Adolescent Deliveries in a Secondary-Level Care Hospital of Cameroon: A Retrospective Analysis of the Prevalence, 6-Year Trend, and Adverse Outcomes.
Adolescents are generally ill-equipped to deal with the burden of a pregnancy. A high prevalence of adolescent pregnancies is among the indicators of limitations toward the achievement of the Millennium Development Goals in most developing countries. We sought to determine the prevalence, 6-year trend, and adverse outcomes of adolescent deliveries. We also tested whether being married decreased the risk of adverse fetal outcomes in these adolescents. A 6-year retrospective register analysis. Buea Regional Hospital. Birth records from 2007 to 2012. None. Prevalence and 6-year trend in the rate of adolescent deliveries; adverse fetal outcomes. The overall prevalence of adolescent deliveries was 9.9% (491 of 4941). There was no significant change in the annual prevalence of adolescent deliveries over 6 years (P trend = .8). Adolescent pregnancies were at higher risk of preterm deliveries (deliveries at gestational age <37 completed weeks; odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.2; P < .01), low birth weight (defined as birth weight <2600 g; OR, 1.8; 95% CI, 1.4-2.3; P < .01), and neonatal asphyxia (OR, 1.4; 95% CI, 1.1-1.7; P < .01). There was no significant difference in the frequency of adverse outcomes between married and single adolescents. One of every 10 babies is born from adolescent mothers in the Buea Regional Hospital. Whether these mothers are married or not, their neonates are exposed to higher morbidity. This emphasizes the need for more adolescent-friendly public health policies geared toward reducing the prevalence of this condition to improve the chances of attaining the Millennium Development Goals in Cameroon.


Normal morphogenesis of epithelial tissues and progression of epithelial tumors.
Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted.


Normal reference values of three-dimensional speckle-tracking echocardiography-derived right atrial volumes and volume-based functional properties in healthy adults (Insights from the MAGYAR-Healthy Study).
The right atrium (RA) roles include being a systolic reservoir, an early diastolic conduit, and a late-diastolic booster pump. The present study aimed to assess normal reference values of three-dimensional speckle-tracking echocardiography (3DSTE)-derived RA volumetric data and volume-based functional properties in healthy adult subjects. We included 260 healthy adult subjects in sinus rhythm with complete clinical and demographic dataset, but excluded 110 of them because of inferior image quality. The remaining population sample comprised 150 subjects (31.0 ± 11.6 years, 79 males). Complete two-dimensional Doppler echocardiography and 3DSTE have been performed in all subjects. Systolic RA volumetric variables did not show changes over time, but after 50 years, a significant reduction could be demonstrated in RA stroke volume and emptying fraction. While early diastolic RA volume increased over time, RA stroke volume and emptying fraction decreased. While late-diastolic RA volume increased over age decades, similar increase could be detected in RA stroke volume but a reduction occurred in older ages. Late-diastolic RA emptying fraction showed an increasing (after the 40s)-decreasing (after the 50s) pattern. Our study provides normal reference values of 3DSTE-derived RA volumes and volume-based functional properties and their age- and gender dependency in healthy adult subjects.


[Testicular lymphoma: a clinicopathological study of 65 cases].
To summarize the clinicopathological features of testicular lymphomas (TL). The medical records of 65 patients diagnosed with TL between 2008.1.1 and 2014.11.30 were retrospectively reviewed. TL was classified as primary (PTL) when there's no prior diagnosis of an extara-testicular lymphoma/leukemia and no concurrent widespread disease, except for the concomitant involvement of ipsilateral inguinal lymph nodes; otherwise it was classified as secondary (STL). Of our patients group, 46 (70.8%) cases were classified primary TL as and the other 19 (29.2%) cases were secondary TL. All patients presented with painless testicular swelling. The median age of STL was significantly younger than that of PTL [65 (12-88) ys vs 13 (1-75) ys, P<0.001]. Additionally, a striking difference in the distribution of histological subtypes was observed between the PTL and STL patients group. Primary TLs were more common than secondary. Striking differences in the distribution of patients'age and histology were found between STL and PTL.


Results of in vitro fertilization with embryo cryopreservation and a recommendation for uniform reporting.
The analyzed data from 295 cycles in which certain embryos were frozen demonstrate a comparable aptitude for development of embryos either fresh or frozen-thawed in cycles yielding four or more embryos. This supports the clinical advantage of freezing certain embryos in this situation. However, there was no advantage in freezing embryos if only one to three were available in the IVF cycle. A formula is proposed to give the current outcome and to compare the success rate of IVF-ET according to various parameters, including the policy for embryo cryopreservation. This formula enables all teams to present their data in an identical manner.


Two-step heat fusion kinetics and mechanical performance of thermoplastic interfaces.
Thermoplastic polymers and composites are ubiquitous in the industry for their reshaping and fusing capabilities at elevated temperatures. The quality of heat-fused thermoplastic interfaces is of great concern for adhesion, coating, and welding applications, especially those between dissimilar materials. Kinetic evolution of the microstructures defines the mechanical performance of heat-fusion thermoplastic interfaces, which is studied here using polyethylene and polypropylene as an example. Key factors such as the viscosity and compatibility of polymers and the time and temperature of fusion are discussed by combining molecular-level simulations and structural-level hot-compression experiments. Inter-diffusion and entanglement of polymer chains are identified as the two elementary kinetic steps of the fusion, which dominate the control on the stiffness and strength of the interfaces, respectively. Experimental data shows that the quality of fused interfaces can be improved by reducing the viscosity and the interaction parameter. Following the same set of time-scaling relations as identified in the simulations, the two-step characteristics and their effects on the stiffness and strength are experimentally validated. Both simulation and the experiment results show that Young's modulus of fused interfaces recovers faster than the strength that is controlled by polymer entanglement to a large extent, rather than diffusion. These findings add insights into the design of fusion processes, laying the ground for the applications of thermoplastic polymers and composites.


A viral peptide can mimic an endogenous peptide for allorecognition of a major histocompatibility complex class I product.
Alloreactive class I-restricted T cells may recognize the class I structure alone, in association with a specific peptide, or with any stabilizing peptide. We have tested the role of endogenous peptides in the recognition of H-2Kb molecules by two alloreactive cytolytic T lymphocyte (CTL) clones using the mutant tumor line RMA-S, which expresses its surface H-2b molecules devoid of peptides and is not lysed by these two CTL clones. Empty H-2b molecules on RMA-S cells can be stabilized by binding exogenously added peptides. H-2Kb-specific recognition of the RMA-S cells by one of the CTL clones was restored by endogenous peptide extracts which only minimally stabilized H-2Kb on the surface of RMA-S cells, indicating the requirement for a specific peptide on a limited number of H-2Kb molecules. In addition, one out of three peptides which greatly enhance the expression of H-2Kb, the nucleoprotein peptide 52-59 from vesicular stomatitis virus (VSV), was also able to restore the lysis of RMA-S cells by the clone. The recognition of a common motif by an alloreactive clone (H-2k anti-H-2Kb) and virus-specific Kb-restricted clones suggests that both H-2k and H-2b thymic environments allow selection of T cells capable of recognizing H-2Kb+VSV and that tolerance to self, as would be the case in the (H-2k x H-2b)F1 mice, would partially delete the repertoire of antiviral T cells.


Establishment of a Medication Acuity Scoring Tool at a Tertiary Pediatric Teaching Hospital: A 2-Phase Process.
Currently, there is no validated objective rating system to address the acuity of medication orders that pharmacists review. The objective was to assess the acuity of a given medication through creating and validating an acuity scoring tool. Phase I included the development of the medication acuity scoring tool (MAST) from national safety standards and clinical experience. A survey was administered to pharmacists nationwide to establish a consensus on the individual components of the tool and their associated weighted scores. Phase II was designed to assess MAST's predictive validity by comparing a medication acuity rating generated by MAST to a rating assigned based upon clinical experience of experts. Additionally, in phase II, interrater and intrarater reliability of MAST was evaluated. In phase I, most of MAST's components and their associated scores achieved >75% agreement for inclusion in the final tool. In phase II, without MAST, approximately 50% of pharmacist-assigned acuity ratings were statistically consistent with tool-generated acuity ratings, and there was fair agreement between respondents (k=0.31). With the use of MAST, agreement in acuity ratings improved to substantial (k=0.69), and intrarater reliability was almost perfect (k=0.88). MAST is a validated rating system that captures the acuity of medications.


Semi-free radial forearm flap for head and neck reconstruction in vessel-depleted neck after radiotherapy or radical neck dissection.
Venous thrombosis is the main cause of radial forearm flap failure, especially when recipient vessels are compromised by prior radiation therapy or neck dissection. In such conditions, semi-free radial forearm flap (SF-RFF) can be performed to reduce this risk. We reviewed all SF-RFF procedures performed in our institution for head and neck reconstruction. The flap was harvested as a conventional radial forearm flap but the cephalic vein was dissected along the arm up to the deltopectoral crease and used as the sole drainage vein. Seven SF-RFFs were harvested for head and neck reconstructions. The dissection of the cephalic vein lasted less than 25 min in all cases. No flap loss or thrombosis was observed. The SF-RFF is a reliable and versatile procedure for facial, oral, or larynx reconstruction. This hybrid version of the radial forearm free flap is particularly appropriate when no suitable recipient veins are available as a result of radiation or prior surgery.


Reducing Delirium in Hospitalized Adults Through a Structured Sleep Promotion Program.
Delirium affects approximately 1 in 4 patients during their hospitalization and is associated with numerous complications. Sleep deprivation is a significant risk factor for developing delirium and is a patient dissatisfier. An internal assessment revealed that up to 25% of all patients on medical-surgical units had a diagnosis of delirium while in the hospital. An evidence-based practice project was implemented to reduce the development of delirium through sleep promotion on 2 inpatient units. A dedicated time was selected, and key strategies were identified to promote sleep with minimal interruptions. Delirium decreased by 33% and 45% on the 2 units over 1 year. Overall, patient satisfaction for quietness at night survey responses also increased (P = .0005; CI, 0.05 to 0.67) with ongoing sustainment. Implementation of a dedicated period to sleep was associated with a reduction in delirium and increased patient satisfaction for quietness at night.


