Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy

Hypoxia is a critical factor for cell death or survival in ischemic stroke, but the pathological consequences of combined ischemia-hypoxia are not fully understood. Here we examine this issue using a modified Levine/Vannucci procedure in adult mice that consists of unilateral common carotid artery occlusion and hypoxia with tightly regulated body temperature. At the cellular level, ischemia-hypoxia produced proinflammatory cytokines and simultaneously activated both prosurvival (eg, synthesis of heat shock 70 protein, phosphorylation of ERK and AKT) and proapoptosis signaling pathways (eg, release of cytochrome c and AIF from mitochondria, cleavage of caspase-9 and -8). However, caspase-3 was not activated, and very few cells completed the apoptosis process. Instead, many damaged neurons showed features of autophagic/lysosomal cell death. At the tissue level, ischemia-hypoxia caused persistent cerebral perfusion deficits even after release of the carotid artery occlusion. These changes were associated with both platelet deposition and fibrin accumulation within the cerebral circulation and would be expected to contribute to infarction. Complementary studies in fibrinogen-deficient mice revealed that the absence of fibrin and/or secondary fibrin-mediated inflammatory processes significantly attenuated brain damage. Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain.     

Related carbapenemase-producing <Emphasis Type="Italic">Klebsiella</Emphasis> isolates detected in both a hospital and associated aquatic environment in Sweden

Carbapenem antibiotics are one of the last-resort agents against multidrug-resistant (MDR) bacteria. The occurrence of carbapenemase-producing Enterobacteriaceae (CPE) in wastewater and aquatic environments is an indication of MDR bacteria in the community. This study evaluated CPE in aquatic environments and compared them to the local hospital isolates in Sweden. Phenotypic and genotypic analyses of antibiotic resistance of environmental and clinical CPE were performed. The relatedness of the isolates and possible clonal dissemination was evaluated using phylogenetic and phyloproteomic analysis. Klebsiella oxytoca carrying carbapenemase genes (bla_VIM-1, bla_IMP-29) were isolated from wastewater and the recipient river, while K. oxytoca (bla_VIM-1) and Klebsiella pneumoniae (bla_VIM-1, bla_OXA-48, bla_NDM-1, bla_KPC-3) were isolated from patients at the local clinics or hospital. The K. oxytoca classified as sequence type 172 (ST172) isolated from the river was genotypically related to two clinical isolates recovered from patients. The similarity between environmental and clinical isolates suggests the dispersion of bla_VIM-1 producing K. oxytoca ST172 from hospital to aquatic environment and the likelihood of its presence in the community. This is the first report of CPE in aquatic environments in Sweden; therefore, surveillance of aquatic and hospital environments for CPE in other urban areas is important to determine the major transfer routes in order to formulate strategies to prevent the spread of MDR bacteria.     

Protocols for the dosimetry of high-energy photon and electron beams: a comparison of the IAEA TRS-398 and previous international codes of practice. International Atomic Energy Agency

A new international Code of Practice for radiotherapy dosimetry co-sponsored by several international organizations has been published by the IAEA, TRS-398. It is based on standards of absorbed dose to water, whereas previous protocols (TRS-381 and TRS-277) were based on air kerma standards. To estimate the changes in beam calibration caused by the introduction of TRS-398, a detailed experimental comparison of the dose determination in reference conditions in high-energy photon and electron beams has been made using the different IAEA protocols. A summary of the formulation and reference conditions in the various Codes of Practice, as well as of their basic data, is presented first. Accurate measurements have been made in 25 photon and electron beams from 10 clinical accelerators using 12 different cylindrical and plane-parallel chambers, and dose ratios under different conditions of TRS-398 to the other protocols determined. A strict step-by-step checklist was followed by the two participating clinical institutions to ascertain that the resulting calculations agreed within tenths of a per cent. The maximum differences found between TRS-398 and the previous Codes of Practice TRS-277 (2nd edn) and TRS-381 are of the order of 1.5-2.0%. TRS-398 yields absorbed doses larger than the previous protocols, around 1.0% for photons (TRS-277) and for electrons (TRS-381 and TRS-277) when plane-parallel chambers are cross-calibrated. For the Markus chamber, results show a very large variation, although a fortuitous cancellation of the old stopping powers with the ND,w/NK ratios makes the overall discrepancy between TRS-398 and TRS-277 in this case smaller than for well-guarded plane-parallel chambers. Chambers of the Roos-type with a 60Co ND,w calibration yield the maximum discrepancy in absorbed dose, which varies between 1.0% and 1.5% for TRS-381 and between 1.5% and 2.0% for TRS-277. Photon beam calibrations using directly measured or calculated TPR20,10 from a percentage dose data at SSD = 100 cm were found to be indistinguishable. Considering that approximately 0.8% of the differences between TRS-398 and the NK-based protocols are caused by the change to the new type of standards, the remaining difference in absolute dose is due either to a close similarity in basic data or to a fortuitous cancellation of the discrepancies in data and type of chamber calibration. It is emphasized that the NK-ND,air and ND,w formalisms have very similar uncertainty when the same criteria are used for both procedures. Arguments are provided in support of the recommendation for a change in reference dosimetry based on standards of absorbed dose to water.     

