Physiology education in North American dental schools: the basic science survey series.
As part of the Basic Science Survey Series for Dentistry, members of the American Dental Education Association (ADEA) Physiology, Pharmacology, and Therapeutics Section surveyed directors of physiology courses in North American dental schools. The survey was designed to assess, among other things, faculty affiliation and experience of course directors, teaching methods, general course content and emphasis, extent of interdisciplinary (shared) instruction, and impact of recent curricular changes. Responses were received from forty-four of sixty-seven (65.7 percent) U.S. and Canadian dental schools. The findings suggest the following: substantial variation exists in instructional hours, faculty affiliation, class size, and interdisciplinary nature of physiology courses; physiology course content emphasis is similar between schools; student contact hours in physiology, which have remained relatively stable in the past fifteen years, are starting to be reduced; recent curricular changes have often been directed towards enhancing the integrative and clinically relevant aspects of physiology instruction; and a trend toward innovative content delivery, such as use of computer-assisted instruction, is evident. Data from this study may be useful to physiology course directors, curriculum committees, and other dental educators with an interest in integrative and interprofessional education.


Effects of commercial organic acid blends on male broilers challenged with E. coli K88: Performance, microbiology, intestinal morphology, and immune response.
This study assessed the effects of 3 commercial organic acid (OA) preparations on growth performance, intestinal morphology, cecal microbiology, and immunity of Escherichia coli K88-challenged (ETEC) broiler chickens. One thousand one-day-old male broiler chickens were divided into 8 treatments of 5 replicate pens: Negative control (NC) birds received a basal diet (BD) and were not challenged with ETEC; positive control (PC) birds fed the BD and challenged with ETEC; BD + 0.2% (S1) or 0.4% (S2) of an OA mixture (Salkil) from one to 35 d; BD + 0.1, 0.075, and 0.05% (O1) of another OA mixture (Optimax) in the starter (one to 10 d), grower (11 to 24 d), and finisher (25 to 35 d) diets, respectively, or 0.1% (O2) from one to 35 d; BD + 0.07, 0.05, and 0.05% (P1) or 0.1, 0.07, and 0.05% (P2) of a further OA mixture (pHorce) in the starter, grower, and finisher diets, respectively. All groups (not NC) were challenged with one mL of ETEC (1 × 108 cfu/mL) at 7 d of age. The 3 OA mixtures are commercial formic and propionic acid preparations. Birds challenged with ETEC (PC) had reduced (P < 0.05) growth performance, ileal morphological parameters (not crypt depth, which was increased), cecal lactobacilli, and immune responses, and increased cecal E. coli compared with unchallenged, NC birds. The addition of OA to the diets of ETEC challenged birds (S1-P2) either numerically or significantly (P < 0.05) improved growth performance, ileal morphology and immune responses, increased cecal lactobacilli, and reduced cecal E. coli. For most OA additions, the assessed parameters were generally enhanced to equivalence to NC birds. The results suggest that dietary OA supplementation can enhance the growth performance, ileal morphology, cecal microbiota, and immunity of ETEC-challenged broilers to an extent that, under such circumstances, the formulations used in this study provided similar performance and assessed parameters as non-challenged birds.


Transcriptome reprogramming through alternative splicing triggered by apigenin drives cell death in triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and resistance to cancer-specific transcriptome alterations. Alternative splicing (AS) is a major contributor to the diversification of cancer-specific transcriptomes. The TNBC transcriptome landscape is characterized by aberrantly spliced isoforms that promote tumor growth and resistance, underscoring the need to identify approaches that reprogram AS circuitry towards transcriptomes, favoring a delay in tumorigenesis or responsiveness to therapy. We have previously shown that flavonoid apigenin is associated with splicing factors, including heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2). Here, we showed that apigenin reprograms TNBC-associated AS transcriptome-wide. The AS events affected by apigenin were statistically enriched in hnRNPA2 substrates. Comparative transcriptomic analyses of human TNBC tumors and non-tumor tissues showed that apigenin can switch cancer-associated alternative spliced isoforms (ASI) to those found in non-tumor tissues. Apigenin preferentially affects the splicing of anti-apoptotic and proliferation factors, which are uniquely observed in cancer cells, but not in non-tumor cells. Apigenin switches cancer-associated aberrant ASI in vivo in TNBC xenograft mice by diminishing proliferation and increasing pro-apoptotic ASI. In accordance with these findings, apigenin increased apoptosis and reduced tumor proliferation, thereby halting TNBC growth in vivo. Our results revealed that apigenin reprograms transcriptome-wide TNBC-specific AS, thereby inducing apoptosis and hindering tumor growth. These findings underscore the impactful effects of nutraceuticals in altering cancer transcriptomes, offering new options to influence outcomes in TNBC treatments.


Degradation of GRK2 and AKT is an early and detrimental event in myocardial ischemia/reperfusion.
Identification of signaling pathways altered at early stages after cardiac ischemia/reperfusion (I/R) is crucial to develop timely therapies aimed at reducing I/R injury. The expression of G protein-coupled receptor kinase 2 (GRK2), a key signaling hub, is up-regulated in the long-term in patients and in experimental models of heart failure. However, whether GRK2 levels change at early time points following myocardial I/R and its functional impact during this period remain to be established. We have investigated the temporal changes of GRK2 expression and their potential relationships with the cardioprotective AKT pathway in isolated rat hearts and porcine preclinical models of I/R. Contrary to the maladaptive up-regulation of GRK2 reported at later times after myocardial infarction, successive GRK2 phosphorylation at specific sites during ischemia and early reperfusion elicits GRK2 degradation by the proteasome and calpains, respectively, thus keeping GRK2 levels low during early I/R in rat hearts. Concurrently, I/R promotes decay of the prolyl-isomerase Pin1, a positive regulator of AKT stability, and a marked loss of total AKT protein, resulting in an overall decreased activity of this pro-survival pathway. A similar pattern of concomitant down-modulation of GRK2/AKT/Pin1 protein levels in early I/R was observed in pig hearts. Calpain and proteasome inhibition prevents GRK2/Pin1/AKT degradation, restores bulk AKT pathway activity and attenuates myocardial I/R injury in isolated rat hearts. Preventing transient degradation of GRK2 and AKT during early I/R might improve the potential of endogenous cardioprotection mechanisms and of conditioning strategies.


Forward Inverse Relaxation Model Incorporating Movement Duration Optimization.
A computational trajectory formation model based on the optimization principle, which introduces the forward inverse relaxation model (FIRM) as the hardware and algorithm, represents the features of human arm movements well. However, in this model, the movement duration was defined as a given value and not as a planned value. According to considerable empirical facts, movement duration changes depending on task factors, such as required accuracy and movement distance thus, it is considered that there are some criteria that optimize the cost function. Therefore, we propose a FIRM that incorporates a movement duration optimization module. The movement duration optimization module minimizes the weighted sum of the commanded torque change term as the trajectory cost, and the tolerance term as the cost of time. We conducted a behavioral experiment to examine how well the movement duration obtained by the model reproduces the true movement. The results suggested that the model movement duration was close to the true movement. In addition, the trajectory generated by inputting the obtained movement duration to the FIRM reproduced the features of the actual trajectory well. These findings verify the use of this computational model in measuring human arm movements.


Non-verbal communication of compassion: measuring psychophysiologic effects.
Calm, compassionate clinicians comfort others. To evaluate the direct psychophysiologic benefits of non-verbal communication of compassion (NVCC), it is important to minimize the effect of subjects' expectation. This preliminary study was designed to a) test the feasibility of two strategies for maintaining subject blinding to non-verbal communication of compassion (NVCC), and b) determine whether blinded subjects would experience psychophysiologic effects from NVCC. Subjects were healthy volunteers who were told the study was evaluating the effect of time and touch on the autonomic nervous system. The practitioner had more than 10 years' experience with loving-kindness meditation (LKM), a form of NVCC. Subjects completed 10-point visual analog scales (VAS) for stress, relaxation, and peacefulness before and after LKM. To assess physiologic effects, practitioners and subjects wore cardiorespiratory monitors to assess respiratory rate (RR), heart rate (HR) and heart rate variability (HRV) throughout the 4 10-minute study periods: Baseline (both practitioner and subjects read neutral material); non-tactile-LKM (subjects read while the practitioner practiced LKM while pretending to read); tactile-LKM (subjects rested while the practitioner practiced LKM while lightly touching the subject on arms, shoulders, hands, feet, and legs); Post-Intervention Rest (subjects rested; the practitioner read). To assess blinding, subjects were asked after the interventions what the practitioner was doing during each period (reading, touch, or something else). Subjects' mean age was 43.6 years; all were women. Blinding was maintained and the practitioner was able to maintain meditation for both tactile and non-tactile LKM interventions as reflected in significantly reduced RR. Despite blinding, subjects' VAS scores improved from baseline to post-intervention for stress (5.5 vs. 2.2), relaxation (3.8 vs. 8.8) and peacefulness (3.8 vs. 9.0, P < 0.05 for all comparisons). Subjects also had significant reductions in RR (P < 0.0001) and improved HRV (P < 0.05) with both tactile and non-tactile LKM. It is possible to test the effects of LKM with tactile and non-tactile blinding strategies; even with blinding in this small preliminary study, subjects reported significant improvements in well-being which were reflected in objective physiologic measures of autonomic activity. Extending compassion is not only good care; it may also be good medicine. US National ClinicalTrials.gov registration number, NCT01428674.