Management of hemorrhage from severe scalp lacerations with Raney clips.
A 23-year-old man was assaulted about the head and face with a wrench, sustaining multiple severe scalp lacerations. Massive bleeding from the lacerations ensued, resulting in refractory hypovolemic shock. Emergency department control of this hemorrhage was accomplished by the application of Raney clips to the edges of the scalp lacerations. Following stabilization and radiologic studies, the patient was admitted to the ICU, where his scalp wounds were managed definitively. The remainder of his hospital course was unremarkable, and he was discharged on the third hospital day to be followed in the surgical clinic as an outpatient.


Specificity of the pyruvate dehydrogenase kinase for pyruvate dehydrogenase component bound to the surface of the kidney pyruvate dehydrogenase complex and evidence for intracore migration of pyruvate dehydrogenase component.
Using the bovine kidney pyruvate dehydrogenase complex we have investigated the mechanism whereby about three pyruvate dehydrogenase (active form) kinase molecules, tightly bound to the dihydrolipoyl transacetylase core, can rapidly phosphorylate and inactivate about 20 pyruvate dehydrogenase (active form) (PDHa) tetramers which are also bound to the 60-subunit core. Evidence is presented that PDHa kinase activity is not serviced by a process of dissociation and reassociation of PDHa. Rapid inactivation of a full complement of PDHa occurs at a rate exceeding the rate of dissociation of PDHa, indicating that a PDHa must move to the fixed kinase subunits without dissociating from the dihydrolipoyl transacetylase core. Consistent with that concept, at low concentrations of complex where a significant portion of PDHa is free, bound PDHa was inactivated at a rate equivalent to that at higher concentrations of complex, and free PDHa was phosphorylated more slowly at a rate closely approximated by the rate of association of free PDHa with the transacetylase core. Thus, with a low number of PDHa molecules bound, PDHa either is preferentially positioned for phosphorylation and inactivation by PDHa kinase or can rapidly become so positioned without dissociating from the transacetylase core.


A system model for halothane closed-circuit anesthesia. Structure considerations and performance evaluation.
Previously, the authors described a physiologic model for closed-circuit inhalational anesthesia. The basic version of this system model was clinically validated for isoflurane. An extended version adopted nonpulmonary elimination causing a constant fraction of anesthetic to be irreversibly lost. This version improved the accuracy of the model for enflurane. The model's performance for other inhalational anesthetics that are not biochemically inert, such as halothane, remained to be evaluated. The current study quantified the predictive performance of four versions of the model by comparison of the predicted and measured alveolar halothane concentration-time profiles in 53 patients. Version A did not incorporate nonpulmonary elimination, whereas version D adopted a nonlinear hepatic nonpulmonary elimination following Michaelis-Menten kinetics. A and D used fixed partition coefficients. Their counterparts, A' and D', were formulated to examine the impact of age-adjusted partition coefficients on the accuracy of our model. Each concentration measured by mass spectrometry was compared to four predicted concentrations calculated by four computer simulations (one per version). For each patient, the authors calculated the root mean squared error (rmse; typical error size), bias (systematic component), and scatter of the prediction errors. Fifty-three patients were anesthetized with 330 ml of liquid halothane via 426 bolus injections during more than 61 h; 21,890 alveolar concentrations (average 0.6 vol%) were measured. Version D' showed the best overall performance with an rmse of 19.6 +/- 7.2%, a bias of 0.5 +/- 15.9%, and a scatter of 13.2 +/- 3.5% (mean +/- SD). The model incorporating nonpulmonary elimination and age-adjusted partition coefficients (D') is sufficiently reliable and accurate to represent halothane closed-circuit anesthesia. This system model, with its various versions, is a valuable tool to predict the dynamics of isoflurane, enflurane, and halothane for clinical, educational, and research purposes.


Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes.
Antisense miRNA oligonucleotides against miR-21 (AMO-21) have a therapeutic potential for treatment of glioblastoma. However, glioblastoma-targeted delivery through systemic injection requires development of an efficient targeting carrier. For this purpose, a glioblastoma-targeting carrier was developed using the T7 peptide and exosomes. The transferrin receptor is overexpressed on the surface of glioblastoma cells, and T7 is a transferrin receptor-binding peptide. A T7 peptide-decorated exosome (T7-exo) was produced by incorporation of T7 into the exosome membrane as a fusion protein of T7 and Lamp2b. As a control, rabies virus glycoprotein (RVG) peptide targeting brain neuron cells was incorporated into the exosome membrane. AMO-21 was loaded into the exosomes by electroporation. In vitro studies of AMO-21 delivery showed that T7-exo had a higher delivery efficiency to C6 glioblastoma cells than unmodified exosome (Unmod-exo) and RVG-decorated exosome (RVG-exo). For in vivo delivery studies, T7-exo with AMO-21 was delivered into intracranial glioblastoma rat models by intravenous injection through the tail vein. The results showed that T7-exo delivered AMO-21 into the brain more efficiently than Unmod-exo and RVG-exo. In addition, delivery of AMO-21 using T7-exo reduced the miR-21 level in the glioblastoma efficiently. Reduction of miR-21 by AMO-21 induced the expression of PDCD4 and PTEN in tumors, resulting in reduction of tumor sizes. Taken together, these findings indicate that T7-exo is an efficient carrier of AMO-21 into the glioblastoma and may be useful in development of glioblastoma therapy.


The relationship between sex hormones and glycated hemoglobin in a non-diabetic middle-aged and elderly population.
Sex hormones are strongly linked to the occurrence and development of diabetes, and influence glycated hemoglobin (HbA1c) levels in diabetic population; but, the relationship between sex hormones and HbA1c in non-diabetic population remains unknown. This study aimed to explore the extent of influence of sex hormones on HbA1c levels in non-diabetic population. A total of 1409 non-diabetic subjects, including 601 men and 808 postmenopausal women were recruited from Shanghai community. HbA1c was detected using high performance liquid chromatography, and hemoglobin level was determined by sodium lauryl sulfate colorimetry. Serum estradiol (E2), total testosterone (TT), and sex hormone binding globulin (SHBG) were measured by chemiluminescent microparticle immunoassays. The level of HbA1c was 5.6 (5.4-5.9) % in all subjects, with 5.6 (5.4-5.8) % in men and 5.7 (5.5-5.9) % in postmenopausal women. After adjusting for age, body mass index (BMI), and hemoglobin, E2 was positively correlated with HbA1c in men (r = 0.122, P = .003), and SHBG was inversely correlated with HbA1c (r = - 0.125, P < .001) in women. Other hormones were not correlated with HbA1c (all P > .05). Multivariate linear regression analysis showed that, except for traditional factors, such as age, hemoglobin, and BMI, E2 was another determinant of HbA1c (standardized β = 0.137, P = .003) in men; besides, in women, SHBG was another determinant of HbA1c (standardized β = - 0.178, P < .001), except for age and systolic blood pressure. After controlling for confounding factors, two sex hormones, as E2 and SHBG could influence HbA1c levels in non-diabetic population.


Postpartum lymphocytic thyroiditis in American women: a spectrum of thyroid dysfunction.
Six episodes of primary hypothyroidism followed pregnancy in five women. Within 6 months post partum, all were clinically hypothyroid, with a diffuse goiter of two or three times normal size, altered thyroid function tests (average thyroxine [T4] = 2.6 micrograms/dl, thyroid-stimulating hormone [TSH] = 58.2 microunits/ml), and elevated antithyroid antibodies. (All had antimicrosomal antibody titers of 1:6,400 or more.) After 5 more months, all patients had a decrease in antibody titer, resolution of symptoms, and recovery of thyroid hormone levels (average T4 = 7.3 micrograms/dl), although two patients had compensated hypothyroidism (their average TSH = 9.3 microunits/ml). Four patients had lymphocytic thyroiditis diagnosed by fine-needle aspiration biopsy. Despite the apparent transience of postpartum hypothyroidism, all five patients have chronic thyroid dysfunction: three women have persistent goiters (all less than twice normal size) and two have compensated hypothyroidism; one patient had previous Graves' hyperthyroidism, and two had recurrent transient hypothyroidism (at 21 months postpartum in one patient, and 5 months after another pregnancy in the other). Three women had transient, painless hyperthyroidism (average T4 = 16.1) before becoming hypothyroid: two patients within 8 weeks post partum, and the third patient at 20 months (preceding an episode of recurrent hypothyroidism). Previous reports of postpartum hypothyroidism have come from scattered locales abroad, and it is unclear whether local environmental factors are pathogenic. Nevertheless, this syndrome may, in general, have gone unrecognized and may be a significant cause of illness in postpartum women.


Differences in attractiveness comparing female profile modifications of Class II Division 1 malocclusion.
Our objective was to study the perceptions of laypeople for digital alterations and the amount of nasolabial angle increase that is tolerable and how much chin-neck length increase is needed to achieve a desirable profile in Class II Division 1 women with mandibular retrognathia. The profile image of a white woman with a Class II Division 1 mandibular rethrognatic profile was digitally modified to create 6 images: 3 with stepwise increased nasolabial angles of 113°, 121°, and 129°, and 3 with stepwise increased chin-neck distances of 51, 54, and 57 mm. These images were assessed and ranked by 155 white laypeople. The baseline profile was judged significantly as the least attractive. A nasolabial angle of 129° was judged as unattractive as the baseline profile. Profiles with a chin-neck length of 54 and 57 mm were equally judged as most attractive. The untreated (baseline) profile was found to be least esthetic, as well as the profile with the largest nasolabial angle. Nasolabial angle increases up to 121° seem to be acceptable. Profiles simulating a chin-neck length increase as produced by surgery seem to be most favored.


