Efficacy of the Ghajar Guide revisited: a prospective study.
The goal of this study was to compare the freehand technique of catheter placement using external landmarks with the technique of using the Ghajar Guide for this procedure. The placement of a ventricular catheter can be a lifesaving procedure, and it is commonly performed by all neurosurgeons. Various methods have been described to cannulate the ventricular system, including the modified Friedman tunnel technique in which a soft polymeric tube is inserted through a burr hole. Paramore, et al., have noted that two thirds of noninfectious complications have been related to incorrect positioning of the catheter. Forty-nine consecutive patients were randomized between either freehand or Ghajar Guide-assisted catheter placement. The target was the foramen of Monro, and the course was through the anterior horn of the lateral ventricle approximately 10 cm above the nasion, 3 cm from the midline, to a depth of 5.5 cm from the inner table of the skull. In all cases, the number of passes was recorded for successful cannulation, and pre- and postplacement computerized tomography scans were obtained. Calculations were performed to determine the bicaudate index and the distance from the catheter tip to the target point. Successful cannulation was achieved using either technique; however, the catheters placed using the Ghajar Guide were closer to the target.


Proposed classification of segments of the internal carotid artery: anatomical study with angiographical interpretation.
The nomenclature and borders of the segments of the internal carotid artery (ICA) remain confusing. A classification of segments of the ICA is proposed based on constant anatomical structures, such as the carotid foramen and canal, the petrous bone, the petrolingual ligament (PLL), and the proximal and distal dural rings. The bilateral ICAs were dissected in 15 cadaveric head specimens using different neurosurgical approaches. The bilateral lacerum foramina were studied in five dry skulls. The bilateral segments of the ICA were also examined on carotid angiograms of 10 normal patients and another with the ophthalmic artery originating from the intracavernous portion of the ICA. The present classification divides the ICA into five segments in the direction of the blood flow. The cervical segment is extradural and extracranial, the petrous segment is extradural and intraosseous, the cavernous segment is interdural and intracavernous, the clinoidal segment is interdural and paracavernous, and the cisternal segment is intradural and intracisternal. The ICA did not pass through the lacerum foramen in any specimen. In all specimens, 1/8 to 5/8 of the lacerum foramen was under the deep dural layer of the cavernous sinus. The term 'lacerum segment' as used previously and called the 'trigeminal segment' by us cannot be justified. The PLL is the posterolateral border of the cavernous sinus and the lacerum and trigeminal segments should be included in the cavernous and petrous segments. The ophthalmic artery may originate from the clinoidal ICA, from the cavernous ICA, or from the middle meningeal artery. Instead of using the term 'ophthalmic segment,' the term 'cisternal segment' should be used for the anatomically distinct ICA in the subarachnoid space. This classification should be minimally affected by anatomical variations.


Temperature effect on ADH response of isolated perfused rabbit collecting tubules.
The time course of the water permeability response to synthetic arginine vasopressin (AVP) was examined in isolated perfused rabbit collecting tubules. When experiments were conducted at 37 degrees C, addition of AVP in a concentration of 100 microU/ml increased hydraulic water permeability (Lp) from 18 +/- 4 X 10(-7) to 153 +/- 15 X 10(-7) cm x s-1 x atm-1. However, in contrast to results obtained at 25 degrees C, the Lp immediately decreased in spite of the continued presence of AVP, reaching half the peak value in 67 +/- 6 (SE) min. A similar decline was observed at 37 degrees C when a cyclic 3',5'-adenosine monophosphate analogue was added to the bathing medium. Corticosteroids greatly enhanced the peak water absorption but did not stabilize the subsequent response to AVP at 37 degrees C. A decline in diffusional water permeability measured in the absence of a transtubule osmotic gradient excluded the possible roles of cellular hypotonicity, increased cell volume, or osmotic water absorption in the unstable response to hormone. The peritubular membrane remained highly permeable to water, independent of AVP and temperature. Duration of exposure to 37 degrees C was more important than AVP in determining the unstable response. On the basis of these studies we conclude that isolated rabbit cortical collecting tubules progressively become insensitive to AVP at 37 degrees C, possibly due to alterations in the responsiveness of the urinary plasma membrane to cAMP.


Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRVγ9+ γδ T lymphocytes.
Human γδ cells expressing TCRVγ9 are T lymphocytes with great potential for cancer immunotherapy and unconventional pattern of antigen specificity. These HLA-unrestricted lymphocytes are specifically reactive to non-peptide metabolites (phosphoantigens) and to the butyrophilin 3A (BTN3A/CD277) protein. Whether recognition of such highly different structures trigger the same activation signaling pathway remains unclear, however. Here we combined fluorescent cell barcoding and phosphoflow analysis of TCRVγ9(+) T lymphocytes to compare simultaneously the level of several signaling phosphoproteins after activation by phosphoantigen (BrHPP) or by anti-BTN3A (monoclonal antibody 20.1). This approach shows that the same pathways involving ZAP70, PLCγ2, Akt, NFκB p65, MAPK p38 and Erk1, were induced by either of these stimuli. These data strongly suggest the TCRVγ9(+) T lymphocytes detect phosphoantigens and butyrophilin A3 by the same recognition process.


[Infantile capillary hemangioma of the outer ala nasi. Report of a case].
We report a case of inferior turbinate capilar hemangioma in a 12-year-old patient. Clinical and radiological findings are commented and the limited literature up to the present is reviewed. We think that the present publication is opportune because of the patient's age and the nature and origin of the mass. Surgery appears to be the elective treatment in most cases.


The role of peritoneal biopsy in the diagnosis of ascites.
Percutaneous biopsies of the peritoneum were obtained in 23 patients with ascites of unknown cause. The only case of tuberculous peritonitis was correctly diagnosed. Peritoneal biopsy provided a diagnosis of malignancy in 6 patients (one lymphoma, one mesothelioma, 4 cases of disseminated carcinoma) but failed to recognize a further 13 cases of disseminated carcinoma. Previous literature is reviewed and the diagnostic usefulness of this procedure is discussed.


Recommendations for the use of long-term experience sampling in bipolar disorder care: a qualitative study of patient and clinician experiences.
Self-monitoring has been shown to improve the self-management and treatment of patients with bipolar disorder. However, current self-monitoring methods are limited to once-daily retrospectively assessed mood, which may not suit the rapid mood fluctuations in bipolar disorder. The experience sampling method (ESM), which assesses mood in real-time several times a day, may overcome these limitations. This study set out to assess the experiences of patients and clinicians with the addition of ESM monitoring, real-time alerts, and personalized feedback to clinical care. Participants were twenty patients with bipolar disorder type I/II and their clinicians. For four months, patients completed five ESM assessments per day on mood, symptoms, and activities. Weekly symptom questionnaires alerted patients and clinicians to potential episodes. After the monitoring, a personalized feedback report based on the patient's data was discussed between patient and clinician. Three months later, patient and clinician were both interviewed. Thematic analysis of the transcripts resulted in four themes: perceived effects of the monitoring, alerts, and feedback, and recommendations for implementation of ESM. ESM was perceived as helping patients to cope better with their disorder by increasing awareness, offering new insights, and encouraging life style adjustments. ESM was further believed to facilitate communication between patient and clinician and to lead to new treatment directions. However, high assessment burden and pre-occupation with negative mood and having a disorder were also described. Patients and clinicians advocated for increased personalization and embedding of ESM in care. This study demonstrates that long-term ESM monitoring, alerts, and personalized feedback are perceived as beneficial to the treatment and self-management of patients with bipolar disorder. Future research should further test the clinical utility of ESM. Clinically relevant feedback and technology need to be developed to enable personalized integration of ESM in clinical care.


Serotonin facilitates peripheral pain sensitivity in a manner that depends on the nonproton ligand sensing domain of ASIC3 channel.
Tissue acidosis and inflammatory mediators play critical roles in inflammatory pain. Extracellular acidosis activates acid-sensing ion channels (ASICs), which have emerged as key sensors for extracellular protons in the central and peripheral nervous systems and play key roles in pain sensation and transmission. Additionally, inflammatory mediators, such as serotonin (5-HT), are known to enhance pain sensation. However, functional interactions among protons, inflammatory mediators, and ASICs in pain sensation are poorly understood. In the present study, we show that 5-HT, a classical pro-inflammatory mediator, specifically enhances the proton-evoked sustained, but not transient, currents mediated by homomeric ASIC3 channels and heteromeric ASIC3/1a and ASIC3/1b channels. Unexpectedly, the effect of 5-HT on ASIC3 channels does not involve activation of 5-HT receptors, but is mediated via a functional interaction between 5-HT and ASIC3 channels. We further show that the effect of 5-HT on ASIC3 channels depends on the newly identified nonproton ligand sensing domain. Finally, coapplication of 5-HT and acid significantly increased pain-related behaviors as assayed by the paw-licking test in mice, which was largely attenuated in ASIC3 knock-out mice, and inhibited by the nonselective ASIC inhibitor amiloride. Together, these data identify ASIC3 channels as an unexpected molecular target for acute actions of 5-HT in inflammatory pain sensation and reveal an important role of ASIC3 channels in regulating inflammatory pain via coincident detection of extracellular protons and inflammatory mediators.


