Toxoplasma gondii inclusions in peripheral blood leukocytes of a red-necked wallaby (Macropus rufogriseus).
A 2-year-old, male, red-necked (Bennett's) wallaby (Macropus rufogriseus) from a zoological facility was presented for peracute onset of severe depression, unresponsiveness, ataxia, and loose feces. Serum biochemical abnormalities included azotemia, hypoalbuminemia, increased alanine aminotransferase activity, hyperbilirubinemia, hyperphosphatemia, and hyperkalemia, consistent with multi-organ system failure. Severe thrombocytopenia suggested possible disseminated intravascular coagulation. Peripheral blood smear examination revealed numerous ovoid, protozoal inclusions within monocytes and occasionally within neutrophils. Despite aggressive supportive therapy, the patent died within 5 hours of presentation. Gross necropsy and histopathologic findings included severe multifocal necrotizing lesions in multiple organs. Numerous intralesional protozoal organisms were observed and were identified as Toxoplasma gondii by immunohistochemistry. Macropods (wallabies and kangaroos) are known to be highly susceptible to toxoplasmosis, with high mortality rates; diagnosis most often is obtained at necropsy. Detection of protozoal organisms in peripheral blood leukocytes is reported rarely and has not been documented previously in a macropod. Parasitemia in this case was attributed to severe, disseminated disease. Careful examination of peripheral blood smears in macropods suspected of toxoplasmosis may be warranted.


Predicting Site-Binding Modes of Ions and Water to Nucleic Acids Using Molecular Solvation Theory.
Site binding of ions and water shapes nucleic acids folding, dynamics, and biological function, complementing the more diffuse, nonspecific "territorial" ion binding. Unlike territorial binding, prediction of site-specific binding to nucleic acids remains an unsolved challenge in computational biophysics. This work presents a new toolset based on the 3D-RISM molecular solvation theory and topological analysis that predicts cation and water site binding to nucleic acids. 3D-RISM is shown to accurately capture alkali cations and water binding to the central channel, transversal loops, and grooves of the Oxytricha nova's telomeres' G-quadruplex ( Oxy-GQ), in agreement with high-resolution crystallographic data. To improve the computed cation occupancy along the Oxy-GQ central channel, it was necessary to refine and validate new cation-oxygen parameters using structural and thermodynamic data available for crown ethers and ion channels. This single set of parameters that describes both localized and delocalized binding to various biological systems is used to gain insight into cation occupancy along the Oxy-GQ channel under various salt conditions. The paper concludes with prospects for extending the method to predict divalent cation binding to nucleic acids. This work advances the forefront of theoretical methods able to provide predictive insight into ion atmosphere effects on nucleic acids function.


Female Sex, Bilateral Disease, Age Below 3 Years, and Apprehension for Enucleation Contribute to Treatment Abandonment in Retinoblastoma.
Treatment abandonment is a major obstacle for treating retinoblastoma in developing countries. The aim was to evaluate plausible causes, outcome, and rate of treatment abandonment in patients with retinoblastoma. The study was retrospective and conducted in a University hospital in North-India. Two cohorts of patients were studied. One was a larger cohort (n=602) of all patients with retinoblastoma in the institution from 2000 to 2014. Limited variables (age, sex, and laterality) were examined in this cohort due to incomplete data/lack of contact. A detailed interview was conducted with contactable caregivers in a smaller cohort (n=104). Noncompliance was observed in 170/602 (28%) patients. Patients below 3 years were more likely to be noncompliant (65.1%), compared with older patients (34.9%) (P=0.003). Compliance was greater among male individuals (64%) than in female individuals (36%) (P=0.017) and in those with unilateral disease (72%) compared with those who had bilateral disease (28%) (P=0.009). Apprehension for enucleation (64% vs. 8%, P=0.0001) and difficulty in attending outpatient services of different departments (61.4% vs. 13.3%, P=0.003) for multimodality treatment were expressed more frequently in the noncompliant than in the compliant group, respectively. The mortality in compliant and noncompliant patients was 7% and 68%, respectively (P=0.0001). The rate of treatment abandonment in 602 patients over a 15-year period was a sizable 28%. The factors contributing to noncompliance included female sex, bilateral disease, age below 3 years, apprehension for enucleation, and difficulty in attending outpatient services of different departments.


Spectral-reflectance reconstruction in the near-infrared region by use of conventional charge-coupled-device camera measurements.
Our aim is to develop a method for obtaining the reflectance spectra of samples in the near-infrared (NIR) region (800-1,000 nm) by using a small number of measurements performed with a conventional CCD camera (multispectral imaging). We experimentally determined the spectral sensitivity of the CCD camera in the NIR range, used a method based on principal component analysis to reconstruct the spectral reflectance of the samples, and analyzed the number and shape of the filters that need tobe used to apply this method. Finally we obtained the reflectance spectra of a set of 30 spectral curves by numerical simulation. The small amount of errors in the spectral reconstruction shows the potential of this method for reconstructing spectral reflectances in the NIR range.


Spatial scale of visual analysis for vernier acuity does not vary over time.
The visual system filters spatial pattern through a range of narrowly tuned spatial mechanisms, but the rules by which the outputs of these mechanisms are combined across time to extract precise geometrical information are not yet clear. One hypothesis is that spatial analysis shifts over time from coarse to finer spatial scales, in order to extract fine spatial information. An alternative hypothesis is that thresholds are determined by the signal-to-noise ratio within an optimal spatial scale. In this study, we measured vernier acuity across exposure duration for equally visible long lines and short lines and found no improvement in spatial precision with time. Using a simultaneous spatial-masking paradigm, we determined the active spatial scales at 100 and 1000 ms. The results show no significant changes in spatial scale, or in the size-range of active scales, for the two exposure durations. Furthermore, whereas vernier thresholds vary markedly with line contrast, we find only modest shifts in spatial scale. Taken together, our results suggest that for vernier acuity, spatial scale is selected very early, and that vernier thresholds are predominantly limited by signal strength within that spatial scale.


