Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells

Cell to cell communication via gap junctions is essential in the maintenance of the homeostatic balance of multicellular organisms. Aberrant intercellular gap junctional communication (GJIC) has been implicated in tumor promotion, neuropathy and teratogenesis. Oxidative stress has also been implicated in similar pathologies such as cancer. We report a potential link between oxidative stress and GJIC. Hydrogen peroxide, a known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible as indicated by the complete recovery of GJIC with the removal of H2O2 via a change of fresh media. Free radical scavengers, such as t-butyl alcohol, propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2, which indicated that the effects of H2O2 on GJIC was probably not a consequence of aqueous free radical damage. The depletion of intracellular GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of glutathione- sufficient cells with H2O2 resulted in the hyperphosphorylation of connexin43, which is the basic subunit of the hexameric gap junction protein, as determined by Western blot analysis. TPA, a well-known tumor promoter, also inhibits GJIC via hyperphosphorylation of GJIC, which is a result of protein kinase-C activation. However, H2O2 also induced hyperphosphorylation in GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism of GJIC inhibition must be different from the TPA-pathway and involves GSH.      

Closed loop control of anaesthesia: an assessment of the bispectral index as the target of control

We investigated the performance of a closed-loop system for administration of general anaesthesia, using the bispectral index as a target for control. One hundred patients undergoing gynaecological or general surgery were studied. In 60 patients, anaesthesia was maintained by intravenous infusion of a propofol/alfentanil mixture. In 40, an isoflurane/nitrous oxide based technique was used. For each technique, patients were randomly allocated to receive either closed-loop or manually controlled administration of the relevant agents (propofol/alfentanil or isoflurane), with an intra-operative target bispectral index of 50 in all cases. Closed-loop and manually controlled administration of anaesthesia resulted in similar intra-operative conditions and initial recovery characteristics. During maintenance of anaesthesia, cardiovascular and electro-encephalographic variables did not differ between closed-loop and manual control groups and deviation of bispectral index from the target value was similar. Intra-operative concentrations of propofol, alfentanil and isoflurane were within normal clinical ranges. Episodes of light anaesthesia were more common in the closed-loop group for patients receiving propofol/alfentanil anaesthesia and in the manual group for patients receiving isoflurane/nitrous oxide anaesthesia. Convenience aside, the closed-loop system showed no clinical advantage over conventional, manually adjusted techniques of anaesthetic administration.     

Adolescent Intimate Heterosexual Relationships: Measurement Issues

During adolescence, individuals develop increased ability to have emotionally and physically intimate relationships. The type of intimate relationship will make a difference as to whether the adolescent engages in protective behaviors or avoids risky behaviors. However, in reviewing the literature on the association of relationship type and sexual risk and protective behaviors, four methodological challenges were noted. These challenges limit our understanding of the impact of relationship type. These four challenges are: (a) inconsistent definitional frameworks; (b) lack of adolescent voices; (c) lack of consideration of gender; and (d) poor differentiation between individual and relationship risk. These issues direct the course of future work in this area and are necessary to advance the field of adolescent sexual health, particularly with regard to the development and testing of appropriate interventions designed to reduce untoward outcomes of adolescent sexuality.     

Cue Consistency Associated with Physical Activity Automaticity and Behavior

Physical activity is partly regulated by automatic processes such as habits (ie, well-learned responses to cues), but it remains unclear what cues trigger these processes. This study examined the relations of physical activity automaticity and behavior with the consistency of people, activity, routine, location, time, and mood cues present upon initiation of physical activity behavior. Australian adults (N = 1,244, 627 female, M age = 55 years) reported their physical activity automaticity, behavior, and the degree of consistency of these cues each time they start a physical activity behavior. Multiple regression models, which accounted for gender and age, revealed that more consistent routine and mood cues were linked to more physical activity automaticity; whereas more consistent time and people cues were linked to more physical activity behavior. Interventions may more effectively translate into long-lasting physical activity habits if they draw people's attention to the salient cues of time, people, routine, and mood.     

The international migration of dentists: directions for research and policy

In 2010, the World Health Organization Global Code of Practice for International Recruitment of Health Personnel (the WHO Code) was adopted by the 193 Member States of the WHO. The WHO Code is a tool for global diplomacy, providing a policy framework to address the challenges involved in managing dentist migration, as well as improving the retention of dental personnel in source countries. The WHO Code recognizes the importance of migrant dentist data to support migration polices; minimum data on the inflows, outflows and stock of dentists are vital. Data on reasons for dentist migration, job satisfaction, cultural adaptation issues, geographic distribution and practice patterns in the destination country are important for any policy analysis on dentist migration. Key challenges in the implementation of the WHO Code include the necessity to coordinate with multiple stakeholders and the lack of integrated data on dentist migration and the lack of shared understanding of the interrelatedness of workforce migration, needs and planning. The profession of dentistry also requires coordination with a number of private and nongovernmental organizations. Many migrant dentist source countries, in African and the South‐Asian WHO Regions, are in the early stages of building capacity in dentist migration data collection and research systems. Due to these shortcomings, it is prudent that developed countries take the initiative to pursue further research into the migration issue and respond to this global challenge.     

Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

Sea urchin spines in the stratum corneum: an early finding related to trauma

Penetrating trauma from sea urchin (Echinoidea) spines has been shown to cause numerous cutaneous reactions, ranging from initial pain that rapidly dissipates and resolves to chronic inflammation and formation of characteristic sea urchin granulomas. Many of these skin‐colored or violaceous papules and nodules form weeks to months after injury, and may be surgically excised. Histopathologic examination commonly shows well‐defined granulomas, the majority of which represent sarcoidal‐type granulomas. Other microscopic patterns, such as foreign body reactions and chronic inflammation, have also been shown. Retained spine fragments are birefringent on polarized microscopic examination and are most likely found in the dermal layer. Herein, we describe a case of traumatic sea urchin cutaneous injury with a unique early cutaneous trauma reaction in a young male who lived in Hawaii. Histopathologic exam was significant for retained spines in the layer of the stratum corneum, but no signs of granulomatous inflammation were observed. This case report emphasizes the unique features of our case and reviews the common clinical and histopathologic features of sea urchin cutaneous reactions.