Tissue Expansion Using Hyaluronic Acid Filler for Single-Stage Ear Reconstruction: A Novel Concept for Difficult Areas.
Auricular reconstruction is one of the most challenging procedures in plastic surgery. An adequate skin envelope is essential for cartilage framework coverage, yet few good options exist without additional surgery. We propose a novel method for minimally invasive tissue expansion, using hyaluronic acid (HA) filler to allow for single-stage ear reconstruction. To introduce the novel concept of HA filler for tissue expansion in ear reconstruction, and as an alternative to traditional expansion techniques. Macrolane is a large particle HA gel developed for large volume restoration. Expansion of the non-hair-bearing mastoid skin was performed in our clinic weekly or every other week. Final expansion was completed one week prior to reconstructive surgery. Tissue from one patient's expanded pocket was sent for histological analysis. Ten patients underwent single-stage auricular reconstruction with preoperative expansion. Injection sessions ranged from 7 to 13 (mean, 9.7). Mean injected volume per session was 2.03 mL per patient, for an average total of 19.8 mL (range, 14.5-30 mL). There were no major complications. One minor complication required removal of exposed wire from the antihelix in the office. Hematoxylin and eosin stain revealed similar histology to that seen with traditional expanders. This novel expansion technique using serial HA injections allowed for optimized skin coverage in single-stage ear reconstruction. The concept of tissue expansion using HA filler is a new frontier for research that may be applicable to other arenas of reconstruction. 4.


[Value of arterioscopy in the prevention of renal artery stenosis after transplantation].
Renal artery stenosis is frequent after transplantation. The systematic pre-operative search for arterial injuries by angioscopy allows a reduction in their incidence. The authors report a series of 60 transplantations with pre-operative angioscopy, which revealed benign injuries and two major injuries which were successfully treated surgically. This prevention allows a reduction in the incidence of stenosis from 12 to 6.6% according to a previous series of 210 transplantations without angioscopy.


Osteoclasts' Ability to Generate Trenches Rather Than Pits Depends on High Levels of Active Cathepsin K and Efficient Clearance of Resorption Products.
Until recently, it was well-accepted that osteoclasts resorb bone according to the resorption cycle model. This model is based on the assumption that osteoclasts are immobile during bone erosion, allowing the actin ring to be firmly attached and thereby provide an effective seal encircling the resorptive compartment. However, through time-lapse, it was recently documented that osteoclasts making elongated resorption cavities and trenches move across the bone surface while efficiently resorbing bone. However, it was also shown that osteoclasts making rounded cavities and pits indeed resorb bone while they are immobile. Only little is known about what distinguishes these two different resorption modes. This is of both basic and clinical interest because these resorption modes are differently sensitive to drugs and are affected by the gender as well as age of the donor. In the present manuscript we show that: 1. levels of active cathepsin K determine the switch from pit to trench mode; 2. pit and trench mode depend on clathrin-mediated endocytosis; and 3. a mechanism integrating release of resorption products and membrane/integrin recycling is required for prolongation of trench mode. Our study therefore contributes to an improved understanding of the molecular and cellular determinants for the two osteoclastic bone resorption modes.


Differences in HPA-axis and heart rate responsiveness to psychosocial stress in children with autism spectrum disorders with and without co-morbid anxiety.
Children and adolescents with autism spectrum disorder (ASD) have much higher rates of anxiety disorders relative to their typically developing peers. However, there have been few attempts to investigate what physiological parameters may be associated with this elevated rate of anxiety. Therefore, this study investigated the physiological correlates of anxiety in ASD, with a focus on whether measures of heart rate and cortisol responsiveness to psychosocial stress differentiate those participants with ASD with and without a co-occurring anxiety disorder. A total of 75 male participants aged 10-16 years with normal intellectual ability underwent a psychosocial stress test. The participants included healthy controls (n=23), ASD only (ASD; n=20) and ASD with a comorbid anxiety disorder (ASDanx; n=32). Heart rate, heart rate variability and salivary cortisol were compared by fitting a piecewise regression model to examine baseline levels and change over time within and between the rest, stress and recovery phases of the stress test. The ASDanx group had different response patterns from both the ASD and control groups. The ASDanx group was characterized by a blunted cortisol and heart rate response to psychosocial stress. Furthermore, in the ASDanx group, reduced heart rate and cortisol responsiveness were significantly related to increased anxiety symptoms. This is the first study to report a possible physiological basis for co-occurring anxiety disorders in children and adolescents with ASD. It is possible that a non-adaptive physiological response to psychosocial stress may be related to the high prevalence of co-occurring anxiety disorders in people with ASD.


Progesterone receptor-Grb2 interaction is associated with better outcomes in breast cancer.
In addition to mediating nuclear transcription, PR mediates extranuclear functions mainly through the PR polyproline domain (PPD) interaction with the SH3 domain of cytoplasmic signaling molecules. PR-PPD-SH3 interaction inhibits EGF-mediated signaling and decreases lung cancer cell proliferation. Grb2 is an essential adaptor molecule with an SH2 domain flanked by two SH3 domains. In this study, we examined whether PR, through interaction between PR-PPD and Grb2-SH3, can interact with Grb2 in cells and breast cancer tissues. Our previous study shows that interaction between PR-PPD and Grb2 could interfere with cytoplasmic signaling and lead to inhibition of EGF-mediated signaling. GST-pulldown analysis shows that PR-PPD specifically interacts with the SH3 domains of Grb2. Immunofluorescence staining shows colocalization of PR and Grb2 in both the nucleus and cytoplasm in BT-474 breast cancer cells. Using Bimolecular Fluorescence Complementation (BiFC) analysis, we show that PR and Grb2 interact in breast cancer cells through the Grb2-SH3 domain. Proximity Ligation Assay (PLA) analysis of 43 breast cancer specimens shows that PR-Grb2 interaction is associated with low histological stage and negatively correlates with lymph node invasion and metastasis in breast cancer. These results, together with our previous findings, suggest that PR-PPD interaction with Grb2 plays an essential role in PR-mediated growth factor signaling inhibition and could contribute significantly to better prognosis in PR- and Grb2-positive breast cancer. Our finding provides a basis for additional studies to explore a novel therapeutic strategy for cancer treatment.


Trends in twin birth outcomes and prenatal care utilization in the United States, 1981-1997.
Multiple births account for an increasing percentage of all low-birth-weight infants, preterm births, and infant mortality in the United States. Since 1981, the percentage of women with multiple births who received intensive prenatal care (defined as a high number of visits, exceeding the recommendation of the American College of Obstetricians and Gynecologists by approximately 1 SD beyond the mean number of visits for women initiating care within each trimester) has increased significantly. To explore the hypothesis that more aggressive management of twin-birth pregnancies may be associated with changes in birth outcomes in this population. Cross-sectional and trend analysis of data from the National Center for Health Statistics' birth and infant death records for all twin births occurring in the United States between 1981 and 1997, excluding those with missing or inconsistent data. Trends in preterm birth, low birth weight, preterm and term small-for-gestational-age (SGA) births, and infant mortality, by level of prenatal care utilization. The preterm birth rate for twins increased from 40.9% in 1981 to 55.0% in 1997. The percentage of low-birth-weight infants increased from 51.0% to 54.0%. The preterm SGA rate also increased from 11.9% to 14.1%, while the term SGA rate decreased from 30.7% to 20.5%. For women with intensive prenatal care utilization, the preterm birth rate increased from 35.1% to 55.8%, compared with an increase from 50.6% to 59.2% among women with only adequate use. Twin preterm deliveries involving either induction or first cesarean delivery also increased from 21.9% to 27.3% between 1989-1991 and 1995-1997. The twin infant mortality rate for women with intensive prenatal care use declined between 1983 and 1996 and remained lower than the overall twin infant mortality rate. An apparent increase in medical interventions in the management of twins may result in the seeming incongruity of more prenatal care and more preterm births; however, these data suggest that women with intensive prenatal care utilization also have a lower infant mortality rate. JAMA. 2000;283:335-341


Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach.
Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.


UV-induced -OCH3 rotamerization in a matrix-isolated methoxy-substituted ortho-hydroxyaryl Schiff base.
A new methoxy-substituted ortho-hydroxyaryl Schiff base, 4-(3-methoxy-2-hydroxybenzylidene-amino) phenol was synthesized from 4-aminophenol and 2-hydroxy-3-methoxybenzaldehyde in methanol solution and characterized by 1H-NMR, 13C-NMR and infrared spectroscopies and elemental analysis. The compound was isolated in a cryogenic (10 K) argon matrix, and the analysis of the infrared spectrum of the matrix-isolated compound revealed that it corresponds to the E-enol-imine isomeric form, with 3 different conformers being present in the matrix. These conformers share as common structural features the conformation of the free hydroxyl group (trans relatively to the para-substituent of the ring) and the presence of an OH…N intramolecular H-bond involving the methoxy-substituted phenol ring and the azomethine bridge, while they differ in the orientation of the methoxy-substituent group. The structures and relative energies of the conformers of the molecule, and relevant barriers for their interconversion were obtained through quantum chemical calculations, which were also used to calculate the infrared spectra of the different forms. Calculations were also carried out for the higher-energy Z-enol-imine and keto-amine forms of the compound. Upon UV (230 nm) irradiation, -OCH3 rotamerization was observed, leading to conversion of the lowest energy conformer, where the methoxy group is aligned with the plane of the ring, into the other two conformers initially present in the matrix, in which the OCH3 group is out-of-the-plane of the ring. As for other phenolic compounds previously studied, spontaneous quantum mechanical tunneling conversion of the cis-OH conformers present in the gas-phase into the three observed conformers was found to take place during matrix deposition.


[Comparative immunological analysis of echinoderm cellular and humoral defense factors].
Coelomocyte are found in the fluid filling coelomic cavity of echinoderms and depending on species can be a mixture of several morphologically different types. There are among them: granular and agranular amoebocytes, morula cells, vibratile and lymphocyte-like cells. All these cells take part in cellular response to immune challenges through phagocytosis, clotting, encapsulation of foreign particles, cytotoxicity, and the production of antimicrobial agents, such as reactive oxygen and nitric oxide. The data are given on a variety of humoral factors found in the coelomic fluid, including different types of lectines, agglutinins, hemolysins, acute phase proteins and antimicrobial factors. The discussion on cooperation between cellular and humoral arms of defense reactions during inflammation reveals the crucial role of coelomocytes in immune response. It is suggested that the sea urchin complement system (that is homologous to the alternative pathway in vertebrates) is appeared initially in echinoderms as a protein cascade that points to opsonization of foreign cells and particles, augmenting their phagocytosis and subsequent destruction by coelomocytes. So the identification of a simple complement system as a part of the echinoderm immune response shows that these animals as well as all invertebrate deuterostomes share innate immune system homologies with vertebrates. Studying the simpler immune response demonstrated by echinoderms is important for understanding the ancestral deuterostome defense system and reconstructing the evolution of immune system in higher vertebrates.