Monosomy for the most telomeric, gene-rich region of the short arm of human chromosome 16 causes minimal phenotypic effects.
We have examined the phenotypic effects of 21 independent deletions from the fully sequenced and annotated 356 kb telomeric region of the short arm of chromosome 16 (16p13.3). Fifteen genes contained within this region have been highly conserved throughout evolution and encode proteins involved in important housekeeping functions, synthesis of haemoglobin, signalling pathways and critical developmental pathways. Although a priori many of these genes would be considered candidates for critical haploinsufficient genes, none of the deletions within the 356 kb interval cause any discernible phenotype other than alpha thalassaemia whether inherited via the maternal or paternal line. These findings contrast with previous observations on patients with larger (> 1 Mb) deletions from the 16p telomere and therefore address the mechanisms by which monosomy gives rise to human genetic disease.


Individual genetic diversity and probability of infection by avian malaria parasites in blue tits (Cyanistes caeruleus).
Understanding the importance of host genetic diversity for coping with parasites and infectious diseases is a long-standing goal in evolutionary biology. Here, we study the association between probability of infection by avian malaria (Plasmodium relictum) and individual genetic diversity in three blue tit (Cyanistes caeruleus) populations that strongly differ in prevalence of this parasite. For this purpose, we screened avian malaria infections and genotyped 789 blue tits across 26 microsatellite markers. We used two different arrays of markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found a significant relationship between probability of infection and host genetic diversity estimated at the subset of neutral markers that was not explained by strong local effects and did not differ among the studied populations. This relationship was not linear, and probability of infection increased up to values of homozygosity by locus (HL) around 0.15, reached a plateau at values of HL from 0.15 to 0.40 and finally declined among a small proportion of highly homozygous individuals (HL > 0.4). We did not find evidence for significant identity disequilibrium, which may have resulted from a low variance of inbreeding in the study populations and/or the small power of our set of markers to detect it. A combination of subtle positive and negative local effects and/or a saturation threshold in the association between probability of infection and host genetic diversity in combination with increased resistance to parasites in highly homozygous individuals may explain the observed negative quadratic relationship. Overall, our study highlights that parasites play an important role in shaping host genetic variation and suggests that the use of large sets of neutral markers may be more appropriate for the study of heterozygosity-fitness correlations.


Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation.
Inflammation, caused by both external and endogenous factors, has been implicated as a main pathophysiological feature of chronic mental illnesses, including schizophrenia. An increase in pro-inflammatory cytokines has been described both in experimental models and in schizophrenia patients. However, not much is known about the effects that antipsychotic drugs have on intra- and intercellular mechanisms controlling inflammation. The aim of the present study was to investigate the possible anti-inflammatory effect of a standard schizophrenia treatment not only at the level of soluble mediators, but also at intra- and intercellular inflammatory pathways. The present study was conducted in a model of mild neuroinflammation using a lipopolysaccharide (LPS) challenge that was not an endotoxaemic dose (0.5 mg/kg i.p.) in young adult rats. single doses of risperidone (0.3-3.0 mg/kg i.p.) prevented increased inflammatory parameters induced by LPS in brain cortex [expression of inflammatory cytokines, interleukin (IL)-1β and tumour necrosis factor (TNF)-α, activity of the inducible inflammatory enzymes nitric oxide synthase and cyclooxygenase, p38 mitogen-activated protein kinase (MAPK) and inflammatory nuclear transcription factor κB] and restored anti-inflammatory pathways decreased by LPS challenge (deoxyprostaglandins and peroxisome proliferator activated receptor γ). This is the first study demonstrating that risperidone elicits a preventive effect on the anti-inflammatory arm of the homeostatic mechanism controlling inflammation in a model of mild encephalitis in rats. Our findings suggest a possible protective effect of risperidone on brain cells.


Paramedics' Newborn Life Support Knowledge and Skills Before and After a Targeted Simulation-Based Educational Intervention.
Objective: Resuscitation of neonates after birth in the out-of-hospital setting is challenging. Thus, we aimed to assess paramedics' newborn life support knowledge and skills before and after targeted simulation-based training. Methods: Voluntary paramedics were recruited from a single Red Cross division. During a 1-day simulation-based educational intervention, essential aspects of neonatal resuscitation were taught and practiced. Before and after simulation-based training, we assessed (1) knowledge of current European Resuscitation Council (ERC) guidelines using a 20-item-questionnaire and (2) the quality of simulated bag-valve-mask ventilation by measuring face mask leakage, using a respiratory function monitor (Standardized Measurement of Airway Resuscitation Training [SMART], GM Instruments Ltd., United Kingdom). Results: Forty-one paramedics participated in the initial survey and 12 took part in the simulation-based educational intervention. There was a significant increase in the number of correctly answered questions: median 62.1% (IQR 37.5-77.4%) vs. 91.7% (IQR 83.3-100%; p = 0.001). A total of 1,332 inflations were analyzed. The incidence of substantial mask leakage >75% decreased significantly after training (15.8 vs. 6.1%; p < 0.001), while median mask leakage was similar (17.0% [IQR 0.0-55.0%] vs. 18.0% [IQR 6.0-34.0%]; p = 0.414). Conclusions: Among paramedics, theoretical knowledge of current ERC guidelines was moderate in this study. Participation in a targeted simulation-based educational intervention was associated with a significant increase in theoretical knowledge. The initially high incidence of substantial mask leakage >75% was decreased after simulation-based training using respiratory function monitoring.