Radiation doses for Marshall Islands Atolls affected by U.S. nuclear testing: all exposure pathways, remedial measures, and environmental loss of (137)Cs.
Radiation doses calculated for people resettling Bikini Island at Bikini Atoll, Enjebi Island at Enewetak Atoll, Rongelap Island at Rongelap Atoll, and Utrōk Island at Utrōk Atoll are presented. Residence is assumed to begin in 2010. In previous dose assessments it was shown that (137)Cs accounts for about 98% of the total dose for returning residents. About 85 to 90% (depending on the atoll) is via consumption of locally grown foods containing (137)Cs, and about 10 to 15% is due to external exposure from (137)Cs in the soil. These assessments were made using only the radiological half-life of (137)Cs (30.1 y). We have shown since that there is an environmental loss of (137)Cs from soil to groundwater that results in a more rapid loss of (137)Cs from the atoll ecosystem. The mean effective half-life of (137)Cs at the atolls is 8.5 y. Moreover, treatment of coconut trees with potassium (K) reduces (137)Cs concentration in drinking coconut meat at Bikini Atoll to about 5% of pretreatment concentrations. The magnitude of reduction is dependent on the concentration of (137)Cs in soil, and thereby in food crops, and is less for Enjebi and Rongelap Islands than for Bikini Island. Treatment of food crops and fruit trees with K and removal of the top 15 cm of soil around houses and community buildings prior to construction to reduce external exposure where people spend most of their time has been presented to the communities as a "Combined Option" remediation strategy. Doses presented here are calculated using the Combined Option, effective half-life of (137)Cs at the atolls, and a diet of both imported and local foods. The average natural background dose in the Marshall Islands, plus the anthropogenic nuclear test-related dose at Bikini, Enjebi, and Rongelap Islands, is less for each of the islands than the average background dose in the U.S. and Europe.


[Ionic mechanisms of the transmembrane current induced by injection of cyclic adenosine monophosphate into identified edible snail neurons].
The ionic mechanisms of transmembrane current evoked by cAMP injection (cAMP-current) into identified neurons of the snail were studied using the voltage clamp. cAMP-current was shown to consist of two components. The early component has a reversal potential in the region of -5 divided by +20 mV and the late one in the region of -55 divided by -60 mV. It is suggested that the early component of cAMP-current is associated with an increase in the neuron membrane permeability mainly for sodium ions and the late one for potassium ions, respectively. In LPa8 neuron AMP injection also evoked the transmembrane inward current which was independent of the holding potential and was not accompanied by changes in the membrane conductance.


Imaging Voids and Defects Inside Li-Ion Cathode LiNi0.6Mn0.2Co0.2O2 Single Crystals.
Li-ion battery cathode active materials obtained from different sources or preparation methods often exhibit broadly divergent performance and stability despite no obvious differences in morphology, purity, and crystallinity. We show how state-of-the-art, commercial, nominally single crystalline LiNi0.6Mn0.2Co0.2O2 (NMC-622) particles possess extensive internal nanostructure even in the pristine state. Scanning X-ray diffraction microscopy reveals the presence of interlayer strain gradients, and crystal bending is attributed to oxygen vacancies. Phase contrast X-ray nano-tomography reveals two different kinds of particles, welded/aggregated, and single crystal like, and emphasizes the intra- and interparticle heterogeneities from the nano- to the microscale. It also detects within the imaging resolution (100 nm) substantial quantities of nanovoids hidden inside the bulk of two-thirds of the overall studied particles (around 3000), with an average value of 12.5%v per particle and a mean size of 148 nm. The powerful combination of both techniques helps prescreening and quantifying the defective nature of cathode material and thus anticipating their performance in electrode assembly/battery testing.


Anaemia and its treatment in neurologically critically ill patients: being reasonable is easy without prospective trials.
Most healthy humans have a haemoglobin concentration of 12 to 15 g/dL and most intensivists now transfuse packed red blood cells for haemoglobin <7 g/dL. Higher haemoglobin is associated with improved intermediate and clinical outcomes after subarachnoid hemorrhage (from ruptured brain aneurysm) or neurotrauma. An observational study in a recent issue shows that higher haemoglobin was associated with better functional outcomes in patients with spontaneous intracerebral haemorrhage; few patients received a packed red blood cell transfusion, so it is not known if that treatment is better than the disease. The mechanism of anaemia's purported impact on outcome is unclear, although altered metabolism in brain tissue that is sensitive to reduced oxygen delivery is plausible. These data may intensify the differences of opinion between intensivists: whether neurologic patients are better served by higher haemoglobin and potentially by more packed red blood cell transfusion, or simply need to be studied more in prospective clinical trials, remains unclear.


Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus.
Cyclophosphamide (CYC) therapy for systemic lupus erythematosus (SLE), a disease predominantly affecting women of childbearing age, causes an unacceptably high incidence of irreversible premature ovarian failure (POF). This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a), for protection against POF during CYC therapy. Young women with severe SLE treated in a standardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH-a (depot leuprolide acetate; a 3.75-mg monthly injection during the standard CYC regimen). Patients treated with GnRH-a were compared with controls individually matched by age (+/-5 years) and by cumulative CYC dose (+/-5 gm). Reproductive status was determined after a minimum followup of 3 years after CYC therapy. The primary outcome was time to POF. Paired summary statistical analyses, Kaplan-Meier survival estimates, and Cox regression analyses were performed to assess differences in outcome between groups. POF developed in 1 of 20 women treated with GnRH-a (5%) compared with 6 of 20 controls (30%) matched by age and cumulative CYC dose (matched odds ratio 0.09, P < 0.05). Kaplan-Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH-a-treated group (P = 0.04). Treatment with GnRH-a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE.


Intensive induction chemotherapy without methotrexate in adult patients with localized osteosarcoma: results of the Institut Gustave-Roussy phase II trial.
To improve outcomes in localized osteosarcoma and to reduce the duration of preoperative chemotherapy, we conducted a phase ii trial assessing the efficacy of an intensive protracted regimen without methotrexate (api-ai regimen) in adolescent and adult patients with newly diagnosed disease. Induction chemotherapy consisted of 2 cycles (4 courses) of doxorubicin 60 mg/m(2) (days 1 and 15), cisplatin 100 mg/m(2) (day 1), and ifosfamide 5 g/m(2) (days 2 and 15). The primary endpoint was good histologic response [ghr (≤5% identifiable tumour cells)]. From March 1993 to March 2000, 32 patients [median age: 21 years (range: 15-49 years)] were administered 126 induction courses. The median time between chemotherapy courses was 15 days (range: 12-32 days). All but 3 patients underwent conservative surgery. Toxicity was mainly hematologic, with febrile neutropenia occurring in 35% of patients and grades 3-4 thrombocytopenia in 35%. The ghr rate was 47%. The median follow-up was 64 months (range: 30-115 months). The 5-year event-free and overall survivals were 65% [95% confidence interval (ci): 48%-79%] and 69% (95% ci: 50%-83%) respectively. Two secondary hematologic malignancies occurred: 1 acute myelocytic leukemia (M5) in a poor responder with concomitant relapse, and 1 myelodysplastic syndrome in a patient achieving ghr. Despite hematologic toxicity, the results observed with the api-ai regimen compare favourably with those observed during previous induction chemotherapy containing methotrexate in adult patients and the pediatric population treated at our institution. These promising results have to be validated by an ongoing national multicentre trial coordinated by the French Sarcoma Group.


Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects.
Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined. Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis. Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.


Feasibility and Preliminary Efficacy of a Multimodal Approach to Increase Physical Activity in Older Adults With Memory Complaints: The Education for Action Study.
In this randomized controlled pilot trial, the authors explored the feasibility, technology compliance, and preliminary efficacy of the Education for Action (EDU-ACT), a multimodal intervention combining evidence-based strategies of physical activity (PA) education and coaching in PA levels over 4 weeks between EDU-ACT and control groups. The authors also assessed pre-post changes in neurocognitive function, functional mobility and dual-task performance, sleep and quality of life. Thirty-two sedentary older adults with memory complaints (age = 66 ± 5.3) completed the study (EDU-ACT = 18 and control = 14). The EDU-ACT adherence rate was 95%, and compliance of daily PA reporting was, on average, 22.7 days (94.6%). The EDU-ACT group demonstrated a significantly greater number of steps, processing speed, and dual-task performance when compared with controls (p < .05). In this study, a multimodal, evidence-based, low-cost intervention was feasible, well-accepted, with high adherence and compliance rates, and effective at promoting clinically meaningful increases in PA, for at least 1 month postintervention, in older adults with memory complaints.


Quality of life in low-grade glioma patients receiving temozolomide.
The purpose of this study was to describe the quality of life (QOL) of low-grade glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of temozolomide (TMZ) chemotherapy. Patients with histologically confirmed LGG with only prior surgery were given TMZ for 12 cycles. QOL assessments by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) were obtained at baseline prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with LGG at baseline prior to chemotherapy had higher reported social well-being scores (mean difference = 5.0; p < 0.01) but had lower reported emotional well-being scores (mean difference = 2.2; p < 0.01) compared to a normal population. Compared to patients with left hemisphere tumors, patients with right hemisphere tumors reported higher physical well-being scores (p = 0.01): 44% could not drive, 26% did not feel independent, and 26% were afraid of having a seizure. Difficulty with work was noted in 24%. Mean change scores at each chemotherapy cycle compared to baseline for all QOL subscales showed either no significant change or were significantly positive (p < 0.01). Patients with LGG on TMZ at baseline prior to chemotherapy reported QOL comparable to a normal population with the exception of social and emotional well-being, and those with right hemisphere tumors reported higher physical well-being scores compared to those with left hemisphere tumors. While remaining on therapy, LGG patients were able to maintain their QOL in all realms. LGG patients' QOL may be further improved by addressing their emotional well-being and their loss of independence in terms of driving or working.


