Inactivation of a sperm motility gene by insertion of an epidermal growth factor receptor transgene whose product is overexpressed and compartmentalized during spermatogenesis.
Transgenic mice were generated with a human epidermal growth factor (EGF) receptor cDNA driven by the chicken beta-actin gene promoter. One line (AE24) that exhibited a unique expression pattern in which dramatically elevated levels of EGF receptor RNA were found only in the testis was established, suggesting that the beta-actin promoter was being influenced by an adjacent testis-specific enhancer. EGF receptor RNA was detected in primary spermatocytes, whereas the synthesis of receptor protein was restricted to elongate spermatids, indicating that transgene expression was under translational control. At spermiation, the EGF receptor was sequestered in residual bodies and excluded from mature sperm by a compartmentalization mechanism. About half of AE24 homozygous males were sterile because of sperm paralysis, whereas heterozygous males and females of either genotype were completely fertile. Electron microscopic analysis of sperm flagella from sterile AE24 homozygotes revealed an aberrant axonemal structure in which outer doublet microtubules were missing from the middle piece, resembling changes observed in the sperm of some infertile humans. Flagellar axonemal disassembly was observed in the vas deferens and epididymis but not in the testis, suggesting that outer doublets were assembled in a grossly normal manner but possessed a latent instability. These results demonstrate that in the AE24 mouse line the EGF receptor transgene was integrated into and inactivated an endogenous autosomal gene, causing sperm flagellar axonemal disruption and male sterility.


A prospective randomized controlled study comparing two doses of gestodene in cyclic combined HRT preparations on endometrial physiology.
Postmenopausal women taking oestradiol 17-beta 2 mg daily were randomized to receive either 25 or 50 microg gestodene from day 17 to 28 of the cycle in a double-blind study. Placental protein P14 (PP14) and CA 125 concentrations in uterine flushing, endometrial morphology and irregular bleeding after 12 cycles of study were observed. Eleven and 12 women in the 25 and 50 microg groups respectively completed the study. There were no significant differences in pre-treatment biochemical and morphological indices between the groups. The median PP14 concentration increased from 332 to 5800 ng/ml (P < 0.001) and from 145 to 27 160 ng/ml (P < 0.001) in the 25 and 50 microg gestodene groups respectively. No between-group significant rise of PP14 was observed. Similarly, no significant change was seen between the initial and post-treatment concentrations of CA 125 for either group. All biopsies were atrophic at inception of the study, and both regimens produced secretory endometrial transformation in the majority of biopsies. No between-group difference was observed in the morphometric indices measured, or any significant correlation between the concentrations of PP14 or CA 125 and morphology. The mean number of days of withdrawal bleeding (3.8 and 4.2 days for 25 and 50 microg respectively) were similar. In conclusion, both regimens produced a significant rise in uterine flushing concentrations of PP14, but not CA 125. PP14 is a sensitive biochemical marker in the assessment of endometrial response to hormone replacement therapy.


Effect of prolonged sitting on body-seat contact pressures among quay crane operators: A pilot study.
Quay crane operators are specialized in moving containers to and from vessels while adopting constrained sitting postures for prolonged periods (4-6 consecutive hours) in a very challenging environment. Thus, they are exposed to discomfort or pain that may result in deterioration of their performance with consequent reduction of operational safety levels. Such discomfort can be indirectly and partially assessed by measuring contact pressure at the body-seat interface. The aim of the study was to assess the feasibility, usefulness, and effectiveness of monitoring the variations in seat-body interface pressure during a regular work shift of 4 hours performed in a simulated environment. Eight professional operators performed a four-hour shift in a realistic control station set inside a quay crane simulator. Seat-body contact pressures were measured at 10 Hz using two pressure-sensitive mats placed on the seat pan and the backrest. Raw pressure data were processed to extract pressure vs. time curves related to the whole seat surface and, for the seat pan only, values associated with four anatomical regions (i.e. left and right thighs and buttocks). During the work shift, the mean backrest pressure was low and fairly constant. Seat pan pressure increased by 10%, rising from 7.4 (1.5) to 8.2 (2.3) kPa over the simulated shift. Detailed analysis of the four sub-regions revealed that as the trial progressed the mean contact pressure on buttocks decreased (-6% at the end of the trial) while thigh pressures increased (by 10 and 20% for right and left sides, respectively). Although further studies with larger samples are needed, long-term monitoring of the body-seat contact pressures of crane operators in a simulated environment appears to be a useful tool to identify specific postural strategies to reduce discomfort originated by prolonged sitting posture.


Symmetric array of the urothelium surface controlled by the lipid lattice composition.
Proteins on the luminal surface of the mammalian membrane urothelium form an hexagonal two-dimensional (2D) lattice of approximately 12nm particles embedded in a lipid matrix. The establishment and/or maintenance of this two-dimensional lattice have not yet been elucidated. To understand the lipid involvement in these effects, which may have a potential role on the permeability barrier, the lattice structural changes induced by different dietary fatty acids were analyzed. Image analysis of the uranyl formate stained urothelial membrane from mice fed with a commercial diet (control) or a formula containing 5% (w/w) corn oil (CO) or olein (O) and our previous data of fluorescence anisotropy indicated that the olein diet profoundly alters the two-dimensional particle network. Besides the increase from 15nm (control) to 17nm center-to-center particle, a statistically significant increase of the particle size was induced by the olein diet. The same parameters on urothelial membranes from animals fed with a corn diet differed on the long-range super-array from the control values. A specific structural change of the urothelial plaque particle organization as a response to changes of lipid composition is described for the first time. These results are a starting point for further research of the lipid implications on the permeability barrier.


Impact of age, injury severity score, and medical comorbidities on early complications after fusion and halo-vest immobilization for C2 fractures in older adults: a propensity score matched retrospective cohort study.
Propensity score matched retrospective cohort study. To report early complication rates and associated risk factors in patients with C2 fractures who underwent fusion or halo immobilization. There is limited data on the impact of age, injury severity score, and medical comorbidities on overall complication rates from surgical fixation versus halo-vest immobilization of C2 fractures. The Nationwide Inpatient Sample database from 2002 to 2008 was queried to identify cohorts of adult patients (age ≥ 18 years) with C2 fractures without spinal cord injury who were treated with either fusion or halo-vest immobilization. Complication rates, hospital length of stay, and costs were compared in a propensity score matched sample. Multivariate analysis was used to identify predictors of in-hospital complications. A total of 3758 patients (1627 fusion and 2131 halo) were identified. Fusion was associated with greater overall complication rates (20.2% vs. 10.1%, P < 0.0001), increased length of stay (8.9 d vs. 6.4 d, P < 0.0001), higher charges ($80,000 vs. $41,000, P < 0.0001), but a lower rate of nonroutine discharge (52.6% vs. 62.6%, P < 0.0001). There was no difference in mortality between the fusion group (2.75%) and the halo group (3.33%). Age, injury score, and comorbidity increased complication rates by a similar degree (odds ratio) in both cohorts. Patients aged 80 years and older were 3.5 times more likely to have a complication than those younger than 60 years. Fusion patients had greater overall complication rates, increased length of stay, and greater resource utilization but were discharged home in a greater proportion. Both fusion and halo were associated with significant (more than 3-fold) increase in complication rates in elderly patients aged 80 years or older. Given the similar mortality rate between the fusion group and the halo group and the higher cost and complication rate in the fusion group, our study supports the use of halo-vest immobilization in patients where operative therapy is contraindicated.


Recurrence of Urothelial Bladder Carcinoma in the Colon Presenting as Hematochezia.
Patients with superficial bladder cancers remain clinically indolent after treatment with even a modicum of urologic intervention. However, with more invasive disease, the majority of patients experience recurrence. The conventional route of metastasis and recurrence in primary urothelial cell carcinoma is through lymphatic system, with regional lymph nodes, lungs, liver, brain, and bone being the most common sites. Isolated intraluminal colonic recurrence in the absence of local invasion is extremely rare. We report a unique case of urothelial cell carcinoma presenting with an isolated colonic mass, which unexpectedly, on immunohistostaining, proved to be primarily of urothelial rather than colonic origin.


Infrared spectra of MF2, MF2+, MF4-, MF3, and M2F6 molecules (M = Sc, Y, La) in solid argon.
Reactions of laser-ablated Sc, Y and La atoms with F(2) in excess argon gave new absorptions in the M-F stretching region, which are assigned to metal fluoride neutral species MF(2) and MF(3) and ions MF(2)(+) and MF(4)(-). Dibridged MF(3) dimers, M(2)F(6), were also identified through terminal M-F and bridge M-F-M stretching modes. Density functional theory (DFT) calculations substantiated the experimental assignments. Mulliken and natural charge distributions indicate significant electron transfer from metal d orbitals to F ligands that increase from Sc to La, suggesting that strong participation of La 5d orbital hybridization drives the F-La-F bond angle below 120 degrees.


Surgical management of locally advanced and locally recurrent colon cancer.
Locally advanced and locally recurrent colon cancers pose a surgical challenge with tumors extending into surrounding structures and organs. Anticipation of the need for an extended surgical resection, often with multivisceral en bloc organ removal, is critical for surgical planning. For both primary and recurrent tumors, postsurgical long-term survival is achievable but only after complete resection. The role of neoadjuvant and adjuvant therapy continues to be redefined in this era of biologic chemotherapeutics, and multimodality therapy holds promise in aiding resection and improving postsalvage survival.


[The conservative surgery of Crohn's disease: the long-term results].
Patients with Crohn's disease (CD) receive one or more surgical interventions throughout their clinical history. Conservative surgery has recently been proposed as a safe and effective option for the treatment of complicated CD and for the prevention of short bowel syndrome and stoma. One hundred nineteen patients affected by CD were treated with stricture plasty and mini-resection in our Department between January 1993 and January 1998. At admission, the prior complete clinical and surgical history of each patient was collected and then inserted in a prospectively maintained data base. Analysis of recurrence was made using the Kaplan-Meier function and the influence of certain variables on the risk of recurrence was analyzed using a Cox proportional hazard model. Perioperative mortality was nil, postoperative complications occurred in 8 patients (6.7%). Overall long term surgical recurrence at 5 years was 28%, 35% in patients operated on within one year and 15% in those treated after one year from the diagnosis (p < .05). Stricture plasty and minimal resections show lower perioperative mortality and postoperative complications similar to resective surgery. From risk factor analysis, a group of patients with high risk of surgical recurrence emerged. In this group and whenever technically possible, we consider stricture plasty and minimal resection the gold standard in the treatment of complicated CD.


