 cells.

Results

Propidium iodide staining showed that P10 in combination with SAHA induced cell death in Nalm6 cells, in which PARP expression and activity is high with a combination index of <0.2. Annexin-FITC/PI staining, JC-1 staining, and other biochemical assays revealed that P10 in combination with SAHA induced apoptosis by causing a change in mitochondrial membrane potential in >65 % cells. Importantly, combinatorial treatment induced S phase arrest in 40-45 % cells due to DNA damage and plausible replicative stress. Finally, we demonstrated that treatment with P10 led to DNA strand breaks, which were further potentiated by SAHA (p?<?0.01), leading to activation of apoptosis and increased cell death in PARP-positive leukemic cells.

Conclusions

Our study reveals that coadministration of PARP inhibitor with SAHA could be used as a combination therapy against leukemic cells that possess high levels of intrinsic PARP activity.
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Hellenic Journal of Surgery - Fournier’s gangrene is an acute necrotising fasciitis affecting the perineal, perianal regions and genitalia. Cornerstones in treatment of Fournier’s...  相似文献   
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Targeting DNA repair with small-molecule inhibitors is an attractive strategy for cancer therapy. Majority of DNA double-strand breaks in mammalian cells are repaired through nonhomologous end-joining (NHEJ). It has been shown that small-molecule inhibitors of NHEJ can block efficient repair inside cancer cells, leading to cell death. Previously, we have reported that SCR7, an inhibitor of NHEJ can induce tumor regression in mice. Later studies have shown that different forms of SCR7 can inhibit DNA end-joining in Ligase IV-dependent manner. Recently, we have derivatized SCR7 by introducing spiro ring into core structure. Here, we report the identification of a novel inhibitor of NHEJ, named SCR130 with 20-fold higher efficacy in inducing cytotoxicity in cancer cell lines. SCR130 inhibited DNA end-joining catalyzed by rat tissue extract. Specificity analysis revealed that while SCR130 was specific to Ligase IV, it showed minimal or no effect on Ligase III and Ligase I mediated joining. Importantly, SCR130 exhibited the least cytotoxicity in Ligase IV-null cell line as compared with wild type, confirming Ligase IV-specificity. Furthermore, we demonstrate that SCR130 can potentiate the effect of radiation in cancer cells when used in combination with γ-radiation. Various cellular assays in conjunction with Western blot analysis revealed that treatment with SCR130 led to loss of mitochondrial membrane potential leading to cell death by activating both intrinsic and extrinsic pathways of apoptosis. Thus, we describe a novel inhibitor of NHEJ with higher efficacy and may have the potential to be developed as cancer therapeutic.  相似文献   
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