Case Report: Living on the Edge-Transcatheter Mitral Valve Repair Related Infective Endocarditis.
Background: Infective endocarditis (IE) following mitral valve edge-to-edge repair is a rare complication with high mortality. Case summary: A 91-year-old male patient was admitted to intensive care unit with sepsis due to urinary tract infection after insertion of a urinary catheter by the outpatient urologist. Two weeks ago, the patient was discharged from hospital after successful transcatheter edge-to-edge mitral valve repair (TEER) using a PASCAL Ace device. The initially withdrawn blood revealed repeatedly Proteus mirabilis bacteremia as causal for the sepsis due to urinary tract infection. An antibiotic regime with Ampicillin/Sulbactam was initiated and discontinued after 7 days. During the clinical course the patient again developed fever and blood cultures again revealed P. mirabilis. In transesophageal echocardiography (TOE), IE of the PASCAL Ace device was confirmed by a vegetation accompanied by a mild to moderate mitral regurgitation. While the patient was stable at this time and deemed not suitable for cardiac surgery, the endocarditis team made a decision toward a prolonged 6-week antibiotic regime with an antibiotic combination of Ampicillin 2 g qds and Ciprofloxacin 750 mg td. Due to posterior leaflet perforation severe mitral regurgitation developed while PASCAL Ace vegetations were significantly reduced by the antibiotic therapy. Therefore, the patient underwent successful endoscopic mitral valve replacement. Another 4 weeks of antibiotic treatment with Ampicillin 2 g qds followed before the patient was discharged. Discussion: P. mirabilis is able to form biofilms, resulting in a high risk for endocarditis following transcatheter mitral valve repair especially when device endothelization is incomplete. Endoscopic mitral valve replacement could serve as a bailout strategy in refractory Clip-endocarditis.


PCR and RT-PCR in the Diagnosis of Laboratory Animal Infections and in Health Monitoring.
Molecular diagnostics (PCR and RT-PCR) have become commonplace in laboratory animal research and diagnostics, augmenting or replacing serological and microbiologic methods. This overview will discuss the uses of molecular diagnostics in the diagnosis of pathogenic infections of laboratory animals and in monitoring the microbial status of laboratory animals and their environment. The article will focus primarily on laboratory rodents, although PCR can be used on samples from any laboratory animal species.


[Pleuroamniotic shunting--case report].
Fetal hydrothorax refers to a collection of fluid within the fetal thorax that may be the result of chylous leak from the thoracic duct (primary hydrothorax) or generalized fluid retention associated with immune or no immune fetal hydrops (secondary hydrothorax). The authors' presents a case report occurred in 2002, of a pregnant woman that at 25 weeks' gestation that was referred to Maternidade Bissaya-Barreto-Coimbra because of a fetal hydrothorax at left, under tension and with cardiac decompensation signs. A fetal thoracocentesis was performed and the diagnosis was chylothorax. Because of a rapid reaccumulation of fluid a pleuroamniotic shunt was placed. The effusion and the cardiac decompensation signs regressed. The delivery was at 38 weeks' gestation. The newborn had been stable. Actually he has 10 months, is healthy and has a normal grow and development.


Aripiprazole-induced liver injury: a spontaneous reporting database study.
Background: There have been individual case reports of aripiprazole in recent years, both domestically and internationally, but no analysis of the characteristics of the occurrence of adverse reactions/events of drug-induced liver injury with aripiprazole using spontaneous reports has been seen. Methods: Using a retrospective study approach, the 452 adverse reaction/event reports of aripiprazole-induced liver injury collected by the China Adverse Drug Reaction Monitoring System from 1 January 2012 to 31 December 2016 were analyzed and evaluated, and exploring it's the clinical characteristics and related risk factors for liver injury occurrence. Results: Among 452 cases of aripiprazole-induced liver injury ADR/ADE reports, there were 121 cases classified as serious, accounting for 26.8% of the total. There were 250 male and 202 female patients, with a male-to-female ratio of 1.24:1. The age of patients ranged from 11 to 77 years old, with an average age of (34.56 ± 12.81) years old, and a high proportion of young adults in the total population. Some patients had used the drug off-label or at a higher than recommended dosage. The onset of liver injury was generally within 15-90 days after continuous use, while some patients are also accompanied by nausea, vomiting, and weight gain. 70% of the combined drug instructions listed that may cause liver injury. Conclusion: In clinical practice, healthcare professionals should pay closely attention to the adverse reactions and risk factors of liver injury caused by aripiprazole. If there are potential risk factors for liver injury, early and regular monitoring of liver function should be carried out to reduce the occurrence of adverse reactions.


Comparative efficiency of Proproten-100 during the therapy of patients with alcoholism in the stage of therapeutic remission.
An open comparative clinical study evaluated the efficiency of Proproten-100 in reliving affective, somatovegetative, behavioral, and cognitive post-withdrawal disorders and manifestations of primary pathological alcohol addiction in patients with alcohol dependence in the stage of therapeutic remission. We compared the efficiency of Proproten-100 and standard symptomatic drugs. The preparation possessed anxiolytic, antidepressant, and vegetostabilizing properties, produced a moderate soporific effect, and had no sedative activity in patients with dysphoric depressions and psychopathic disorders. Proproten-100 was more effective during the therapy of patients with anxious and wistful depressions. Proproten-100 increased the contents of IgG and natural antibodies against S100 protein in the blood from patients. The preparation did not cause side effect or development of tolerance. Proproten-100 has psychotropic properties and holds much promise for long-term treatment of patients with alcohol dependence to reduce the incidence of recurrences.


Evidence for plical support of the patella.
There is a consensus that there is no overt anterior joint capsule in the knee. However, other anterior structures act in lieu of a joint capsule: the quadriceps tendon and patellar retinacular fibres. In the absence of a capsule, the synovium forms the suprapatellar pouch. Other synovial structures, the plicae, are more controversial. They are often described as embryonic remnants with no function, despite surrounding the patella. We aimed to identify plical anatomy and histology on cadaveric dissection and to examine their embryology using the human virtual embryo website. Plicae were identified by two independent observers. Plical histology was examined using a panel of stains: H&E, Ab H&E, EVG and MSB trichrome. Embryonic knees were examined from Carnegie stages 20-23. Each knee had a suprapatellar plica and mediopatellar plica (MPP). The lateropatellar plica (LPP) appeared as a band in 5/10 cadavers, and as a ridge in the remainder. The overall impression, consistent across all specimens, was that the plicae formed a continuous band of synovial tissue around the proximal three-quarters of the patella. The infrapatellar fat pad (IFP) surrounded the remainder. Histologically, the plicae and IFP consisted of three layers (in order): a synovial layer, an undulated collagenous layer, and an adipose or areoloadipose layer. The subsynovial collagenisation is normally associated with the synovio-capsular boundary. Embryologically, plicae were not seen in either knee at any level for any given Carnegie stage. We suggest that plicae, along with the dynamic IFP, provide internal support to the patella mirroring the external support of retinacular fibres. Thus, the plicae complete the tissue complex acting in lieu of an anterior joint capsule. Evidence of plical functionality lends credence to the theory that the plicae are anatomical structures not functionless embryonic remnants.