Atopic, contact, and seborrheic dermatitis in adolescents.
Atopic dermatitis, contact dermatitis, and seborrheic dermatitis are chronic or recurrent inflammatory dermatoses that commonly affect adolescents. They may present a diagnostic and therapeutic challenge for physicians, and can be frustrating for patients. This article reviews the pathogenesis, diagnosis, and management of these diseases.


From Insulating PMMA Polymer to Conjugated Double Bond Behavior: Green Chemistry as a Novel Approach to Fabricate Small Band Gap Polymers.
Dye-doped polymer films of Poly(methyl methacrylate) PMMA have been prepared with the use of the conventional solution cast technique. Natural dye has been extracted from environmentally friendly material of green tea (GT) leaves. Obvious Fourier transform infrared (FTIR) spectra for the GT extract were observed, showing absorption bands at 3401 cm-1, 1628 cm-1, and 1029 cm-1, corresponding to O⁻H/N⁻H, C=O, and C⁻O groups, respectively. The shift and decrease in the intensity of the FTIR bands in the doped PMMA sample have been investigated to confirm the complex formation between the GT dye and PMMA polymer. Different types of electronic transition could be seen in the absorption spectra of the dye-doped samples. For the PMMA sample incorporated with 28 mL of GT dye, distinguishable intense peak around 670 nm appeared, which opens new frontiers in the green chemistry field that are particularly suitable for laser technology and optoelectronic applications. The main result of this study showed that the doping of the PMMA polymer with green tea dye exhibited a strong absorption peak around 670 nm in the visible range. The absorption edge was found to be shifted towards the lower photon energy for the doped samples. Optical dielectric loss and Tauc's model were used to estimate the optical band gaps of the samples and to specify the transition types between the valence band (VB) and conduction band (CB), respectively. A small band gap of around 2.6 eV for the dye-doped PMMA films was observed. From the scientific and engineering viewpoints, this topic has been found to be very important and relevant. The amorphous nature of the doped samples was found and ascribed to the increase of Urbach energy. The Urbach energy has been correlated to the analysis of X-ray diffraction (XRD) to display the structure-properties relationships.


Protocol for a pilot randomised controlled trial of metformin in pre-diabetes after kidney transplantation: the Transplantation and Diabetes (Transdiab) study.
Post-transplant diabetes mellitus (PTDM) is a common complication of kidney transplantation and is associated with significant morbidity and mortality. In the general population, metformin has been used for diabetes prevention in high-risk individuals. Improving insulin sensitivity is one of many proven favourable effects of metformin. Despite the high incidence of PTDM in kidney transplant recipients, there is a lack of evidence for the role of metformin in the prevention of diabetes in this setting. METHODS AND ANALYSIS: Transplantation and Diabetes (Transdiab) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants will undergo an oral glucose tolerance test in the 4-12 weeks post-transplantation; those with IGT will be randomised to standard care or standard care and metformin 500 mg twice daily, and followed up for 12 months. The primary outcomes of the study will be the feasibility of recruitment, the tolerability of metformin assessed using the Gastrointestinal Symptom Rating Scale at 3 and 12 months, and the efficacy of metformin assessed by morning glucose and glycated haemoglobin at 3, 6, 9 and 12 months. Despite the significant morbidity and mortality of PTDM, there are currently no randomised clinical trials assessing pharmacological interventions for its prevention after kidney transplantation. The Transdiab trial will thus provide important data on the feasibility, safety, tolerability and efficacy of metformin after renal transplantation in patients with IGT; this will facilitate undertaking larger multicentre trials of interventions to reduce the incidence or severity of diabetes after kidney transplantation. This study has been approved by the Northern B Health and Disability Ethics Committee of the Ministry of Health in New Zealand. On study completion, results are expected to be published in a peer-reviewed journal. Australian New Zealand Clinical Trials Registry Number: ACTRN12614001171606.


Bringing diverse knowledge sources together--a meta-model for supporting integrated catchment management.
Integrated catchment management (ICM), as promoted by recent legislation such as the European Water Framework Directive, presents difficult challenges to planners and decision-makers. To support decision-making in the face of high complexity and uncertainty, tools are required that can integrate the evidence base required to evaluate alternative management scenarios and promote communication and social learning. In this paper we present a pragmatic approach for developing an integrated decision-support tool, where the available sources of information are very diverse and a tight model coupling is not possible. In the first instance, a loosely coupled model is developed which includes numerical sub-models and knowledge-based sub-models. However, such a model is not easy for decision-makers and stakeholders to operate without modelling skills. Therefore, we derive from it a meta-model based on a Bayesian Network approach which is a decision-support tool tailored to the needs of the decision-makers and is fast and easy to operate. The meta-model can be derived at different levels of detail and complexity according to the requirements of the decision-makers. In our case, the meta-model was designed for high-level decision-makers to explore conflicts and synergies between management actions at the catchment scale. As prediction uncertainties are propagated and explicitly represented in the model outcomes, important knowledge gaps can be identified and an evidence base for robust decision-making is provided. The framework seeks to promote the development of modelling tools that can support ICM both by providing an integrated scientific evidence base and by facilitating communication and learning processes.


Imaging of the active B1 field in vivo.
The authors describe a method for accurate in vivo multislice imaging of the active component of the B1 field which is based on a previously proposed method, which uses the signal intensity ratio of two images measured with different excitation angles, and a repetition time TR 5 > or = 5 T1. The new method essentially reduces repetition and scan time by means of an additional compensating pulse. The suppression of T1 effects by this pulse are verified with simulations and measurements. Further investigations concerned the influence of slice selective excitation and magnetization transfer in multislice imaging to the B1 field determination. The stability and accuracy of the presented method is shown by several phantom and in vivo measurements. With the described method the active B1 field can be determined in vivo in 23 cross-sections in less than 6 min.


Unintended consequences of evolution of the Common Terminology Criteria for Adverse Events.
Adverse events (AEs) on Children's Oncology Group (COG) trials are reported manually by clinical research assistants (CRAs). The Common Terminology Criteria for Adverse Events (CTCAE) was developed to provide standardized definitions for identifying and grading AEs. The CTCAE has expanded significantly over its five versions, but the impact of CTCAE definitional changes has not been examined. This study compared AE number and ascertainment among the first four CTCAE versions using a case vignette. Each CTCAE version was used to create a list of AEs and grades by two separate CRAs. The CTCAE expanded from 9 categories and 49 AEs in v1.0 to 26 categories and 790 AEs in v4.0. CRAs independently selected different approaches to AE ascertainment-comprehensive and parsimonious. The number of AEs identified in the parsimonious approach was stable with 10-14 in each CTC version. The comprehensive approach identified 9, 20, 29, and 37 AEs in CTC versions 1.0, 2.0, 3.0, and 4.0, respectively. Only approximately 65% of AEs were conclusively graded in versions 2.0 to 4.0 using the comprehensive approach. CTCAE has increased in complexity. Although this increased complexity allows for more granular AE reporting, these data demonstrate potential unintended negative consequences of increasing CTC AE complexity, including the risk of varying approaches to AE capture. A comprehensive evaluation of CTC AE definitions and CRA reporting practices across COG institutions and AEs are needed to improve the accuracy and efficiency of AE reporting.


Downregulation of microRNA-448 improves isoflurane-induced learning and memory impairment in rats.
The present study aimed to investigate the potential role of microRNA‑448 (miR‑448) in isoflurane-induced learning and memory impairment in rats. Sprague‑Dawley rats were used for the construction of isoflurane‑treated models. The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding the following para-meters: Swimming speed, escape latency and time in original quadrant. Influences of isoflurane on neuron apoptosis and miR‑448 expression in rat hippocampus tissue were analyzed by flow cytometry and reverse transcription‑quantitative polymerase chain reaction, respectively. Furthermore, the effects of miR‑448 on the expression of cell apoptosis‑associated proteins were investigated by flow cytometry. The results demonstrated that isoflurane treatment induced higher escape latency and lower time spent in original quadrant compared with the control rats. In addition, isoflurane treatment induced neuron apoptosis and miR‑448 was highly expressed in the hippocampal tissue of isoflurane‑treated rats. Furthermore, Bcl‑x was significantly downregulated while caspase‑3 expression was upregulated by an miR‑448 inhibitor. Combined the results of the current study indicate that miR‑448 knockdown may have pivotal roles in improving isoflurane-induced learning and memory impairment via suppressing neuron apoptosis.


Efficacy of contingency management in improving retention and compliance to methadone maintenance treatment: a random controlled study.
Compliance with methadone maintenance treatment (MMT) in China is poor. To evaluate the effects of adjunctive contingency management (CM) on the efficacy of methadone maintenance treatment (MMT) in patients with opioid dependence. A 12-week prize-based contingency management (CM) intervention can increase the retention and compliance of heroin abusers to standardized MMT programs in Shanghai. 160 heroin-dependent patients from three voluntary MMT clinics in Shanghai were randomly assigned to a treatment as usual group (MMT, n=80) and an intervention group (MMT+CM, n=80). Daily use of methadone was recorded and urine drug tests were conducted weekly during the first 12 weeks and then at week 16, week 20 and week 24. The 12-week retention rates for the intervention (MMT+CM) and treatment-as-usual (MMT) groups were both quite high: 87.5% and 86.2%, respectively. The average durations of using methadone in the two groups were equal (70 days versus 71 days, respectively). There was a non-significant increase in the mean longest drug-free period (7.4 weeks versus 6.5 weeks) and in the mean number of negative urine tests (7.9 versus 7.6). Secondary analysis of the 24-week outcomes (12 weeks after termination of the adjunctive CM treatment) also found no significant differences between the groups. Among those who remained in the program the severity of addiction as assessed by the Addiction Severity Index decreased dramatically over the 24 weeks but, again, there were no significant differences in the addiction measures between those in the intervention group and those in the treatment-as-usual group. Prize-based CM is not effective in improving the retention and compliance of heroin abusers to MMT in Shanghai. The main reasons for failure to replicate western studies were the unexpectedly high baseline rates of compliance in this sample (86%) and the relatively weak financial incentives provided by the CM program. CM programs are context dependent so a careful preliminary situational analysis is needed to determine their potential effectiveness at a particular site and to identify the types of incentives (prizes) that will effectively encourage behavioral change in the target participants.