Evaluation of a rule base for identifying contact allergens by using a regulatory database: Comparison of data on chemicals notified in the European Union with "structural alerts" used in the DEREK expert system.
To assess the suitability of the use of structural alerts to identify the skin-sensitising properties of chemicals, the 40 originally published structural alerts for the prediction of skin-sensitisation properties used by the DEREK system (which now contains 59 structural alerts), have been evaluated against a database developed in the German Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV), which contains data submitted under the procedure for notifying new chemicals within the European Union. The evaluation of the 40 structural alerts used in DEREK revealed that eight of the 40 structural alerts for the prediction of skin-sensitising potential could be used without any further refinement. Ten structural alerts may need further specifications or refinements in order avoid false-positive predictions - proposals for refinement are discussed. Not enough substances were found within the BgVV database (containing data for more than 1000 substances) to evaluate ten of the DEREK substructures; hence, for these structural alerts, a judgement on their suitability for prediction of skin-sensitisation properties in expert systems is not possible. For 12 structural alerts, no comparative result could be obtained, because these rules did not "fire" for any of the examined chemicals. As a general result of the evaluation process, the approach of using structural alerts for the prediction of skin-sensitising properties of chemicals proved to be reliable. Proposals are given for a refinement of the structural alerts for prediction of contact allergy used in the DEREK system. In addition, advice and several preconditions are given, that apply when trying to teach a computer system to use structural alerts to predict toxicological properties.


Color detection using chromophore-nanotube hybrid devices.
We present a nanoscale color detector based on a single-walled carbon nanotube functionalized with azobenzene chromophores, where the chromophores serve as photoabsorbers and the nanotube as the electronic read-out. By synthesizing chromophores with specific absorption windows in the visible spectrum and anchoring them to the nanotube surface, we demonstrate the controlled detection of visible light of low intensity in narrow ranges of wavelengths. Our measurements suggest that upon photoabsorption, the chromophores isomerize from the ground state trans configuration to the excited state cis configuration, accompanied by a large change in dipole moment, changing the electrostatic environment of the nanotube. All-electron ab initio calculations are used to study the chromophore-nanotube hybrids and show that the chromophores bind strongly to the nanotubes without disturbing the electronic structure of either species. Calculated values of the dipole moments support the notion of dipole changes as the optical detection mechanism.


Recognition of LPS by TLR4: potential for anti-inflammatory therapies.
LPS molecules of marine bacteria show structures distinct from terrestrial bacteria, due to the different environment that marine bacteria live in. Because of these different structures, lipid A molecules from marine bacteria are most often poor stimulators of the Toll-like receptor 4 (TLR4) pathway. Due to their low stimulatory potential, these lipid A molecules are suggested to be applicable as antagonists of TLR4 signaling in sepsis patients, where this immune response is amplified and unregulated. Antagonizing lipid A molecules might be used for future therapies against sepsis, therapies that currently do not exist. In this review, we will discuss these differences in lipid A structures and their recognition by the immune system. The modifications present in marine lipid A structures are described, and their potential as LPS antagonists will be discussed. Finally, since clinical trials built on antagonizing lipid A molecules have proven unsuccessful, we propose to also focus on different aspects of the TLR4 signaling pathway when searching for new potential drugs. Furthermore, we put forward the notion that bacteria probably already produce inhibitors of TLR4 signaling, making these bacterial products interesting molecules to investigate for future sepsis therapies.


Snoezelen, structured reminiscence therapy and 10-minutes activation in long term care residents with dementia (WISDE): study protocol of a cluster randomized controlled trial.
People with dementia are often inapproachable due to symptoms of their illness. Therefore nurses should establish relationships with dementia patients via their remaining resources and facilitate communication. In order to achieve this, different targeted non-pharmacological interventions are recommended and practiced. However there is no sufficient evidence about the efficacy of most of these interventions. A number of publications highlight the urgent need for methodological sound studies so that more robust conclusions may be drawn. The trial is designed as a cluster randomized controlled trial with 20 nursing homes in Saxony and Saxony-Anhalt (Germany) as the units of randomization. Nursing homes will be randomly allocated into 4 study groups consisting of 5 clusters and 90 residents: snoezelen, structured reminiscence therapy, 10-minutes activation or unstructured verbal communication (control group). The purpose is to determine whether the interventions are effective to reduce apathy in long-term care residents with dementia (N = 360) as the main outcome measure. Assessments will be done at baseline, 3, 6 and 12 months after beginning of the interventions. This trial will particularly contribute to the evidence on efficacy of non-pharmacological interventions in dementia care. ClinicalTrials.gov NCT00653731.


[An operative case of a chronic traumatic thoracic aortic aneurysm 16 years after a jet skiing crash; report of a case].
Injury of the thoracic aorta following a major blunt trauma to the chest occurs most frequently at the aortic isthmus and more than 80% of such patients die within 1st 30 minutes. However, less than 5% of patients survive and later develop chronic thoracic aortic aneurysm (TAA). Usually, most cases of chronic traumatic TAA have no symptoms for a long time after an accident. We report a case of successful repair for a chronic traumatic TAA 16 years after a jet skiing crash. A 37-year-old woman complained of left chest pain, back pain, and cough. A computed tomography showed a descending TAA, which was 5 cm in a maximum diameter. The final diagnosis was chronic traumatic TAA. Thoracic endovascular aortic repair (TEVAR) or graft replacement was considered as an operative procedure. We performed graft replacement to avoid complications of TEVAR, considering her small external iliac arteries.


Prostate specific antigen values after radical retropubic prostatectomy for adenocarcinoma of the prostate: impact of adjuvant treatment (hormonal and radiation)
Prostate specific antigen (PSA) levels were obtained before and after radical retropubic prostatectomy in 192 patients: 78 (41%) had pathological stage B2 cancer or less, 83 (43%) had stage C or C+ and 31 (16%) had stage D1 disease. Of those with stages B2 or less, C, C+ and D1 disease 82, 86, 65 and 90%, respectively, had postoperative PSA values of 0.2 ng./ml. or less (when first evaluated 30 or more days postoperatively). At 1 year postoperatively 94% of the stages C and C+ cancer patients treated with adjuvant radiation had PSA levels of 0.2 ng./ml. or less, which was significantly different from those not treated adjuvantly (p = 0.02). This effect of adjuvant radiation on PSA was temporary in the small number of patients with longer followup. Adjuvant orchiectomy for stage D1 lesions resulted in female PSA levels in virtually all cases. This decrease may be misleading and may reflect a direct hormonal effect rather than a decrease in tumor volume. Positive surgical margins did not significantly affect postoperative PSA levels, possibly because of the frequent use of adjuvant treatment.


Management of Nephrolithiasis in Pregnancy: Multi-Disciplinary Guidelines From an Academic Medical Center.
Introduction: The management of nephrolithiasis during pregnancy can be stressful for urologists due to concerns for investigations and treatments that may pose risk of fetal harm, and unfamiliarity with optimal management of these complex patients. In response, we created multi-disciplinary evidence-based guidelines to standardize the care for obstetric patients presenting with flank pain and suspicion for nephrolithiasis. Methods: A multi-disciplinary team involving Urology, Obstetric Anesthesiology, Obstetrics and Gynecology, Diagnostic Radiology, and Interventional Radiology from a single academic medical center was assembled. A PubMed search was performed using keywords of pregnancy/antepartum, nephrolithiasis/calculi/kidney stones, ureteroscopy, non-obstetric surgery, complications, preterm delivery, MRI, computerized tomography, renal bladder ultrasound (RBUS), and anesthesia to identify relevant articles. Team members reviewed their respective areas to create a comprehensive set of guidelines. One invited external expert reviewed the guidelines for validation purposes. Results: A total of 54 articles were reviewed for evidence synthesis. Four guideline statements were constructed to guide diagnosis and imaging, and seven statements to guide intervention. Guidelines were then used to create a diagnostic and intervention flowchart for ease of use. In summary, RBUS should be the initial diagnostic study. If diagnostic uncertainty still exists, a non-contrast CT scan should be obtained. For obstetric patients presenting with a septic obstructing stone, urgent decompression should be achieved. We recommend ureteral stent placement as the preferred intervention if local factors allow. Conclusions: We present a standardized care pathway for the management of nephrolithiasis during pregnancy. Our aim is to standardize and simplify the clinical management of these complex scenarios for urologists.


Impact of glycated pea proteins on the activity of free-swimming and immobilised bacteria.
Glycation (non-enzymatic glycosylation), a spontaneously occurring process, is responsible for alteration of the structures and biological activities of proteins, making them highly active. Regrettably, information regarding the impact of glycated food proteins on intestinal bacteria still remains sparse. Pea seeds are considered to be a biological material of a high nutritional value, low content of anti-nutritional substances and proven health-promoting action and therefore they were used in this study. Since glycated pea proteins are proven to display a lowered susceptibility to the enzymatic digestion, their impact on the activity of both free-swimming and immobilised bacteria was studied. In vitro model systems were used to prove the stimulatory impact of glycated pea proteins on the proliferation rate and survival, as well as on the metabolic activity of free-swimming and immobilised bacteria. This phenomenon is of great importance because glycated food proteins are not only a source of nutrients and energy but also display new properties and increased biological activities. Additionally, they are able to modify the bacterial intestinal ecosystem, thus affecting the general health status of a consumer.


HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010-2019.
WHO/UNICEF estimates for HPV vaccination coverage from 2010 to 2019 are analyzed against the backdrop of the 90% coverage target for HPV vaccination by 2030 set in the recently approved global strategy for cervical cancer elimination as a public health problem. As of June 2020, 107 (55%) of the 194 WHO Member States have introduced HPV vaccination. The Americas and Europe are by far the WHO regions with the most introductions, 85% and 77% of their countries having already introduced respectively. A record number of introductions was observed in 2019, most of which in low- and middle- income countries (LMIC) where access has been limited. Programs had an average performance coverage of around 67% for the first dose and 53% for the final dose of HPV. LMICs performed on average better than high- income countries for the first dose, but worse for the last dose due to higher dropout. Only 5 (6%) countries achieved coverages with the final dose of more than 90%, 22 countries (21%) achieved coverages of 75% or higher while 35 (40%) had a final dose coverage of 50% or less. When expressed as world population coverage (i.e., weighted by population size), global coverage of the final HPV dose for 2019 is estimated at 15%. There is a long way to go to meet the 2030 elimination target of 90%. In the post-COVID era attention should be paid to maintain the pace of introductions, specially ensuring the most populous countries introduce, and further improving program performance globally.


Microfluidic Manipulation of Core/Shell Nanoparticles for Oral Delivery of Chemotherapeutics: A New Treatment Approach for Colorectal Cancer.
A microfluidics approach to synthesize core-shell nanocarriers with high pH tunability is described. The sacrificial shell protects the core layer with the drugs and prevents their release in the severe pH conditions of the gastrointestinal tract, while allowing for drug release in the proximity of a tumor. The proposed nanoparticulate drug-delivery system is designed for the oral administration of cancer therapeutics.


[Hypersalivation - inauguration of the S2k Guideline (AWMF) in short form].
Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This reduces social interaction chances and burdens daily care. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, and saliva aspiration. Therefore, a multidisciplinary S2k guideline was developed. Diagnostic tools such as fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing studies generate important data on therapy selection and control. Especially traumatic and oncologic cases profit from swallowing therapy programmes in order to activate compensation mechanisms. In children with hypotonic oral muscles, oralstimulation plates can induce a relevant symptom release because of the improved lip closure. In acute hypersalivation, the pharmacologic treatment with glycopyrrolate and scopolamine in various applications is useful but its value in long-term usage critical. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long lasting saliva reduction. Surgical treatment should be reserved for isolated cases. External radiation is judged as ultima ratio. Therapy effects and symptom severity has to be followed, especially in neurodegenerative cases. The resulting xerostomia should be critically evaluated by the responsible physician regarding oral and dental hygiene.


SERUM URIC ACID LEVELS OF HEALTHY CAUCASIAN, CHINESE AND HAIDA INDIAN MALES IN BRITISH COLUMBIA.
Because previous studies have shown that serum uric acid levels are higher in members of the Filipino and Maori races than in Caucasians, and because gout seemed unexpectedly common in the Chinese population of Vancouver, a study of serum uric acid levels in Caucasian, Chinese and Haida Indian males was undertaken. The serum uric acid levels of 200 Caucasian, 100 Chinese and 237 Haida Indian males were determined by the ultraviolet spectrophotometric method of Dubbs, which gives a result 0.5 mg. % below that of the more commonly employed method of Grayzel. The mean level of the Caucasians was 4.55 mg. % and that of the Haida Indians 4.41 mg. %; in contrast, the Chinese mean was 5.44 mg. %, a significantly higher figure than the means of the other two groups. No explanation for this finding can be given at present.


Activated microglia stimulate transcriptional changes in primary oligodendrocytes via IL-1beta.
No therapy currently exists to repair demyelinated lesions in multiple sclerosis. However, the use of IgM antibodies may provide a valuable therapeutic avenue for evoking such repair. Unfortunately, the mechanism of immunoglobulin action in CNS repair is currently unknown but may depend upon complex interactions between multiple cell types rather than upon direct activation of a single cell type. Using rat mixed glial cultures containing oligodendrocytes, microglia, and astrocytes, we found that the Fc portion of human IgM shifts microglia to an activated phenotype, reduces glial proliferation, upregulates a variety of immediate early genes, including JunB, Egr-1, and c-Fos, and stimulates microglial production and release of IL-1beta. Microglia-derived IL-1beta consequently triggers transcriptional upregulation of immediate early genes such as c-Jun, Egr-1, and c-Fos in the mixed glial cultures, and stimulates the upregulation of late response genes such as lipocalin in purified oligodendrocytes. Treatment with an IL-1beta receptor antagonist abrogates the effects of Fcmu on glial proliferation and prevents the upregulation of lipocalin in response to Fcmu, but does not prevent Fcmu-mediated upregulation of IL-1beta, suggesting that IL-1beta mediates at least some of the downstream effects of Fcmu in mixed glial cultures. We hypothesize that Fcmu-stimulated IL-1beta-induced upregulation of immediate early and late response genes in oligodendrocytes may promote CNS repair.


Redefining the abdominal seatbelt sign: Enhanced CT imaging metrics improve injury prediction.
The abdominal seatbelt sign (ASBS) has an established association with abdominal injury, yet its definition remains ill-defined. We hypothesize specific imaging characteristics associated with the ASBS such as location above the pelvic brim and depth of abdominal wall contusion would better predict underlying injury and need for operative intervention. We performed a retrospective chart review of subjects suffering from restrained motor vehicle collisions (MVC) evaluated at a level one trauma facility from 2010 to 2015. CT imaging was reviewed for the presence of a transverse abdominal wall contusion consistent with lap belt use. Contusion location was determined in relation to the anterior superior iliac spine (ASIS). Abdominal wall thickness as well as contusion depth were measured at the contusion level and an abdominal seatbelt sign depth index (ASBSI) was calculated. Sample size for the cohort was 551 subjects. Operative need was 19.73% in those with ASBS on CT (CT ASBS) above the ASIS and 4.05% (p-value < 0.01) in those with only clinical evidence of ASBS (CL ASBS). CT ASBS above the ASIS was associated with higher incidence of intra-abdominal injuries (31.97% vs 16.45%; p = 0.01) and a higher rate of abdominal operations (19.73% vs. 7.59%; p < 0.01) compared to below the ASIS. In contrast, CT ASBS below the ASIS was associated with a higher incidence of pelvic fractures (17.72% vs. 8.16%; p = 0.01) with fractures being an independent risk factor for abdominal injury requiring intervention. Logistic regression analyses and receiver-operator characteristic curves demonstrated ASBSI was significantly associated with abdominal injury requiring operative intervention. Characteristics of abdominal wall injury on imaging such as location and contusion depth (ASBSI) are better predictors of abdominal operative need than standard clinical measures. This analysis substantiates a novel diagnostic tool which may have the potential to facilitate clinical diagnosis and management decisions in patients with abdominal seatbelt sign.


Epidemiology of physical activity-related injuries in Chinese university students.
Knowledge gaps of the physical activity-related injury (PARI) problem among general undergraduates exist. We conducted a study in four universities, where 1421 students graded 1-3 were interviewed face-to-face during April and May after their completion of the baseline survey in March and April 2017, aiming to describe the incidence and characteristics of PARI. PARI experience and physical activity (PA) participation in the past 12 months were collected. Injury incidence density (IID) and risk, and injury characteristics were evaluated for the overall sample and by gender. Pearson chi-square or Fisher's exact tests and independent-sample t tests were used to test between-group differences. We found that 486 PARIs were reported totally by 289 participants, with an overall IID of 0.57 per 1000 hours of exposure (males: 1.07, females: 0.45) and an injury risk of 0.34 injuries/student/y (males: 0.52; females: 0.28). Higher IIDs were found in roller skating, football, and basketball. The majority of injuries occurred outdoors and involved the lower extremities, with sprain and strain being the primary injury types. Moreover, most injuries were new, acute, and happened in non-contact situations. Of all injuries, 52.1% required medical attention and 64.6% resulted in inactivity of one or more days. Some significant differences were observed between males and females. Our study indicates that PARI is a public health concern among Chinese university students, which can provide direction for targeted prophylactic interventions to underpin the sex-specific injury mechanism to reduce PARI.


Structural Insight into Complexation Ability and Coordination of Uranyl Nitrate by 1,10-Phenanthroline-2,9-diamides.
Reprocessing of spent nuclear fuel (SNF) is an important task in a frame of ecology and rational use of natural resources. Uranium, as the main component of SNF (>95%), can be recovered for further use as fresh nuclear fuel. To minimize an amount of solid radioactive waste generated during SNF reprocessing, new extractants are under investigation. Diamides of 1,10-phenanthroline-2,9-dicarboxylic acid are perspective tetradentate N-donor ligands that form strong complexes with f-elements, which are soluble in polar organic solvents. As an example of three ligands of this class, we conducted a comparative study and showed how the substituent in the amide functional group affects the extraction ability toward uranyl nitrate from nitric acid media. We have performed a careful study (NMR, FT-IR, XRD, RMC-EXAFS) of the structures of synthesized complexes of new ligands with uranyl nitrate and used quantum mechanical calculations to explain the discovered regularities through.


The effect of COVID-19 on long memory in returns and volatility of cryptocurrency and stock markets.
We examine long memory (self-similarity) in digital currencies and international stock exchanges prior and during COVID-19 pandemic. Specifically, ARFIMA and FIGARCH models are respectively employed to evaluate long memory parameter in returns and volatility. The dataset contains 45 cryptocurrency markets and 16 international equity markets. The t-test and F-test are performed to estimated long memory parameters. The empirical findings follow. First, the level of persistence in return series of both markets has increased during the COVID-19 pandemic. Second, during COVID-19 pandemic, variability level in persistence in return series has increased in both digital currencies and stock markets. Third, return series in both markets exhibited comparable level of persistence prior and during the COVID-19 pandemic. Fourth, return series in volatility series of cryptocurrency exhibited high degree of persistence compared to international stock markets during the COVID-19 pandemic. Therefore, it is concluded that COVID-19 pandemic significantly affected long memory in return and volatility of cryptocurrency and international stock markets. In addition, our results suggest that the hybrid long memory model represented by the integration of ARFIMA-FIGARCH is significantly suitable to describe returns and volatility of cryptocurrencies and stocks and to reveal differences before and during COVID-19 pandemic periods.