Solution structure of an A-tract DNA bend.
The solution structure of a DNA dodecamer d(GGCAAAAAACGG)/d(CCGTTTTTTGCC) containing an A-tract has been determined by NMR spectroscopy with residual dipolar couplings. The structure shows an overall helix axis bend of 19 degrees in a geometry consistent with solution and gel electrophoresis experiments. Fourteen degrees of the bending occurs in the GC regions flanking the A-tract. The remaining 5 degrees is spread evenly over its six AT base-pairs. The A-tract is characterized by decreasing minor groove width from the 5' to the 3' direction along the A strand. This is a result of propeller twist in the AT pairs and the increasing negative inclination of the adenine bases at the 3' side of the run of adenine bases. The four central thymine bases all have negative inclination throughout the A-tract with an average value of -6.1 degrees. Although this negative inclination makes the geometry of the A-tract different from all X-ray structures, the proton on N6 of adenine and the O4 of thymine one step down the helix are within distance to form bifurcated hydrogen bonds. The 5' bend of 4 degrees occurs at the junction between the GC flank and the A-tract through a combination of tilt and roll. The larger 3' bend, 10 degrees, occurs in two base steps: the first composed of tilt, -4.1 degrees, and the second a combination of tilt, -4.2 degrees, and roll, 6.0 degrees. This second step is a direct consequence of the change in inclination between an adjacent cytosine base, which has an inclination of -12 degrees, and the next base, a guanine, which has 3 degrees inclination. This bend is a combination of tilt and roll. The large change in inclination allows the formation of a hydrogen bond between the protons of N4 of the 3' cytosine and the O6 of the next 3' base, a guanine, stabilizing the roll component in the bend. These structural features differ from existing models for A-tract bends.For comparison, we also determined the structure of the control sequence, d(GGCAAGAAACGG)/d(CCGTTTCTTGCC), with an AT to GC transition in the center of the A-tract. This structure has no negative inclination in most of the bases within the A-tract, resulting in a bend of only 9 degrees. When ligated in phase, the control sequence has nearly normal mobility in gel electrophoresis experiments.


[Pituitary dwarfism in a German shepherd dog (author's transl)].
Pituitary dwarfism has been described in more than 20 German shepherd dogs. Some cases probably were caused by persistent cysts of Rathke's pouch. This is the first histopathological, immunohistochemical and endocrinological study. A 13-month-old, 7-kg, dwarf purebred German shepherd bitch with alopecia and hyperpigmentation was admitted to the clinic for euthanasia. Retardation of growth was noticed when the dog was about two months old. No littermates had this condition. Two subsequent breedings from the same parents produced normal offspring. The clinical parameters in our dog (hematology, function of liver and kidney) were normal. Grossly, the pituitary gland had small and large multiple cysts, which light microscopy showed to be exclusively within the adenohypophysis. The latter had pressure atrophy, and immunohistochemically showed only remnants of the hormone-producing cells (growth hormone-GH; prolactin-PRL; thyrotropin-TSH; luteinizing hormone-LH; adrenocorticotrophin-ACTH/MSH). The thyroid was relatively small, and histologically showed focally resting follicles without lumen. Endocrinological studies showed a surprisingly high value for serum growth hormone (cGH 4.1 ng/ml; normal range 1.8-3.8 ng/ml as determined by a specific homologous radioimmunoassay) and a pathologically low serum somatomedin (SM 0.132; normal value more than 0.50 unit/ml, determined by 35S incorporation in piglet rib cartilage). Hypothyroidism was verified by a low T4 binding value (T4 0.9 micrograms/100 ml; normal 4.1 +/- 0.9 micrograms/100 ml) and a low thyroid binding index (TBI 0.54; normal 0.61 +/- 0.05). While ACTH was lowered (ACTH less than 10 pg/ml; normal 74-210 pg/ml), cortisol was normal (0.81 micrograms/100 ml; normal 0.5-2.5 micrograms/100 ml). Pituitary dwarfism in the 13-month-old bitch can be ascribed to the persistence of one end of the ductus craniopharyngeus, Rathke's pouch. Pressure atrophy of the adenohypophysis led to the loss of most of the hormone-producing tissue. An increase in growth hormone with lowered somatomedin raises questions. We have no conclusive explanation for this, due to the present lack of knowledge of how growth is regulated. High growth hormone and low somatomedin values are found in Laron's syndrome in infants. The literature indicates that pituitary dwarfism in German shepherd dogs may be a hereditary autosomal recessive trait.


[Efficacy of a cardiac rehabilitation program in a municipal sports center compared to the hospital program: randomized controlled trial eCARCEX].
This study aimed to analyze the effects of an outpatient cardiac rehabilitation program in a municipal sports center on functional capacity and adherence to physical exercise - among other variables - compared to an in-hospital program. Randomized clinical trial that included two parallel groups of acute coronary syndrome patients who performed a cardiac rehabilitation program that consisted of moderate physical exercise intervals along with learning healthy habits in a municipal sports center (experimental group) and in a tertiary hospital (control group) between September 2019 and June 2020. We collected the following data: compliance, anthropometrical, clinical, psychological variables, diet and tobacco habits, strength and functional capacity from ergospirometry. Twenty-two patients completed the cardiac rehabilitation program (experimental group=12, control group=10). Significant improvement was observed for cholesterol, the sit-and-stand test, cardiac frequency in VT1 and VT2, and watts in VT1 in the control group, and for HDL-cholesterol, triglycerides, the sit-and-stand test, and frequency, and watts in VT1 in the experimental group. Better achievement was found in the control group for cardiac frequency in VT2 (11.17 vs 2.88 bpm) and in EG for HDL-cholesterol (11.0 vs 0.63 mg/dL). We are unable to determine the effectiveness of the out-of-hospital cardiac rehabilitation program due to a lack of power (high number of withdrawals caused by COVID-19 lockdown). However, the experimented group achieved higher HDL-cholesterol levels, while cardiac frequency in VT2 was higher in the control group.