Allobetulone rearrangement to l8αH,19βH-ursane triterpenoids with antiviral activity.
Allobetulone E-ring rearrangement under treating with HClO4 in Ac2O under reflux afforded new triterpenoids: 3,28-diacetoxy-21-acetyl-2(3),20(21)-18α,19βH-ursandiene 3 and 3,28-diacetoxy-2(3),18(19)-oleandiene 4. 18α,19βH-Ursanes were transformed at A- and E-rings into indolo- and bis-furfurylidene 7 derivatives. Structure elucidation was performed using COSY, NOESY, HSQC and HMBC experiments, and X-Ray analysis for 3. The potential of newly obtained 18α,19βH-ursanes was evaluated against HCMV and HPV-11, the NCI-60 cancer cell panel and inhibition of α-glucosidase. All of the compounds have shown viral inhibition towards HCMV compared to standard drug Acyclovir. 3β-Acetoxy-21β-acetyl-20β,28-epoxy-18α,19βН-ursane 1 showed moderate activity (EC50 4.87 μM) towards the HCMV-resistant isolate (GDGr K17) compared to standard drug Cidofovir and was four times more potent than Ganciclovir. Compound 7 inhibited the cell growth of the three melanoma and one colon cancer cell. 3-Oxo-21β-acetyl-20β,28-epoxy-18α,19βН-ursane 5 and compound 7 inhibited α-glucosidase with IC50 28.0 µM and 4.0 µM being from 6 to 44 times more active than acarbose.


3D and Porous RGDC-Functionalized Polyester-Based Scaffolds as a Niche to Induce Osteogenic Differentiation of Human Bone Marrow Stem Cells.
Polyester-based scaffolds covalently functionalized with arginine-glycine-aspartic acid-cysteine (RGDC) peptide sequences support the proliferation and osteogenic differentiation of stem cells. The aim is to create an optimized 3D niche to sustain human bone marrow stem cell (hBMSC) viability and osteogenic commitment, without reliance on differentiation media. Scaffolds consisting of poly(lactide-co-trimethylene carbonate), poly(LA-co-TMC), and functionalized poly(lactide) copolymers with pendant thiol groups are prepared by salt-leaching technique. The availability of functional groups on scaffold surfaces allows for an easy and straightforward method to covalently attach RGDC peptide motifs without affecting the polymerization degree. The strategy enables the chemical binding of bioactive motifs on the surfaces of 3D scaffolds and avoids conventional methods that require harsh conditions. Gene and protein levels and mineral deposition indicate the osteogenic commitment of hBMSC cultured on the RGDC functionalized surfaces. The osteogenic commitment of hBMSC is enhanced on functionalized surfaces compared with nonfunctionalized surfaces and without supplementing media with osteogenic factors. Poly(LA-co-TMC) scaffolds have potential as scaffolds for osteoblast culture and bone grafts. Furthermore, these results contribute to the development of biomimetic materials and allow a deeper comprehension of the importance of RGD peptides on stem cell transition toward osteoblastic lineage.


[Introduction to qualitative research: the main approaches and designs].
Introduction to qualitative research: the main approaches and designs. The main methods (phenomenology, ethnography, Grounded, narrative enquiry and case studies) and sampling technique of qualitative research are briefly outlined. A practical example is presented for each method.


Role of Pepsin and Oropharyngeal pH-Monitoring to Assess the Postoperative Outcome of Patients with Laryngopharyngeal Reflux: Results of a Pilot Trial.
The aim of this study was to evaluate the value of salivary pepsin and oropharyngeal pH-monitoring to assess the surgical outcome of patients with laryngopharyngeal reflux (LPR). Twenty consecutive patients with LPR despite proton pump inhibitor treatment received laparoscopic antireflux surgery. Twenty-four hour esophageal pH-monitoring (multichannel intraluminal impedance monitoring [MII]-pH) and esophageal manometry (high-resolution manometry) data were documented preoperatively and at 3-month follow-up. An ears, nose and throat (ENT) examination was performed, including assessment of Belafsky Reflux Finding Score (RFS). Clinical symptoms were evaluated with the Belafsky Reflux Symptom Index (RSI) and the Gastrointestinal Quality of Life Index (GIQLI). Simultaneous to the MII-pH and collection of saliva samples, detection of oropharyngeal reflux events was performed. Treatment failure was defined as postoperative pathologic RFS or RSI score and improvement of GIQLI of <10 points, despite showing a normal DeMeester score. At baseline, all patients had a pathological ENT examination, RSI score, and MII-pH data. All patients showed postoperatively a normal DeMeester score (mean 6.39 ± 4.87). Five patients were defined as treatment failures with a change of pepsin concentration from median 157.0 (95% confidence interval [CI]: 0-422) to 180.7 (95% CI: 0-500). In patients defined as treatment success, median pepsin value decreased from 206.3 (95% CI: 89-278) to 76.0 (95% CI: 55-205); (P = .093). Oropharyngeal pH-monitoring data showed no significant change in both groups. Salivary pepsin could be a marker for treatment success, while oropharyngeal pH-monitoring seems to be inadequate in these terms. However, larger studies are required to reach firm conclusions.


Calcification in adult Onchocerca volvulus.
Calcified worm fragments of adult Onchocerca volvulus from patients in West Africa were collected for a chemical analysis. The material contained predominantly calcium carbonate. Some results of investigations on the occurrence of calcified worms in untreated populations are reported on. Relations between the numbers of old parasites and those of calcified worms are discussed. The significance of possible resorption of calcified worm fragments for the interpretation of the effects of drug trials or other control measures are mentioned.


Therapy response testing of breast cancer in a 3D high-throughput perfused microfluidic platform.
Breast cancer is the most common invasive cancer among women. Currently, there are only a few models used for therapy selection, and they are often poor predictors of therapeutic response or take months to set up and assay. In this report, we introduce a microfluidic OrganoPlate® platform for extracellular matrix (ECM) embedded tumor culture under perfusion as an initial study designed to investigate the feasibility of adapting this technology for therapy selection. The triple negative breast cancer cell lines MDA-MB-453, MDA-MB-231 and HCC1937 were selected based on their different BRCA1 and P53 status, and were seeded in the platform. We evaluate seeding densities, ECM composition (Matrigel®, BME2rgf, collagen I) and biomechanical (perfusion vs static) conditions. We then exposed the cells to a series of anti-cancer drugs (paclitaxel, olaparib, cisplatin) and compared their responses to those in 2D cultures. Finally, we generated cisplatin dose responses in 3D cultures of breast cancer cells derived from 2 PDX models. The microfluidic platform allows the simultaneous culture of 96 perfused micro tissues, using limited amounts of material, enabling drug screening of patient-derived material. 3D cell culture viability is improved by constant perfusion of the medium. Furthermore, the drug response of these triple negative breast cancer cells was attenuated by culture in 3D and differed from that observed in 2D substrates. We have investigated the use of a high-throughput organ-on-a-chip platform to select therapies. Our results have raised the possibility to use this technology in personalized medicine to support selection of appropriate drugs and to predict response to therapy in a real time fashion.


Novel low resolution ADC-DSP optimization based on non-uniform quantization and MLSE for data centers interconnects.
A new generation of combined ADC-DSP scheme is proposed. It is based on a novel non-uniform quantization method, optimized for MLSE based receivers. This inclusive optimization enables the use of extremely low-resolution analog-to-digital-converters devices, which form a major bottleneck in high speed optical communications receivers' architecture. Through Monte-simulation it is demonstrated that the proposed method leads to a significant SNR gain over conventional designs, and may provide low cost and low power consumption digital implementation solution for datacenter interconnects.


Infratentorial arachnoid cysts.
The infratentorial compartment represents the second most common location of arachnoid malformations. Ten arachnoid cysts of the posterior fossa, operated on between 1970 and 1983, are reviewed. These lesions, although congenital and developmental in nature, may present at any age, and males are more frequently affected. A high rate of birth-related trauma (50% in this series) is conceivably due to fetal macrocranium, and the enlarged head and psychomotor retardation prevail in infancy and childhood. In arachnoid cysts occurring during adulthood, symptoms and signs more clearly indicate a dysfunction of the posterior fossa. Besides computerized tomography, pneumoencephalography and metrizamide techniques are recommended to rule out a Dandy-Walker syndrome in doubtful cases, and to obtain information about the cerebrospinal fluid (CSF) circulation. It is particularly important to establish the presence and type of communication of cysts with the CSF pathways. Although infratentorial cysts often communicate, they can be space-occupying masses because of increasing CSF retention, which may be due to a ball-valve mechanism or to inadequate communication. The frequently associated hydrocephalus (seven of the 10 cases in this series had hydrocephalus) seemed to be dependent mainly upon mechanical factors. The authors discuss the indications for intracranial surgery versus shunting procedures and report the results achieved by direct cyst excision.


Three-dimensional telesurgery and remote proctoring over a 5G network.
To present 2 cases of vitreoretinal surgery performed on a three-dimensional (3D) heads-up display surgical platform with real-time transfer of 3D video over a fifth-generation (5G) cellular network. An epiretinal membrane peel and tractional retinal detachment repair performed at Massachusetts Eye and Ear in April 2019 were broadcast live to the Verizon 5G Lab in Cambridge, MA. Both surgeries were successful. The heads-up digital surgery platform, combined with a 5G network, allowed telesurgical transfer of high-quality 3D vitreoretinal surgery with minimal degradation. Average end-to-end latency was 250 ms, and average round-trip latency was 16 ms. Fine surgical details were observed remotely by a proctoring surgeon and trainee, with real-time communication via mobile phone. This pilot study represents the first successful demonstration of vitreoretinal surgery transmitted over a 5G network. Telesurgery has the potential to enhance surgical education, provide intraoperative consultation and guidance from expert proctors, and improve patient outcomes, especially in remote and low-resource areas.