Interacting Learning Processes during Skill Acquisition: Learning to control with gradually changing system dynamics.
There is increasing evidence that sensorimotor learning under real-life conditions relies on a composition of several learning processes. Nevertheless, most studies examine learning behaviour in relation to one specific learning mechanism. In this study, we examined the interaction between reward-based skill acquisition and motor adaptation to changes of object dynamics. Thirty healthy subjects, split into two groups, acquired the skill of balancing a pole on a cart in virtual reality. In one group, we gradually increased the gravity, making the task easier in the beginning and more difficult towards the end. In the second group, subjects had to acquire the skill on the maximum, most difficult gravity level. We hypothesized that the gradual increase in gravity during skill acquisition supports learning despite the necessary adjustments to changes in cart-pole dynamics. We found that the gradual group benefits from the slow increment, although overall improvement was interrupted by the changes in gravity and resulting system dynamics, which caused short-term degradations in performance and timing of actions. In conclusion, our results deliver evidence for an interaction of reward-based skill acquisition and motor adaptation processes, which indicates the importance of both processes for the development of optimized skill acquisition schedules.


Identification and Validation of Ferroptosis-Related Genes in Sevoflurane-Induced Hippocampal Neurotoxicity.
Sevoflurane is one of the most popular inhalational anesthetics during perioperative period but presenting neurotoxicity among pediatric and aged populations. Recent experiments in vivo and in vitro have indicated that ferroptosis may contribute to the neurotoxicity of sevoflurane anesthesia. However, the exact mechanism is still unclear. In current study, we explored the differential expressed genes (DEGs) in HT-22 mouse hippocampal neuronal cells after sevoflurane anesthesia using RNA-seq. Differential expressed ferroptosis-related genes (DEFRGs) were screened and analyzed by Gene Ontology (GO) and pathway enrichment analysis. Protein-to-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes (STRING). Significant modules and the hub genes were identified by using Cytoscape. The Connectivity Map (cMAP) was used for screening drug candidates targeting the identified DEFRGs. Potential TF-gene network and drug-gene pairs were established towards the hub genes. In final, we validated these results in experiments. A total of 37 ferroptosis-related genes (18 upregulated and 19 downregulated) after sevoflurane exposure in hippocampal neuronal cells were finally identified. These differentially expressed genes were mainly involved into the biological processes of cellular response to oxidative stress. Pathway analysis indicated that these genes were involved in ferroptosis, mTOR signaling pathway, and longevity-regulating pathway. PPI network was constructed. 10 hub genes including Prkaa2, Chac1, Arntl, Tfrc, Slc7a11, Atf4, Mgst1, Lpin1, Atf3, and Sesn2 were found. Top 10 drug candidates, gene-drug networks, and TFs targeting these genes were finally identified. These results were validated in experiments. Our results suggested that ferroptosis-related genes play roles in sevoflurane anesthesia-related hippocampal neuron injury and offered the hub genes and potential therapeutic agents for investigating and treatment of this neurotoxicity after sevoflurane exposure. Finally, therapeutic effect of these drug candidates and function of potential ferroptosis targets should be further investigated for treatment and clarifying mechanisms of sevoflurane anesthesia-induced neuron injury in future research.


Clustered structural and functional plasticity of dendritic spines.
The configuration of synaptic circuits underlies their ability to process and store information. Research on dendritic spines has revealed that their structural and functional alterations are clustered along the parent dendrite. Here we review the evidence supporting such notion of clustered synaptic plasticity, discuss its functional implications and possible contributing factors, and suggest potential strategies to deal with open challenges.


Genotypic variation in genome-wide transcription profiles induced by insect feeding: Brassica oleracea--Pieris rapae interactions.
Transcriptional profiling after herbivore attack reveals, at the molecular level, how plants respond to this type of biotic stress. Comparing herbivore-induced transcriptional responses of plants with different phenotypes provides insight into plant defense mechanisms. Here, we compare the global gene expression patterns induced by Pieris rapae caterpillar attack in two white cabbage (Brassica oleracea var. capitata) cultivars. The two cultivars are shown to differ in their level of direct defense against caterpillar feeding. Because Brassica full genome microarrays are not yet available, 70-mer oligonucleotide microarrays based on the Arabidopsis thaliana genome were used for this non-model plant. The transcriptional responses of the two cultivars differed in timing as characterized by changes in their expression pattern after 24, 48 and 72 hours of caterpillar feeding. In addition, they also differed qualitatively. Surprisingly, of all genes induced at any time point, only one third was induced in both cultivars. Analyses of transcriptional responses after jasmonate treatment revealed that the difference in timing did not hold for the response to this phytohormone. Additionally, comparisons between Pieris rapae- and jasmonate-induced transcriptional responses showed that Pieris rapae induced more jasmonate-independent than jasmonate-dependent genes. The present study clearly shows that global transcriptional responses in two cultivars of the same plant species in response to insect feeding can differ dramatically. Several of these differences involve genes that are known to have an impact on Pieris rapae performance and probably underlie different mechanisms of direct defense, present in the cultivars.


Adsorption and exchange reactions of iodine molecules at the alumina surface: modelling alumina-iodine reaction mechanisms.
Harnessing aluminum oxidation energy requires navigating the particle's passivation shell composed of alumina. The shell is a barrier to aluminum oxidation but can also exothermically react with halogenated species and therefore contribute to the overall energy generated during aluminum particle combustion. Fluorination reactions with alumina have been studied because fluorine is abundant in binder formulations that commonly surround aluminum particles in an energetic mixture. However, iodine has emerged as an alternative halogenated-based binder or oxidizer because iodine gas provides ancillary benefits such as chemical neutralization of biological agents or sterilization of contaminated environments. This study used density functional theory (DFT) calculations to evaluate potential reaction pathways for aluminum-iodine combustion. Relative to fluorinated fragments such as HF and F-, the adsorption energies associated with HI and I- are nearly triple the exchange reaction energy available from fluorination reactions with alumina (-189 and -278 kJ mol-1 for HI and I-, respectively). However, exchange reactions between iodinated species and the alumina surface are energetically unfavorable. These results explain that through adsorption, alumina surface exothermic reactions with iodine are more energetic than with fluorine fragments. Experiments performed with differential scanning calorimetry (DSC) confirm the higher magnitude of energy generated for iodination compared with fluorination reactions with alumina. Additionally, strong adsorption energies can promote synthesis of new shell chemistries. Adsorption in solution will promote alumina dissolution and iodine precipitation reactions to produce hydroxyl complexes and iodinated species synthesized on the surface of the particle, thereby replacing alumina with alternative passivation shell chemistry.


Heart failure patients have enhanced cerebral autoregulation response in acute ischemic stroke.
The cerebrovascular effects of a failing heart-pump are largely unknown. Chronic heart failure (HF) might cause pre-conditioning effect on cerebral hemodynamics but not study so far in acute stroke. We aimed to investigate if HF induces effects in dynamic cerebral autoregulation (CA), within 6 h of symptom-onset through chronic stage of ischemic stroke. We enrolled 50 patients with acute ischemic stroke. Groups with (N = 8) and without HF and 20 heathy controls were compared. Arterial blood pressure (Finometer) and cerebral blood flow velocity (transcranial Doppler) were monitored within 6 and at 24 h from symptom-onset and at 3 months. We assessed dynamic CA by transfer function analysis and cardiac disease markers. HF associated with higher phase (better dynamic CA) at ischemic hemisphere within 6 (p = 0.042) and at 24 h (p = 0.006) but this effect was not evident at 3 months (p > 0.05). Gain and coherence trends were similar between groups. We found a positive correlation between phase and admission troponin I levels (Spearman's r = 0.348, p = 0.044). Our findings advances on the knowledge of how brain and heart interact in acute ischemic stroke by showing a sustained dynamic cerebral autoregulation response in HF patients mainly with severe aortic valve disease. Understanding the physiological mechanisms that govern this complex interplay can be useful to find novel therapeutic targets which can improve outcome in ischemic stroke.


Mortality in Tonga over three triennia, 2010-2018.
Tonga is a South Pacific Island country with a population of 100,651 (2016 Census). This study examines Tongan infant mortality rates (IMR), under-five mortality rates (U5MR), adult mortality and life expectancy (LE) at birth from 2010 to 2018 using a recent collation of empirical mortality data over the past decade for comparison with other previously published mortality estimates. Routinely collected mortality data for 2010-2018 from the Ministry of Health, national (Vaiola) hospital, community nursing reports, and the Civil Registry, were consolidated by deterministic and probabilistic linkage of individual death records. Completeness of empirical mortality reporting was assessed by capture-recapture analysis. The reconciled data were aggregated into triennia to reduce stochastic variation, and used to estimate IMR and U5MR (per 1000 live births), adult mortality (15-59, 15-34, 35-59, and 15-64 years), and LE at birth, employing the hypothetical cohort method (with statistical testing). Mortality trends and differences were assessed by Poisson regression. Mortality findings were compared with published national and international agency estimates. Over the three triennia in 2010-2018, levels varied minimally for IMR (12-14) and U5MR (15-19) per 1000 births (both ns, p > 0.05), and also for male LE at birth of 64-65 years, and female LE at birth 69-70 years. Cumulated risks of adult mortality were significantly higher in men than women; period mortality increases in 15-59-year women from 18 to 21% were significant (p < 0.05). Estimated completeness of the reconciled data was > 95%. International agencies reported generally comparable estimates of IMR and U5MR, with varying uncertainty intervals; but they reported significantly lower adult mortality and higher LE than the empirical estimates from this study. Life expectancy in Tonga over 2010-2018 has remained relatively low and static, with low IMR and U5MR, indicating the substantial impact from premature adult mortality. This analysis of empirical data (> 95% complete) indicates lower LE and higher premature adult mortality than previously reported by international agencies using indirect and modelled methods. Continued integration of mortality recording and data systems in Tonga is important for improving the completeness and accuracy of mortality estimation for local health monitoring and planning.