[The costs of physical inactivity in the world: a general review].
There is convincing evidence in the scientific literature of the effectiveness of regular physical activity and physical exercise in the conservation of health and the prevention of various ailments. However, studies into the association between costs of medical services and physical inactivity have not been duly addressed. International studies have quantified these costs and revealed the association between physical activity and/or sedentary behavior. Therefore, this review sought to gather information available from several countries and analyze the global costs associated with physical inactivity over the past few decades. The results of twenty-four original and well-researched articles in nine countries, including Brazil, were analyzed. The results showed that physical inactivity, irrespective of the method of classification, is burdensome to the economy of health worldwide, and directly responsible for the high cost of medication, the incidence of hospitalization and the frequency of medical appointments. The costs of the group of the physically inactive population affected by chronic diseases feature among the major components of the total costs involved in public health.


Acute aortic rupture from cross clamp injury.
We report a case of transmural disruption and perforation of the abdominal aorta secondary to clamp injury. The literature is reviewed in reference to the traumatic effects of vascular clamps. Steps are outlined to reduce the risk of this injury.


Impact of the Affordable Care Act Medicaid expansion on emergency department high utilizers with ambulatory care sensitive conditions: A cross-sectional study.
The effect of the Affordable Care Act on emergency department (ED) high utilizers has not yet been thoroughly studied. We sought to determine the impact of changes in insurance eligibility following the 2014 Medicaid expansion on ED utilization for ambulatory care sensitive conditions (ACSC) by high ED utilizers in an urban safety net hospital. High utilizers were defined as patients with ≥4 visits in the 6months before their most recent visit in the study period (July-December before and after Maryland's Medicaid expansion in January 2014). A differences-in-differences approach using logistic regression was used to investigate if differences between high and low utilizer cohorts changed from before and after the expansion. During the study period, 726 (4.1%) out of 17,795 unique patients in 2013 and 380 (2.4%) of 16,458 during the same period in 2014 were high utilizers (p-value <0.001). ACSC-associated visit predicted being a high utilizer in 2013 (OR 1.66 (95% CI [1.37, 2.01])) and 2014 (OR 1.65 (95% CI [1.27, 2.15])) but this was not different between years (OR ratio 0.99, 95% CI [0.72, 1.38], p-value 0.97). Although the proportion of high utilizers decreased significantly after Maryland's Medicaid expansion, ACSC-associated ED visits by high ED utilizers were unaffected.


Acupuncture points of the typical spinal nerves.
Typical spinal nerves have six cutaneous branches which reach to the skin of the body wall in the thorax and abdomen. Each of these six cutaneous branches correlates to an acupuncture point. This communication describes acupuncture points found in the thoracic and abdominal walls using anatomic nomenclature relating to cutaneous branches of the spinal nerves.


[Prolapse of the urethral mucosa in girls].
In the recent 9 years 39 girls aged from 2 to 10 years were treated at the clinic for prolapse of the urethral mucosa. Among them 24 had circular and 15 had segmental prolapse. The disease was encountered most frequently between 6 and 10 years of age, predominantly in the summer. Complex treatment was started with nonoperative measures which were followed by operation if the prolapse persisted or recurred. Spontaneous reduction of the mucosa occurred in 6 of 22 children who were treated by nonoperative measures, in 3 cases the effect was temporary and a recurrence developed. Operative excision of the mucosa was carried out in 36 girls. The results were good. The article discusses the etiopathogenesis of the disease and analyses the morphological changes in the removed urethral mucosa.


Effectiveness of physical therapy for patients with adhesive capsulitis: a randomized controlled trial.
To compare the effectiveness of a combined technique of physical and ibuprofen for the treatment of adhesive capsulitis with ibuprofen alone. 122 subjects were randomly allocated to have 3 weeks treatment either with ibuprofen (n=61) or ibuprofen and a combined technique of physical therapy (n=61). Outcome measures were carried out 3 weeks and 12 weeks after randomization. Primary outcome measures were the success of treatment measured by improvement in the Shoulder Pain and Disability Index, and global rating. At 3 weeks, 21 (35.0%) of 60 patients in the study group were considered to have had successful treatment compared with 11 (18.6%) of 59 in the control group (difference between groups 16.4%, 95% CI: 4.0-31.3, p=0.044). There was no significant difference in the success rate between the two groups at the 12th week follow-up. The results of this study support the use of physical therapy for patients with adhesive capsulitis.


Identifying patterns of movement behaviours in relation to depressive symptoms during adolescence: A latent profile analysis approach.
Movement behaviour guideline adherence has been associated with lower depressive symptoms during adolescence, yet no studies have used person-centered approaches to examine this relationship. The purpose of the present study was to identify whether unique adolescent movement behaviour profiles exist, evaluate predictors of profile membership, and determine whether profile membership was associated with differences in depressive symptoms cross sectionally and longitudinally. This study involved secondary analysis of the public-use data from Wave 1 and Wave 2 of the National Study of Adolescent Health. Adolescents (N = 6436; 48% male) in grades 7 to 12 (Mage = 16.03 ± 1.75) completed measures to assess moderate-to-vigorous physical activity (MVPA), recreational screen time (ST), and sleep - collectively known as movement behaviours - and depressive symptoms. Latent profile analysis identified four profiles that had similar sleep patterns and were thus characterized by different levels of MVPA and ST: high MVPA/low ST (29%), high MVPA/high ST (4%), low MVPA/low ST (53%), and low MVPA/high ST (14%). Several socio-demographic variables were found to influence profile membership. After adjusting for covariates, findings revealed depressive symptoms were lowest among the high MVPA/low ST profile and this trend was evident one year later. Engaging in high levels of either MVPA or ST alone did not provide additive benefits for depressive symptoms compared to those who engaged in low levels of both MVPA and ST. These findings suggest intervention efforts should take an integrative approach to improve mental health outcomes among adolescents by considering each of the movement behaviours concurrently.