Brazilian Black Women are at Higher Risk for COVID-19 Complications: An Analysis of REBRACO, a National Cohort.
To evaluate the impact of the race (Black versus non-Black) on maternal and perinatal outcomes of pregnant women with COVID-19 in Brazil. This is a subanalysis of REBRACO, a Brazilian multicenter cohort study designed to evaluate the impact of COVID-19 on pregnant women. From February 2020 until February 2021, 15 maternity hospitals in Brazil collected data on women with respiratory symptoms. We selected all women with a positive test for COVID-19; then, we divided them into two groups: Black and non-Black women. Finally, we compared, between groups, sociodemographic, maternal, and perinatal outcomes. We obtained the frequency of events in each group and compared them using X2 test; p-values < 0.05 were considered significant. We also estimated the odds ratio (OR) and confidence intervals (CI). 729 symptomatic women were included in the study; of those, 285 were positive for COVID-19, 120 (42.1%) were Black, and 165 (57.9%) were non-Black. Black women had worse education (p = 0.037). The timing of access to the health system was similar between both groups, with 26.3% being included with seven or more days of symptoms. Severe acute respiratory syndrome (OR 2.22 CI 1.17-4.21), intensive care unit admission (OR 2.00 CI 1.07-3.74), and desaturation at admission (OR 3.72 CI 1.41-9.84) were more likely to occur among Black women. Maternal death was higher among Black women (7.8% vs. 2.6%, p = 0.048). Perinatal outcomes were similar between both groups. Brazilian Black women were more likely to die due to the consequences of COVID-19.


Future of 34 meniscectomies after bucket-handle meniscus tear: a retrospective study with a follow-up over 22 years.
After a bucket-handle meniscus tear, a partial meniscectomy by arthroscopy is recommended, when a meniscal suture is impossible. Short-term results of meniscectomy after bucket-handle meniscus tear, without cartilage or ligament additional injury, are mostly excellent: pain and blocking disappear, return to sports activities is possible. The aim of this retrospective study is to follow a partial meniscectomy evolution with a long follow-up between March 1990 and April 1994, and a senior surgeon operated 34 meniscectomies for bucket-handle meniscus tear by 34 patients (29 male and 5 female) with a mean age of 31.7 years (16-52 years) at time of surgery. The bucket-handle meniscus tear had a traumatic etiology on a knee with no cartilage lesion. The functional results were assessed by IKDC subjective score (International Knee Documentation Committee) and ARPEGE score (Association pour la Recherche et la Promotion de l'Etude du Genou). These scores were obtained by phone call questionnaire in March 2014 with a mean follow-up of 22.7 years (20-24 years). In this study, patients were reviewed and got a clinical examination to determine the Lequesne score, a radiological knee assessment according to Ahlbäck classification and a weight-bearing teleradiography. With an IKDC mean score of 85.8 after surgery, we observed that 29 patients go back to sports activities with the same level as before injury. The level of sports activity, with a regular practice after a mean follow-up of 22.7 years, was the same as immediately after surgery or just the level under for 85.3 % of patients. With ARPEGE score, 48.5 % of patients had a global excellent result and 38.2 % had a global good result after a long follow-up. With a mean Lequesne score of 2.38, osteoarthritis of knee is still clinical minimal after meniscectomy at long term. The score was worse after external meniscectomy (EM) than after an internal meniscectomy (IM). 57.7 % of patients have osteoarthritis on X-rays. In our study, functional results after partial meniscectomy for bucket-handle meniscus tear are similar than in the literature. More than half of our patients, reviewed after a long follow-up, had radiological osteoarthritis of knee with a variable clinical result, but often minimal to moderate, intensity modulated by the lower limb axis.


Delayed activation of post-transcriptional gene silencing and de novo transgene methylation in plants with the coat protein gene of sweet potato feathery mottle potyvirus.
The relationship between post-transcriptional gene silencing (PTGS) and DNA methylation was examined using Nicotiana benthamiana transformed with the coat protein gene including the 3' non-translated region of sweet potato feathery mottle potyvirus. Line 4.28 showed a delayed activation of the transgene silencing in comparison with the other silenced lines, and showed complete resistance against the recombinant potato virus X engineered to contain the sequence homologous to the transgene when the silencing was activated. The transgene methylation in line 4.28 was less extensive in comparison with those of the other silenced lines before the silencing was activated. However, the extent of methylation increased in the course of plant development and became comparable with those in the other silenced lines. The activated silencing and the increased transgene methylation were reset after meiosis. However, the characters of delayed activation of the silencing and developmentally increased transgene methylation were meiotically transmitted to the next generation. These results suggest that transgene(s) itself has a potential to trigger and reset DNA methylation, which could determine a state of PTGS.


CCCDTD5: Individual and community-based psychosocial and other non-pharmacological interventions to support persons living with dementia and their caregivers.
Current pharmacological therapies for dementia have limited efficacy. Thus it is important to provide recommendations on individual and community-based psychosocial and non-pharmacological interventions for persons living with dementia (PLWDs) and their caregivers. Phase 1: A systematic review for developing recommendations on psychosocial and non-pharmacological interventions at the individual and community level for PLWDs and their caregivers. Phase 2: Rating of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Phase 3: Delphi process (>50 dementia experts) for approving recommendations by the 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5). The CCCDTD5 approved the following recommendations: Exercise (1B) and group cognitive stimulation for PLWDs (2B), psychosocial and psychoeducational interventions for caregivers (2C), development of dementia friendly organization and communities (2C), and case management for PLWDs (2B). The CCCDTD5 provides for the first time, evidence-based recommendations on psychosocial and non-pharmacological interventions for PLWDs and their caregivers that can inform evidence-based policies for PLWDs in Canada.


Radiological features of pulmonary oedema.
A clinical classification embracing most of the causes of pulmonary oedema is given, as well as a radiological classification, and the different ways in which pulmonary oedema may present radiologically are briefly described.


The effects of dose and repeated administration on the longer-term hypophagia produced by amphetamine in rats.
Rats are hypophagic approximately 1-3 and 13-27h after receiving amphetamine (2.0mg/kg). This study examined how these short- and longer-term phases of hypophagia were affected by repeated administration of different amphetamine doses. Throughout eight five-day tests, the rats could lever press for food pellets for 1-hour periods beginning every three hours. On test day 1, the rats were treated with saline, and on test day 3, they were treated with a dose of amphetamine. Across tests, for one group, treatment on day 3 alternated between 0.0 (saline) and 0.5mg/kg amphetamine; for a second, group treatment on day 3 alternated between 1.0 and 2.0mg/kg amphetamine; and for a third group, treatment on day 3 was always 1.0mg/kg amphetamine. The patterns of food intake following day 1 saline and day 3 treatment were compared. Short-term food intake was abolished by 0.5, 1.0, and 2.0mg/kg amphetamine, and no tolerance was observed to this effect. Longer-term hypophagia was produced by 1.0 and 2.0 but not by 0.5mg/kg. Tolerance to longer-term hypophagia was seen when 1.0mg/kg alone was used as the day 3 treatment, but not when 1.0 and 2.0mg/kg were alternated across tests as the day 3 treatment. Short- and longer-term hypophagia were dissociated by threshold doses for elicitation and by differential tolerance. Occasional receipt of a higher amphetamine dose may sometimes increase the longer-term hypophagia produced by a lower dose.


Quality of life in patients with liver tumors treated with holmium-166 radioembolization.
Holmium-166 radioembolization is a palliative treatment option for patients with unresectable hepatic malignancies. Its influence on quality of life has not been evaluated yet. Since quality of life is very important in the final stages of disease, the aim of this study was to evaluate the effect of holmium-166 radioembolization on quality of life. Patients with hepatic malignancies were treated with holmium-166 radioembolization in the HEPAR I and II studies. The European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 questionnaires were used to evaluate quality of life at baseline, 1 week, 6 weeks and at 6, 9 and 12 months after treatment. The course of the global health status and symptom and functioning scales were analyzed using a linear mixed model. Quality of life was studied in a total of 53 patients with a compliance of 94%. Role functioning was the most affected functioning scale. Fatigue and pain were the most affected symptom scales. Changes in almost all categories were most notable at 1 week after treatment. A higher WHO performance score at baseline decreased global health status, physical functioning, role functioning and social functioning and it increased symptoms of fatigue, dyspnea and diarrhea. Quality of life in salvage patients with liver metastases treated with holmium-166 radioembolization was not significantly affected over time, although a striking decline was seen during the first week post-treatment. A WHO performance score > 0 at baseline significantly influenced quality of life.


Effect of perinatal food deficiencies on the compound action potential evoked in sensory nerves of developing rats.
The aim of this study was to analyze the possible alterations produced by inadequate perinatal food intake, in quantity (undernutrition) or quality (malnutrition), on the generation and propagation of the compound action potential (CAP) evoked in sensory sural nerves, during the postnatal development of the rat. Low intensity stimulation (2-3 times the threshold of the most excitable nerve fibers; xT) of the sural nerve evoked an early potential (CAP-A component) which is due to activation of low-threshold, fast-conducting myelinated group A afferent fibers. Meanwhile, at higher stimulus intensity (20-30T) it produced a second, long-lasting potential (CAP-C component) probably due to activation of high-threshold, slow-conducting group Adelta or C afferent fibers. Compared to control nerves, the CAP-A component, but not the CAP-C component of undernourished and malnourished nerves showed significant changes in amplitude, area, electrical threshold and conduction velocity (except absolute refractory period) at several postnatal ages. Our results may suggest that a relative large number of myelinated group A afferent fibers in the sural nerve of undernourished and malnourished animals suffer severe alterations on their electrophysiological properties of generation and propagation of the action potential during the postnatal development of the rat.


The developing cortex.
Cortical maturation is associated with a series of developmental programs encompassing neuronal and network-driven patterns. Thus, voltage-gated and synapse-driven ionic currents are very different in immature and adult neurons with slower kinetics in the former than in the latter. These features are neuron and developmental stage dependent. GABA, which is the main inhibitory neurotransmitter in adult brain, depolarizes and excites immature neurons and its actions are thought to exert a trophic role in developmental processes. Networks follow a parallel sequence with voltage-gated calcium currents followed by calcium plateaux and synapse-driven patterns in vitro. In vivo, early activity exhibits discontinuous temporal organization with alternating bursts. Early cortical patterns are driven by sensory input from the periphery providing a basis for activity-dependent modulation of the cortical networks formation. These features and notably the excitatory GABA underlie the high susceptibility of immature neurons to seizures. Alterations of these sequences play a central role in developmental malformations, notably migration disorders and associated neurological sequelae.