Moderating effects of aggression on the associations between social withdrawal subtypes and peer difficulties during early adolescence.
Recent research has revealed significant heterogeneity in the peer difficulties associated with social withdrawal subtypes during early adolescence, but little is known about possible sources of that heterogeneity. This study of 194 Indian young adolescents (48% female; 90% Hindu; M age= 13.35 years) evaluated whether the peer adversity related to self-reported social withdrawal subtypes (shyness, unsociability, avoidance) varied as a function of peer-nominated overt and relational aggression, and gender. Regression analyses revealed that overt aggression and gender moderated the pathways between shyness and peer exclusion and peer victimization such that the associations were significant and positive only for boys who were high and girls who were low in overt aggression. Several additional moderator effects were found, including results revealing that relational aggression (in certain cases, in conjunction with gender) moderated the association between: (1) avoidance and peer exclusion and peer rejection, (2) shyness and peer rejection, and (3) unsociability and peer victimization. For adolescents who were average and low in relational aggression, avoidance was positively related to peer rejection, and unsociability was positively related to peer victimization. However, only for boys who were high in relational aggression, avoidance was found to be positively related to peer exclusion, and shyness was positively related to peer rejection. The findings highlight the importance of considering additional individual risk factors in studies of social withdrawal subtypes and point to important differences for young adolescent withdrawn boys and girls.


Quality Improvement Within a Mental Health Setting: Alcohol Detoxification.
Aims We describe a clinical audit on alcohol detoxification, using NICE guidelines as a comparable standard. NICE guidelines recommend completing a thorough alcohol history, documentation of a physical examination including screening for Wernicke's encephalopathy, monitoring of vital signs and liver investigations. Breath alcohol level and standardised assessment of withdrawal should be completed in addition to documentation of chlordiazepoxide and thiamine prescriptions. The reported mental health service completed the first cycle of the audit as part of a large-scale, international audit on alcohol detoxification by the Prescribing Observatory for Mental Health, UK (POMH-UK). Two additional audit cycles were completed within the service to ensure continuous quality improvement and clinical effectiveness. Methods Retrospective chart reviews were performed for admissions within pre-defined 6-month periods. Inclusion criteria: ICD-10 F10 diagnosis; prescription of alcohol detoxification schedule. Results This mental health service demonstrated greater compliance with the NICE standards in comparison to other services in the POMH-UK audit. The second-cycle audit showed increased compliance in most areas compared to the initial results. The third-cycle audit focused on two specific areas that required improvement to optimise quality improvement - Breath Alcohol Level and Clinical Institute of Withdrawal Assessment, documentation of which improved from 79% to 85% and 39% to 91% respectively in the final audit cycle. Conclusion The results of this audit indicate that adherence to defined clinical standards within this mental health service exceeds that of the benchmark POMH-UK data. The effectiveness of electronic patient records in improving adherence to set clinical standards, specifically in relation to documentation of clinical parameters is evident. The report also confirms continued improved results with each audit cycle within the service.


Selective whole blood lipoprotein apheresis to prevent pancreatitis in drug refractory hypertriglyceridemia.
Severe hypertriglyceridemia is a known cause of acute pancreatitis, and apheresis treatment, most commonly plasmapheresis, has been used to treat patients with drug refractory hypetriglyceridemia for more than 30 years. We report a case in which a woman with Crohn's disease and type 2 diabetes mellitus developed recurrent episodes of acute pancreatitis due to extreme hypertriglyceridemia. After the initiation of lipoprotein apheresis from whole blood, a marked reduction of triglyceride and lipoprotein levels was observed. Some inflammatory parameters were increased even if most of the cytokines were not detectable, indicating good biocompatibility of the filter. Triglyceride levels were lowered after initiating selective lipoprotein apheresis. More importantly, the patient did not experience any relapses of pancreatitis after the treatment was started. Hence this treatment is feasible in drug refractory hypertiglyceridemia, but the treatment concept needs to be tested in additional studies.


Interprofessional service-learning definition.
In 2010, the World Health Organization (WHO) published the WHO's Framework for Action on Interprofessional Education and Collaborative Practice recognizing the significance of improved quality of patient care, lower healthcare costs and decrease medical errors through the use of interprofessional teams. This concept was embraced by the Midwest Interprofessional Practice Education and Research Center (MIPERC) and its Service-Learning workgroup, through the development of multiple interprofessional service-learning experiential opportunities for area health and medical students. Throughout MIPERC's journey of developing and providing interprofessional service-learning opportunities, we have unsuccessfully sought to find a definition of interprofessional service-learning to assist us in better framing our work. We have found definitions of service-learning and interprofessional learning as well as case examples of service-learning, interprofessional learning, and interprofessional service-learning but, no definition of interprofessional service-learning. Following a review of the relevant literature, we have developed a definition of interprofessional service-learning that we believe is comprehensive and will be of use to other interprofessional service-learning organizations in framing and developing interprofessional service-learning opportunities for their health and medical students.


Real-time quantitative PCR analysis of regions involved in gene amplification reveals gene overdose in low-grade astrocytic gliomas.
We have studied gene amplification of genes located in 1q32 (GAC1, ELF3, MDM4, and ren1), 4q11 (PDGFR-alpha), and in 12q13-14 (MDM2 and CDK4) using quantitative real-time PCR in a group of 86 tumors consisting of 44 WHO grade IV glioblastomas (GBM) (34 primary and 10 secondary tumors), 21 WHO grade III anaplastic astrocytomas (AA), and 21 WHO grade II astrocytomas (AII). Gene amplification was present in 56 of the 86 samples (65%) in at least 1 gene in our series. GAC1 (51%) and MDM4 (27%) were the most frequently amplified genes within the 1q32 amplicon, and their higher amplification frequency was statistically significant (P<0.05, chi) in the low-grade astrocytomas. Concordant co-amplification was determined for ELF3 and ren1 or ren1 and MDM4 in the grade III-IV tumors. MDM2 amplification was significantly more frequent in primary GBM (16%) than was in secondary GBM (0%). The present study shows that gene amplification in the studied regions is already present in low-grade astrocytic tumors and that amplification of some genes may represent another molecular marker to differentiate primary from secondary GBM.


Interactions between Glucose and Inorganic Carbon Metabolism in Chlorella vulgaris Strain UAM 101.
Chlorella vulgaris strain UAM 101 has been isolated from the effluent of a sugar refinery. This alga requires glucose to achieve maximal growth rate even under light saturating conditions. The growth rate of cultures grown on light + CO(2) + glucose (3.16 per day) reaches the sum of those grown on light + CO(2) (1.95 per day) and on dark + glucose (1.20 per day). Unlike other Chlorella strains, uptake of glucose (about 2 micromoles per milligram dry weight per hour) was induced to the same extent in the light and dark and was not photosensitive. The rate of dark respiration was not affected by light and was strongly stimulated by the presence of glucose (up to about 40% in 4 hours). The rate of photosynthetic O(2) evolution was measured as a function of the CO(2) concentration. These experiments were conducted with cells which experienced different concentrations of CO(2) or glucose during growth. The maximal photosynthetic rate was inhibited severely by growing the cells in the presence of glucose. A rather small difference in the apparent photosynthetic affinity for extracellular inorganic carbon (from 10-30 micromolar) was found between cells grown under low and high CO(2). Growth with glucose induced a reduction in the apparent affinity (45 micromolar) even though cells had not been provided with CO(2). Experiments performed at different pH values indicate CO(2) as the major carbon species taken from the medium by Chlorella vulgaris UAM 101.


Monoclonal anti-idiotypic antibodies as functional internal images of enzyme active sites: production of a catalytic antibody with a cholinesterase activity.
Monoclonal antibody 9A8 was selected by immunizing mice with AE-2, a monoclonal antibody directed against the active site of acetylcholinesterase. In accordance with the idiotypic network theory, monoclonal anti-idiotypic antibody 9A8 displayed internal-image properties of the original immunogen, the acetylcholinesterase active site. Hydrolysis of acetylthiocholine and related esters of thiocholine by 9A8 follows saturation kinetics and kinetic parameters were determined. The hydrolytic activity is characterized by a lowered kcat value (81 s-1) and an increased Km value (0.6 mM) when compared with the original enzyme. However, the rate acceleration (kcat/kuncat = 4.15 x 10(8) remains higher than for the esterase activities usually described for catalytic antibodies directed against transition-state analogs. The 9A8 activity exhibits a relaxation of specificity toward both substrates and inhibitors. This specificity does not correspond to a known enzymatic activity. The anti-idiotypic approach should be valuable for producing different structural and functional copies of the same enzyme active site. This should allow further insights into structure-activity relationships. Furthermore, use of chemically modified enzymes as immunogens may result in anti-idiotypic antibodies with catalytic activities not found in the native enzymes.


[High-grade cervical intraepithelial neoplasia during pregnancy: experience in a service in southern Brazil].
to evaluate the results of treatment to which patients with high grade intraepithelial cervical neoplasia (HSIL) are submitted, as well as their follow-up during pregnancy. retrospective study based on the review of the medical report of 30 patients with diagnosis of high-grade squamous intraepithelial lesions (HSIL) during pregnancy and attended to at a tertiary hospital in southern Brazil from 1990 to 2002. Diagnosis was performed by colposcopy and biopsy, with repetition of the colposcopy during the pregnancy and after delivery. The diagnoses of regression and progression of lesions were evaluated. from 30 patients, 3 were excluded of the sample because the diagnosis of high-grade squamous intraepithelial lesions (HSIL) was not confirmed by the colposcopy with biopsia. Four patients were submitted to treatment during pregnancy, and one of them presented preterm delivery at the 32nd week. Twenty-three patients were submitted to expectant treatment, underwent a new colposcopy and biopsy, and then were submitted to conisation surgery at about the 11(th) week after the end of pregnancy. In 7.4% of the cases, there was lesion regression in the surgical specimen. all patients with diagnosis should be submitted to colposcopy and biopsy to exclude the possibility of invasive lesion. The expectant procedure for intraepithelial lesions is the most widely chosen and safe due to the possibility of regression in the postpartum period.