Two new species of Aporhynchus (Cestoda: Trypanorhyncha) from deep water lanternsharks (Squaliformes: Etmopteridae) in the Azores, Portugal.
New collections of cestodes from the spiral intestines of the lanternsharks Etmopterus spinax and Etmopterus pusillus off the island of Faial, in the Azores, Atlantic Ocean, have yielded 2 new species of trypanorhynchs belonging to Aporhynchus. Both species share the distinctive lack of all elements of the rhyncheal system that are characteristic of this genus. The identity of Aporhynchus norvegicus is clarified to allow it to be distinguished from A. menezesi n. sp., which also parasitizes E. spinax. This new species differs conspicuously from its congeners in that its mature and gravid proglottids are wider than long, rather than longer than wide, and also in its lack of spinitriches on the scolex. Aporhynchus pickeringae n. sp., the new species from E. pusillus , differs from all of its congeners except A. norvegicus in that it is a relatively delicate worm with relatively fewer testes. It also possesses fewer proglottids and a wider pedunculus scolecis than does A. norvegicus. Sections through the scolex of A. menezesi n. sp. support use of the term bothriate, rather than difossate, in reference to the scolex configuration of some trypanorhynchs. A key to the 4 species of Aporhynchus is provided.


Pattern of leukocytes in the blood of healthy African neonates.
Serial leukocyte counts were performed on 107 full-term, 40 preterm and 35 postterm African neonates during the first 4 weeks of life. In addition, WBC differential counts were done on 85 of these neonates, selected randomly. Both the absolute and relative amounts of each cell type were determined. The main features of leukocyte counts during the neonatal period were: a mean leukocyte count of 12,580 cells/mm3 (range 3,500-20,500) on day 1, with no statistical difference observed between any two of the three groups studied; a decline in mean leukocyte count by day 7 which remained stable throughout the neonatal period, and a neutrophil count of 5,670 cells/mm3 (range 980-12,900) on day 1. This figure is much lower, both in relative and absolute numbers, than that reported for babies in Europe and North America. Lastly, the lymphocyte count was consistently higher than in comparable reports from Europe and North America. The constant leukocyte count, particularly that of neutrophils, may be of importance in detecting infected African neonates.


Vedolizumab in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Safety, Efficacy, and Place of Therapy.
Selective blockade of the integrins and mucosal adhesion molecules is a promising therapeutic strategy for ulcerative colitis (UC). Vedolizumab (VDZ), a humanized IgG1 monoclonal antibody against α4β7 integrin, selectively blocks the trafficking of the leukocytes into the gastrointestinal tract through its binding with the α4β7 integrin. In this review, we provide an overview of the unique mechanism of VDZ, along with its efficacy, safety, and pharmacokinetic and pharmacodynamic data obtained from clinical trials, observational studies, and meta-analyses. A positive exposure-efficacy relationship with regard to clinical remission and clinical response was apparent in VDZ induction therapy. No drug-specific safety signals are currently available. VDZ has been shown to be effective as first- or second-line induction and maintenance therapy in UC. VDZ is a safe and effective treatment option for patients with UC. Prolonged VDZ induction therapy may contribute to improved outcomes in patients with UC, particularly those previously treated with tumor necrosis factor-α. Prospective head-to-head study of VDZ and other biologics would alter the positioning of VDZ much more clearly.


Meiotic chromosome mobility in fission yeast is resistant to environmental stress.
The formation of healthy gametes requires pairing of homologous chromosomes (homologs) as a prerequisite for their correct segregation during meiosis. Initially, homolog alignment is promoted by meiotic chromosome movements feeding into intimate homolog pairing by homologous recombination and/or synaptonemal complex formation. Meiotic chromosome movements in the fission yeast, Schizosaccharomyces pombe, depend on astral microtubule dynamics that drag the nucleus through the zygote; known as horsetail movement. The response of microtubule-led meiotic chromosome movements to environmental stresses such as ionizing irradiation (IR) and associated reactive oxygen species (ROS) is not known. Here, we show that, in contrast to budding yeast, the horsetail movement is largely radiation-resistant, which is likely mediated by a potent antioxidant defense. IR exposure of sporulating S. pombe cells induced misrepair and irreparable DNA double strand breaks causing chromosome fragmentation, missegregation and gamete death. Comparing radiation outcome in fission and budding yeast, and studying meiosis with poisoned microtubules indicates that the increased gamete death after IR is innate to fission yeast. Inhibition of meiotic chromosome mobility in the face of IR failed to influence the course of DSB repair, indicating that paralysis of meiotic chromosome mobility in a genotoxic environment is not a universal response among species.


Ultrasonic vocalization in rats self-administering heroin and cocaine in different settings: evidence of substance-specific interactions between drug and setting.
Clinical and preclinical evidence indicates that the setting of drug use affects drug reward in a substance-specific manner. Heroin and cocaine co-abusers, for example, indicated distinct settings for the two drugs: heroin being used preferentially at home and cocaine preferentially outside the home. Similar results were obtained in rats that were given the opportunity to self-administer intravenously both heroin and cocaine. The goal of the present study was to investigate the possibility that the positive affective state induced by cocaine is enhanced when the drug is taken at home relative to a non-home environment, and vice versa for heroin. To test this hypothesis, we trained male rats to self-administer both heroin and cocaine on alternate days and simultaneously recorded the emission of ultrasonic vocalizations (USVs), as it has been reported that rats emit 50-kHz USVs when exposed to rewarding stimuli, suggesting that these USVs reflect positive affective states. We found that Non-Resident rats emitted more 50-kHz USVs when they self-administered cocaine than when self-administered heroin whereas Resident rats emitted more 50-kHz USVs when self-administering heroin than when self-administering cocaine. Differences in USVs in Non-Resident rats were more pronounced during the first self-administration (SA) session, when the SA chambers were completely novel to them. In contrast, the differences in USVs in Resident rats were more pronounced during the last SA sessions. These findings indicate that the setting of drug taking exerts a substance-specific influence on the ability of drugs to induce positive affective states.