[Concepts and assessment methods in lower urinary tract symptoms: From symptom score to Patient-Reported Outcomes and Outcomes (PRO)].
The evaluation of pelvic perineal treatments has changed significantly in recent years. Initially focused on the assessment of symptoms, quality of life or patient satisfaction, it has gradually turned to new concepts, such as Patient Reported Outcome (PRO) and Goal Attainment (GA). To describe the different concepts and methods of assessment available, in recent years, in the context of urinary functional pathologies such as bladder overactivity or urinary incontinence. We conducted a non-systematic literature review to identify the main questionnaires and tools available to evaluate treatment outcomes. Oncology and pediatrics questionnaire has been excluded. In functional pathology (overactive bladder or incontinence), the objective of treatment is to meet the expectations of patients and it is important to be able to assess the feelings of patients. In this context, new specific questionnaires have been developed to evaluate the PROs. For about ten years, these subjective criteria, are more and more widespread in the evaluation of treatments. A new field then appeared, namely Goal Attainment Scaling (GAS) and Self Appreciation Goal Attainment (SAGA), allowing to determine with the patient, the expected objectives of the treatment. These concepts of PRO and GAS open up a new domain in the evaluation of treatments, with a subjective view of the results. They deserve to be integrated into the usual, objective evaluations, in order to adapt the treatment of the patients, according to the real impact of the treatment.


Superoxide production from human polymorphonuclear leucocytes stimulated with immunoglobulins of different classes and fragments of IgG bound to polystyrene dishes.
Polystyrene surfaces coated with proteins at alkaline pH were found to be useful to investigate the stimulation of neutrophils independently of phagocytosis. Human neutrophils, when exposed to appropriate stimuli, release superoxide anion (O2-). We have measured superoxide dismutase-inhibitable cytochrome c reduction by cells stimulated with various kinds of protein coated on polystyrene dishes. Native immunoglobulins in solution did not stimulate O2- generation in neutrophils. IgG and IgA adherent to polystyrene dishes stimulated O2- generation in neutrophils, but IgM, IgD, IgE, albumin, Fab, and Fc of IgG on polystyrene dishes did not.


Phospholipid alterations and membrane injury during myocardial ischemia.
Several independent studies have demonstrated that there is a degradation of membrane phospholipids during myocardial ischemia. At present, most of the data support the initial activation of a phospholipase A pathway of phospholipid degradation. The extent of total phospholipid degradation is in the nanomole per gram wet weight quantity, as opposed to ischemic liver, in which the extent of phospholipid depletion approaches the micromole per gram wet weight level. However, in vitro studies suggest that calcium permeability properties and other myocardial cell membrane functions are sensitive to nanomole levels of phospholipid degradation. Clearly, further work is necessary in intact cell and heart preparations to correlate the degradation of phospholipid with the development of irreversible membrane injury during ATP depletion and hypoxia.


ZnO Rods with Exposed {100} Facets Grown via a Self-Catalyzed Vapor-Solid Mechanism and Their Photocatalytic and Gas Sensing Properties.
We present a new method for vapor deposition of columnar ZnO structures in the form of rods on various substrates without the need for substrate modification with catalyst seed particles and at relatively low temperatures compared to other vapor deposition methods. These structures are used for the photodegradation of stearic acid (C18H36O2) and the photoactivated detection of gases such as carbon monoxide (CO), ethanol (C2H6O), toluene (C7H8), and nitrogen dioxide (NO2) at room temperature, showing improved selectivity compared to tests performed in themoactivated mode.


Validating the Student-Teacher Relationship Scale: testing factor structure and measurement invariance across child gender and age in a Dutch sample.
The Student-Teacher Relationship Scale (STRS) is widely used to examine teachers' relationships with young students in terms of closeness, conflict, and dependency. This study aimed to verify the dimensional structure of the STRS with confirmatory factor analysis, test its measurement invariance across child gender and age, improve its measurement of the dependency construct, and extend its age range. Teachers completed a slightly adapted STRS for a Dutch sample of 2335 children aged 3 to 12. Overall, the 3-factor model showed an acceptable fit. Results indicated metric invariance across gender and age up to 8years. Scalar invariance generally did not hold. Lack of metric invariance at ages 8 to 12 primarily involved Conflict items, whereas scale differences across gender and age primarily involved Closeness items. The adapted Dependency scale showed strong invariance and higher internal consistencies than the original scale for this Dutch sample. Importantly, the revealed non-invariance for gender and age did not influence mean group comparisons.


Surgical management of acoustic neuromas during the last five years. Part II: Results for facial and cochlear nerve function.
Postoperative facial and cochlear nerve function in 83 consecutive patients with acoustic neuromas, who were undergoing their initial surgical procedure during 1980-1984, have been examined. The facial nerve was preserved in anatomic continuity in 71% of cases. Various nerve grafting procedures were used when the facial nerve was divided; the most common of these was a faciohypoglossal anastomosis, which was performed in 20 cases. The facial and cochlear nerves were anatomically preserved in 30.1% of all patients having their initial surgical procedure. Good speech discrimination was preserved in four patients, whereas more crude hearing was preserved in six other patients.


Mercury biomagnification in the food web of a neotropical stream.
Anthropogenic and natural mercury (Hg) contamination have been a major concern in South America since the early 1900s, but it remains unclear whether Hg levels pose a hazard to human health in regions that lack point sources. We studied Hg biomagnification patterns in the food web of Río Las Marías, an Andean piedmont stream in northern Venezuela, which supports a major subsistence fishery. Mercury concentrations and trophic positions in the food web (based on stable isotopes of nitrogen and carbon) were characterized for 24 fish species representing seven trophic guilds (piscivore, generalized carnivore, omnivore, invertivore, algivore, terrestrial herbivore, detritivore). Mercury showed significant biomagnification through the food web, but vertical trophic position explained little of the variation. Muscle Hg concentrations also increased with body mass across the food web. Trophic guild assignments offered a useful alternative to explicit analysis of vertical trophic position; piscivores showed the highest Hg concentrations and terrestrial herbivores had the lowest. There were no consistent seasonal differences in Hg concentrations within the 5 species sampled during both the wet and dry seasons, suggesting that bioavailability is unaffected by strong seasonal variation in rainfall. From a human health perspective, many medium- to large-bodied species that are commonly eaten had Hg concentrations that exceeded International Marketing Limit (IML) (0.5 μg/g) and World Health Organization (WHO) guidelines (0.2 μg/g) for consumption. We conclude that Hg concentrations may pose a health concern for local subsistence fishermen and their families. Our results suggest a need to perform risk assessment and better understand contaminant levels in subsistence and commercial fisheries even in areas that lack known Hg point sources.


Why is the hyperplastic polyp a marker for the precancerous condition of the gastric mucosa?
It is well known from the older literature that gastric carcinomas are more likely to develop in a stomach containing hyperplastic polyps. The reason why such a stomach should represent a precancerous condition is, however, largely unexplained. The aim of this study was to determine the disorders of the gastric mucosa in which hyperplastic polyps occur. In 244 patients with hyperplastic polyp, in whom at least two additional biopsies each from the antrum and corpus were available, gastritis was classified on the basis of the updated Sydney System. In none of the 244 patients was the gastric mucosa found to be normal. The most common disorder, at 51.3%, was autoimmune gastritis of the corpus mucosa, while chronic active Helicobacter pylori (Hp) gastritis was seen in 37.3% of the patients. Of the patients with Hp gastritis, 56.1% had corpus-dominant Hp gastritis. Other forms were relatively rare: when A-gastritis, corpus-dominant Hp gastritis and any other form of Hp gastritis were lumped together as a precancerous condition, these changes were found in 88.6% of the patients with hyperplastic polyps of the stomach. In the presence of hyperplastic polyps of the gastric mucosa, additional biopsies obtained from the antrum and corpus should always be performed to obtain a basis for deciding whether to apply Hp eradication treatment as potential carcinoma prophylaxis.


Anti-RNP positivity in primary Sjögren's syndrome is associated with a more active disease and a more frequent muscular and pulmonary involvement.
To describe and compare the clinical and biological characteristics of subjects with primary Sjögren's syndrome (pSS) with and without anti-RNP antibodies. Patients fulfilling the American College of Rheumatology (ACR)/EULAR 2016 criteria for pSS and having anti-RNP antibodies, without other connective tissue disease diagnosed and no anti-dsDNA antibodies were retrieved from the database from our French National Reference Center. These patients were compared with all other patients with pSS with negative anti-Sm, anti-RNP and anti-dsDNA antibodies. Overall, 21 patients with pSS positive for anti-RNP antibodies and 446 negative for anti-RNP antibodies were retrieved. Anti-RNP-positive patients had a lower median age at onset of pSS symptoms (41.0 vs 50.0 years, p=0.01), a higher median EULAR Sjögren's syndrome disease activity index at inclusion (8.0 vs 3.0, p<0.01), more frequently constitutional symptoms (14.3% vs 0.01%, p<0.01), myositis (19.0% vs 2.3%, p<0.01) and pulmonary (19.0% vs 5.7%, p=0.04) involvement. Moreover, anti-RNP-positive patients had higher median gammaglobulin levels (22.5 vs 13 g/L, p<0.01), more frequently anti-SSA antibodies (90.5% vs 67.1%, p=0.03), but less frequent lymphocytic sialadenitis with a focus score ≥1 (66.7% vs 85.5%, p=0.03). If the analysis is restricted to anti-SSA-positive patients, anti-RNP positivity is associated with the same clinicobiologic features except the pulmonary involvement. Patients with pSS with anti-RNP antibodies displayed a more active systemic disease, with more frequent muscular and pulmonary involvement, and increased gammaglobulin level, compared with anti-RNP-negative patients.


Association between excess body weight and urine protein concentration in healthy dogs.
Markedly overweight people can develop progressive proteinuria and kidney failure secondary to obesity-related glomerulopathy (ORG). Glomerular lesions in dogs with experimentally induced obesity are similar to those in people with ORG. The aim of this study was to evaluate if urine protein and albumin excretion is greater in overweight and obese dogs than in dogs of ideal body condition. Client-owned dogs were screened for underlying health conditions. These dogs were assigned a body condition score (BCS) using a 9-point scoring system. Dogs with a BCS of ≥ 6 were classified as being overweight/obese, and dogs with a BCS of 4 or 5 were classified as being of ideal body weight. The urine protein:creatinine ratio (UPC) and urine albumin:creatinine ratio (UAC) were then determined, and compared between 20 overweight/obese dogs and 22 ideal body weight control dogs. Median UPC (0.04 [range, 0.01-0.14; interquartile range, 0.07]) and UAC (0.41 [0-10.39; 3.21]) of overweight/obese dogs were not significantly different from median UPC (0.04 [0.01-0.32; 0.07]) and UAC (0.18 [0-7.04; 1.75]) in ideal body weight dogs. Clinicopathologic abnormalities consistent with ORG were absent from overweight/obese dogs in this study.