Administration of a probiotic associated with nasal vaccination with inactivated Lactococcus lactis-PppA induces effective protection against pneumoccocal infection in young mice.
Streptococcus pneumoniae is a serious public health problem, especially in developing countries, where available vaccines are not part of the vaccination calendar. We evaluated different respiratory mucosa immunization protocols that included the nasal administration of Lactococcus lactis-pneumococcal protective protein A (PppA) live, inactivated, and in association with a probiotic (Lc) to young mice. The animals that received Lc by the oral and nasal route presented the highest levels of immunoglobulin (Ig)A and IgG anti-PppA antibodies in bronchoalveolar lavages (BAL) and IgG in serum, which no doubt contributed to the protection against infection. However, only the groups that received the live and inactivated vaccine associated with the oral administration of the probiotic were able to prevent lung colonization by S. pneumoniae serotypes 3 and 14 in a respiratory infection model. This would be related to a preferential stimulation of the T helper type 1 (Th1) cells at local and systemic levels and with a moderate Th2 and Th17 response, shown by the cytokine profile induced in BAL and by the results of the IgG1/IgG2a ratio at local and systemic levels. Nasal immunization with the inactivated recombinant strain associated with oral Lc administration was able to stimulate the specific cellular and humoral immune response and afford protection against the challenge with the two S. pneumoniae serotypes. The results obtained show the probiotic-inactivated vaccine association as a valuable alternative for application to human health, especially in at-risk populations, and are the first report of a safe and effective immunization strategy using an inactivated recombinant strain.


[Efficacy and safety of endothelin receptor antagonists combined with phosphodiesterase 5 inhibitor in the treatment of pulmonary arterial hypertension: a network meta-analysis].
Objective: To examine the efficacy and safety of endothelin receptor antagonists (ERA) combined with phosphodiesterase 5 inhibitors (PDE5i) in the treatment of pulmonary artery hypertension (PAH). Methods: Computer-based retrieval was performed on PubMed, Cochrane Library, CNKI, Wanfang, and VIP database (up to February 12th, 2021). Randomized controlled trials about endothelin receptor antagonists (ERAs) or PDE5i in patients with PAH were collected. The change of 6-minute walking distance (6MWD) in 12-16 weeks was used as primary outcome index. Case fatality rate, worsening clinical events, WHO functional class (FC) improvement, adverse events (AEs), serious adverse events (SAE) were the key secondary outcomes indicators. STATA 16.0 software was used for network meta-analysis, and the pooled estimates of odds ratios (ORs) or weighted mean differences (WMDs) and 95% confidence intervals (CIs) of the results were shown. To help explain ORs and WMDs, we used the surface under the cumulative ranking curve (SUCRA) to calculate the probability of each intervention. Results: We included 29 trials with 5 949 participants. In network meta-analysis, Bosentan combined with Sildenafil (WMD=53.93, 95%CI=6.19-101.66) had shown the greatest improvement in 6MWD compared with placebo, followed by Bosentan combined with Tadalafil (WMD=50.84, 95%CI=7.05-94.62), Ambrisentan combined with Tadalafil (WMD=46.67, 95%CI=15.88-77.45), Bosentan (WMD=29.44, 95%CI=5.86-53.02), Ambrisentan (WMD=23.90, 95%CI=0.31-47.48) and Macitentan (WMD=21.57, 95%CI=2.45-40.69). According to SUCRA, the effects of different intervention measures on improving 6MWD in patients with arterial pulmonary hypertension were as follows: Bosentan+Sildenafil (82.9%)>Bosentan+Tadalafil (78.4%)>Ambrisentan+Tadalafil (77.1%)>Bosentan (49.2%)>Sildenafil (48.5%)>Ambrisentan (40.3%)>Macitentan (37.3%)>Tadalafil (33.0%)>Placebo (3.3%). For the WHO functional class, Sildenafil (OR=2.90, 95%CI=1.04-8.08) was optimal compared with placebo, followed by Bosentan (OR=2.15, 95%CI=1.15-4.04), and there was no significant difference in the rest. For clinical worsening, Bosentan combined with Tadalafil (OR=0.08, 95%CI=0.01-0.49) performed best compared with placebo, followed by Bosentan (OR=0.20, 95%CI=0.11-0.38), Bosentan combined with Sildenafil (OR=0.21, 95%CI=0.09-0.46), Ambrisentan combined with Tadalafil (OR=0.27, 95%CI=0.15-0.50), Sildenafil (OR=0.33, 95%CI=0.17-0.66) and Tadalafil (OR=0.44, 95%CI=0.21-0.90). There was no statistical difference between all interventions and placebo in terms of the incidence of adverse events and serious adverse events. For case fatality rate, Ambrisentan (OR=0.28, 95%CI=0.11-0.74) was statistically superior to placebo and there was no statistics difference in the rest. Conclusions: The combination therapy of ERAs and PDE5i performed well in the short-term improvement of motor function. Furthermore, there was no significant difference with monotherapy in terms of safety. However, it is worth emphasizing that the choice of treatment should be based on the patient's individualized situation and the patient's requirements.


[Online harassment in Japan: Dissecting the targeting of a female journalist].
Harassment on the Internet, particularly on social media such as Twitter, has reached a level where it can, without exaggeration, be characterised as a real-world societal problem in Japan. However, studies on this phenomenon in the Japanese language environment, especially adopting a victim-centric perspective, are rare. In this paper, we incorporated the concept of online harassment and reviewed existing studies about online harassment from Japan and abroad. We then conducted a detailed case analysis of the "flaming" of a female journalist and those who targeted her on Twitter. Based on our analysis, we observed that there were three layers of users who targeted the journalist: influencers, users who responded to the instigation by influencers, and trolls. Each harassed the journalist, but in a different manner. Given Japan's particular difficulty of imposing domestic regulations on social media companies that are mostly from abroad, we propose and describe possible measures that individuals and their employers should consider taking.


The footprint of kynurenine pathway in every cancer: a new target for chemotherapy.
Treatment of cancers has always been a challenge for physicians. Typically, several groups of anti-cancer medications are needed for effective management of an invasive and metastatic cancer. Recently, therapeutic potentiation of immune system markedly improved treatment of cancers. Kynurenine pathway has an interwoven correlation with immune system. Kynurenine promotes T Reg (regulatory) differentiation, which leads to increased production of anti-inflammatory cytokines and suppression of cytotoxic activity of T cells. Overactivation of kynurenine pathway in cancers provides an immunologically susceptible microenvironment for mutant cells to survive and invade surrounding tissues. Interestingly, kynurenine pathway vigorously interacts with other molecular pathways involved in tumorigenesis. For instance, kynurenine pathway interacts with phospoinosisitide-3 kinase (PI3K), extracellular signal-regulated kinase (ERK), Wnt/β-catenin, P53, bridging integrator 1 (BIN-1), cyclooxygenase 2 (COX-2), cyclin-dependent kinase (CDK) and collagen type XII α1 chain (COL12A1). Overactivation of kynurenine pathway, particularly overactivation of indoleamine 2,3-dioxygenase (IDO) predicts poor prognosis of several cancers such as gastrointestinal cancers, gynecological cancers, hematologic malignancies, breast cancer, lung cancer, glioma, melanoma, prostate cancer and pancreatic cancer. Furthermore, kynurenine increases the invasion, metastasis and chemoresistance of cancer cells. Recently, IDO inhibitors entered clinical trials and successfully passed their safety tests and showed promising therapeutic efficacy for cancers such as melanoma, brain cancer, renal cell carcinoma, prostate cancer and pancreatic cancer. However, a phase III trial of epacadostat, an IDO inhibitor, could not increase the efficacy of treatment with pembrolizumab for melanoma. In this review the expanding knowledge towards kynurenine pathway and its application in each cancer is discussed separately.


Secondary aortoduodenal fistula and the unrecognised herald bleed.
A 65-year-old man with history of aortobifemoral surgery 4 years ago was admitted to hospital after sudden abdominal pain. Initially misdiagnosed as renal colic, he was treated with analgesics, and while on observation he started with haematemesis, rapidly responding to volume infusion. Upper gastrointestinal endoscopy showed fresh blood in the stomach with no visible active bleeding. CT scan showed an important contrast extravasation from the aorta to the third duodenal portion, restarting haemodynamic instability and a cardiac arrest. Cardiopulmonary resuscitation (CPR) manoeuvres followed by intense fluid resuscitation and urgent laparotomy with a fast transabdominal supracoeliac aortic clamping was performed. After multiple blood and plasma unit transfusion and intravenous norepinephrine, two more cardiac arrests were recovered. Unfortunately, after aggressive management, the patient rapidly deteriorated and deceased on the table. Aortoduodenal fistula is a rare entity causing life-threatening bleeding. Its diagnosis requires high clinical suspicion and surgery offers the only hope for survival.


The effect of various adhesives, enamel etching, and base treatment on the failure frequency of customized lingual brackets: a randomized clinical trial.
The aim of this paper was to compare failure differences in precious metal customized lingual brackets bonded with three adhesive systems. Also, differences in failure of non-precious metal brackets with and without a silicatized base layer bonded with the same adhesive, as well as the influence of enamel etching prior to using a self-etching dual cure resin were explored. Five different groups were defined in a semi-randomized approach. Group 1 (IME): Maxcem Elite with 378 Incognito brackets and etched teeth, Group 2 (IMNE): Maxcem Elite with 193 Incognito brackets on non-etched teeth, Group 3 (INE): Nexus+Excite with 385 Incognito brackets, Group 4 (IRE): Relyx with 162 Incognito brackets, Group 5 (HRME) and Group 6 (HNRME): Maxcem Elite with 182 Harmony brackets with silicatized and non-slicatized bases respectively. Bracket failures were recorded over a 12-month period. The number of failures during the observation period was small in the various adhesives types of groups, as well as in HRME and HNRME groups, and the comparisons among those groups were non-significant (P > 0.05). A statistically significant difference (P < 0.05) was found between the IME and IMNE groups. 1. During the first year of treatment customized lingual brackets failure frequencies (rates) are not different for the three adhesive materials tested. 2. Eliminating the etching stage when using self-etch/self-adhesive adhesives, may lead to a dramatic increase in the failure rates. 3. Silicoating of stainless steel customized lingual brackets does not seem to influence the failure of the bonds.