Peripheral neuropathy in mouse hereditary diabetes mellitus. II. Ultrastructural correlates of degenerative and regenerative changes.
The fine structural changes in some peripheral nerves and sensory ganglia from mice (C57BL/KsJ, db/db) with an hereditary diabetic syndrome, similar to human maturity-onset diabetes mellitus, were studied during development of the mild peripheral neuropathy. The abnormalities observed included axonal degeneration, disruption of myelin, accumulation of electro-dense material in axons, satellite cells and Schwann cells, increased frequency of pi granules of Reich in Schwann cells, enlarged mitochondria, and proliferated and thickened Schwann cell basal laminae. Distal hind limb nerves were most affected. Sensory ganglion neurons were normal except for occasional chromatolytic cells, so that nerve cell loss was not present in this peripheral neuropathy. Morphological indications of Schwann cell hyperplasia, hypertrophy, and axonal sprouting supported the contention that a continuous cycle of axonal degeneration and regeneration was occurring. The ultrastructural changes and accumulation of electron-opaque, lipid material suggested that a defect in lipid metabolism, secondary to the diabetic condition, could be an important factor in the peripheral neuropathy in the diabetic mouse.


Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort.
The four dengue virus serotypes (DENV1-4) are mosquito-borne flaviviruses that infect ∼ 390 million people annually; up to 100 million infections are symptomatic, and 500,000 cases progress to severe disease. Exposure to a heterologous DENV serotype, the specific infecting DENV strains, and the interval of time between infections, as well as age, ethnicity, genetic polymorphisms, and comorbidities of the host, are all risk factors for severe dengue. In contrast, neutralizing antibodies (NAbs) are thought to provide long-lived protection against symptomatic infection and severe dengue. The objective of dengue vaccines is to provide balanced protection against all DENV serotypes simultaneously. However, the association between homotypic and heterotypic NAb titers and protection against symptomatic infection remains poorly understood. Here, we demonstrate that the titer of preinfection cross-reactive NAbs correlates with reduced likelihood of symptomatic secondary infection in a longitudinal pediatric dengue cohort in Nicaragua. The protective effect of NAb titers on infection outcome remained significant when controlled for age, number of years between infections, and epidemic force, as well as with relaxed or more stringent criteria for defining inapparent DENV infections. Further, individuals with higher NAb titers immediately after primary infection had delayed symptomatic infections compared with those with lower titers. However, overall NAb titers increased modestly in magnitude and remained serotype cross-reactive in the years between infections, possibly due to reexposure. These findings establish that anti-DENV NAb titers correlate with reduced probability of symptomatic DENV infection and provide insights into longitudinal characteristics of antibody-mediated immunity to DENV in an endemic setting.


Phenotype characterisation using integrated gene transcript, protein and metabolite profiling.
Multifactorial diseases present a significant challenge for functional genomics. Owing to their multiple compartmental effects and complex biomolecular activities, such diseases cannot be adequately characterised by changes in single components, nor can pathophysiological changes be understood by observing gene transcripts alone. Instead, a pattern of subtle changes is observed in multifactorial diseases across multiple tissues and organs with complex associations between corresponding gene, protein and metabolite levels. This article presents methods for exploratory and integrative analysis of pathophysiological changes at the biomolecular level. In particular, novel approaches are introduced for the following challenges: (i) data processing and analysis methods for proteomic and metabolomic data obtained by electrospray ionisation (ESI) liquid chromatography-tandem mass spectrometry (LC/MS); (ii) association analysis of integrated gene, protein and metabolite patterns that are most descriptive of pathophysiological changes; and (iii) interpretation of results obtained from association analyses in the context of known biological processes. These novel approaches are illustrated with the apolipoprotein E3-Leiden transgenic mouse model, a commonly used model of atherosclerosis. We seek to gain insight into the early responses of disease onset and progression by determining and identifying--well in advance of pathogenic manifestations of disease--the sets of gene transcripts, proteins and metabolites, along with their putative relationships in the transgenic model and associated wild-type cohort. Our results corroborate previous findings and extend predictions for three processes in atherosclerosis: aberrant lipid metabolism, inflammation, and tissue development and maintenance.


Barriers to diagnostic resolution after abnormal mammography: a review of the literature.
Breast cancer remains the most common cancer in women, and screening mammography is the best method for early detection. Approximately 10% to 15% of women undergoing screening mammography have abnormal or incomplete findings that require further diagnostic studies. The time to follow up is reported to be between 9 weeks and more than 19 weeks. Evidence indicates that a delay of more than 3 months in women with symptomatic breast cancer is associated with increased rates of breast cancer recurrence and death. The reasons for the delay are varied, and study findings suggest that minority and low-income women experience more delays than other groups do. The results from 22 studies are summarized. The identified barriers to completion of screening mammography were grouped as patient, provider, and system categories. Most of the studies were descriptive, retrospective studies that describe and measure the barriers in varied ways. Patient barriers were the most extensively described barrier, with little attention given to specific provider and system barriers. Women of nonwhite race with lack of insurance emerged as a subgroup that experienced more delay after abnormal or incomplete results. Provider and system barriers are also not well documented, and further exploration of these barriers is also recommended.


Can we rely on blind endometrial biopsy for detection of focal intrauterine pathology?
To compare the diagnostic power of random endometrial biopsy with hysteroscopy for intrauterine lesions. A retrospective cohort study of 639 women evaluated by diagnostic office hysteroscopy and endometrial biopsy (Novak curette) was carried out between 10/1997-6/2000. Reasons for evaluation were postmenopausal bleeding, abnormal uterine bleeding, ultrasound or hystero-salpingography findings, intrauterine device removal, suspected retained products of conception, infertility, late abortions and recurrent abortions. The women's mean age was 43.4+/-13.3 years (range, 18-88). The most prevalent indication for investigation was abnormal uterine bleeding (n=218, 34.1%), followed by sonographic or hystero-salpingographic findings (n=167, 26.1%). Hysteroscopy revealed a normal uterine cavity in 367 (57.4%) women. Endometrial polyps and submucosal fibroids were the most common hysteroscopic findings (in 151 [23.6%] and 72 [11.3%], respectively). The hysteroscopic findings were compared with the pathology results in 558 cases. The sensitivity of the Novak curette for detection of endometrial polyps and submucosal fibroids was only 8.4% and 1.4%, respectively. The positive predictive value (30.9%) and the negative predictive value (57.9%) for both lesions were likewise low. On the other hand, hysteroscopy was not effective in diagnosing the 27 cases of hyperplasia (26 simple and one complex) all without atypia. Random endometrial sampling alone is not effective for diagnosing focal lesions of the uterine cavity and should be combined with other modalities, preferably diagnostic hysteroscopy.