The influence of macro-textural designs over implant surface on bone on-growth: A computational mechanobiology based study.
The longerterm secondary stability of an uncemented implant depends primarily on the quality and extent of bone in-growth or on-growth at the bone-implant interface. Investigations are warranted to predict the influences of implant macro-textures on bone on-growth pattern. Mechanoregulatory tissue differentiation algorithms can predict such patterns effectively. There is, however, a dearth of volumetric in silico study to assess the influence of macro-textures on bone growth. The present study investigated the influence of macro-textural grooves/ribs on changes in tissue formation at the bone-implant interface by carrying out a 3D finite element (FE) analysis. Three distinct macro-textures, loosely based on commercially viable hip stem models, were comparatively assessed for varying levels of interfacial micromotion. The study predicted elevated fibrogenesis and chondrogenesis, followed by a suppressed osteogenesis for higher levels of micromotion (60 μm and 100 μm), resulting in weak bone-implant interface strength. However, small judicious modifications in implant surface texture may enhance bone growth to a considerable extent. The numerical scheme can further be used as a template for more rigorous parametric and multi-scale studies.


Investigating the role of FUS exonic variants in essential tremor.
Essential Tremor is the most common form of movement disorder. Aggregation in families suggests a strong genetic component to disease. Linkage and association studies have identified several risk loci but the specific causal variants are still unknown. A recent study using whole exome sequencing identified a rare nonsense variant in the FUS gene (p.Q290X) that segregated with Essential Tremor in a large French Canadian family. In addition, two other rare FUS variants were identified (p.R216C and p.P431L) in Essential Tremor patients however co-segregation analysis with disease was not possible. In the present study, we sequenced all 15 exons of FUS in 152 familial probands with Essential Tremor and genotyped three reported FUS variants in 112 sporadic Essential Tremor patients and 716 control subjects recruited at Mayo Clinic Florida. Only known synonymous SNPs unlikely to be pathogenic were detected in our sequencing and not any of the recently identified mutations or novel ones. We conclude that the FUS mutations associated with risk of Essential Tremor are probably a rare occurrence.


Eight free flaps in 24 hours: a training concept for postgraduate teaching of how to raise microvascular free flaps.
Microvascular free flaps are complex but important tools in oral and maxillofacial surgery (OMFS), and though techniques to raise flaps are challenging surgeons often have little structured training. In this study we have evaluated a structured, three-day, hands-on, practical training course on raising flaps. Five human, Thiel-embalmed cadavers were used for training in how to raise the following flaps: radial forearm, anterolateral thigh, lateral arm, fibular, latissimus dorsi, scapular, iliac crest, and rectus abdominis. The total duration of the course was 24 hours over three days. All participants were asked to evaluate the design and conduct of the course, their own learning curve, and general questions about their knowledge of how to raise flaps and microsurgery. There was a significant increase in participants' assessments of how they raised all free flaps, except the lateral arm flap (4.74 (0.68) compared with 2.42 (0.81); p=0.052) before and after the course. The radial forearm flap was thought to be the most relevant in clinical practice (n=40; 75%), followed by the anterolateral thigh (n=5; 9%) and fibular (n=4; 8%) flaps. Comparisons between residents and consultants showed unsurprising differences in experience with microsurgery and self-assessment in raising particular free flaps before the course. We have shown that a structured, hands-on course using a well-established simulation model can significantly improve postgraduate surgeons' skills in raising free flaps.


The Therapeutic Potential of Psychedelic-assisted Therapies for Symptom Control in Patients Diagnosed With Serious Illness: A Systematic Review.
People affected by serious illness usually experience suffering in its various dimensions, not only in the physical but also in the psychosocial and spiritual aspects. The interest in psychedelic-assisted therapies as a potential new therapeutic modality has increased since evidence suggests a significant impact of their use on the outcomes of patients with serious illness. To systematically review the available evidence on the effects of psychedelic-assisted therapies for symptom control in patients diagnosed with serious illness. The protocol of this systematic review has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. This review included randomized and non-randomized controlled trials published in peer-reviewed scientific journals. A comprehensive search for studies was carried out in the main scientific databases, including Web of Science, Scopus, Cochrane Library, PsycINFO, PubMed, CINAHL, and EMBASE. There were no limitations regarding the year or language of publication. The sample was composed of 20 studies. The results suggest positive effects of psychedelic-assisted therapies for symptom control in patients diagnosed with serious illness, with considerable safety of use. Most studies have been conducted with lysergic acid diethylamide, psilocybin, and N,N-dipropyltryptamine in cancer patients. The adverse effects reported were of physical and/or psychological nature and of mild to moderate intensity, transient, and self-resolutive. The evaluated evidence suggests positive effects of psychedelic-assisted therapies for symptom control in patients diagnosed with serious illness, especially regarding symptoms of psychological and spiritual nature.


Rapid detection of porcine reproductive and respiratory syndrome virus by reverse transcription loop-mediated isothermal amplification assay.
A rapid detection assay based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been developed for detecting porcine reproductive and respiratory syndrome virus (PRRSV). The RT-LAMP assay utilized a set of six primers to amplify the open reading frame 6 (ORF6) of the PRRSV. The amplified products were analyzed by agarose gel electrophoresis or visualized by colorimetric method. The results demonstrated that the RT-LAMP assay detected all 22 different PRRSV isolates, had no cross-reaction with four other swine viruses (i.e., PCV2, SIV, CSFV, and PEDV), and obtained a 91.3% sensitivity in 23 positive clinical samples in reference to the permissive cells-based virus isolation procedure. Therefore, the RT-LAMP assay provides a specific and sensitive means for detecting PRRSV in a simple, fast, and cost-effective manner. Furthermore, the RT-LAMP assay can be performed in less well-equipped laboratories as well as fields.


Biology and Targetability of the Extended Spectrum of PIK3CA Mutations Detected in Breast Carcinoma.
Alpelisib is a PI3K alpha (PI3Kα)-selective inhibitor approved for the treatment of hormone receptor-positive/HER2-negative (HR+/HER2-) PIK3CA-mutated advanced breast cancer (ABC) based on the SOLAR-1 trial, which defined 11 substitutions in exons 7, 9, and 20 in PIK3CA (SOLAR1m). We report alpelisib effectiveness for ABC harboring SOLAR1m, as well as other pathogenic PIK3CA mutations (OTHERm) using comprehensive genomic profiling (CGP). A total of 33,977 tissue and 1,587 liquid biopsies were analyzed using hybrid capture-based CGP covering the entire coding sequence of PIK3CA. Clinical characteristics and treatment history were available for 10,750 patients with ABC in the deidentified Flatiron Health-Foundation Medicine clinico-genomic database (FH-FMI CGDB). PIK3CAm were detected in 11,767/33,977 (35%) of tissue biopsies, including 2,300 (7%) samples with OTHERm and no SOLAR1m. Liquid biopsy had 77% sensitivity detecting PIK3CAm, increasing to 95% with circulating tumor DNA fraction ≥2%. In patients with HR+/HER2- ABC and PIK3CAm receiving alpelisib/fulvestrant (ALP+FUL; n = 182) or fulvestrant alone (FUL; n = 119), median real-world progression-free survival (rwPFS) was 5.9 months on ALP+FUL [95% confidence interval (CI): 5.1-7.4] versus 3.1 months on FUL (95% CI: 2.7-3.7; P < 0.0001). In patients with OTHERm, median rwPFS was 4.0 months on ALP+FUL (95% CI: 2.8-10.1) versus 2.5 months on FUL (95% CI: 2.2-3.7; P = 0.0054). CGP detects diverse PIK3CAm in a greater number of patients with ABC than PCR hotspot testing; 20% of patients with PIK3CAm do not have SOLAR1m. These patients may derive benefit from alpelisib. See related commentary by Tau and Miller, p. 989.


Chromium-doped inverse spinel electrocatalysts with optimal orbital occupancy for facilitating reaction kinetics of lithium-oxygen batteries.
Tailored electrocatalysts that can modulate their electronic structure are highly desirable to facilitate the reaction kinetics of oxygen evolution reaction (OER) and oxidation reduction reaction (ORR) in lithium-oxygen batteries (LOB). Although octahedron predominant inverse spinels (e.g., CoFe2O4) have been proposed as promising candidates for catalytic reactions, their performance has remained unsatisfactory. Herein, the chromium (Cr) doped CoFe2O4 nanoflowers (Cr-CoFe2O4) are elaborately constructed on nickel foam as a bifunctional electrocatalyst that drastically improves the performance of LOB. The results show that the partially oxidized Cr6+ stabilizes the cobalt (Co) sites at high-valence and regulates the electronic structure of Co sites, facilitating the oxygen redox kinetics of LOB due to their strong electron-withdrawing capability. Moreover, DFT calculations and ultraviolet photoelectron spectrometer (UPS) results consistently demonstrate that Cr doping optimizes the eg electron filling state of the active octahedral Co sites, significantly improves the covalency of Co-O bonds, and enhances the degree of Co 3d-O 2p hybrids. As a result, Cr-CoFe2O4 catalyzed LOB can achieve low overpotential (0.48 V), high discharge capacity (22030 mA h g-1) and long-term cycling durability (over 500 cycles at 300 mA g-1). This work promotes the oxygen redox reaction and accelerates the electron transfer between Co ions and oxygen-containing intermediates, highlighting the potential of Cr-CoFe2O4 nanoflowers as bifunctional electrocatalysts for LOB.


Comparative in vitro study of cementing techniques for implant-supported restorations.
Various techniques are used to cement implant-supported restorations. Excess residual cement is a concern. The purpose of this in vitro study was to evaluate 3 techniques for cementing implant-supported restorations. Twelve crowns and implant-abutment complexes (IAC) were cemented with 3 techniques: technique 1, a certain amount of cement evenly placed and excess cement removed with an explorer; technique 2, a smaller amount of cement without removal of excess cement; technique 3, a resin abutment replica used for excess cement removal after using a large amount of cement. Each specimen was treated with each technique 3 times. Precementing discrepancies (predis) and postcementing discrepancies (postdis) between IACs and crowns and the postcementing linear roughness (Ra and Rz) on designated junction areas of each specimen were measured. Tensile strength of the specimens was recorded with a universal testing machine at a crosshead speed of 0.5 mm/min. Repeated measures analysis with mixed models was used for differences among the 3 cementing techniques (α=.05). Compared with techniques 1 and 2, the specimens with technique 3 showed significantly lower mean differences between postdis and predis and Ra and Rz and higher mean tensile strength (P<.05). The application of a resin abutment replica for the cementation of implant-supported restorations decreased the discrepancy between the restoration and abutment, reduced cement residue, and increased restoration retention.