Role of Fc receptor gamma-chain in platelet glycoprotein Ib-mediated signaling.
Interaction between von Willebrand factor (vWF) and glycoprotein Ib (GPIb) stimulates tyrosine kinases and subsequent tyrosine phosphorylation events in human platelets. This study found that the combination of vWF and botrocetin, by interacting with GPIb, induced tyrosine phosphorylation of Fc receptor gamma-chain (FcR gamma-chain), Syk, linker for activation of T cells (LAT), and phospholipase C gamma2 (PLCgamma2). Pretreatment of platelets with 10 microM PP1 completely inhibited these tyrosine phosphorylation events. On GPIb stimulation, Src and Lyn formed a complex with FcR gamma-chain and Syk, suggesting that Src and Lyn are involved in FcR gamma-chain tyrosine phosphorylation and downstream signals. In spite of the PLCgamma2 tyrosine phosphorylation, however, there was no intracellular calcium release and inositol 1,4,5-trisphosphate production. In Brij 35 lysates, FcR gamma-chain was found to constitutively associate with GPIb. The number of GPIb expressed on FcR gamma-chain-deficient platelets was comparable to that of the wild-type, as assessed by flow cytometry. However, tyrosine phosphorylation of Syk, LAT, and PLCgamma2 in response to vWF plus botrocetin was significantly suppressed, suggesting that FcR gamma-chain mediates activation signals related to GPIb. Compared with the aggregation response of wild-type platelets, that of FcR gamma-chain-deficient platelets in response to vWF plus botrocetin was impaired, implying that FcR gamma-chain is required for the full activation of platelets mediated by GPIb. (Blood. 2001;97:3836-3845)


[Two cases of pleomorphic adenoma of the nasal cavity].
Pleomorphic adenoma in the otorhinolaryngological field is frequently found in the major salivary glands, but is rare in minor salivary glands. Two cases of pleomorphic adenoma of the nasal cavity are reported. Case 1. A 26-year-old female who complained of nasal obstruction had a tumor arising from the right side of the nasal septum. The tumor, 1.5 x 1.5 x 1.2cm in size, was surgically removed utilizing an intranasal approach. Histologically, it was diagnosed as a pleomorphic adenoma of the nasal septum. There has been no recurrence. Case 2. A 51-year-old male had a tumor in the left lateral nasal wall. The tumor, 0.6 x 0.6 x 0.6 cm in size, was surgically removed by the intranasal approach. Histologically, it was diagnosed as a pleomorphic adenoma of the lateral nasal wall. There has been no recurrence. Including the present cases, 59 cases of pleomorphic adenoma arising from the nasal cavity have been reported in Japan. Of these, 51 arose from the nasal septum. Only 8 adenomas had arisen from the lateral nasal wall. Attention has been called especially to differences in the reported incidences of malignant tumors and recurrent tumors. In the present survey, the incidences were unusually low. Four cases (6.8%) have been reported as malignant tumors, and 3 (5.1%) as recurrent tumors.


Obesity Treatment in African American Churches: Current Treatment Targets and Preferences among Parishioners.
Obesity is prevalent among African Americans, and church-based weight management programs may help address this public health issue. To develop more effective interventions, a survey was administered to members of a large, African American faith-based organization that assessed weight management intervention targets and preferences. Respondents (N = 1,439) represented the Midwestern and Southern United States. Mean body mass index was 30.8 ± 9.2 kg/m2, and 82.5% of respondents were overweight/obese. The majority (65.0%) wanted a weight management intervention conducted with the church and preferred an in-person (69.0%), group-based (68.0%) program that meets weekly for one hour or less (72%) and addresses identified barriers including access to healthy foods, childcare, and physical activity support. Church support was linked to better dietary quality and higher physical activity among parishioners (p's ≤ 0.02), suggesting church support may be important for healthy eating and exercise. This study provides a clear path forward for developing and delivering weight loss interventions within African American churches.


Risk factors for severe Muckle-Wells syndrome.
Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease resulting in excessive interleukin-1 release. It is unknown whether demographic, clinical, or laboratory characteristics at the time of diagnosis may identify patients who are at high risk for severe disease activity. This study was undertaken to analyze clinical and laboratory features of MWS, compare genetically defined subcohorts, and identify risk factors for severe MWS. A multicenter cohort study of consecutive MWS patients was performed. Parameters assessed included clinical features, MWS Disease Activity Score (MWS-DAS), inflammation markers, and cytokine levels. E311K mutation-positive patients were compared with E311K mutation-negative patients. Putative risk factors for severe MWS (defined as an MWS-DAS score of ≥10) were assessed in univariate analyses, and significant predictors were entered into a multivariate model. Thirty-two patients (15 male and 17 female) were studied. The most frequent organ manifestations were musculoskeletal symptoms and eye and skin disorders. Renal disease and hearing loss were seen in >50% of the patients. Genetically defined subcohorts had distinct phenotypes. Severe disease activity was documented in 19 patients (59%). Predictors of severe MWS identified at the time of diagnosis were female sex, hearing loss, musculoskeletal disease, increased erythrocyte sedimentation rate, and low hemoglobin level. Female sex and hearing loss remained significant after adjustment for age in a multivariate model (relative risk 1.8 and 2.6, respectively). MWS patients at high risk for severe disease can be identified at the time of diagnosis. Female patients presenting with hearing loss have the highest likelihood of manifesting severe MWS and should be considered a high-risk group.


Dynamics of bacterial translocation in acute liver injury induced by D-galactosamine in rat.
Bacterial translocation may play a role in acute liver injuries as high rates of infectious and septic complications are observed in these clinical conditions. Increased passage of endotoxin and translocating bacteria not only potentiates the extent of liver injury, but may also play a determining role in its final outcome. In this paper the incidence of bacteria] translocation in acute liver injury in rats is evaluated with other important pathological changes observed at different time points after liver injury induced by intraperitoneal administration of D-galactosamine. The bacterial translocation to the blood and other extraintestinal sites starts 3 h after induction of liver injury and is not found to be related to light microscopic changes in the liver or ileal or cecal mucosa, detectable levels of endotoxin in the portal blood, or DNA changes in the small and large intestinal mucosa, but corresponds to the release of liver enzymes in the serum.


Molecular Dynamics and Hyperpolarization Performance of Deuterated β-Cyclodextrins.
We discuss the temperature dependence of the 1H and 13C nuclear spin-lattice relaxation rate 1/ T1 and dynamic nuclear polarization (DNP) performance in β-cyclodextrins with deuterated methyl groups. It is shown that 13C DNP-enhanced polarization is raised up to 10%. The temperature dependence of the buildup rate for nuclear spin polarization and of 1/ T1, below 4.2 K, is analyzed in the framework of the thermal mixing regime and the origin of the deviations from the theoretical behavior discussed. 13C 1/ T1 is determined at low temperature by the glassy dynamics and at high temperature by the rotational molecular motions of the deuterated methyl groups. Thanks to deuteration, relaxation times approaching 30 s are achieved at room temperature, making this material interesting for molecular imaging applications. The effect of molecular dynamics on the line width of the NMR spectra is also discussed.


Fingerprinting TCE in a bedrock aquifer using compound-specific isotope analysis.
A dual isotope approach based on compound-specific isotope analysis (CSIA) of carbon (C) and chlorine (Cl) was used to identify sources of persistent trichloroethylene (TCE) that caused the shut-down in 1994 of a municipal well in an extensive fractured dolostone aquifer beneath Guelph, Ontario. Several nearby industrial properties have known subsurface TCE contamination; however, only one has created a comprehensive monitoring network in the bedrock. The impacted municipal well and many monitoring wells were sampled for volatile organic compounds (VOCs), inorganic parameters, and CSIA. A wide range in isotope values was observed at the study site. The TCE varies between -35.6‰ and -21.8‰ and from 1.6‰ to 3.2‰ for δ(13) C and δ(37) Cl, respectively. In case of cis-1,2-dichloroethene, the isotope values range between -36.3‰ and -18.9‰ and from 2.4‰ to 4.7‰ for δ(13) C and δ(37) Cl, respectively. The dual isotope approach represented by a plot of δ(13) C vs. δ(37) Cl shows the municipal well samples grouped in a domain clearly separate from all other samples from the property with the comprehensive well network. The CSIA results collected under non-pumping and short-term pumping conditions thus indicate that this particular property, which has been studied intensively for several years, is not a substantial contributor of the TCE presently in the municipal well under non-pumping conditions. This case study demonstrates that CSIA signatures would have been useful much earlier in the quest to examine sources of the TCE in the municipal well if bedrock monitoring wells had been located at several depths beneath each of the potential TCE-contributing properties. Moreover, the CSIA results show that microbial reductive dechlorination of TCE occurs in some parts of the bedrock aquifer. At this site, the use of CSIA for C and Cl in combination with analyses of VOC and redox parameters proved to be important due to the complexity introduced by biodegradation in the complex fractured rock aquifer. It is highly recommended to revisit the study when the municipal well is back into full operation.


New Eye Lens Dose Limit: Status of Knowledge in Campania Hospitals.
The International Commission on Radiation Protection (ICRP) in 2011 recommended the lowering of the annual eye lens dose limit from 150 mSv/year to 20 mSv/year in order to reduce the risk of X-ray-induced lens opacity in medical staff. The purpose of this study was to assess the status of knowledge of the new eye lens dose limit and of the radioprotection culture among operators. To this end, a questionnaire was administered to physicians, X-ray technicians, and nurses working in five hospitals of the Campania region, Italy. A total of 64 questionnaires were collected in the hospital departments in which procedures involving ionizing radiation were routinely performed. The data analyzed yielded the following results: 12 operators affirmed to know the new eye lens dose limit, 53 operators routinely wore lead aprons, and 23 operators used lead glasses. Four workers performed eye lens dosimetry through specific dosimeters. A significant lack of knowledge of the reduced eye lens dose limit suggests the need to implement radioprotection-training programs aimed at raising awareness about the importance of health care in the workplace and at reducing the risk of radio-induced effects to the eye lens.


Development of recombinant inhibitors specific to human kallikrein 2 using phage-display selected substrates.
The reactive site loop of serpins undoubtedly defines in part their ability to inhibit a particular enzyme. Exchanges in the reactive loop of serpins might reassign the targets and modify the serpin-protease interaction kinetics. Based on this concept, we have developed a procedure to change the specificity of known serpins. First, reactive loops are very good substrates for the target enzymes. Therefore, we have used the phage-display technology to select from a pentapeptide phage library the best substrates for the human prostate kallikrein hK2 [Cloutier, S.M., Chagas, J.R., Mach, J.P., Gygi, C.M., Leisinger, H.J. & Deperthes, D. (2002) Eur. J. Biochem. 269, 2747-2754]. Selected substrates were then transplanted into the reactive site loop of alpha1-antichymotrypsin to generate new variants of this serpin, able to inhibit the serine protease. Thus, we have developed some highly specific alpha1-antichymotrypsin variants toward human kallikrein 2 which also show high reactivity. These inhibitors might be useful to help elucidate the importance of hK2 in prostate cancer progression.