Late referrals to palliative care units in Japan: nationwide follow-up survey and effects of palliative care team involvement after the Cancer Control Act.
Referral to palliative care units tends to be delayed. In Japan, the Cancer Control Act was established in 2006 to improve the quality of life of cancer patients by facilitating greater access to specialized palliative care services. The primary aims of this study were to clarify the family-perceived appropriateness of the timing of referral to palliative care units after the Cancer Control Act, and to determine the effects of the involvement of the palliative care team on the family-perceived referral timing. An additional aim of this study was to clarify the family-perceived usefulness of the palliative care team. A multicenter questionnaire survey was conducted on a sample of 661 bereaved family members of cancer patents who were admitted to palliative care units in Japan. A total of 451 responses were analyzed (response rate: 68%). Half of the bereaved family members regarded the timing of referrals to palliative care units as late or too late: too late (25%, n=114), late (22%, n=97), appropriate (47%, n=212), early (2.4%, n=11), and very early (1.8%, n=8). Among 228 families who reported that patients had commented on the timing of referrals, about half reported that the patients said the timing of referral was late or too late: too late (23%, n=52), late (21%, n=49), appropriate (48%, n=110), early (4.4%, n=10), and very early (3.1%, n=7). The families of patients with a palliative care team (n=191) tended to report less frequently that they believed the referral timing to be late or too late (43% vs. 51%, P=0.073); they also reported significantly less frequently that the patients said that the referral timing was late or too late (36% vs. 52%, P=0.037). The percentages of families who evaluated the palliative care team as useful or very useful were: 93% (symptom control), 90% (emotional support), 92% (family support), and 87% (care coordination). Half of the Japanese bereaved families of patients admitted to palliative care units regarded the timing of referrals as late or too late, and the rates identified in the survey were similar to those recorded before the Cancer Control Act. Involvement of the palliative care team, however, significantly correlated with lower family- and patient-perceived late referrals, and palliative care team activity was generally perceived as useful by the bereaved family members. Further dissemination of palliative care teams could contribute to better access to palliative care units and quality palliative care throughout the country.


[The life of Joseph Haydn from a medical point of view (author's transl)].
Joseph Haydn (1732 to 1809) had hardly been troubled by any illness of note, apart from a chronic nasal polyp until 1799. During the composition of the oratoria "The Seasons" (1799 to 1801), the signs of cerebral arteriosclerosis with cardiac insufficiency made their appearance. Haydn's creative strength subsequently declined rapidly and he was virtually unable to compose any more after he had finished "The Seasons" until his death in 1809. The plan to compose a third oratoria "The Last Judgement" ended abortively. Haydn himself suffered acutely from the inactivity imposed on him by the illness, as documented by various sources. Hadyn remained fully conscious right up to the time of his death, which presumably resulted from cardiac failure. Haydn's grave was ransacked only a few days after the funeral and his skull was snatched. It has been finally restored to his resting place in Eisenstadt only as recently as 1954 after a protracted and devious journey.


Color-Word Stroop test performance across the adult life span.
In the Color-Word Stroop test (CWST), the basic task is to name the ink color of rows of XXXs, and performance in this condition is compared with performance in naming the ink-color of color words under conditions where word meanings and ink colors mismatch or are incongruent (e.g., the word red printed in green ink). The present study investigated whether Stroop test interference, defined as the cost associated with ink-color naming in the incongruous stimulus condition versus in the basic color-naming condition, provides positive evidence for a kind of processing qualitatively different than that which is required for color naming or for word reading. Does the pattern of age-related differences in Stroop interference force the conclusion that the incongruous condition taps a qualitatively different kind of processing than that required for color naming or for word reading? We gave the CWST to 310 healthy adults. Their performance in each condition of the test replicates and extends previous findings. Structural equation modeling of the data showed a significant, direct link between age and performance in the latent factor associated with the incongruent condition. However, this direct link with age produced a relatively small increase in the model's fit; it amounted to only a .024 increase in the proportion of variance explained in the incongruent condition. In light of this small direct influence due to age, the most parsimonious explanation of our findings is that age effects in Stroop interference are due to age-related slowing (which is also indexed by color naming and by word reading) primarily; the findings do not provide evidence for a qualitatively different kind of processing that declines with age.


Characterization of two Turkish beta-hexosaminidase mutations causing Tay-Sachs disease.
Two homoallelic mutations have recently been identified in the alpha-subunit of hexosaminidase A (EC 22.214.171.124) causing the infantile form of Tay-Sachs disease in Turkish patients. Both of these mutations, a 12 bp deletion (1096-1107 or 1098-1108 or 1099-1109) in exon 10 and a point mutation (G1362 to A, Gly454 to Asp) in exon 12, are located in the catalytic domain of the hexosaminidase alpha-chain. In order to determine whether these mutations affect the function of the catalytic domain or result in an instable protein, both mutant cDNAs were overexpressed in COS-1 cells. As judged by Western blotting, transfections of wild-type cDNA produced pro-alpha-chain and mature alpha-chain in parallel with a fivefold increase in cellular hexosaminidase activity using the synthetic substrate 4-methylumbelliferyl beta-N-acetylglucosamine 6-sulfate (MUGS). However, both mutants produced only pro-alpha-chains, although no mature form or detectable hexosaminidase activity towards two different synthetic substrates was observed. These data are consistent with the biochemical phenotype of infantile Tay-Sachs disease. We conclude that the overexpressed mutant pro-alpha-chains were misfolded and could not undergo further proteolytic processing to the active form of the enzyme in the lysosome.


Post-parathyroidectomy restoration of normal calcium homeostasis in neonatal primary hyperparathyroidism.
Total parathyroidectomy is required to cure neonatal primary hyperparathyroidism (NPH) as any parathyroid remnant quickly becomes hyperplastic, causing recurrent hypercalcaemia. We present a patient with NPH who had total removal of his eutopic parathyroid glands but continued to have parathyroid hormone secretion from presumed ectopic parathyroid tissue. Hypercalcaemia initially recurred but normal calcium homeostasis was established as the child grew older. We postulate that the underlying defect in NPH is decreased sensitivity to the serum ionic calcium feedback inhibition at the parathyroid receptor level and that this sensitivity can improve with age.


Innate immunity in viral encephalitis: role of C5.
The complement system is a critical component of both the innate and acquired immune systems. It is important in host defense against viruses, bacteria, and fungi for opsonization and for lysis of pathogens. However, activated complement can also cause tissue damage. There is compelling evidence that complement factors are presented in the central nervous system (CNS). Complement activation (by any of the three pathways: classical, alternate, and lectin) can lead to inflammation and tissue damage, while at the same time may also restrict certain pathogens in the CNS. C5a is formed by proteolytic cleavage C5. C5a is considered the most potent proinflammatory mediator, often called an anaphylotoxin. In this communication, we examine the roles of C5 (C5a) in vesicular stomatitis virus (VSV)-induced encephalitis. We found that C5a is produced during VSV infection, but C5-deficient mice had similar pathology as their controls. We concluded that C5 is not a critical factor in mediating the host response during VSV encephalitis.


Key clinical features a general internist needs to know about Brugada syndrome: a case-based discussion.
Brugada syndrome (BrS) is an autosomal dominant genetic disorder involving the abnormal function of cardiac voltage-gated sodium ion channels. Sodium channel loss of function can lead to early repolarization and loss of the Phase 2 action potential dome in cardiomyocytes. In BrS, this sodium channelopathy occurs in some, but not all, epicardial cells thus creating 1) juxtaposition of depolarized and repolarized cells in the epicardium and 2) a transmural voltage gradient. Together, these conditions can set up a Phase 2 reentry and resultant malignant cardiac arrhythmia. Of the three types of electrocardiogram (EKG) changes seen in BrS, only the Type 1 EKG is considered diagnostic. In a controlled setting, sodium channel blockers and Brugada EKG leads may be used to unmask this diagnostic EKG finding. Fever and certain medications that interfere with the sodium channel can also trigger these changes, which can be catastrophic. A 26-year-old white male presented with febrile upper respiratory infection symptoms and had an EKG change, which was initially misinterpreted as an ST elevated myocardial infarction due to ST-T segment elevation in leads V1 and V2. The patient reported past recurrent syncopal episodes leading to a recent suspected diagnosis of BrS. A later episode of febrile illness, triggering a Type 1 EKG pattern, led to a subsequent hospital admission for continuous cardiac monitoring. On that occasion, he was placed on a wearable external defibrillator pending placement of implantable cardioverter defibrillator (ICD) device. Due to the gravity of symptoms that can manifest in the BrS patient, it is important to recognize and treat this condition promptly and effectively. BrS patients require admission for continuous cardiac monitoring when febrile and certain medications interfering with the sodium channel should be avoided in this population. Although medications may be used as one treatment modality, definitive therapy is placement of an ICD device.