Novel 5-flucytosine-resistant clade of Candida dubliniensis from Saudi Arabia and Egypt identified by Cd25 fingerprinting

DNA fingerprinting of Candida dubliniensis isolates using the species-specific probe Cd25 previously showed that this species consists of two distinct groups, termed Cd25 group I and Cd25 group II. The present study investigated the population structure of 30 C. dubliniensis oral isolates from Saudi Arabia and Egypt using Cd25 fingerprinting and rRNA gene internal transcribed spacer region-based genotyping. Cd25 fingerprinting analysis of these isolates revealed two distinct populations, the first of which consisted of 10 closely related genotype 1 isolates (average similarity coefficient [S(AB)] value, 0.86). The second population of 20 isolates was much more heterogeneous (average S(AB) value, 0.35) and consisted of two distinct subpopulations, one of which consisted of genotype 3 isolates (n = 13) and the other of genotype 4 isolates (n = 7). A mixed dendrogram generated from the fingerprint data from the 30 Saudi Arabian and Egyptian isolates, 5 Israeli isolates, and 51 previously characterized international isolates (32 of Cd25 group I and 19 of Cd25 group II) revealed the presence of three distinct main clades. The first corresponded to the previously described Cd25 group I and contained all the Saudi Arabian, Egyptian, and Israeli genotype 1 isolates mixed with international isolates. The second clade corresponded to the previously described Cd25 group II and contained three Israeli isolates, one genotype 2 isolate, one genotype 3 isolate, and a genotype 4 variant isolate, which were mixed with international isolates. The third clade has not been described before and consisted solely of the 20 Saudi Arabian and Egyptian genotype 3 and 4 isolates identified in this study and a previously described genotype 4 Israeli isolate. All 20 Cd25 group III isolates exhibited high-level resistance to 5-flucytosine (MIC > or = 128 microg/ml), whereas all Cd25 group I and Cd25 group II isolates tested (10 Saudi Arabian and Egyptian, 16 Israeli, and 24 international) were susceptible to 5-flucytosine (MIC < or = 0.125 microg/ml). The results of this study show for the first time the presence of a novel 5-flucytosine-resistant clade of C. dubliniensis (Cd25 group III) that is predominant among isolates from Saudi Arabia and Egypt and absent from a previously characterized international collection of 98 isolates from 15 countries.     

Spousal relations and well‐being: A comparative analysis of Jewish and Arab dual‐earner families in Israel

The study examined differences in division of household tasks and spousal support among a sample of educated dual‐earner families from two national groups in Israel: Jews (n = 116), and Arabs (n = 163). The contribution of the spousal interaction variables (household roles and spousal support) toward explaining two dimensions of psychological well‐being (burnout and life satisfaction) was also examined. The research findings indicate that in general, the Arabs maintain a more traditional orientation toward gender roles than their Jewish counterparts. Arab men showed a greater tendency to perform outside tasks than their Jewish counterparts who participate more in domestic chores. By contrast, no differences were found between the two groups with regard to the mutual support provided by spouses. Gender role attitudes were found to be a key predictor of the two psychological well‐being dimensions in both national groups. Regarding sex differences, men of both nationalities were more likely than women to report that they perform all types of household tasks. Concomitantly, the women reported higher levels of burnout, while no differences between the sexes were found with respect to life satisfaction. © 2003 Wiley Periodicals, Inc.     

Why do primigravidae request caesarean section in a normal pregnancy? A qualitative study in Iran

Objective

to gain a deeper understanding of why Iranian primigravidae request caesarean section without any medical indication.

Design

qualitative study. Data were gathered through semi-structured interviews, and thematic analysis was undertaken.

Setting

four health care centres at Hamadan University of Medical Sciences, Hamadan, Iran.

Participants

14 primigravidae who requested caesarean section without any medical indication.

Findings

reasons for requesting caesarean section were related to fear of childbirth (labour pain, injury to mother or infant), complications after vaginal delivery (vaginal prolapse, urinary incontinence, sexual dysfunction), trust in obstetricians, and lack of trust in maternity ward staff.

Key conclusions and implications for practice

the main reasons given for requesting caesarean section show that there is urgent need for effective antenatal assessment to enable pregnant women to ask questions and express their concerns. In order to promote vaginal birth, there is a need to develop antenatal education and strategies to enhance women's knowledge, confidence and competence about vaginal birth. Health care providers should be re-educated about the observance of medical ethics and professional rules in their practices, and change their attitudes and behaviours to vaginal birth. Evaluation, improvement and change in maternity care policies are recommended to promote natural childbirth.     

Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort

Background

To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG).

Method

Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin.

Results

Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor “A” allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases.

Conclusion

Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.