Hypersexuality, Gender, and Sexual Orientation: A Large-Scale Psychometric Survey Study.
Criteria for hypersexual disorder (HD) were proposed for consideration in the DSM-5 but ultimately excluded for a variety of reasons. Regardless, research continues to investigate hypersexual behavior (HB). The Hypersexual Behavior Inventory (HBI) is one of the most robust scales assessing HB, but further examination is needed to explore its psychometric properties among different groups. Therefore, the aim of the present study was to examine the generalizability of the HBI in a large, diverse, non-clinical sample (N = 18,034 participants; females = 6132; 34.0%; Mage = 33.6 years, SDage = 11.1) across both gender and sexual orientation. Measurement invariance testing was carried out to ensure gender- and sexual orientation-based comparisons were meaningful. Results demonstrated when both gender and sexual orientation were considered (i.e., heterosexual males vs. LGBTQ males vs. heterosexual females vs. LGBTQ females), LGBTQ males had significantly higher latent means on the HBI factors. Results also demonstrated LGBTQ males had the highest scores on other possible indicators of hypersexuality (e.g., frequency of masturbation, number of sexual partners, or frequency of pornography viewing). These findings suggest LGBTQ males may be a group most at risk of engaging in hypersexual behavior, and LGBTQ females are at a higher risk of engaging in hypersexual activities due to coping problems. Given the large-scale nature of the study, the findings contribute to the currently growing body of the literature on hypersexuality.


Shame and guilt in the aftermath of terror: the Utøya Island study.
In recent years, there has been increased interest in trauma-related shame and guilt and their relationship to mental health. Little is known, however, about shame and guilt following mass traumas, such as terrorism. This study investigates the potential associations of trauma-related shame and guilt with posttraumatic stress (PTS) reactions after the terrorist attack of July 22, 2011 on Utøya Island in Norway. Interviews were conducted with 325 of the 490 survivors 4 to 5 months after the event. Multiple linear regression analyses were employed to investigate associations. In the month previous to the interview, 44.1% (n = 143) of participants had experienced at least some guilt for what happened during the attack, and 30.5% (n = 99) had experienced at least some shame. Shame and guilt were both uniquely associated with PTS reactions after adjusting for terror exposure, gender, and other potential confounders (frequent shame: B = 0.54, frequent guilt: B = 0.33). We concluded that trauma-related shame and guilt are related to mental health after mass trauma.


Cannabis and caries--does regular cannabis use increase the risk of caries in cigarette smokers?
The use of cannabis by adolescents in Switzerland has almost doubled in the past decade. Empirical observations in private dental practices indicate that cannabis users have more carious lesions than those who do not use cannabis. The aim of this study was to investigate the hypothesis that regular cannabis use increases the risk of caries because of hyposalivation or lifestyle. Forty-three regular cannabis users were enrolled in the test group and 42 tobacco smokers were used as a negative control group. All subjects were 18-25 years old. Data were obtained using a standardized questionnaire and a clinical examination. There was no significant difference between groups in decayed and filled surfaces (DFS), saliva flow rate and plaque and gingival indices. The cannabis group had, however, significantly higher DS (decayed surface) values (p = 0.0001) and significantly lower frequencies of daily tooth brushing and dental control visits (p < 0.0001) than the control group. Additionally, the cannabis group reported a significantly higher consumption of sugar-containing beverages than the control group (p = 0.0078). To obtain more objective data relations, the DS values of male cannabis users were also compared with those of Swiss military recruits found in another study. The cannabis users had more caries on smooth surfaces than the military recruits. Although comparison with epidemiological data suggested that the prevalence of caries on smooth surfaces is elevated in cannabis users, DFS data indicated that cannabis users do not have an increased risk of caries. Lifestyle combined with short-term hyposalivation after delta-9-tetrahydrocannabinol consumption is the most probable cause of the high prevalence of caries on smooth surfaces in cannabis users. Further studies are needed to investigate the effects of cannabis use on oral health.


Ginsenoside Rh2 differentially mediates microRNA expression to prevent chemoresistance of breast cancer.
Chemoresistance is the most common cause of chemotherapy failure during breast cancer (BCA) treatment. It is generally known that the mechanisms of chemoresistance in tumors involve multiple genes and multiple signaling pathways,; if appropriate drugs are used to regulate the mechanisms at the gene level, it should be possible to effectively reverse chemoresistance in BCA cells. It has been confirmed that chemoresistance in BCA cells could be reversed by ginsenoside Rh2 (G-Rh2). Preliminary studies of our group identified some drug- resistance specific miRNA. Accordingly, we proposed that G-Rh2 could mediate drug-resistance specific miRNA and corresponding target genes through the gene regulatory network; this could cut off the drug-resistance process in tumors and enhance treatment effects. G-Rh2 and breast cancer cells were used in our study. Through pharmaceutical interventions, we could explore how G-Rh2 could inhibit chemotherapy resistance in BCA, and analyze its impact on related miRNA and target genes. Finally, we will reveal the anti-resistance molecular mechanisms of G-Rh2 from a different angle in miRNA-mediated chemoresistance signals among cells.


31P magnetic resonance spectroscopy (MRS) of experimental orbital myositis.
We described a model of orbital myositis that was induced by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) injection into the superior rectus muscle of New Zealand white rabbits. In this study, in vivo 31P magnetic resonance spectroscopy (MRS) was performed with a 4.7 Tesla Oxford (Oxford Instruments, Oxford, England) magnet to monitor the evolution of muscle inflammation in control animals and the response of this model to external beam radiation. 31P MRS showed a dramatic increase in high-energy phosphorus and phospholipid metabolites 48 hr after TPA injection. These spectra were similar to those from implanted allogenic fibroblasts. Within 18-48 hr after a single dose (400 cGy) or sequential doses (3 days at 400 cGy) of orbital irradiation, reduced extraocular muscle swelling and a significant decrease of all 31P metabolites occurred. A decrease (63 +/- 6%) in the signal-to-noise (S/N) ratio of the control inflamed muscle 31P MR spectra increased by 28 days after inflammation. Two days after single-dose radiation, 31P MR metabolites were significantly lower (58 +/- 5%, P less than 0.012) than control spectra. These postradiation spectra mirror the 28-day control spectra and are consistent with previous histologic data that show decreased fibroblastic activity. Change in 31P MRS was a sensitive indicator of treatment response latency.


Gastric cancer with obstructive uropathy: clinical experience with 17 cases.
Gastric cancer can spread to either the paraaortic area or pelvis causing ureteral obstruction. Between 1984 and 1996, 17 patients with gastric cancer were proven to have obstructive uropathy (OU). Of these, 12 (70%) had poorly differentiated adenocarcinomas. The obstructed levels were at the proximal ureter (7 cases), distal ureter (7 cases), and at multiple sites in the ureter (3 cases). The mucosa of the ureter tended to be spared. In 3 cases, OU was the initial presentation. Peritoneal carcinomatosis was noted in all cases. Most cases demonstrated obvious paraaortic lymph node and/or pelvic metastases. Management of ureteral obstruction included percutaneous nephrostomy (PCN) in 8 cases, and cystoscopic placement of a ureteral stent in 9 cases with double-J stents used in 8. Insertion of the double-J stent failed in 1 case initially. Four cases using double-J stents resulted in occlusion within 1 month, of which 3 subsequently were successfully changed to PCN. Gastric cancer with OU can obstruct the ureter at any level. Double-J stents exhibited a high failure rate in these patients necessitating a switch to PCN. We could also choose PCN as the initial procedure to preserve renal function.


Comparative Evaluation of Longevity of Fluoride Release From three Different Fluoride Varnishes - An Invitro Study.
Fluoride varnishes play a pivotal role in inhibition of dental caries by increasing remineralization. To determine the longevity of fluoride release from 3 different fluoride varnishes over a period of time through salivary fluoride estimation. Twenty four extracted human deciduous anterior teeth were divided into four groups, i.e., ClinproTM XT, Flouritop SR, Flourprotector and Control group. Fluoride varnishes were applied on 3mm x 3mm window on labial surface of the teeth and then the teeth were immersed and stored in artificial saliva. The concentration of fluoride in ppm was measured after 1 week, 1 month, 3 months and 6 months. Fluoride release at each time interval for different groups was statistically analyzed using ANOVA and Post Hoc Tukey's test. Although all the fluoride varnishes released fluoride, with greatest release observed during 1(st) week by Fluoritop SR (66.92±16.30ppm), ClinproTM XT Varnish released consistently and substantially more fluoride than Fluoritop SR and Fluorprotector during 6 months analysis (p<0.05). Fluorprotector showed the lowest rate of F release among all the groups compared. Over a period of 6 months ClinproTM XT Varnish released consistently and substantially more fluoride than other tested products.


Modification of the N-terminus of human factor IX by defective propeptide cleavage or acetylation results in a destabilized calcium-induced conformation: effects on phospholipid binding and activation by factor XIa.
The propeptide of human coagulation factor IX (FIX) directs the gamma-carboxylation of the first 12 glutamic acid residues of the mature protein into gamma-carboxyglutamic acid (Gla) residues. The propeptide is normally removed before secretion of FIX into the blood. However, mutation of Arg-4 in the propeptide abolishes propeptide cleavage and results in circulating profactor IX in the blood. We studied three such genetic variants, factor IX Boxtel (Arg-4-->Trp), factor IX Bendorf (Arg-4-->Leu) and factor IX Seattle C (Arg-4-->Gln). These variant profactor IX molecules bind normally to anti-FIX:Mg(II) antibodies, which indicates that the mutations do not seriously affect gamma-carboxylation. Metal ion titration of the binding of variant profactor IX to conformation-specific antibodies demonstrates that the calcium-induced conformation is destabilized in the variant molecules. Also the binding of FIX Boxtel to phospholipids and its activation by factor XIa requires a high (>5 mM) calcium concentration. The three-dimensional structure of the Gla domain of FIX in the presence of calcium indicates that the acylation of the amino-terminus, rather than the presence of the propeptide, was responsible for the destabilization of the calcium-induced conformation. In order to confirm this, the alpha-amino group of Tyr1 of FIX was acetylated. This chemically modified FIX showed a similar destabilization of the calcium-induced conformation to variant profactor IX. Our data imply that the amino-terminus of FIX plays an important role in stabilizing the calcium-induced conformation of the Gla domain of FIX. This conformation is important for the binding to phospholipids as well as for the activation by factor XIa. Our results indicate that mutations in FIX that interfere with propeptide cleavage affect the function of the protein mainly by destabilizing the calcium-induced conformation.