Effect of indapamide SR in the treatment of hypertensive patients with type 2 diabetes.
To evaluate the effect of the sustained-release formulation of indapamide (indapamide SR) in type 2 diabetic patients with mild-to-moderate hypertension and its possible side effects, particularly on glucose metabolism and lipid profiles. A total of 64 patients randomly received 1.5 mg of indapamide SR or placebo once daily for 3 months. The effects were evaluated by 24-h ambulatory blood pressure monitor, fasting blood sampling for biochemistry, lipid profiles, and frequently sampled intravenous glucose tolerance test. The changes in standing and supine blood pressure (BP) were significant (154.7 +/- 9.4/94 +/- 2.9 mm Hg v 134.4 +/- 5.1/82.4 +/- 5 mm Hg and 155 +/- 9.8/94.6 +/- 3.6 mm Hg v 135.1 +/- 4.9/82.1 +/- 4.7 mm Hg) in the indapamide group, but not in the placebo group. According to the 24-h ambulatory blood pressure monitor reading, a significant reduction was observed in not only in the whole-day mean BP (mean systolic BP/mean diastolic BP, 149 +/- 19.3/87.6 +/- 11.3 mm Hg v 135.7 +/- 12.6/79.6 +/- 9 mm Hg) but also the whole-day mean median arterial pressure (109 +/- 12.7 mm Hg v 98.7 +/- 8.2 mm Hg) for the indapamide group, but not the placebo group. There were no changes in biochemical data including serum sodium, potassium, chloride, uric acid, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lipid profiles, fasting blood glucose, insulin, hemoglobin Alc, and glucose metabolism parameters (insulin sensitivity, glucose effectiveness, and acute insulin response) from frequently sampled intravenous glucose tolerance test after indapamide or placebo therapy. Indapamide SR can significantly lower the whole-day BP in hypertensive patients with type 2 diabetes. Also, it did not alter or aggravate patients' lipid profiles, glucose metabolism, and did not exert possible side effects of hypokalemia and hyperuricemia. Therefore, monotherapy with indapamide SR should be suggested in type 2 diabetic patients with mild-to-moderate hypertension.


Effects on bone mineral density of gonadotropin releasing hormone analogs used in the treatment of central precocious puberty.
The aim of this study was to compare vertebral bone mass values of patients with central precocious puberty (CPP) with healthy age and puberty matched controls and to determine the effect of gonadotropin releasing hormone (GnRH) analogs on bone mass in patients who had been treated at least for 1 year. Girls with idiopathic CPP, 11 pretreatment, 14 post-treatment, and 19 pubertal girls as controls were enrolled in the study. The mean ages of the controls and the patients with CPP pre- and post-treatment were 10.25 +/- 1.06, 8.23 +/- 1.11, and 10.36 +/- 1.82 years, respectively. Leuprolide acetate (Lucrin) 3.75 mg was administered s.c. monthly. Bone measurements were performed by dual energy X-ray absorptiometry (DEXA) (Norland) at the anterior-posterior vertebrae (L2-L4). The post-treatment group's mean BMD value was 0.66 +/- 0.12; Z scores according to CA and BA were 0.32 +/- 10 and 0.30 +/- 1.1, respectively. In the study group, BMD values compared to the control group were normal. No significant change in BMD values was observed after treatment. Neither osteopenia nor osteoporosis was observed in patients taking GnRH analog.


Glucose-induced preproinsulin gene expression is inhibited by the free fatty acid palmitate.
Prolonged exposure to elevated FFA levels has been shown to induce peripheral insulin resistance and to alter the beta-cell secretory response to glucose. To investigate the effects of FFAs on preproinsulin gene expression, we measured insulin release, cell content, and messenger RNA (mRNA) levels in rat islets after a 24-h exposure to 1 mM palmitate. Insulin release increased at all glucose concentrations studied; in contrast, preproinsulin mRNA levels were specifically reduced by palmitate at high glucose with a decrease in insulin stores, suggesting that palmitate inhibits the glucose-stimulated increase in preproinsulin gene expression. The mechanisms by which palmitate affects preproinsulin gene expression implicate both preproinsulin mRNA stability and transcription, as suggested by an actinomycin D decay assay, quantification of primary preproinsulin transcripts, and transient transfection experiments in Min6 cells. Metabolism of palmitate is not required to obtain these effects, inasmuch as they can be reproduced by 2-bromopalmitate. However, oleate and linoleate did not significantly influence preproinsulin mRNA levels. We conclude that insulin release and preproinsulin gene expression are not coordinately regulated by palmitate and that chronically elevated FFA levels may interfere with beta-cell function and be implicated in the development of noninsulin-dependent diabetes.


Food safety knowledge of cheese consumers.
The aim of this study was to evaluate habits and practices of cheese consumers toward their level of knowledge of food safety. A total of 1000 people were interviewed in several cities of the state of Rio de Janeiro, Brazil. Five hundred thirty-eight (53.8%) people consume cheese daily, while 318 (31.8%) and 144 (14.4%) consume cheese weekly and monthly, respectively. Five hundred twenty-two (52%) people reported its usage as an ingredient used in the preparation of other dishes, while 320 (32%) of the interviewed people consume cheese directly as a part of the diet. Typical Brazilian cheeses such as "Minas Frescal" and "Prato" cheese are preferred by 528 (52.8%) of the consumers. Of the total consumers, 764 (76.4%) purchase cheese from supermarkets, while 236 (23.6%) from open-air markets. Inspected cheese is purchased by 350 (35%) consumers, while 650 (65%) buy it without knowing if they were submitted to previous fiscalization. Four hundred thirty (43%) consumers do not know any disease transmitted by cheese that has not been inspected. Overall, educational campaigns must be developed by the Sanitary Surveillance and the Health Agencies to improve the knowledge of the consumer about food safety of cheeses.


School water, sanitation, and hygiene inequalities: a bane of sustainable development goal six in Nigeria.
The importance of school water, sanitation, and hygiene (WASH) in achieving the Sustainable Development Goal targets 6.1 and 6.2 in developing countries cannot be overemphasized. However, widespread WASH inequalities remain an impediment to achieving the targets by 2030. Hence, this study was conducted to examine current school-WASH disparities among public and private schools in a low-income Nigerian community using mixed methods. The cross-sectional survey utilized multi-stage sampling to select 400 students from five public and five private schools in Akinyele, Ibadan. Semi-structured questionnaires and observational checklists were used to obtain data. Inferential statistics were measured at a 95% confidence interval. Independent variables like the students' sociodemographic characteristics, school type, and available WASH facilities were associated with dependent variables like respondents' hand hygiene and sanitation practices and WASH-associated knowledge and attitude to examine existing inequalities. Classifying the available WASH facilities based on the WHO/UNICEF Joint Monitoring Programme, none of the public schools provided any sanitation and hygiene service, while all the private schools provided both services. Furthermore, the private-school students had significantly better WASH knowledge (p<0.001; Ƞ2p=0.152) and attitude (p<0.001; Ƞ2p=0.036) compared with the public-school students. Also, a significantly higher portion of public-school students practiced open defecation at school (p<0.001; odds ratio (OR)=7.4; confidence interval (CI)=4.1-13.5) and at home (p<0.001; OR=7.8; CI=3.7-16.7). WASH disparities among socioeconomic groups remain a persistent challenge. Sole reliance on the Government to narrow the inequalities has persistently proven unfruitful. There is a need to empower local community stakeholders to facilitate sustainable school-WASH interventions.


Semiconductor devices for entangled photon pair generation: a review.
Entanglement is one of the most fascinating properties of quantum mechanical systems; when two particles are entangled the measurement of the properties of one of the two allows the properties of the other to be instantaneously known, whatever the distance separating them. In parallel with fundamental research on the foundations of quantum mechanics performed on complex experimental set-ups, we assist today with bourgeoning of quantum information technologies bound to exploit entanglement for a large variety of applications such as secure communications, metrology and computation. Among the different physical systems under investigation, those involving photonic components are likely to play a central role and in this context semiconductor materials exhibit a huge potential in terms of integration of several quantum components in miniature chips. In this article we review the recent progress in the development of semiconductor devices emitting entangled photons. We will present the physical processes allowing the generation of entanglement and the tools to characterize it; we will give an overview of major recent results of the last few years and highlight perspectives for future developments.


Watch Your Distance: The Role of Laser Fiber Working Distance on Fragmentation When Altering Pulse Width or Modulation.
The Moses technology for the Ho:YAG laser introduces a pulse-shape modulation that optimizes energy delivery through water and can be utilized for lithotripsy at a distance from the target. In light of this advance, we undertook an in vitro study to assess the effect of fiber tip to stone distance on fragmentation, incorporating the use of a variety of pulse modes. Experiments were conducted with a three-dimensional (3D) positioning system, a 30 mm flat plate BegoStone, and a 230 μm core laser fiber connected to a 120W holmium laser utilizing short pulse (SP), long pulse (LP), Moses contact (MC), and Moses distance (MD) modes. Ablation crater volume was measured by 3D confocal microscopy, after a single pulse (1.0 J) was activated with the fiber tip positioned at 0, 0.5, 1, 2, and 3 mm from the stone. Fragmentation efficiency (1 J × 10 Hz) was assessed with the fiber tip at 0 and 1 mm distance, programmed to fragment the stone over 3 minutes. Fragmentation was defined as difference in stone mass before and after each experiment. For all tested pulse modes, ablation crater volume and fragmentation were greatest when the fiber tip was in contact with the stone. Ablation declined as the working distance increased with no ablation occurring at 3 mm. At 1 mm distance, the ablation crater volume using MD mode was significantly higher when compared with SP, LP, and MC modes (p < 0.05). Compared with all pulse modes tested, MD resulted in 28% and 39% greater fragmentation at both 0 and 1 mm working distances, respectively (p < 0.05). Holmium laser lithotripsy is significantly affected by fiber working distance with the greatest ablation obtained with the fiber in contact with the stone. At 0 and 1 mm distance, MD had the greatest fragmentation efficiency, suggesting this mode may have advantages during ureteroscopy.