Substance P mediates atropine-sensitive response of guinea-pig ileum to serotonin.
The action of serotonin (5HT) was investigated on guinea-pig isolated ileum. Low concentrations of 5HT (10(-8) - 2.5 x 10(-7) mol x 1(-1)) produced contractile responses which were abolished by atropine and by methionine enkephalin but not by methysergide. Higher concentrations of 5HT (5 x 10(-7) - 5 x 10(-6) mol x 1(-1)) produced contractions which were inhibited by methysergide. The atropine-sensitive response was also abolished following desensitization of preparations to substance P and by the substance P antagonist [D-Pro2,D-Phe7,D-Trp9]SP. It was concluded that the atropine-sensitive response to 5HT is mediated by substance P.


The relationship between asthma control and quality-of-life impairment due to chronic cough: a real-life study.
The objective of asthma therapy is to achieve optimal disease control and quality-of-life (QoL) improvements. Good correlation is reported between a composite evaluation of asthma control (the Asthma Control Test [ACT]) and QoL, with emphasis on asthma as a frequent cause of chronic cough and worsening of QoL due to chronic cough. To investigate asthma control in real life and to evaluate chronic cough-related impairment of QoL in patients with different degrees of asthma control evaluated by the ACT. Outpatients awaiting physician visits for asthma evaluation were asked to complete the ACT, the Chronic Cough Impact Questionnaire (CCIQ), and a rhinitis symptom score (Total Symptom Score [TSS] 5). A total of 122 patients (mean [SD] age, 44 [15] years; age range, 15-75 years; 61.5% female) were enrolled in the study, of whom 74% reported rhinitis in conjunction with asthma. Overall asthma control was substantially less than optimal (ACT mean score, 14) in 44% of patients. Asthma control correlated to a limited degree with the CCIQ among the total sample. In patients with asthma alone, the correlation between the ACT and the CCIQ was much improved. In patients with comorbid rhinitis, only those with significant symptoms (as determined by the TSS5) reported using rhinitis treatment; among these, no significant correlation between the ACT and the CCIQ was found. Asthma control in real life is less than optimal in substantially few patients. The importance of cough in asthma is highlighted by good correlation between cough and the ACT score in patients without comorbid rhinitis. In patients with comorbid rhinitis, cough appears related more to rhinitis than to asthma control. The combined use of the ACT and the CCIQ may be useful to improve asthma management, especially among patients in whom cough remains a prominent symptom.


A detailed analysis of codon usage patterns and influencing factors in Zika virus.
Recent outbreaks of Zika virus (ZIKV) in Africa, Latin America, Europe, and Southeast Asia have resulted in serious health concerns. To understand more about evolution and transmission of ZIKV, detailed codon usage analysis was performed for all available strains. A high effective number of codons (ENC) value indicated the presence of low codon usage bias in ZIKV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations between nucleotide compositions at third codon positions and ENCs. Correlation analysis between Gravy values, Aroma values and nucleotide compositions at third codon positions also indicated some influence of natural selection. However, the low codon adaptation index (CAI) value of ZIKV with reference to human and mosquito indicated poor adaptation of ZIKV codon usage towards its hosts, signifying that natural selection has a weaker influence than mutational pressure. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern to some extent.


Synthesis of cyclic prodrugs of Aggrastat and its analogue with a modified phenylpropionic acid linker.
[structure: see text] The objective of this work was to synthesize cyclic prodrugs 1a and 1b from Aggrastat 2a and its analogue 2b, respectively, to improve their membrane permeation. Cyclic prodrugs 1a and 1b were formed using an ester bond between the -COOH group of Aggrastat or its analogue and the phenylpropionic acid linker 3 and an amide bond between the piperidinylamine and the -COOH group of the linker 3, respectively, as outlined in Scheme 4.


Kinetic investigations in single muscle fibres using luminescent and fluorescent Ca2+ probes.
The Ca2+-sensitive photoprotein aequorin and the Ca2+-dependent fluorescent indicators quin 2 and TnCDANZ have been used to investigate contractile processes in single crustacean muscle fibres. The investigations with quin 2 indicate that the free Ca2+ rises to a maximum value before peak force as with aequorin light (approximately 200 msec delay at 12 degrees C) and subsequently decays more slowly, unlike the majority of the aequorin signal, although an aequorin 'tail' signal remains. The resting quin 2 fluorescence from the cell suggests an upper limit of 348 nM for the resting calcium concentration. Experiments with TnCDANZ indicate that this fluorescence response rises rapidly but then the rate of rise slows to reach a maximum value at a time when peak force is achieved and then the fluorescence signal decays more slowly than force. The latter result implies that Ca2+ is attached to the Ca2+-specific sites of TnC when externally recorded force is small.


Immunoreactive pancreatic polypeptide (PP) occurs in the central and peripheral nervous system: preliminary immunocytochemical observations.
Pancreatic polypeptide (PP) is a candidate hormone of unknown physiological significance. It is produced by a population of endocrine cells in the pancreas. In the present study a PP-like peptide was found to occur in the mammalian and avian central andperipheral nervous systems. Immunoreactive nerve fibres and nerve cell bodies were widely distributed in the brain. Dense accumulations of nerve fibres occurred in the following areas: nucleus accumbens, interstitial nucleus of the stria terminalis, para- and periventricular hypothalamic nuclei, and medical preoptic area. In addition, nerve fibres were regularly seen in cortical areas. Immunoreactive perikarya were observed in the following regions: cortex, nucleus accumbens, neostriatum and septum. In the gut, immunoreactive nerve fibers were distributed in the myenteric plexus, in smooth muscle, around blood vessels, and in the core of the villi. Immunoreactive perikarya occurred in the submucosal and myenteric plexus, suggesting that PP immunonal PP-like peptide could be demonstrated with an antiserum raised against avian PP, but not with those raised against bovine or human PP. Thus, neuronal PP is distinct from the PP that occurs in pancreatic endocrine cells.


Comprehensive pouch clinic concept for follow-up of patients after ileal pouch anal anastomosis: report of 3 years' experience in a tertiary referral center.
We designed and evaluated a novel concept in enhancing postoperative care of patients following restorative proctocolectomy (RPC) for ulcerative colitis (UC) and determined the risk factors, incidence, and nature of RPC-associated complications in this population. The study cohort consisted of consecutive UC patients post-RPC attending a comprehensive pouch clinic run by a gastroenterologist and a colorectal surgeon in a tertiary care medical center (from January 2003 to December 2005). Data were collected on their medical history, physical examination, laboratory tests, pouch endoscopy and biopsies, and anonymous in-house patient satisfaction questionnaires mailed to the first 90 patients. Assessment was also done on data regarding risk factors, incidence, and nature of RPC-associated complications. A total of 120 UC patients with a functioning pouch visited the clinic: mean age 37 years, range 13-75; 57 males; mean disease duration 11 years; mean follow-up 65 months. Of the 55 patients who responded to the questionnaire, 48 (87%) felt that the comprehensive clinic significantly improved the quality of their care. The major complications were pouchitis (52%), extraintestinal manifestations, pouch-related fistula, and mechanical dysfunction. The risk factors for the development of pouchitis were time since surgery, >1-stage surgery, and reason for surgery (acute exacerbation/intractable disease more than dysplasia/cancer); the latter was the only independent risk factor. The pouch clinic concept significantly enhanced patient satisfaction. The most common RPC-associated complication was pouchitis. Risk factors for developing pouchitis were duration since operation, >1-stage operation, and indication for surgery.


Correction: Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis.
[This corrects the article DOI: 10.1371/journal.pbio.1002382.].


Pseudomonas putida actively forms biofilms to protect the population under antibiotic stress.
Antibiotics are frequently used for clinical treatment and by the farming industry, and most of these are eventually released into the surrounding environment. The impact of these antibiotic pollutants on environmental microorganisms is a concern. The present study showed that after Pseudomonas putida entered the logarithmic growth phase, tetracycline strongly stimulated its biofilm formation in a dose-dependent manner. This was supported by the increased expression of the key adhesin gene lapA in response to tetracycline treatment. Tetracycline treatment also changed the expression levels of the exopolysaccharide gene clusters alg, bcs and pea and the adhesin gene lapF. However, these genes did not participate in the tetracycline-induced biofilm formation. When a biofilm had been established, the P. putida population became more tolerant to tetracycline. Confocal laser scanning microscopic images showed that the interior of the biofilm provided favorable conditions that protected bacterial cells from tetracycline. Besides, biofilm formation of P. putida was also promoted by several other antibiotics, including oxytetracycline, fluoroquinolones, rifampicin, and imipenem, but not aminoglycosides. Susceptibility tests suggested that biofilm conferred a higher tolerance on P. putida cells to specific antibiotics (e.g., tetracyclines and fluoroquinolones). These antibiotics exerted a stronger inducing effect on biofilm formation. Together, our results indicate that P. putida actively forms robust biofilms in response to antibiotic stress, and the biofilms improve the survival of bacterial population under such stress.


Comparison of unilateral and bilateral microdissection testicular sperm extraction (MD-TESE) in patients with non-obstructive azoospermia: a prospective study.
To compare sperm retrieval rates between unilateral and bilateral microdissection testicular sperm extraction (MD-TESE) procedures in patients with non-obstructive azoospermia and to contribute to the literature by comparing them with literature data. This prospective study included 84 males with primary infertility who had azoospermic NOA, who had been married for at least one year, and whose female partners did not have a history of infertility. The study was conducted between January 2019 and January 2020. MD-TESE was applied bilaterally to 48% (n:41) (Group 1) and unilaterally to 52% (n:43) (Group 2) of the patients, and sperm retrieval rates were compared. There was no statistically significant difference between Group 1 patients and Group 2 patients in terms of sperm availability (61%, 56.5%, p=0.495, respectively). In addition, while no complications were observed in unilateral MD-TESEs, 3 complications were observed in bilateral MD-TESEs. In our study, it was determined that there was no significant difference between the groups in terms of sperm availability in patients with NOA. Considering the operative time and complication rates of bilateral MD-TESE in patients diagnosed with NOA and the possible MD-TESE procedures that may be performed later, we believe that unilateral MD TESE is a more preferable procedure for the patient and surgeon in this patient group.