Importance of phosphatidylethanolamine for association of protein kinase C and other cytoplasmic proteins with membranes.
Biological membranes exhibit an asymmetric distribution of phospholipids. Phosphatidylserine (PS) is an acidic phospholipid that is found almost entirely on the interior of the cell where it is important for interaction with many cellular components. A less well understood phenomenon is the asymmetry of the neutral phospholipids, where phosphatidylcholine (PC) is located primarily on exterior membranes while phosphatidylethanolamine (PE) is located primarily on interior membranes. The effect of these neutral phospholipids on protein-phospholipid associations was examined using four cytoplasmic proteins that bind to membranes in a calcium-dependent manner. With membranes containing PS at a charge density characteristic of cytosolic membranes, protein kinase C and three other proteins with molecular masses of 64, 32, and 22 kDa all showed great selectively for membranes containing PE rather than PC as the neutral phospholipid; the calcium requirements for membrane-protein association of the 64- and 32-kDa proteins were about 10-fold lower with membranes containing PE; binding of the 22-kDa protein to membranes required the presence of PE and could not even be detected with membranes containing PC. Variation of the PS/PE ratio showed that membranes containing about 20% PS/60% PE provided optimum conditions for binding and were as effective as membranes composed of 100% PS. Thus, PE, as a phospholipid matrix, eliminated the need for membranes with high charge density and/or reduced the calcium concentrations needed for protein-membrane association. A surprising result was that PKC and the 64- and 32-kDa proteins were capable of binding to neutral membranes composed entirely of PE/PC or PC only. The different phospholipid headgroups altered only the calcium required for membrane-protein association. For example, calcium concentrations at the midpoint for association of the 64-kDa protein with membranes containing PS, PE/PC, or PC occurred at 6, 100, and 20,000 microM, respectively. Thus, biological probes detected major differences in the surface properties of membranes containing PE versus PC, despite the fact that both of these neutral phospholipids are often thought to provide "inert" matrices for the acidic phospholipids. The selectivity for membranes containing PE could be a general phenomenon that is applicable to many cytoplasmic proteins. The present study suggested that the strategic location of PE on the interior of the membranes may be necessary to allow some membrane-protein associations to occur at physiological levels of calcium and PS.


Pheophorbide A and Paclitaxel Bioresponsive Nanoparticles as Double-Punch Platform for Cancer Therapy.
Cancer therapy is still a challenging issue. To address this, the combination of anticancer drugs with other therapeutic modalities, such as light-triggered therapies, has emerged as a promising approach, primarily when both active ingredients are provided within a single nanosystem. Herein, we describe the unprecedented preparation of tumor microenvironment (TME) responsive nanoparticles exclusively composed of a paclitaxel (PTX) prodrug and the photosensitizer pheophorbide A (PheoA), e.g., PheoA≅PTX2S. This system aimed to achieve both the TME-triggered and controlled release of PTX and the synergistic/additive effect by PheoA-mediated photodynamic therapy. PheoA≅PTX2S were produced in a simple one-pot process, exhibiting excellent reproducibility, stability, and the ability to load up to 100% PTX and 40% of PheoA. Exposure of PheoA≅PTX2S nanoparticles to TME-mimicked environment provided fast disassembly compared to normal conditions, leading to PTX and PheoA release and consequently elevated cytotoxicity. Our data indicate that PheoA incorporation into nanoparticles prevents its aggregation, thus providing a greater extent of ROS and singlet oxygen production. Importantly, in SK-OV-3 cells, PheoA≅PTX2S allowed a 30-fold PTX dose reduction and a 3-fold dose reduction of PheoA. Our data confirm that prodrug-based nanocarriers represent valuable and sustainable drug delivery systems, possibly reducing toxicity and expediting preclinical and clinical translation.


Plasmonic multimode waveguides with transversely structured core.
We analyze the propagation of surface plasmons in metallic multimode waveguides that consist of alternating stripes of different metals in the transverse direction and that are homogeneous in the longitudinal direction. The purpose of structuring the waveguide in the transverse direction is to take advantage of the different attenuation and propagation constants for different metals. Here, in particular, alternating stripes of Ag and Au are considered. This allows one to influence the modal spectrum. We consider two different, well-defined waveguide configurations. For these, the propagating plasmonic modes are calculated. Based on the numerical simulations, we discuss the attenuation and propagation behavior and show the resulting eigenmodes for different values of the structural parameters, i.e., widths and thicknesses.


Continuous chest compression resuscitation in arrested swine with upper airway inspiratory obstruction.
This study was designed to compare 24-h survival rates and neurological function of swine in cardiac arrest treated with one of three forms of simulated basic life support CPR. Thirty swine were randomized equally among three experimental groups to receive either 30:2 CPR with an unobstructed endotracheal tube (ET) or continuous chest compression (CCC) CPR with an unobstructed ET or CCC CPR with a collapsable rubber sleeve on the ET allowing air outflow but completely restricting air inflow. The swine were anesthetized but not paralyzed. Two min of untreated VF was followed by 9 min of simulated single rescuer bystander CPR. In the 30:2 CPR group, each set of 30 chest compressions was followed by a 15-s pause to simulate the realistic duration of interrupted chest compressions required for a single rescuer to deliver 2 mouth-to-mouth ventilations. The other two groups were provided continuous chest compressions (CCC) without assisted ventilations. At 11 min post-arrest a biphasic defibrillation shock (150 J) was administered followed by a period of advanced cardiac life support. In the 30:2 group, 8 of 10 animals had good neurological function at 24-h post-resuscitation. In the CCC open airway group, 10 of 10, and in the CCC inspiratory obstructed group, 9 of 10. The number of shocks (P<0.05) and epinephrine doses (P<0.05) required for ROSC was greater in the 30:2 CPR group than in the other two groups. There were no differences in 24-h survival with good neurological function among these three different CPR protocols.


[Possible approach to evaluating the energy potential of mitochondria in morphological studies].
Based on histoenzymatic, cytospectrophotometric, electron microscopy and stereometric studies of the activity of mitochondrial enzymes and mitochondrial areas the authors developed integral indicators of the mitochondrial energy potential. The indicators permit forming a more concrete and complete judgement about the structural and functional status of the mitochondria and cell on the whole as well as about the contribution to the maintenance of intracellular homeostasis of individual substrates and components of redox processes, which widens the diagnostic and prognostic potentialities of the morphological and cytological assay.


The experience of cognitive behavioural therapy in depressed adolescents who are fatigued.
Fatigue is a common and debilitating symptom of major depressive disorder (MDD). Cognitive behavioural therapy (CBT) is a recommended psychological treatment for adolescents with moderate to severe depression. This study explored the experience of CBT in fatigued adolescents with MDD. A qualitative study was conducted using existing data from the qualitative arm of a large randomized control trial, the IMPACT study. Data were obtained from semi-structured interviews conducted after therapy. Participants were 18 adolescents (aged 13-18 years) who reached the clinical threshold for fatigue on diagnostic assessment before starting treatment. The data were analysed using thematic framework analysis. Three themes and seven sub-themes were developed. Adolescents appeared to find taking part in initial sessions, engaging in ongoing sessions and completing homework challenging. Perceiving the therapist as genuine seemed to provide a sense of safety which enabled adolescents to open up in sessions. When the therapist was not perceived as genuine, adolescents appeared to find CBT less helpful. The structure of CBT appeared to enable treatment goals to be set, and facilitated an increase in meaningful activity. Ensuring that tasks were perceived as manageable and goals as achievable seemed important for participation. Cognitive restructuring appeared useful, although some adolescents tended to engage in distraction from thoughts as an alternative strategy. This study provides an initial insight into how fatigued adolescents with MDD experience CBT. Further research is required to establish whether the themes are pervasive and relatedly, how best to treat depression in fatigued adolescents receiving CBT. Fatigued adolescents with depression found engaging in CBT sessions and therapeutic homework demanding. Establishing a collaborative therapeutic relationship, where the therapist was perceived as genuine, appeared helpful for participation. The structured approach to therapy, combined with flexibility, was experienced as helpful. Adolescents who perceived the pace of sessions to be manageable and therapeutic goals as achievable seemed to find CBT helpful overall. These findings provide insight into how fatigued adolescents with depression experience CBT and highlight the importance of being aware of fatigue and adapting therapy accordingly.


Exercise and Cancer-related Fatigue.
Cancer-related fatigue is the most common side effect reported by cancer patients during and after treatment. Cancer-related fatigue significantly interferes with a patient's ability to perform activities of daily living and maintain functional independence and quality of life. Cancer-related fatigue can also interfere with a patient's ability to complete treatments. The purpose of this article is to provide an overview of cancer-related fatigue, its pathopsychophysiology, and the role of exercise in the management of this side effect.