A Rare Report of Infectious Emphysematous Aortitis Secondary to Clostridium septicum without Prior Vascular Intervention.
The term "mycotic aneurysm" was first used by Osler in 1882 to describe a mushroom-shaped aneurysm in subacute bacterial endocarditis. Mycotic aneurysms account for only 2.6% of all aneurysms of the aorta. Rarer still are anaerobic infections secondary to organisms such as Clostridium septicum, which results in emphysematous aortitis. The vast majority of emphysematous aortic infections occur as a result of instrumentation; however, in this case we present an infection de novo. A 75-year-old male presented with a 2-week history of progressive fatigue and chest pain that then developed into constitutional symptoms. Chest radiograph demonstrated an obvious widened mediastinum. CT angiogram of his chest then confirmed this finding as well as significant periaortic gas and focal outpouching. Numerous diverticuli with inflammatory changes consistent with diverticulitis was observed on CT abdomen. Blood cultures returned positive for Clostridium septicum. Definitive treatment was discussed including debridement and graft insertion; however, patient decided on conservative management and was discharged on intravenous antibiotics. Unfortunately, as in most cases of emphysematous aortitis that do not undergo surgical management, the patient succumbed to his illness. The lesson provided will be the epidemiology of emphysematous aortitis, presentation, diagnosis, management, and prognosis through a case report.


Mechanism of corepressor binding and release from nuclear hormone receptors.
The association of transcription corepressors SMRT and N-CoR with retinoid and thyroid receptors results in suppression of basal transcriptional activity. A key event in nuclear receptor signaling is the hormone-dependent release of corepressor and the recruitment of coactivator. Biochemical and structural studies have identified a universal motif in coactivator proteins that mediates association with receptor LBDs. We report here the identity of complementary acting signature motifs in SMRT and N-CoR that are sufficient for receptor binding and ligand-induced release. Interestingly, the motif contains a hydrophobic core (PhixxPhiPhi) similar to that found in NR coactivators. Surprisingly, mutations in the amino acids that directly participate in coactivator binding disrupt the corepressor association. These results indicate a direct mechanistic link between activation and repression via competition for a common or at least partially overlapping binding site.


Advanced interdisciplinary treatment protocol for pediatric obstructive sleep apnea including medical, surgical, and orthodontic care: a narrative review.
To suggest an updated interdisciplinary treatment protocol for pediatric obstructive sleep apnea (POSA) based on the integration of craniofacial growth modification into medical and surgical sleep practice. PubMed, Scopus, and Cochrane library were searched up to February 2020 using keywords. Among 184 articles, 80 studies were finally included. An integrated treatment protocol for POSA encompassing craniofacial skeletal management as well as medical and surgical care was attempted. A differential diagnostic workflow for identifying the phenotype of POSA was suggested, and a phenotype-based treatment protocol for POSA was proposed. Despite the lack of high level of evidence, timely skeletal growth modification in three dimensions using craniofacial growth potential could be valuable treatment for upper airway development in POSA patients with craniofacial phenotypic cause. A novel precision treatment protocol will advance clinicians to determine the primary option or to apply the combined strategy for POSA patients.


Donor site morbidity of the posterior conchal region.
The perichondral cutaneous graft (PCCG) from the posterior conchal region is an elegant solution for the coverage of facial defects with particular stability requirements. The donor defect can easily be covered with a transposition flap from the postauricular region. Although this region is a common donor site for skin grafts and has an important supporting function for glasses or hearing aids, little is known about long-term morbidity after graft harvest. To assess the morbidity of the posterior concha and the postauricular region in terms of pain, scar formation, and patient satisfaction. A retrospective study of 16 patients who had a PCCG harvested from the posterior concha. Two patients presented with a postoperative wound dehiscence on the postauricular region and one with a keloid scar on the posterior concha. One case of transitory hyperesthesia and pain when sleeping on the operated site was observed. None had complaints related to wearing glasses or hearing aids. Donor site morbidity of the postauricular and posterior conchal region is minimal and associated with high patient satisfaction, excellent aesthetic results, and emotional detachment from the hidden donor site.


Electrical coupling of individual electrocatalytic oscillators.
The catalytic electro-oxidation of some small organic molecules is known to display kinetic instabilities, which reflect on potential and/or current oscillations. Under oscillatory conditions, those systems can be considered electrocatalytic oscillators and, therefore, can be described by their amplitude, frequency, and waveform. Just like mechanical oscillators, the electrocatalytic ones can be coupled and their dynamics can be changed by setting different coupling parameters. In the present work, we study the unidirectional coupling of electrocatalytic oscillators, namely, those comprehending the catalytic electro-oxidation of methanol and formic acid on polycrystalline platinum in acidic media under potentiostatic control. Herein, we explore two different scenarios (the coupling of compositionally identical and non-identical oscillators) and investigate the effects of the master's identity and of the coupling constant on the slave's dynamics. For the master (methanol)-slave (methanol) coupling, the oscillators exhibited phase lag synchronization and complete phase synchronization. On the other hand, for the master (formic acid)-slave (methanol) coupling, the oscillators exhibited complete phase synchronization with phase-locking with a 2:3 ratio, complete phase synchronization with phase-locking with a 1:2 ratio, phase lag synchronization, and complete phase synchronization. The obtained results suggest that both the master's identity and the coupling constant (sign and magnitude) are parameters that play an important role on the coupled systems, in such a way that even for completely different systems, synchronization could emerge by setting a suitable coupling constant. To the best of our knowledge, this is the first report concerning the electrical coupling of hidden N-shaped-negative differential resistance type systems.


Truck drivers in Brazil: prevalence of HIV and other sexually transmitted diseases, risk behavior and potential for spread of infection.
To determine the prevalence of HIV and syphilis and related risk behavior in a sample of truck drivers in Santos, Brazil. A cross-sectional study was performed of 300 male truck drivers recruited in the port of Santos, Brazil, including a face-to-face interview and blood sampling for HIV and syphilis serology. Of 300 subjects, 4 (1.3%) were positive for HIV, 25 (8.3%) for syphilis by the Venereal Disease Research Laboratory (VDRL) test and 38 (13%) were positive for syphilis by the fluorescent treponemal antibody (absorbed) test (FTA-Abs). Seventy-one per cent had been employed as truck drivers for more than 10 years and 93% lived outside of Santos. Most participants were married (72%); 40% reported having more than one sex partner; 21% reported sex with commercial sex workers; 14% reported sex with girls that they met on the road; 16% had sex with other men's wives; and 3.3% reported sex with men during the past year. The use of rebite, an oral stimulant, was reported by 43% and was associated with being FTA-Abs-positive (P = 0.04). Being HIV-positive was associated with having sex with friends (P = 0.04), partners usually considered 'safe' by truck drivers. Being syphilis-positive (VDRL) was significantly associated with sex with partners also considered as 'safe', namely primary sex partners, steady partners and other men's wives. This is the first study to determine HIV and syphilis seroprevalence among truck drivers in South America. Findings confirm that this group has a high potential risk for HIV infection and other sexually transmitted diseases, and thus currently presents an opportunity for prevention.


Total synthesis, proof of absolute configuration, and biosynthetic origin of stylopsal, the first isolated sex pheromone of strepsiptera.
The asymmetric total synthesis of the diastereomers of stylopsal establishes the absolute configuration of the first reported sex pheromone of the twisted-wing parasite Stylops muelleri as (3R,5R,9R)-trimethyldodecanal. The key steps for the diastereo- and enantiodivergent introduction of the methyl groups are two different types of asymmetric conjugate addition reactions of organocopper reagents to α,β-unsaturated esters, whereas the dodecanal skeleton is assembled by Wittig reactions. The structure of the natural product was confirmed by chiral gas chromatography (GC) techniques, GC/MS and GC/electroantennography (EAD) as well as field tests. An investigation into the biosynthesis of the pheromone revealed that it is likely to be produced by decarboxylation of a 4,6,10-trimethyltridecanoic acid derivative, which was found in substantial amounts in the fat body of the female, but not in the host bee Andrena vaga. This triple-branched fatty acid precursor thus seems to be biosynthesized de novo through a polyketide pathway with two consecutive propionate-propionate-acetate assemblies to form the complete skeleton. The simplified, motionless and fully host-dependent female exploits a remarkable strategy to maximize its reproductive success by employing a relatively complex and potent sex pheromone.


[FTIR spectroscopic study on the stress effect of compositions of macromolecular structure in tectonically deformed coals].
Fourier transform infrared spectroscopy (FTIR) was applied to the study of the stress effect of compositions of macromolecular structure in tectonically deformed coals. The results showed that in different kinds of tectonically deformed coals, the absorption band of aromatic structure, aliphatic structure and oxygen functional groups nearly consistent in the peak wave number, but the intensity of the peak is different which is justly influenced by different deformation degree and deformation mechanism of tectonically deformed coals under tectonic stress. In the metamorphic and deformed environments of the low, middle and high coal rank, for tectonically deformed coals, with the increasing stress, hydrogen-enriched degree and oxygen-enriched degree decrease, while the degree of ring condensation increases. But there are differences in the change of compositions contents of macromolecular structure. This might indicate that the FTIR could be used in the stress effect of compositions of macromolecular structure in tectonically deformed coals.


Properties of Ca++ release induced by puff adder lectin, a novel lectin from the snake Bitis arietans, in sarcoplasmic reticulum.
Puff adder lectin (PAL), a novel lectin venom purified from Bitis arietans, induced Ca++ release from the heavy fraction (HSR) but not from the light fraction of skeletal muscle sarcoplasmic reticulum with EC50 congruent to 10 microM. The potency of PAL was approximately 200-fold higher than that of caffeine. The bell-shaped profile of Ca++ dependence for PAL was almost the same as that for myotoxin a (MYTX), a peptide Ca++ releaser, but was different from that for caffeine. Typical blockers of Ca++ release channels, such as Mg+2, procaine, ruthenium red and ryanodine, markedly reduced PAL-induced Ca++ release from HSR. Interestingly, PAL inhibited 125I-MYTX binding to HSR with IC50 approximately equal to 20 microM. Scatchard analysis revealed that the mode of inhibition by PAL was noncompetitive, which suggests that PAL binds to a different site from that of MYTX. PAL did not affect 3H-ryanodine binding to HSR. These results suggest that PAL binds to a different site from that of MYTX to cause Ca++ release from HSR with novel properties.


Monodisperse hyaluronan polymers: synthesis and potential applications.
In many cases, the cellular response to hyaluronan (HA) depends on the molecular weight (MW) of the polymer chain. Most HA preparations from Nature or its derivatives possess wide size distributions called polydisperse. New chemoenzymatic synthesis technology allows the production of very narrow size distribution polymers called monodisperse. The use of stoichiometrically controlled and synchronized polymerization reactions allows an assortment of new HA reagents in the range of 10 kDa to 2,500 kDa for answering HA biology questions or potentially treating disease.