Chromatin structure, DNA synthesis and transcription through the lifespan of human embryonic lung fibroblasts.
The presence in terminal embryonic fibroblasts of small molecular weight (MW) DNA independent of bulk DNA could be ascertained by three different techniques performed in parallel. This alteration was not artifactually induced, either by high pH and the detergent used or by the release of cellular enzymes. An increased thermolability of old chromatin was also observed. Cells with altered chromatin synthesized DNA and RNA according to a pattern similar to young type nuclei. Long-term treatment with hydrocortisone significantly increased the cell yield but did not prevent, in the late passages, the occurrence of old-type chromatin; the nucleolar filamentous masses, however, maintained a 'young' pattern. Short-term treatment induced only a moderate reversion in the appearance of chromatin lesions. Direct evidence was obtained of increased gene expression in the presence of hydrocortisone.


A zebrafish model for the rapid evaluation of pro-oxidative and inflammatory death by lipopolysaccharide, oxidized low-density lipoproteins, and glycated high-density lipoproteins.
Oxidation and inflammation are leading causes of nearly all chronic metabolic disorders, and play major roles in cardiovascular disease, cancer, and chronic age-dependent disease. High-density lipoprotein (HDL) and apolipoprotein (apo) A-I have strong antioxidant and anti-inflammatory properties in the plasma. Fructose-induced non-enzymatic glycation of apoA-I can lead to the production of dysfunctional apoA-I and HDL. To compare the physiologic effects of dysfunctional apoA-I and HDL, reconstituted HDL containing native apoA-I (nA-I) or glycated apoA-I (gA-I) was injected into zebrafish embryos in the presence of inflammatory molecules. Co-injection of reconstituted HDL containing VLDL and LDL gA-I (gA-I-rHDL) and lipopolysaccaride (LPS) resulted in acute embryo deaths, while rHDL containing nA-I (nA-I-rHDL) and LPS resulted in significantly enhanced survival. Co-injection of oxidized LDL (oxLDL) and nA-I-rHDL improved embryo survival, while co-injection of oxLDL and gA-I-rHDL aggravated inflammatory deaths. Furthermore, co-injection of oxLDL and HDL(2) (5 ng of protein) or HDL(3) (15 ng of protein) from the young group (22 ± 2 years old) showed significantly increased embryo survival compared with the same co-injection of HDL from the elderly group (71 ± 4 years old). In conclusion, our assay system provides a rapid and economic method to screen antioxidant and anti-inflammatory agents using zebrafish embryos.


In Silico Modelling of Transdermal and Systemic Kinetics of Topically Applied Solutes: Model Development and Initial Validation for Transdermal Nicotine.
The purpose was to develop a mechanistic mathematical model for predicting the pharmacokinetics of topically applied solutes penetrating through the skin and into the blood circulation. The model could be used to support the design of transdermal drug delivery systems and skin care products, and risk assessment of occupational or consumer exposure. A recently reported skin penetration model [Pharm Res 32 (2015) 1779] was integrated with the kinetic equations for dermis-to-capillary transport and systemic circulation. All model parameters were determined separately from the molecular, microscopic and physiological bases, without fitting to the in vivo data to be predicted. Published clinical studies of nicotine were used for model demonstration. The predicted plasma kinetics is in good agreement with observed clinical data. The simulated two-dimensional concentration profile in the stratum corneum vividly illustrates the local sub-cellular disposition kinetics, including tortuous lipid pathway for diffusion and the "reservoir" effect of the corneocytes. A mechanistic model for predicting transdermal and systemic kinetics was developed and demonstrated with published clinical data. The integrated mechanistic approach has significantly extended the applicability of a recently reported microscopic skin penetration model by providing prediction of solute concentration in the blood.


Radioactive iodine scanning is not beneficial but its use persists for euthyroid patients.
Radioactive iodine (RAI) scanning is a method of determining the functional status of thyroid nodules. Historically, practitioners thought "cold" or inactive nodules were more likely malignant. However, surgeons no longer find these scans helpful for preoperative management of euthyroid patients. The purpose of this study was to evaluate the utility of RAI scans. We retrospectively reviewed cases of euthyroid patients (thyroid-stimulating hormone > 1.0 mIU/L) who underwent RAI scans before thyroid surgery at our institution between 1994 and 2011. We correlated the RAI scan results with final pathology. We considered RAI scans concordant with pathology when we found a malignancy on the same lobe as a cold nodule. We also tabulated the specialty and affiliation of the ordering physicians. A total of 109 euthyroid patients underwent RAI scanning as part of their preoperative workup. Of these, 88 patients (81%) had a cold nodule. A malignancy concordant with the RAI scan findings occurred in only 15 of these patients (17%). Non-surgical specialties ordered 90 scans (95%). Only 11 of these scans (10%) were performed in the past 5 y, and physicians outside the academic institution ordered all 11 (100%) of these. A linear regression of RAI scanning per year yielded a slightly negative slope (m-0.32 per year). Radioactive iodine scanning is not useful for the surgical management of thyroid disease in euthyroid patients because it poorly predicts malignancy. The overall use of RAI scans is trending downward, but they are still ordered by non-surgical referring physicians.


Plasmacytoid dendritic cell-derived IFNα modulates Th17 differentiation during early Bordetella pertussis infection in mice.
Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). T helper 17 (Th17) cells have a central role in the resolution of the infection. Emerging studies document that type I interferons (IFNs) suppress Th17 differentiation and interleukin (IL)-17 responses in models of infection and chronic inflammation. As plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs, we hypothesize that during B. pertussis infection in mice, pDC-derived IFNα inhibits a rapid increase in Th17 cells. We found that IFNα-secreting pDCs appear in the lungs during the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection or later. The presence of IFNα led to reduced Th17 differentiation and proliferation in vitro. Furthermore, in vivo blocking of IFNα produced by pDCs during infection with B. pertussis infection resulted in early increase of Th17 frequency, inflammation, and reduced bacterial loads in the airways of infected mice. Taken together, the experiments reported here describe an inhibitory role for pDCs and pDC-derived IFNα in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough.


Experimental approaches and analytical technique for determining heavy metals in fallen dust at ferrosilicon production factory in Edfu, Aswan, Egypt.
In this study aimed to evaluate the pollution extent of metals and nonmetals inside and outside the ferrosilicon production factory in Edfu, Aswan, Egypt, raw materials (quartz, cokes, iron oxides), ferrosilicon alloy, silica fume, dust and suspended dust (at different sites) samples were collected from the factory, and fallen dust samples were collected from outside the factory, horizontally (at different sites and different distance and directions) and vertically (at different floors in the selected buildings). Gravimetric methods, X-ray fluorescence (XRF), flame photometer, wide range carbon determinator and atomic absorption spectroscopy tools were used for elements determination. The results indicating that the fallen dust and its element contents on southern factory walls being higher than those on eastern factory walls may be due to the nature of the dusts and effects of wind force and wind direction. Fallen dust levels in different regions outside the factory were found to be affected by the distance, direction and floors. The nature of dust samples was affected by gravity and the suspended dust in different factory units depended on the work capacity and method of handling materials by personnel in different production units. Silica fume was a complicated problem, had dangerous effect against the workers' health, and was characterized by high concentrations of SiO(2) (90.6%approximately 93.6%) and heavy metals (Mn, 420.6 x 10(-6) approximately 520.3 x 10(-6); Fe, 2354 x 10(-6)approximately 2685 x 10(-6); Co, 80.7 x 10(-6) approximately 101.6 x 10(-6) and Ni, 5.3 x 10(-6) approximately 6.05 x 10(-6)). The TSP (Total Suspended Particulate) levels in all factory units were higher than the recommended air quality value (70 microg/m(3)) under Egyptian law. The effect of ferrosilicon factory fallen dust on the surrounding regions decreased with increasing distance between the factory and these regions. The suspended dust samples in the factory units and their components greatly exceeded national and international standards, so health and environmental criteria must be enforced on these units.


Altered expression of genes involved in programmed cell death in primary cultured rat cerebellar granule cells acutely challenged with tetrabromobisphenol A.
In the present study, primary cultures of rat cerebellar granule cells (CGC) and the RT2 Profiler PCR array were used to examine the effect of acutely applied brominated flame retardant tetrabromobisphenol A (TBBPA) on the expression of 84 genes related to the main modes of programmed cell death. CGC, at the 7th day of culture, were exposed to 10 or 25μM TBBPA for 30min. Then, 3, 6, and 24h later, the viability of the cells was examined by the staining with propidium iodide (PI) or using the calcein/ethidium homodimer (CA/ET) live/dead kit, and RNA was extracted for the evaluation of gene expression by RT-PCR. At 3, 6 and 24h after the treatment, the number of viable neurons decreased, according to the PI staining method, to 75%, 58% and 41%, respectively, and with the CA/ET method to 65%, 58% and 28%, respectively. In CGC analyzed 3h after the treatment with 25μM TBBPA or 6h after 10μM TBBPA, the only change in the gene expression was a reduction in the expression of Tnf, which is associated with autophagy and may activate some pro-apoptotic proteins. Six hours after 25μM TBBPA, only 2 genes were over-expressed, a pro-apoptotic Tnfrsf10b and Irgm, which is related to autophagy, and the genes that were suppressed included the anti-apoptotic gene Xiap, the necrosis-related Commd4, pro-apoptotic Abl1, 5 genes involved in autophagy (App, Atg3, Mapk8, Pten, and Snca) and 2 genes that participate in two metabolic pathways: Atp6v1g2 (pro-apoptotic and necrosis) and Tnf (pro-apoptotic, autophagy). Autophagy-related Snca and Tnf remained under-expressed 24h after treatment with 25μM TBBPA, which was accompanied by the over-expression of the pro-apoptotic Casp6, the anti-apoptotic Birc3, 2 genes related to autophagy (Htt and Irgm) and 2 genes (Fas and Tp53) that are involved in both apoptosis (pro-apoptotic) and autophagy. These results show a complex pattern of TBBPA-evoked changes in the expression of the genes involved in the programmed neuronal death, indicating no induction of programmed necrosis, an early suppression of the autophagy and anti-apoptotic genes, followed by a delayed activation of genes associated with apoptosis.