Identification, molecular cloning, and analysis of full-length hepatitis C virus transmitted/founder genotypes 1, 3, and 4.
Hepatitis C virus (HCV) infection is characterized by persistent replication of a complex mixture of viruses termed a "quasispecies." Transmission is generally associated with a stringent population bottleneck characterized by infection by limited numbers of "transmitted/founder" (T/F) viruses. Characterization of T/F genomes of human immunodeficiency virus type 1 (HIV-1) has been integral to studies of transmission, immunopathogenesis, and vaccine development. Here, we describe the identification of complete T/F genomes of HCV by single-genome sequencing of plasma viral RNA from acutely infected subjects. A total of 2,739 single-genome-derived amplicons comprising 10,966,507 bp from 18 acute-phase and 11 chronically infected subjects were analyzed. Acute-phase sequences diversified essentially randomly, except for the poly(U/UC) tract, which was subject to polymerase slippage. Fourteen acute-phase subjects were productively infected by more than one genetically distinct virus, permitting assessment of recombination between replicating genomes. No evidence of recombination was found among 1,589 sequences analyzed. Envelope sequences of T/F genomes lacked transmission signatures that could distinguish them from chronic infection viruses. Among chronically infected subjects, higher nucleotide substitution rates were observed in the poly(U/UC) tract than in envelope hypervariable region 1. Fourteen full-length molecular clones with variable poly(U/UC) sequences corresponding to seven genotype 1a, 1b, 3a, and 4a T/F viruses were generated. Like most unadapted HCV clones, T/F genomes did not replicate efficiently in Huh 7.5 cells, indicating that additional cellular factors or viral adaptations are necessary for in vitro replication. Full-length T/F HCV genomes and their progeny provide unique insights into virus transmission, virus evolution, and virus-host interactions associated with immunopathogenesis. Hepatitis C virus (HCV) infects 2% to 3% of the world's population and exhibits extraordinary genetic diversity. This diversity is mirrored by HIV-1, where characterization of transmitted/founder (T/F) genomes has been instrumental in studies of virus transmission, immunopathogenesis, and vaccine development. Here, we show that despite major differences in genome organization, replication strategy, and natural history, HCV (like HIV-1) diversifies essentially randomly early in infection, and as a consequence, sequences of actual T/F viruses can be identified. This allowed us to capture by molecular cloning the full-length HCV genomes that are responsible for infecting the first hepatocytes and eliciting the initial immune responses, weeks before these events could be directly analyzed in human subjects. These findings represent an enabling experimental strategy, not only for HCV and HIV-1 research, but also for other RNA viruses of medical importance, including West Nile, chikungunya, dengue, Venezuelan encephalitis, and Ebola viruses.


Effectiveness of arbuscular mycorrhizal fungi in phytoremediation of lead- contaminated soil by vetiver grass.
A greenhouse experiment was conducted to evaluate the effectiveness of arbuscular mycorrhizal (AM) fungi in phytoremediation of lead (Pb)-contaminated soil by vetiver grass. Experiment was a factorial arranged in a completely randomized design. Factors included four Pb levels (50, 200, 400, and 800 mg kg(-1)) as Pb (NO3)2, AM fungi at three levels (non mycorrhizal (NM) control, Rhizophagus intraradices, Glomus versiforme). Shoot and root dry weights (SDW and RDW) decreased as Pb levels increased. Mycorrhizal inoculation increased SDW and RDW compared to NM control. With mycorrhizal inoculation and increasing Pb levels, Pb uptake of shoot and root increased compared to those of NM control. Root colonization increased with mycorrhizal inoculation but decreased as Pb levels increased. Phosphorus concentration and uptake in shoot of plants inoculated with AM fungi was significantly higher than NM control at 200 and 800 mg Pb kg(-1). The Fe concentration, Fe and Mn uptake of shoot in plants inoculated with Rhizophagus intraradices in all levels of Pb were significantly higher than NM control. Mycorrhizal inoculation increased Pb extraction, uptake and translocation efficiencies. Lead translocation factor decreased as Pb levels increased; however inoculation with AM fungi increased Pb translocation.


Approaches for peptide and protein cyclisation.
The cyclisation of polypeptides can play a crucial role in exerting biological functions, maintaining stability under harsh conditions and conferring proteolytic resistance, as demonstrated both in nature and in the laboratory. To date, various approaches have been reported for polypeptide cyclisation. These approaches range from the direct linkage of N- and C- termini to the connection of amino acid side chains, which can be applied both in reaction vessels and in living systems. In this review, we categorise the cyclisation approaches into chemical methods (e.g. direct backbone cyclisation, native chemical ligation, aldehyde-based ligations, bioorthogonal reactions, disulphide formation), enzymatic methods (e.g. subtiligase variants, sortases, asparaginyl endopeptidases, transglutaminases, non-ribosomal peptide synthetases) and protein tags (e.g. inteins, engineered protein domains for isopeptide bond formation). The features of each approach and the considerations for selecting an appropriate method of cyclisation are discussed.


Hippocampal atrophy and disconnection in incipient and mild Alzheimer's disease.
Quantitative imaging techniques allow the in vivo investigation of age and disease related changes in the brain and their relation to cognitive function. In this chapter we review imaging evidence indicating that the entorhinal cortex and hippocampus show atrophy very early in Alzheimer's disease (AD) and in individuals who are at risk of developing AD compared to age appropriate controls. Furthermore, the extent and rate of atrophy of the entorhinal cortex, a brain region pathologically involved very early in the disease process, can predict who among the elderly will develop AD. Techniques that assess the integrity of white matter further demonstrate that alterations in the parahippocampal white matter in the region that includes the perforant path could partially disconnect the dentate gyrus and other hippocampal subfields from incoming sensory information. Such partial disconnection and degradation in transmission of sensory information in people at risk of AD and in patients with very mild AD could contribute to the memory dysfunction associated with the early stages of the disease.


Peyer's patches are required for oral tolerance to proteins.
To clarify the role of Peyer's patches in oral tolerance induction, BALB/c mice were treated in utero with lymphotoxin beta-receptor Ig fusion protein to generate mice lacking Peyer's patches. When these Peyer's patch-null mice were fed 25 mg of ovalbumin (OVA) before systemic immunization, OVA-specific IgG Ab responses in serum and spleen were seen, in marked contrast to low responses in OVA-fed normal mice. Further, high T-cell-proliferative- and delayed-type hypersensitivity responses were seen in Peyer's patch-null mice given oral OVA before systemic challenge. Higher levels of CD4(+) T-cell-derived IFN-gamma, IL-4, IL-5, and IL-10 syntheses were noted in Peyer's patch-null mice fed OVA, whereas OVA-fed normal mice had suppressed cytokine levels. In contrast, oral administration of trinitrobenzene sulfonic acid (TNBS) to Peyer's patch-null mice resulted in reduced TNBS-specific serum Abs and splenic B cell antitrinitrophenyl Ab-forming cell responses after skin painting with picryl chloride. Further, when delayed-type hypersensitivity and splenic T cell proliferative responses were examined, Peyer's patch-null mice fed TNBS were unresponsive to hapten. Peyer's patch-null mice fed trinitrophenyl-OVA failed to induce systemic unresponsiveness to hapten or protein. These findings show that organized Peyer's patches are required for oral tolerance to proteins, whereas haptens elicit systemic unresponsiveness via the intestinal epithelial cell barrier.


Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP.
In most conditions, glucose is the best carbon source for E. coli: it provides faster growth than other sugars, and is consumed first in sugar mixtures. Here we identify conditions in which E. coli strains grow slower on glucose than on other sugars, namely when a single amino acid (arginine, glutamate, or proline) is the sole nitrogen source. In sugar mixtures with these nitrogen sources, E. coli still consumes glucose first, but grows faster rather than slower after exhausting glucose, generating a reversed diauxic shift. We trace this counterintuitive behavior to a metabolic imbalance: levels of TCA-cycle metabolites including α-ketoglutarate are high, and levels of the key regulatory molecule cAMP are low. Growth rates were increased by experimentally increasing cAMP levels, either by adding external cAMP, by genetically perturbing the cAMP circuit or by inhibition of glucose uptake. Thus, the cAMP control circuitry seems to have a 'bug' that leads to slow growth under what may be an environmentally rare condition.


New insights on the electronic and molecular structure of cyanide-ligated iron(III) porphyrinates.
The preparation and characterization of several new cyano-ligated six-coordinate low-spin iron(III) porphyrinates are reported. The synthesis and structure of the new bis(cyanide) derivative K(222)][Fe(TMP)(CN)2] (TMP = tetramesitylporphyrinate) is described. Three mixed-ligand species of the general form [Fe(Porph)(CN)(L)], where L = 1-methylimidazole or pyridine, have also been prepared and structurally characterized. All complexes have been studied with EPR spectroscopy in frozen solution and in microcrystalline form. In some cases, especially those of the bis(cyanide) derivative above and the previously reported [Fe(TPP)(CN)2](-), there are significant differences in the EPR spectra as a result of the state change. These spectral differences can be correlated with changes in the electron configuration that are the likely result of a differing environment of the coordinated cyanide ligands; the core conformation and electronic structure of the porphyrin ligand are unlikely to play a role. All four new complexes and [Fe(TPP)(CN)2](-) have been studied by Mössbauer spectroscopy with variable-temperature and applied magnetic-field measurements. The sign of the quadrupole splitting value has been established as negative. These measurements have allowed us to give estimates of the energy difference between the two close-lying dpi (dxz and dyz) orbitals. These splitting values range from approximately 267 cm-1 for [Fe(TPP)(CN)2](-) to approximately 614 cm(-1) for [Fe(TPP)(CN)(Py)].


Case Report: Primary dural based diffuse large B-Cell lymphoma in a 14 year-old boy.
Primary dural lymphoma is a subentity of primary leptomeningeal lymphoma which represents 0.1% of all non-Hodgkin's lymphomas. Only five cases have been reported so far. We report a very rare case of primary dural-based lymphoma in a 14 year-old boy presenting with mass effect. The patient was managed with excision of the lesion and removal of the involved bone. Post-operatively, the patient showed good recovery. He was then referred to the oncology unit for further chemo- and radiation therapy. A high index of suspicion should therefore be kept in order to diagnose the condition in a timely fashion and then plan for appropriate management since diffuse large cell lymphoma has a relatively benign clinical prognosis.