The expressions of HSP70 and αB-crystallin in myocarditis associated with foot-and-mouth disease virus in lambs.
This study describes the expression of heat shock protein70 (HSP70) and alpha-basic-crystallin (α-BC) and their association with apoptosis and some related adaptor proteins in the pathogenesis of foot-and-mouth disease virus (FMDV)-induced myocarditis in lambs. HSP70 was generally overexpressed in the myocardial tissues and inflammatory cells of FMDV-induced myocarditis with differential accumulation and localization in same hearts when compared to non-foot-and-mouth disease control hearts. α-BC immunolabeling showed coarse aggregations in the Z line of the cardiomyocytes in FMDV-infected hearts in contrast to control hearts. Overall, the results of this study show that the anti-apoptotic proteins, HSP70 and α-BC, were overexpressed with increased apoptosis in FMDV-infected heart tissues. Both proteins failed to protect the cardiomyocytes from apoptosis as defense mechanisms to the FMDV during the infection, suggesting that the virus is able to increase apoptosis via both downregulation and/or upregulation of these anti-apoptotic proteins.


Exploring transformative learning and the courage to teach a values based curriculum.
Teaching is a complex art that takes courage to commit to, particularly in the face of stressed students, crowded curricula, tensions in preparation for the graduate role, and ongoing educator shortages. My colleagues and I have been taking on this challenge by imbuing our teaching of nursing with more passion. As Parker Palmer (1998, p. 144), the renowned educationalist once said: "The growth of any craft depends on shared practice and honest dialogue among the people who do it. We grow by trial and error, to be sure--but our willingness to try, and fail, as individuals are severely limited when we are not supported by a community that encourages such risks". The vision that I have is for nursing educators to come together in communities of practice to talk about the challenging aspects of nursing and ways these challenges can be reframed and reapproached through education. This work is underpinned by the pedagogy of Transformative Learning (TL). At its heart this pedagogy is interested in problematic practices that keep afflicting a discipline such as nursing, and in pondering and revising the educational solutions. In nursing, our biggest problems are where stigma, inequality and inertia persist to make vulnerable communities experience more illness and hardship than others who are more privileged. TL treats students as critical agents - who have the potential to rethink problems and change practices. TL aims to make space within the classroom and online for a dialogue that is affirming so that students believe in their own capacity to make a better world for all people.


Sexual attraction, depression, self-harm, suicidality and help-seeking behaviour in New Zealand secondary school students.
To describe the sexual attractions of New Zealand secondary school students and investigate the associations between sexual attraction and self-reported depression, self-harm, suicidality and help-seeking behaviour. Multiple logistic regression was used to examine the associations between sexual attraction and depressive symptoms, suicidality, self-harming and help-seeking behaviours in a nationally representative secondary school health and well-being survey, undertaken in 2007. Of the students surveyed, 92% were attracted to the opposite sex, 1% to the same sex, 3% to both sexes, 2% were not sure and 2% were attracted to neither sex. Students who were attracted to the same or to both sexes consistently had higher prevalence estimates of depression (p = < 0.0001), suicidality (p = < 0.0001) and self-harming (p = < 0.0001). Odds ratios were highest for students who reported they were attracted to both sexes for depressive symptoms (OR 3.7, 95%CI 2.8-4.7), self-harm (OR 5.8, 95%CI 4.4-7.6) and attempted suicide (OR 7.0, 95%CI 5.2-9.4). Students not exclusively attracted to the opposite sex were more likely to report having seen a health professional for an emotional worry and were more likely to have difficulty accessing help for emotional concerns. The study findings highlight significant mental health disparities faced by students attracted to the same or both sexes, with those attracted to both sexes appearing particularly vulnerable. There is a vital need to ensure primary care and mental health services have the capacity and capability to screen and provide appropriate responsive care for youth who are attracted to the same or both sexes.


From new vistas to life lines: psychologists' satisfaction with supervision and confidence in supervising.
This study aimed to provide the first detailed survey of Irish psychologists' supervision practices as well as to identify what is related to satisfaction with supervisory support and to confidence in providing supervision. An online survey was distributed nationwide to Irish psychologists. Participants were mostly clinical and counselling psychologists. Three-quarters of the participants constituted 51% of the total population of Irish health service psychologists, the remainder working in various non-health service settings. The results showed that most Irish psychologists attend supervision but at a low frequency, typically once monthly. One-third were dissatisfied with their supervision, greater satisfaction being related to having more frequent clinical supervision and having external individual clinical supervision. Having a safe and trustworthy relationship with supervisors was a dominant issue, and two-thirds of psychologists wanted separation of their clinical and line management supervision. Although 70% were supervisors, only 40% were confident in their supervisory skills and just 16% had formal supervisor training. Independent predictors of supervisory confidence were experience as a psychologist, having formal supervisor training, experience as a supervisor and confidence as a therapist. A novel finding was that longer experience of personal therapy was related to greater confidence as a supervisor. This study indicates the need for access to more frequent clinical supervision to be facilitated for psychologists and for there to be clear separation of line management and clinical supervision. It is also essential that more resources are put into training supervisors. While most psychologists are engaged in supervision, frequency of attendance is low, with more satisfied psychologists having more frequent supervision. Most psychologists want separation of their clinical and line management supervision and have a preference for external supervision, safe and trustworthy relationships with supervisors being their primary concern. Only 16% of psychologists had formal training in supervision but having such training significantly contributed to greater confidence as a supervisor, indicating an urgent need to provide more supervisor training for psychologists.


Room-Temperature Laser Synthesis in Liquid of Oxide, Metal-Oxide Core-Shells, and Doped Oxide Nanoparticles.
Although oxide nanoparticles are ubiquitous in science and technology, a multitude of compositions, phases, structures, and doping levels exist, each one requiring a variety of conditions for their synthesis and modification. Besides, experimental procedures are frequently dominated by high temperatures or pressures and by chemical contaminants or waste. In recent years, laser synthesis of colloids emerged as a versatile approach to access a library of clean oxide nanoparticles relying on only four main strategies running at room temperature and ambient pressure: laser ablation in liquid, laser fragmentation in liquid, laser melting in liquid and laser defect-engineering in liquid. Here, established laser-based methodologies are reviewed through the presentation of a panorama of oxide nanoparticles which include pure oxidic phases, as well as unconventional structures like defective or doped oxides, non-equilibrium compounds, metal-oxide core-shells and other anisotropic morphologies. So far, these materials showed several useful properties that are discussed with special emphasis on catalytic, biomedical and optical application. Yet, given the endless number of mixed compounds accessible by the laser-assisted methodologies, there is still a lot of room to expand the library of nano-crystals and to refine the control over products as well as to improve the understanding of the whole process of nanoparticle formation. To that end, this review aims to identify the perspectives and unique opportunities of laser-based synthesis and processing of colloids for future studies of oxide nanomaterial-oriented sciences.


Insight on the Intracrinology of Menopause: Androgen Production within the Human Vagina.
In this study, we investigated steroidogenic gene mRNA expression in human vaginas and verified the ability of human vagina smooth muscle cells (hvSMCs) to synthesize androgens from upstream precursor dehydroepiandrosterone (DHEA). As a readout for androgen receptor (AR) activation, we evaluated the mRNA expression of various androgen-dependent markers. hvSMCs were isolated from vagina tissues of women undergoing surgery for benign gynecological diseases. In these cells, we evaluated mRNA expression of several steroidogenic enzymes and sex steroid receptors using real time reverse transcription-polymerase chain reaction. Androgen production was quantified with liquid chromatography tandem-mass spectrometry (LC-MS/MS). In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α, whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of proandrogenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfotransferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short-term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone and DHT secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. This study confirmed that the human vagina is an androgen-target organ with the ability to synthesize androgens, thus providing support for the use of androgens for local symptoms of genitourinary syndrome in menopause.


Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway.
The protection against apoptosis provided by growth factors in several cell lines is due to stimulation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, which results in activation of protein kinase B (PKB; also known as c-Akt and Rac) and phosphorylation and sequestration to protein 14-3-3 of the proapoptotic Bcl-2-family member BAD. A modest increase in intracellular Ca2+ concentration also promotes survival of some cultured neurons through a pathway that requires calmodulin but is independent of PI(3)K and the MAP kinases. Here we report that Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK) activates PKB directly, resulting in phosphorylation of BAD on serine residue 136 and the interaction of BAD with protein 14-3-3. Serum withdrawal induced a three- to fourfold increase in cell death of NG108 neuroblastoma cells, and this apoptosis was largely blocked by increasing the intracellular Ca2+ concentration with NMDA (N-methyl-D-aspartate) or KCl or by transfection with constitutively active CaM-KK. The effect of NMDA on cell survival was blocked by transfection with dominant-negative forms of CaM-KK or PKB. These results identify a Ca2+-triggered signalling cascade in which CaM-KK activates PKB, which in turn phosphorylates BAD and protects cells from apoptosis.


Nursing students' beliefs about poverty and health.
This paper examines baccalaureate nursing students' beliefs about the relationship between poverty and health, and the factors that influence these beliefs. The relationship between poverty and health is well established, and poverty remains a persistent problem in many industrialized nations. Nurses' understanding of how poverty influences health will affect how they interact with individual clients as well as the strategies they employ to address poverty-related issues. No studies have examined nursing students' understandings of how poverty influences health and the factors that influence that understanding. A cross-sectional survey of a random sample (n = 740) of basic baccalaureate nursing students was conducted in three Canadian universities in 2000. Students completed a 59-item questionnaire eliciting data on demographic variables, personal and educational exposure to poverty, beliefs about the relationship between poverty and health (myth, drift, behavioural, structural), and attitudes to poverty. Students were most likely to adhere to a structural explanation of the relationship between poverty and health. Very little of the variance in myth and drift explanations was accounted for by course or personal exposure, programme level, age, and attitudes toward poverty. Greater course exposure and more positive attitudes toward the poor predicted support for the structural explanation. Support for the behavioural explanation was influenced by attitudes toward the poor and, to a lesser extent, by course exposure, age, and programme level. Students would benefit from greater exposure to poverty through coursework that emphasizes the structural factors contributing to poverty and its negative health consequences. Classroom experience should be complemented with clinical placements that provide students with opportunities to interact with families living in poverty and to work collaboratively with others to address the causes and consequences of poverty at community and policy levels.