Analysis of corticosteroids in human adrenal tissue by high pressure liquid chromatography.
High pressure liquid chromatography (HPLC) was demonstrated to be a good tool for the separation, identification and quantitation of corticosteroids (CS) extracted from homogenized tissue of adrenal glands and adrenal tumors in patients with hypercorticism. A chromatographic system consisting of Sorbax-SIL and Sorbax-CN columns, organic solvent extraction and a UV detector was used to analyze both more polar and less polar corticosteroids in the adrenal tissue.


Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells.
ADPKD is a renal pathology caused by mutations of PKD1 and PKD2 genes, which encode for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 plays an important role regulating several signal transducers, including cAMP and mTOR, which are involved in abnormal cell proliferation of ADPKD cells leading to the development and expansion of kidney cysts that are a typical hallmark of this disease. Therefore, the inhibition of both pathways could potentiate the reduction of cell proliferation enhancing benefits for ADPKD patients. The inhibition of cAMP- and mTOR-related signalling was performed by Cl-IB-MECA, an agonist of A3 receptors, and rapamycin, respectively. Protein kinase activity was evaluated by immunoblot and cell growth was analyzed by direct cell counting. The activation of A3AR by the specific agonist Cl-IB-MECA causes a marked reduction of CREB, mTOR, and ERK phosphorylation in kidney tissues of Pkd1 flox/-: Ksp-Cre polycystic mice and reduces cell growth in ADPKD cell lines, but not affects the kidney weight. The combined sequential treatment with rapamycin and Cl-IB-MECA in ADPKD cells potentiates the reduction of cell proliferation compared with the individual compound by the inhibition of CREB, mTOR, and ERK kinase activity. Conversely, the simultaneous application of these drugs counteracts their effect on cell growth, because the inhibition of ERK kinase activity is lost. The double treatment with rapamycin and Cl-IB-MECA may have synergistic effects on the inhibition of cell proliferation in ADPKD cells suggesting that combined therapies could improve renal function in ADPKD patients.


Neurofibromatosis type 2 in Phelan-McDermid syndrome: Institutional experience and review of the literature.
Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by rearrangements on chromosome 22q13.3 or sequence variants in SHANK3. Individuals with PMS caused by a 22q terminal deletion and a ring chromosome are at increased risk for Neurofibromatosis type 2 (NF2). However, the prevalence of NF2 in individuals with PMS and a r (22) is unknown. Individuals with PMS and a r (22) chromosome evaluated at the Greenwood Genetic Center (GGC) or by international collaborators, or identified through the PMS International Registry (PMSIR) were contacted and participated in a clinical questionnaire. Forty-four families completed the questionnaire and consented for the study. Of the individuals with a r (22), 7 (16%) carried a diagnosis of NF2. The average age of diagnosis of r (22) was 18 years old in individuals with NF2 and three years old in individuals without NF2 (p-value <0.001). Clinical findings were similar among all individuals in our sample with the exception of hearing loss, present in 57% of individuals with NF2 and 8% of individuals without NF2 (p-value <0.01). This is the largest clinical report of individuals with PMS and a r (22) chromosome. We show a diagnosis of NF2 in individuals with r (22) is not uncommon and may be under ascertained. Moreover, the presentation of NF2 in this cohort is variable and lifelong routine screening for features of NF2 in this population should be considered.


Strengthening the health claims of the poor: promoting social inclusion and redistribution in the health sector.
The problems for poor people generated by 'disorganised health care markets' in the developing world have grave consequences for their health. In many countries, processes of liberalisation and commercialisation have generated a number of dilemmas for policy-makers, non-governmental organisations and individuals seeking health care. Complex markets for health care provision and financing exist, regulation is lacking and rates of exclusion are high due to the effects of prices and a lack of concerted efforts to make health systems more accessible to the poor. Analysis of health systems and the problems they create for the poor should lead to responses that protect and enhance the rights of poor people to health.


ANG-1 TIE-2 and BMPR signalling defects are not seen in the nitrofen model of pulmonary hypertension and congenital diaphragmatic hernia.
Pulmonary hypertension (PH) is a lethal disease that is associated with characteristic histological abnormalities of the lung vasculature and defects of angiopoetin-1 (ANG-1), TIE-2 and bone morphogenetic protein receptor (BMPR)-related signalling. We hypothesized that if these signalling defects cause PH generically, they will be readily identifiable perinatally in congenital diaphragmatic hernia (CDH), where the typical pulmonary vascular changes are present before birth and are accompanied by PH after birth. CDH (predominantly left-sided, LCDH) was created in Sprague-Dawley rat pups by e9.5 maternal nitrofen administration. Left lungs from normal and LCDH pups were compared at fetal and postnatal time points for ANG-1, TIE-2, phosphorylated-TIE-2, phosphorylated-SMAD1/5/8 and phosphorylated-ERK1/2 by immunoprecipitation and Western blotting of lung protein extracts and by immunohistochemistry on lung sections. In normal lung, pulmonary ANG-1 protein levels fall between fetal and postnatal life, while TIE-2 levels increase. Over the corresponding time period, LCDH lung retained normal expression of ANG-1, TIE-2, phosphorylated-TIE-2 and, downstream of BMPR, phosphorylated-SMAD1/5/8 and phosphorylated-p44/42. In PH and CDH defects of ANG-1/TIE-2/BMPR-related signalling are not essential for the lethal vasculopathy.


Numerical and structural chromosome abnormalities in an ovarian fibrothecoma.
Cytogenetic analysis of a fibrothecoma of ovary revealed numerical and structural chromosome abnormalities, i.e., 44,XX, dup(1)(p13p31),del(3)(p14) add (10p), -16, -22. This is the first report of numerical and structural abnormalities in a fibrothecoma of the ovary.


Biological effect of interferon-gamma during the course of experimental infection of rat by Schistosoma mansoni.
We demonstrate here that a second mechanism of platelet activation dependent on lymphokine could also take place in the expression of platelet cytotoxicity against Schistosoma mansoni in vitro. Indeed, IgE, as previously described, but also IFN-gamma, present in the sera of infected rats, together induce platelets from normal rats into cytotoxic effectors for the parasitic larvae. This second mechanism appears also effective in vivo since the passive transfer of normal platelets treated by recombinant IFN-gamma (rIFN-gamma) and the administration of rIFN-gamma to rats conferred a protective immunity to S. mansoni.


Postmortem submersion interval in human bodies recovered from fresh water in an area of Mediterranean climate. Application and comparison of preexisting models.
The methods developed in recent years for the assessment of the Postmortem Submersion Interval (PMSI) have proven to be promising, but are strictly related to specific geographical areas or climates. The aim of this study is to assess the suitability of two of the most recent total aquatic decomposition scores (TADS) for the determination of the PMSI in bodies recovered from fresh water in an area of Mediterranean climate in the last 15 years. To do this, the correlation coefficient (r2) between PMSI and Accumulate Degrees Days (ADD) or PMSI and days was studied. The correlation between PMSI (expressed in days or in ADD) and the TADS was evaluated considering: (a) bodies recovered during the entire period; (b) bodies recovered during the cold season; (c) bodies recovered during the warm season. A linear regression analysis was set comparing the statistical significance of a model plotting TADS versus ADD, and another model plotting TADS versus PMSI (expressed in days) for both scores. Scores were scarcely applicable when considering the entire casuistry, as regression models showed low r2 values, but both scores showed high correlations after dividing the cases into 2 groups. In fact, after performing the seasonal partition, we observed a strong correlation between PMSI and TADS, using either of the scores. This study helps increase the accuracy, reliability, and validity of PMI estimation in bodies recovered from freshwater in an area of temperate climate, such as Northern Italy, supporting the need to establish regionally-specific equations for estimating PMI in a forensic context.


Political economy of transnational water pollution: what do the LMB data (1985-2000) say?
On the basis of the cross-section and time-series data of the Lower Mekong Basin (LMB)--including large sections of Thailand, Lao PDR, Vietnam, and Cambodia, we find little evidence in support of the environmental Kuznets curve (EKC) hypothesis. Instead, our regressions support the general views that water pollution had been positively related to income level and that, as a result of the end of the Cold War era, it had been significantly reduced in the 1990s vis-à-vis the 1980s. In most circumstances, water resources were more seriously polluted in the transnational border areas than in the other areas. Specifically, the estimated coefficients on the political boundary dummies show that political influence on transnational water pollution was more significant in areas near "the international border along which the river runs" (denoted by BORDER2) than in places near "the international border across which the river runs" (denoted by BORDER1). The estimated coefficients on the ASEAN dummy present some information about the positive role of the Association for Southeast Asian Nations (ASEAN) membership in the reduction of transnational water pollution. Finally, the country-specific dummies are found to present conflicting information about the transnational differences of water pollution, although Thailand is found to have the least water pollution in the LMB.


Swelling of whey and egg white protein hydrogels with stranded and particulate microstructures.
Swelling of protein hydrogels in alkaline conditions strongly depends on the gel microstructure. Stranded transparent gels swell as predicted using a modified Flory-Rehner model with the net protein charge. Particulate opaque gels swell very differently, with a sudden increase at a narrow pH range. Its swelling is not controlled by the protein charge, but by the destruction of the non-covalent interactions. Comparable dissolution thresholds, one with pH and another with the degree of swelling, are observed in both types of microstructures. These conclusions are valid for both whey protein isolate (WPI) gels and egg white gels, suggesting that they are universal for all globular proteins that can form such microscructures. Differences are observed, however, from the prevalent chemical crosslinks in each protein system. Non-covalent interactions dominate WPI gels; when such interactions are destroyed at pH≥11.5 the gels swell extensively and eventually dissolve. In egg white gels, the higher degree of disulphide crosslinking allows extensive swelling when non-covalent interactions are destroyed, but dissolution only occurs at pH≥13 when covalent crosslinks are cleaved. The current study highlights that the microstructure of protein hydrogels, a unique particularity of protein systems compared to other synthetic hydrogels, defines swelling.