Extemporaneously compounded sterile medications: relevance of new United States pharmacopeial standards to pain clinicians.
The United States Pharmacopeia (USP) is the United States' congressionally authorized book of standards for pharmaceutical manufacturing in the United States. The most current edition of the USP includes a new chapter entitled Pharmaceutical Compounding-Sterile Preparations that sets standards for all health care professionals who prepare, store or dispense sterile preparations. Extemporaneously compounded sterile formulations are sometimes needed for symptom control in pain and palliative practice. The implications and relevance of this new USP chapter to pain and palliative care clinicians-and the importance of all clinicians understanding the implications of how their patient's compounded sterile products are prepared-are discussed.


A multicultural perspective on conducting palliative care research in an Indian population in Australia.
Australia's population is culturally and linguistically diverse, with approximately one quarter of the population born overseas (Australian Bureau of Statistics, 2005). Health-care research must be culturally sensitive and due consideration given to the unique ethical, cultural, and other issues that may arise. Issues in palliative care research have become more complex as the options of care at the end of life develop in respect to the requirements of different cultures. This paper highlights the issues that arose when conducting a qualitative study of the needs and experiences of Indian families with a relative requiring palliative care, and also proposes strategies to address the ethical and methodological problems that may arise when researching this vulnerable population.


Proteinaceous alpha-amylase inhibitors.
Proteins that inhibit alpha-amylases have been isolated from plants and microorganisms. These inhibitors can have natural roles in the control of endogenous alpha-amylase activity or in defence against pathogens and pests; certain inhibitors are reported to be antinutritional factors. The alpha-amylase inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha-amylases in complex with inhibitors from five families. These structures indicate major diversity but also some similarity in the structural basis of alpha-amylase inhibition. Mutational analysis of the mechanism of inhibition was performed in a few cases and various protein engineering and biotechnological approaches have been outlined for exploitation of the inhibitory function.


Morphometric and mechanical properties of femora in young adult male turkeys with and without femoral fractures.
Morphologic and torsional mechanical properties of femora were evaluated in three groups of turkeys to determine whether turkeys that incurred femoral fracture have different radiographic, morphologic, and torsional mechanical properties than do turkeys without femoral fracture, and if body weight was a factor differentiating affected and nonaffected turkeys. Nine turkeys with unilateral femoral fractures and nine turkeys without fractures from Farm A were compared with a group of nine age and genetically matched turkeys from Farm B. Turkeys from Farm A were 10 to 25% heavier (26.2+/-0.9 kg) and turkeys from Farm B were 10% lighter (18.2+/-0.9 kg) than expected breed standards. Femoral length, cortical thickness, medullary diameter, and diaphyseal curvature were measured from craniocaudal and lateromedial radiographs. One intact femur from each of five turkeys with a contralateral femoral fracture (Farm A), nine unaffected turkeys from Farm A, and nine turkeys from Farm B were subjected to failure in a torsion test. Geometric and mechanical results were compared. Turkeys from Farm A had a thicker cortex and a smaller medullary diameter than turkeys from Farm B. Turkeys from Farm A had significantly lower torsional stiffness and failure torque values compared with turkeys from Farm B, when differences in body weight were accounted for (analysis of covariance, P < 0.05). Mechanical failure torque calculated from geometric values suggests that organic or inorganic material arrangement and composition may be responsible, in part, for differences between groups. Femoral fractures may be associated with insufficient skeletal adaptation to heavy body weight.


Knowing and Naming: Phage Annotation and Nomenclature for Phage Therapy.
Bacteriophages, or phages, are viruses that infect bacteria shaping microbial communities and ecosystems. They have gained attention as potential agents against antibiotic resistance. In phage therapy, lytic phages are preferred for their bacteria killing ability, while temperate phages, which can transfer antibiotic resistance or toxin genes, are avoided. Selection relies on plaque morphology and genome sequencing. This review outlines annotating genomes, identifying critical genomic features, and assigning functional labels to protein-coding sequences. These annotations prevent the transfer of unwanted genes, such as antimicrobial resistance or toxin genes, during phage therapy. Additionally, it covers International Committee on Taxonomy of Viruses (ICTV)-an established phage nomenclature system for simplified classification and communication. Accurate phage genome annotation and nomenclature provide insights into phage-host interactions, replication strategies, and evolution, accelerating our understanding of the diversity and evolution of phages and facilitating the development of phage-based therapies.


Gravitational-Wave Luminosity of Binary Neutron Stars Mergers.
We study the gravitational-wave peak luminosity and radiated energy of quasicircular neutron star mergers using a large sample of numerical relativity simulations with different binary parameters and input physics. The peak luminosity for all the binaries can be described in terms of the mass ratio and of the leading-order post-Newtonian tidal parameter solely. The mergers resulting in a prompt collapse to black hole have the largest peak luminosities. However, the largest amount of energy per unit mass is radiated by mergers that produce a hypermassive neutron star or a massive neutron star remnant. We quantify the gravitational-wave luminosity of binary neutron star merger events, and set upper limits on the radiated energy and the remnant angular momentum from these events. We find that there is an empirical universal relation connecting the total gravitational radiation and the angular momentum of the remnant. Our results constrain the final spin of the remnant black hole and also indicate that stable neutron star remnant forms with super-Keplerian angular momentum.


Diffusivity and weak clustering in a quasi-two-dimensional granular gas.
We present results from a detailed simulation of a quasi-two-dimensional dissipative granular gas, kept in a noncondensed steady state via vertical shaking over a rough substrate. This gas shows a weak power-law decay in the tails of its pair distribution functions, indicating clustering. This clustering depends monotonically on the dissipation coefficient and disappears when the sphere-sphere collisions are conservative. Clustering is also sensitive to the packing fraction. This gas also displays the standard nonequilibrium characteristics of similar systems, including non-Maxwellian velocity distributions. The diffusion coefficients are calculated over all the conditions of the simulations, and it is found that diluted gases are more diffusive for smaller restitution coefficients.


Neuroimaging measures as endophenotypes in Alzheimer's disease.
Late onset Alzheimer's disease (AD) is moderately to highly heritable. Apolipoprotein E allele ε4 (APOE4) has been replicated consistently as an AD risk factor over many studies, and recently confirmed variants in other genes such as CLU, CR1, and PICALM each increase the lifetime risk of AD. However, much of the heritability of AD remains unexplained. AD is a complex disease that is diagnosed largely through neuropsychological testing, though neuroimaging measures may be more sensitive for detecting the incipient disease stages. Difficulties in early diagnosis and variable environmental contributions to the disease can obscure genetic relationships in traditional case-control genetic studies. Neuroimaging measures may be used as endophenotypes for AD, offering a reliable, objective tool to search for possible genetic risk factors. Imaging measures might also clarify the specific mechanisms by which proposed risk factors influence the brain.


Central venous catheter placement in hemodialysis: evaluation of electrocardiography using a guide-wire.
Internal jugular vein cannulation has become a routine and clinically important aspect of medical care in hemodialysis patients. Mismanagement in the location of a central venous catheter may occur in up to 20% of cases. The aim of the study was to evaluate the utility of endocavitary electrocardiography in right internal jugu-lar vein placement of central venous catheters. We examined 327 central venous catheterizations performed in two Dialysis Units; all catheters were positioned using intra-atrial ECG monitoring by guide-wire and after, by catheter filled with NaCl solution. EC-ECG via guide-wire was successful on 321 occasions (98.1%). Correct placement of the catheter was confirmed by EC-ECG via catheter in each case, and by plain chest-X-ray only in the first hundred cases. In 314 patients (98.1%), insertion of the catheter was successful at the first attempt. In 6 catheterizations, no atrial trace was obtained due to atrial fibrillation in 4 cases, and in 2 cases technical error and guide-wire looping into a right jugular vein. Complications as a direct result of guide-wire or catheter placement were not observed. In our opinion this method can be used safely and makes radiological control usually unnecessary. (The Journal of Vascular Access 2001; 2: 45-50).


[HIV-2 infection in the world. A geographical perspective].
The geographical distribution of HIV-2 is not fully understood. However, there is enough evidence to speculate about the origins and differentiation of this geographical pattern. Foci of infection probably developed in some African countries, such as Guinea-Bissau, Angola and Mozambique, in the 1970s. The decolonization of these countries led to the movement of people, and the virus, to historically associated countries such as Portugal, India and Brazil. In Ivory Coast, a focus was probably created due to the dismantling of the plantation economy, with all its demographic, cultural and social consequences. The virus was dispersed to countries close to the Guinea and Ivory Coast foci by the migration of workers and prostitutes. Thus, the diseases has spread from the Atlantic coast of Africa, where it was endemic-sporadic, to other more distant African countries and out of Africa into Europe and North America. The political emancipation of African countries is further increasing and diversifying human movements between countries. The infection has not created an epidemic, either within or outside Africa. This is due to the limited infectivity of the virus and the particular characteristics of the social and epidemiological system. The high-risk groups do not sustain an epidemic relay of the infection and subjects introducing the virus into new areas outside the African foci rarely set up a new autonomous circulation of the virus.


Suicidality among gambling helpline callers: A consideration of the role of financial stress and conflict.
High rates of suicidal ideation and attempts secondary to gambling are well established among those with gambling disorders. The present study explores potential risk factors for suicidal ideation and/attempt among a sample of help-line callers. Participants (N = 202) completed measures assessing demographics; gambling behavior; and financial, family/social, employment, substance use, and legal difficulties related to gambling. Bivariate analyses, logistic regression, and mediation analyses were used to explore relationship between predictors and risk of suicidal ideation and attempt. Female gender, gambling severity (including engagement in illegal behaviors), a history of mental health problems, financial problems, and conflict related to gambling were associated with current suicidality in this sample. Mediation analyses revealed that financial problems were associated with increased familial conflict, which was in turn associated with increased suicidality. Family and social conflict may be one important way in which financial problems confer risk for suicidality among problem gamblers. These results align with findings from the substance use disorder (SUD) literature and highlight one potential factor that may merit further assessment and/or intervention. Researchers and clinicians may want to consider the overall level of conflict a patient is experiencing when assessing suicide risk among individuals with gambling problems. Professionals may also want to consider the suitability of interventions to address conflict within the context of gambling treatment. (Am J Addict 2018;27:531-537).