[Microscopic DNA cytophotometry of axillary lymph node metastasis in mammary carcinomas].
65 primary mammary carcinomas and their corresponding axillary lymphnode metastases were studied. DNA-histograms were measured in imprints using microscopical Feulgen-cytophotometry (CAS 100). Comparison between DNA histograms according to AUER-typing showed a close consent in all except five cases; with a shifting from euploidy to aneuploidy (one case), and from aneuploidy to euploidy (four cases). The clinical value of these findings should be proved.


Transcriptome Analysis of Pyrethroid-Resistant Chrysodeixis includens (Lepidoptera: Noctuidae) Reveals Overexpression of Metabolic Detoxification Genes.
Chrysodeixis includens (Walker, [1858]) is one of the most important defoliator of soybean in Brazil because of its extensive geographical distribution and high tolerance to insecticides compared with other species of caterpillars. Because of this, we conducted bioassays to evaluate the efficacy of pyrethroid λ-cyhalothrin on a C. includens resistant strain (MS) and a susceptible (LAB) laboratory strain. High throughput RNA sequencing (RNA-seq) of larval head and body tissues were performed to identify potential molecular mechanisms underlying pyrethroid resistance. Insecticide bioassays showed that MS larvae exhibit 28.9-fold resistance to pyrethroid λ-cyhalothrin relative to LAB larvae. RNA-seq identified evidence of metabolic resistance in the head and body tissues: 15 cytochrome P450 transcripts of Cyp6, Cyp9, Cyp4, Cyp304, Cyp307, Cyp337, Cyp321 families, 7 glutathione-S-transferase (Gst) genes, 7 α-esterase genes from intracellular and secreted catalytic classes, and 8 UDP-glucuronosyltransferase (Ugt) were overexpressed in MS as compared with LAB larvae. We also identified overexpression of GPCR genes (CiGPCR64-like and CiGPCRMth2) in the head tissue. To validate RNA-seq results, we performed RT-qPCR to assay selected metabolic genes and confirmed their expression profiles. Specifically, CiCYP9a101v1, CiCYP6ae149, CiCYP6ae106v2, CiGSTe13, CiCOE47, and CiUGT33F21 exhibited significant overexpression in resistant MS larvae. In summary, our findings detailed potential mechanisms of metabolic detoxification underlying pyrethroid resistance in C. includens.


Steric modulation of coordination number and reactivity in the synthesis of lanthanoid(III) formamidinates.
Reactions of a range of the readily prepared and sterically tunable N,N'-bis(aryl)formamidines with lanthanoid metals and bis(pentafluorophenyl)mercury (Hg(C6F5)2) in THF have given an extensive series of tris(formamidinato)lanthanoid(III) complexes, [Ln(Form)3(thf)n], namely [La(o-TolForm)3(thf)2], [Er(o-TolForm)3(thf)], [La(XylForm)3(thf)], [Sm(XylForm)3], [Ln(MesForm)3] (Ln=La, Nd, Sm and Yb), [Ln(EtForm)3] (Ln=La, Nd, Sm, Ho and Yb), and [Ln(o-PhPhForm)3] (Ln=La, Nd, Sm and Er). [For an explanation of the N,N'-bis(aryl)formamidinate abbreviations used see Scheme 1.] Analogous attempts to prepare [Yb(o-TolForm)3] by this method invariably yielded [{Yb(o-TolForm)2(mu-OH)(thf)}2], but [Yb(o-TolForm)3] was isolated from a metathesis synthesis. X-ray crystal structures show exclusively N,N'-chelation of the Form ligands and a gradation in coordination number with Ln3+ size and with Form ligand bulk. The largest ligands, MesForm, EtForm and o-PhPhForm give solely homoleptic complexes, the first two being six-coordinate, the last having an eta1-pi-Ar--Ln interaction. Reaction of lanthanoid elements and Hg(C6F5)2 with the still bulkier DippFormH in THF resulted in C--F activation and formation of [Ln(DippForm)2F(thf)] (Ln=La, Ce, Nd, Sm and Tm) complexes, and o-HC6F4O(CH2)4DippForm in which the formamidine is functionalised by a ring-opened THF that has trapped tetrafluorobenzyne. Analogous reactions between Ln metals, Hg(o-HC6F4)2 and DippFormH yielded [Ln(DippForm)2F(thf)] (Ln=La, Sm and Nd) and 3,4,5-F3C6H2O(CH2)4DippForm. X-ray crystal structures of the heteroleptic fluorides show six-coordinate monomers with two chelating DippForm ligands and cisoid fluoride and THF ligands in a trigonal prismatic array. The organometallic species [Ln(DippForm)2(C[triple chemical bond]CPh)(thf)] (Ln=Nd or Sm) are obtained from reaction of Nd metal, bis(phenylethynyl)mercury (Hg(C[triple chemical bond]CPh)2) and DippFormH, and the oxidation of [Sm(DippForm)2(thf)2] with Hg(C[triple chemical bond]CPh)2, respectively. The monomeric, six-coordinate, cisoid [Ln(DippForm)2(C[triple chemical bond]CPh)(thf)] complexes have trigonal prismatic geometries and rare (for Ln) terminal C[triple chemical bond]CPh groups with contrasting Ln--C[triple chemical bond]C angles (Ln=Nd, 170.9(4) degrees; Ln=Sm, 142.9(7) degrees). Their formation lends support to the view that [Ln(DippForm)2F(thf)] complexes arise from oxidative formation and C--F activation of [Ln(DippForm)2(C6F5)] intermediates.


Personal Factors Determining Patient Satisfaction with All-Ceramic Crown Treatment for Single Anterior Teeth.
The Eysenck Personality Questionnaire's (EPQ) N value (neuroticism) was used to evaluate information from 158 patients before ceramic crown treatment. Patient satisfaction was also evaluated using a satisfaction questionnaire 2 weeks post treatment. Patient expectations were not correlated with sex, age, or N value, and sex was not correlated with patient satisfaction other than in relation to crown shape. Total esthetic satisfaction and feature improvement were positively correlated with age, while satisfaction for five specific criteria was negatively correlated with N value and overall expectation. These observations underscore the importance of considering the physical and psychologic aspects of patient care when planning dental treatment.


Update in drug allergy: novel drugs with novel reaction patterns.
In the last years, many novel drugs have been introduced, generating new patterns of drug hypersensitivity. There are also novel clinical and biologic techniques that have enabled us to understand the mechanisms and diagnosis of reactions to old used drugs. This review summarizes current knowledge on the epidemiology, mechanisms, and clinical and in-vitro diagnosis of these reactions. Traditional and complementary alternate medicines are also causes of adverse drug reactions, and many of them are cataloged as allergy. Research in the field of skin and drug provocation test to antibiotics such as beta-lactams and carbapenems, and iodinated and gadolinium contrast media has allowed the understanding of cross-reactivity reactions and permitted the use of well tolerated alternate drugs in cases of proper negative drug allergy work-up. Many unique cases have been reported, including diverse drugs as infliximab, succinylcholine, hydroxychloroquine, that widen the spectrum of clinical manifestations of drug hypersensitivity to various drugs. Several studies have been published in the field of in-vitro diagnosis, including basophil activation tests, radioallergosorbent test, Immuno-Cap, ELISA, enzyme-linked immunospot assays, and T-cell proliferation tests allowing novel approaches to assess drug allergy. As new and old drugs continue to be used, new reports regarding new and known drug hypersensitivity manifestations are made. Advances in mechanisms are enhanced by the use of new in-vitro techniques to detect specific antibodies or T cells. Research in the field of skin and provocation tests has allowed the use of well tolerated alternate drugs in individuals with proven drug allergy.


Knockdown of UAF1 alleviates sevoflurane-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.
Evidence has shown that suppression of the activation of NLRP3 inflammasome could ameliorate surgery/sevoflurane (SEV)-induced post-operative cognitive dysfunction (POCD). However, the underlying mechanisms remain unclear. UAF1 acts as a binding partner of USP1, which inhibits the ubiquitination-mediated degradation of NLRP3, indicating that UAF1 may be implicated in POCD through regulating the NLRP3 inflammasome. Here, we studied the role of UAF1/NLRP3 in SEV-induced cognitive impairment and neurotoxicity in rats. Neonatal rats were randomly divided into control, SEV, SEV+AAV-shNC and SEV+AAV-shUAF1 (UAF1-downregulated) groups. Morris water maze (MWM) test was applied to assess cognitive impairment. TUNEL staining, qRT-PCR and ELISA were used to assess the apoptosis and inflammation markers, respectively. The levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were quantified to determine oxidative stress. The results showed that SEV treatment led to significant cognitive impairment, increased apoptosis in hippocampal tissues, upregulation of MDA and inflammatory factors (TNF-α, IL-1β, IL-18), as well as a decrease in SOD and CAT levels. All of the above observations were reversed by UAF1 downregulation. Furthermore, depletion of UAF1 neutralized SEV-mediated increase in p-NLRP3, p-IκBα and p-p65 levels. Altogether, the current study demonstrated that knockdown of UAF1 could alleviate SEV-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.


Er:YAG and adhesion in conservative dentistry : clinical overview.
The notion of utilizing laser technology in conservative dentistry was proposed in 1990 by Hibst and Keller, who introduced the possibility of using an Er:YAG laser as alternative to conventional instruments such as the turbine and micro-motor. In subsequent years a continuing effort has been made by clinicians, researchers and commercial companies to improve the technology. The aim of this clinical study is to demonstrate, by the description of different clinical cases, the possibilities and the advantages of using Er:YAG lasers in conservative dentistry and to show that better results may be achieved in terms of stronger adhesion, less invasiveness, reduced pain as well as greater comfort and satisfaction of patients.


Acquired Hemophilia A: Three Cases and Review of the Literature.
Acquired hemophilia A (AHA) is an autoimmune disease caused by autoantibodies against coagulation factor VIII. It is a rare and potentially fatal and often underestimated pathology, mainly in the elderly person and for whom the rapidity of the diagnosis and the initiation of the background treatment are necessary. We reported three cases diagnosed in our hospital. First case: A 55-year-old man, without personal or familial hemorrhagic case history. Admitted to the hospital with anemic and hemorrhagic cutaneous syndromes. His treatment included Transfusion support, concentrate F VIIIa, and corticosteroids with good clinical evolution. Second case: An 82-year-old man, without case history, admitted with cutaneous mucosal hemorrhagic Syndrome with hemorrhage of the puncture sites. Good evolution with treatment based on NovoSeven, corticosteroid, and cyclophosphamide in addition to transfusion support. Third case: A 52-year-old man, was followed for 3 years for pemphigoid. He was hospitalized for surgical Treatment of an extensive and painful hematoma of the anterior aspect of the right leg following a fall and treated with corticosteroid and NovoSeven. Although rare, AHA must be diagnosed early, and may, at any time, commit to the vital prognosis by the appearance of serious hemorrhagic complications.