Droperidol inhibits the effects of intravenous ketamine on central hemodynamics and myocardial oxygen consumption in patients with generalized atherosclerotic disease.
A 2-mg/kg dose of ketamine was administered intravenously to 16 patients with generalized atherosclerotic disease. Eight patients were given 200 mu/kg of droperidol intravenously 10 min before ketamine administration; eight patients not given droperidol served as controls. Central hemodynamics, coronary flow (thermodilution technique) and myocardial oxygen, lactate, hypoxanthine, and catecholamine balances were studied. In control patients, ketamine increased mean blood pressure by 42%, pulmonary capillary wedge pressure by 144%, mean right atrial pressure by 60%, heart rate by 15%, and systemic vascular resistance by 40% without changes in cardiac index, stroke volume index, or left ventricular stroke work index. These data indicate that cardiac performance did not increase in parallel with the rise in afterload. However, the 50% increase in myocardial oxygen demand was associated with a 48% increase in coronary blood flow without changes in coronary vascular resistance or myocardial oxygen extraction. Augmented sympathetic activity was manifested by 397% and 164% increases in plasma levels of epinephrine and norepinephrine, respectively. The hemodynamic and cardiometabolic effects of ketamine were abolished when patients were pretreated with droperidol. The increase in plasma epinephrine levels was likewise inhibited by droperidol; significantly lower plasma norepinephrine levels also were observed. These findings suggest that droperidol inhibits the cardiovascular effects of ketamine by a centrally mediated reduction in sympathetic activity and by peripheral alpha receptor blockade.


Bran tablets and diverticular disease.
Three treatments for patients with symptomatic diverticular disease were compared in a crossover trial. Neither a high-roughage diet (HRD) nor Normacol plus an antispasmodic were as effective as bran tablets, which produced a significant increase in daily stool weight and a decrease in the intestinal transit time. An abnormal rapid electrical rhythm in colonic smooth muscle was found initially in 80% of the patients, but the incidence was reduced by each treatment after one month; it was present in only 40% of patients after treatment with bran tablets. Only bran significantly reduced a high percentage motility to within normal limits. Bran proved to be the most effective treatment, not only in improving the symptoms in patients with diverticular disease but also in returning to normal the abnormal pathophysiological changes. Bran tablets were both convenient and acceptable as well as effective.


An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.
Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6 production by seminoma cells may be a practical target for early diagnosis and/or treatment of TGCT.


[The outcomes of chronic parenchymatous parotitis in children].
Time course of the process was examined in 16 patients with chronic parenchymatous parotitis. The follow-up started in children and was proceeded in adults, thus permitting an answer to the problem of parenchymatous parotitis outcome. Dynamic sialographic studies have shown that the process in the gland may develop in three directions, i.e. improvement, deterioration, or stabilization. Positive changes were the most manifest in the initial stage of the disease and not manifest in the late one. The authors' findings help predict the course of parotitis and outcome of the changes in the parotid gland in children.


Negative computed tomography can safely rule out clinically significant intra-abdominal injury in the asymptomatic patient after blunt trauma: Prospective evaluation of 1193 patients.
Computed tomography of the abdomen and pelvis (CTAP) is highly specific for injury identification and commonly used in the evaluation of blunt trauma patients. Despite this, there is no consensus on the required clinical observation period after negative imaging, often impacting patient flow and hospital cost. The purpose of this study was to evaluate the use of CTAP after blunt trauma and the need for observation after negative imaging. A prospective analysis at a large Level I trauma center was conducted from November 2014 to May 2015. All blunt trauma patients, older than 14 years with CTAP on admission were included. Symptomatic patients were defined as having abdominal pain or external signs of trauma on admission. The main outcome was missed injury. Over the study period, there were 1,468 blunt trauma admissions, of which 1,193 patients underwent CTAP. Eight hundred six (67.6%) patients were evaluable on admission (Glasgow Coma Scale score, 15), and of these, 327 (40.6%) were symptomatic, 479 (59.4%) asymptomatic. Among the evaluable asymptomatic patients, there were 65 (13.6%) positive computed tomography scans including 11 patients with grade III, IV, or V solid organ injury and three that required operation. In the 414 evaluable asymptomatic patients with negative imaging, median length of stay was 3 days, and there were zero missed injuries. All images were reviewed by an attending radiologist. Abdominal imaging after trauma is justified in the appropriate clinical setting to evaluate for significant abdominal injury regardless of symptomatology. In asymptomatic, evaluable patients with a negative CTAP, clinically significant abdominal injury is unlikely, and these patients may be considered for early discharge or disposition to another treatment service. Diagnostic, level III; Therapy, level IV.


Re-evaluation of websites from burn centers in Austria, Germany and Switzerland.
Websites serve as information and communication platforms; hence, they are important tools for the self-promotion of hospitals. In 2010, Selig et al. evaluated the online presence of burn centers in Germany, Austria, and Switzerland based on 37 quality criteria. This study aimed to re-evaluate these websites to assess their development over the past 6.5 years. Websites of the German-speaking burn centers were re-evaluated according to criteria previously described by Selig et al. Particular attention was paid to specific information on burns. Additionally, the implementation of social media platforms was investigated. There was an overall increase in the quality of information published on websites. There was a considerable improvement recorded, especially in the categories of "teaching" and "patient care." However, burn-specific information was found to be still sparse. Over 50% of the hospitals were present on social media. Although the quality of information published on German-speaking burn center websites increased, they must be further developed, especially regarding burn-related information. Moreover, a clear structure and design could prevent long searches and facilitate an easier flow of information. The interface from websites and social media platforms appear to be an important tool for up-to-date self-promotion.


What is the quality of economic evaluations of non-drug therapies? A systematic review and critical appraisal of economic evaluations of radiotherapy for cancer.
Breast, cervical and colorectal cancers are the three most frequent cancers in women, while lung, prostate and colorectal cancers are the most frequent in men. Much attention has been given to the economic evaluation of pharmaceuticals for treatment of cancer by the National Institute for Health and Care Excellence (NICE) in the UK and similar authorities internationally, while economic analysis developed for other types of anti-cancer interventions, including radiotherapy and surgery, are less common. Our objective was to review methods used in published cost-effectiveness studies evaluating radiotherapy for breast, cervical, colorectal, head and neck and prostate cancer, and to compare the economic evaluation methods applied with those defined in the guidelines used by the NICE technology appraisal programme. A systematic search of seven databases (MEDLINE, EMBASE, CDSR, NHSEED, HTA, DARE, EconLit) as well as research registers, the NICE website and conference proceedings was conducted in July 2012. Only economic evaluations of radiotherapy interventions in individuals diagnosed with cancer that included quality-adjusted life-years (QALYs) or life-years (LYs) were included. Included studies were appraised on the basis of satisfying essential, preferred and UK-specific methods requirements, building on the NICE Reference Case for economic evaluations and on other methods guidelines. A total of 29 studies satisfied the inclusion criteria (breast 14, colorectal 2, prostate 10, cervical 0, head and neck 3). Only two studies were conducted in the UK (13 in the USA). Among essential methods criteria, the main issue was that only three (10%) of the studies used clinical-effectiveness estimates identified through systematic review of the literature. Similarly, only eight (28%) studies sourced health-related quality-of-life data directly from patients with the condition of interest. Other essential criteria (e.g. clear description of comparators, patient group indication and appropriate time horizon) were generally fulfilled, while most of the UK-specific requirements were not met. Based on this review there is a dearth of up-to-date, robust evidence on the cost effectiveness of radiotherapy in cancer suitable to support decision making in the UK. Studies selected did not fully satisfy essential method standards currently recommended by NICE.


Pattern-Based Interactive Diagnosis of Multiple Disorders: The MEDAS System.
A knowledge-based interactive sequential diagnostic system is introduced which provides for diagnosis of multiple disorders in several body systems. The knowledge base consists of disorder patterns in a hierarchical structure that constitute the background medical information required for diagnosis in the domain under consideration (emergency and critical care medicine, in our case). Utilizing this knowledge base, the diagnostic process is driven by a multimembership classification algorithm for diagnostic assessment as well as for information acquisition [1]. A key characteristic of the system is congenial man-machine interface which comes to expression in, for instance, the flexibility it offers to the user in controlling its operation. At any stage of the diagnostic process the user may decide on an operation strategy that varies from full user control, through mixed initiative to full system control. Likewise, the system is capable of explaining to the user the reasoning process for its decisions. The model is independent of the knowledge base, thereby permitting continuous update of the knowledge base, as well as expansions to include disorders from other disciplines. The information structure lends itself to compact storage and provides for efflcient computation. Presently, the system contains 53 high-level disorders which are diagnosed by means of 587 medical findings.


Reliability of venous blood gas sodium, potassium and creatinine.
To determine the level of correlation between sodium, potassium and creatinine readings between point-of-care venous blood gas (VBG) and laboratory biochemistry measurements (LBM). Data was obtained from three Monash Health (one of the largest health networks in metropolitan Melbourne) emergency departments. 16,527 VBGs were matched with LBM for sodium, 16,437 for potassium and 8,597 for creatinine. Pearson correlation and further subgroup analyses were carried out to explore if acid-base imbalance affected sodium, potassium or creatinine reliability in VBG. The range of VBG values showed more variation in comparison to LBM. There was good correlation (r>0.8, p<0.001) between measured values with the exception of potassium in acidaemia, however, there was consistent and statistically significant difference in measured values. The small mean differences across all three parameters observed although statistically significant are unlikely to be clinically significant. With minor calibrations, this would be an easily corrected problem. As such, we recommend that sodium, potassium and creatinine measurements can be used interchangeably between the VBG and LBM, with the exception of potassium levels in acidaemia. Potassium levels in acidaemia should be used with caution due to lower correlation.