Thermal properties of carbon nanotube-copper composites for thermal management applications.
Carbon nanotube-copper (CNT/Cu) composites have been successfully synthesized by means of a novel particles-compositing process followed by spark plasma sintering (SPS) technique. The thermal conductivity of the composites was measured by a laser flash technique and theoretical analyzed using an effective medium approach. The experimental results showed that the thermal conductivity unusually decreased after the incorporation of CNTs. Theoretical analyses revealed that the interfacial thermal resistance between the CNTs and the Cu matrix plays a crucial role in determining the thermal conductivity of bulk composites, and only small interfacial thermal resistance can induce a significant degradation in thermal conductivity for CNT/Cu composites. The influence of sintering condition on the thermal conductivity depended on the combined effects of multiple factors, i.e. porosity, CNTs distribution and CNT kinks or twists. The composites sintered at 600°C for 5 min under 50 MPa showed the maximum thermal conductivity. CNT/Cu composites are considered to be a promising material for thermal management applications.


Handgrip strength of the elderly after hip fracture repair correlates with functional outcome.
To investigate the relationship between handgrip strength (HG) and upper limb functioning of hip fracture operated elderly patients and their functional outcome 6 months post-op. Retrospectively, data on 105 post-operative hip fracture patients was analyzed. Functional level was measured by the Functional Independence Measure (FIM) and HG by hand dynamometer, 7-10 days, 1, 3 and 6 months post-op. FIM1 up-to FIM4 (FIM1-FIM4) and HG1 up-to HG4 (HG1-HG4) were determined. Pre-fracture upper limb function was evaluated using the disabilities of the arm, shoulder and hand (DASH) questionnaire. The Mini-Mental-State Examination evaluated cognition. FIM1-FIM4 scores increased during the 6-month follow-up; HG1-HG4 scores remained unchanged. No differences were found in FIM1-FIM4 and DASH scores between genders. HG1-HG4 scores were significantly higher in men (p = 0.04-0.005). FIM1-FIM4, HG1-HG4 and DASH scores were higher in the cognitively normal patients (p < 0.001). A fair correlation was found between all HG and FIM scores (R = 0.36-0.71, p < 0.001), and between DASH and FIM scores (R = 0.5-0.7, p < 0.001). Log HG1 and FIM4 scores were highly correlated (R(2) = 0.54, p < 0.001). Regression analysis found that only, and in the following order were Log HG1, FIM1, DASH and age significant factors affect FIM4 score (R(2) = 0.69). HG and FIM scores, a week post-op., combined with upper limb functioning and age, can have a 69% prediction accuracy for motor functioning 6 months post-fracture. HG measurement, a week post-hip fracture repair, might be considered in estimating functional motor outcome, and eventually additional interventions should be employed to increase muscle strength and, thus, improve functional outcome.


Heterogeneity of beta adrenoceptors in right atria isolated from cold-exposed rats.
The chronotropic response of right atria isolated from 5-day-cold-exposed rats to isoproterenol and norepinephrine was studied. A large increase in the sensitivity of the pacemaker to isoproterenol and a decrease in the sensitivity to norepinephrine occurred. Determination of pA2 values of propranolol and metoprolol using isoproterenol and norepinephrine as agonists and analysis of the slopes of Schild plots suggested that in atria isolated from control rats the chronotropic effect of isoproterenol and norepinephrine resulted from the preferential interaction of the catecholamines with a homogeneous beta-1 adrenoceptor population. After cold exposure the affinity of atrial adrenoceptors for propranolol increased when the agonist was isoproterenol and decreased when norepinephrine was used. The slopes of the Schild plots of metoprolol when the agonists were isoproterenol or norepinephrine were not unitary unless the experiments were performed in the presence of butoxamine. However, butoxamine prevented the demonstration of cold-induced super-sensitivity to isoproterenol, leaving the subsensitivity to norepinephrine unaffected. It is concluded that cold-induced heterogeneity of the atrial beta adrenoceptors is responsible for the increased sensitivity to isoproterenol. Probably, subsensitivity to norepinephrine resulted from conformational alterations of the atrial beta-1 adrenoceptors.


Differential involvement of adrenal and gonadal steroids in anterior and intermediate pituitary pro-opiomelanocortin mRNA expression induced by the endogenous benzodiazepine, octadecaneuropeptide, in adult male rats.
The involvement of the endogenous benzodiazepine, octadecaneuropeptide (ODN), in the regulation of proopiomelanocortin (POMC) mRNA expression at the pituitary level, and the influence of adrenal and gonadal steroids, have been studied using a quantitative in situ hybridization technique. I.c.v. injection of ODN (4 micrograms/kg) in sham-operated rats induced a 17 and 7% decrease in the POMC mRNA expression in anterior and intermediate pituitary lobes respectively. To determine the reciprocal involvement of adrenal and gonadal steroids in this regulation, animals were adrenalectomized and/or castrated. Adrenalectomy significantly increased POMC mRNA expression by 48% at the anterior pituitary level, but induced a 10% decrease of hybridization signal at the intermediate pituitary lobe (vs control sham-operated). Adrenal ablation reversed the effect induced by ODN and increased POMC mRNA expression at the anterior and intermediate pituitary levels by 60 and 10% respectively, compared with control sham-operated. By contrast, castration, which produced a decrease in POMC mRNA in the anterior pituitary and an increase in the intermediate lobe, did not modify the negative influence of ODN observed in sham-operated animals. When rats were adrenalectomized and castrated, the adrenalectomy influence was predominant at the anterior pituitary level, since ODN increased significantly the hybridization signal (+68% vs control sham-operated), while the castration influence was predominant at the intermediate pituitary level, since ODN induced an 11% decrease in POMC mRNA signal compared with control sham-operated. These studies indicate that, in vivo, the decrease in POMC mRNA expression in the anterior and intermediate pituitary induced by an endogenous benzodiazepine is differently modulated by adrenal and gonadal steroids, with a predominant influence of adrenal steroids at the anterior pituitary level and gonadal steroids at the intermediate pituitary level.


Prenatal Transmission of Syphilis and Human Immunodeficiency Virus in Brazil: Achieving Regional Targets for Elimination.
Background. The Pan-American Health Organization has called for reducing (1) human immunodeficiency virus (HIV) mother-to-child transmission (MTCT) to ≤0.30 infections/1000 live births (LB), (2) HIV MTCT risk to ≤2.0%, and (3) congenital syphilis (CS) incidence to ≤0.50/1000 LB in the Americas by 2015. Methods. Using published Brazilian data in a mathematical model, we simulated a cohort of pregnant women from antenatal care (ANC) through birth. We investigated 2 scenarios: "current access" (89.1% receive one ANC syphilis test and 41.1% receive 2; 81.7% receive one ANC HIV test and 18.9% receive birth testing; if diagnosed, 81.0% are treated for syphilis and 87.5% are treated for HIV) and "ideal access" (95% of women undergo 2 HIV and syphilis screenings; 95% receive appropriate treatment). We conducted univariate and multivariate sensitivity analyses on key inputs. Results. With current access, we projected 2.95 CS cases/1000 LB, 0.29 HIV infections/1000 LB, 7.1% HIV MTCT risk, and 11.11 intrauterine fetal demises (IUFD)/1000 pregnancies, with significant regional variation. With ideal access, we projected improved outcomes: 1.00 CS cases/1000 LB, 0.10 HIV infections/1000 LB, HIV MTCT risk of 2.4%, and 10.65 IUFD/1000 pregnancies. Increased testing drove the greatest improvements. Even with ideal access, only HIV infections/1000 LB met elimination goals. Achieving all targets required testing and treatment >95% and reductions in prevalence and incidence of HIV and syphilis. Conclusions. Increasing access to care and HIV and syphilis antenatal testing will substantially reduce HIV and syphilis MTCT in Brazil. In addition, regionally tailored interventions reducing syphilis incidence and prevalence and supporting HIV treatment adherence are necessary to completely meet elimination goals.


Optic nerve involvement in ocular toxoplasmosis: 12 year data from a tertiary referral center in Turkey.
To evaluate the prevalence, clinical characteristics, and types of optic nerve involvement in patients with ocular toxoplasmosis. For this retrospective cross-sectional study, we examined all patients with active ocular toxoplasmosis referred to our Uveitis Section during the last 12 years, and we included patients with optic nerve involvement in the study. The primary outcome was the prevalence of optic nerve involvement, and secondary outcomes included the types of optic nerve involvement and the final best-corrected visual acuity after treatment. The prevalence of optic nerve involvement was 14.4%, with the leading cause being the activation of a juxtapapillary lesion (70.5%). We found papillitis in two eyes and neuroretinitis in two eyes (11.7% for each). We only detected one optic nerve involvement secondary to a distant active lesion (5.8%). Sixteen patients (94.1%) had unilateral ocular toxoplasmosis. The overall final best-corrected visual acuity after treatment was 10/10 (LogMAR = 0.0) excluding the three patients with a juxtapapillary scar involving the macula. Optic nerve involvement was common in patients with ocular toxoplasmosis. The main type of optic nerve involvement was caused by activation of an old juxtapapillary lesion. Treatment was quickly effective, but the best-corrected visual acuity was dependent on the presence of a scar in the papillomacular bundle.


Immunohistochemical study of annexin V expression in placentae of preeclampsia.
We investigated the clinical significance of annexin V in the placentae with preeclampsia and found: (1) annexin V was detected on trophoblasts in the placentae and the staining intensity of annexin V in the placentae from such patients was reduced when compared to normal placentae; (2) as expression of annexin V was reduced, the gestosis index from patients with preeclampsia was elevated and the standard deviation value in the infant's standard weight was decreased; plasma level of the fibrin degradation products and thrombin-antithrombin III complex from patients were elevated as the expression of anexin V was reduced. These results suggest that the reduced expression of annexin V in the placentae from patients with preeclampsia may lead to a hypercoagulable state in the intervillous space and may be associated with the development of intrauterine growth restriction.