Disparities in COVID-19 Vaccine Initiation and Completion Among Active Component Service Members and Health Care Personnel, 11 December 2020-12 March 2021.
The objective of this study was to assess overall vaccine initiation and completion in the active component U.S. military, with a focus on racial/ethnic disparities. From 11 December 2020 through 12 March 2021, a total of 361,538 service members (27.2%) initiated a COVID-19 mRNA vaccine. Non-Hispanic Blacks were 28% less likely to initiate vaccination (95% confidence interval: 25%-29%) in comparison to non-Hispanic Whites, after adjusting for potential confounders. Increasing age, higher education levels, higher rank, and Asian/Pacific Islander race/ethnicity were also associated with increasing incidence of initiation after adjustment. When the analysis was restricted to active component health care personnel, similar patterns were seen. Overall, 93.8% of those who initiated the vaccine series completed it during the study period, and only minor differences in completion rates were noted among the demographic subgroups. This study suggests additional factors, such as vaccine hesitancy, influence COVID-19 vaccination choices in the U.S. military. Military leadership and vaccine planners should be knowledgeable about and aware of the disparities in vaccine series initiation.


Ultrafast polyene dynamics: the ring opening of 1,3-cyclohexadiene derivatives.
The light activated ring-opening reaction of the 1,3-cyclohexadiene chromophore finds application in optical control, optical switching, optical memory, light activated molecular machines, photobiology, photochromic materials, and conformation-specific photocatalysts. The development of ultrafast spectroscopic methods and powerful computational methods have accelerated the understanding and facilitated the application of this important chromophore in a wide range of systems. Here we look at the current state of theoretical and experimental understanding for the ring-opening reaction of the isolated cyclohexadiene molecule and the ring-opening reactions of substituted cyclohexadienes, including fulgides, diarylethenes, and provitamin D.


Emerging roles of BRCA1 in transcriptional regulation and DNA repair.
BRCA1 was the first breast cancer susceptibility gene to be identified and cloned. In individuals from high-risk families, mutations in BRCA1 increase the lifetime risk of developing breast cancer eight to tenfold, compared to the general population. How the BRCA1 protein product normally functions to suppress tumor formation and how defects in the gene can ultimately lead to breast cancer have been the focus of intense scrutiny by the scientific and medical communities. BRCA1 has intrinsic transactivation activity and is able to activate the p21 promoter. In addition, BRCA1 is linked to a number of genes involved in transcriptional regulation, including CtIP, c-Myc, the RNA holoenzyme complex, and the histone deacetylase complex. Moreover, BRCA1 is essential for cellular response to DNA damage repair. Inactivation of Brca1 in mouse embryonic stem and fibroblast cells results in increased cell sensitivity to DNA-damaging agents. In human cells, BRCA1 binds to both Rad50 and Rad51 and colocalizes with these proteins at repair foci. Part of BRCA1's response to DNA damage may in fact be corroborated through transcriptional regulation. The expression of GADD45, a DNA damage-responsive gene, is increased immediately after induction of BRCA1. Recently, BRCA1 was shown to repress estradiol (E2)-responsive ER-alpha-mediated transcriptional activity, potentially linking the multiple functions of BRCA1 to specific tissue targets. These recent developments in BRCA1 function are an encouraging step toward understanding the role of BRCA1 in breast cancer formation.


Bilateral Basal Ganglia Calcification: Fahr's Disease.
Fahr's disease/syndrome is a condition defined as bilateral striato-pallido-dentate calcinosis, a neurodegenerative disease with radiological findings of symmetrical and bilateral idiopathic calcifications of the cerebellum, periventricular white matter, and basal ganglia. Clinical correlation with radiological and a calcium metabolism panel is crucial in differentiating between Fahr's disease and Fahr's syndrome. We describe a case that presented with the clinical feature of a cerebrovascular accident and had an incidental radiological finding of Fahr syndrome. The clinical features, laboratory investigations, and clinical management of Fahr's disease/syndrome will be discussed in detail in the article.


Rational Design and Intramolecular Cyclization of Hotspot Peptide Segments at YAP-TEAD4 Complex Interface.
The Yes-Associated Protein (YAP) is a central regulator of Hippo pathway involved in carcinogenesis, which functions through interaction with TEA Domain (TEAD) transcription factors. Pharmacological disruption of YAP-TEAD4 complexes has been recognized as a potential therapeutic strategy against diverse cancers by suppressing the oncogenic activity of YAP. We systematically examine the crystal structure of YAP complex with TEAD4 and rationally identify two hotspot segments at the complex interface; they could be exploited as self-inhibitory peptides to target the complex interaction. Two peptides, termed PS-1 and PS-2 are split from the interfacial context of YAP protein. Dynamics simulations, energetics analyses and fluorescence polarizations are employed to characterize the intrinsic disorder as well as binding energy/affinity of the two YAP peptides to TEAD4 protein. The native conformation of PS-2 peptide is a cyclic loop, which is supposed to be constrained by adding a disulfide bond across the spatially vicinal residue pair Arg87-Phe96 or Met86- Phe95 at the peptide's two ends, consequently resulting in two intramolecular cyclized counterparts of linear PS-2 peptide, namely PS-2(cyc87,96) and PS-2(cyc86,95). The linear PS-2 peptide is determined as a weak binder of TEAD4 (Kd = 190 μM), while the two cyclic PS-2(cyc87,96) and PS-2(cyc86,95) peptides are measured to have moderate or high affinity towards TEAD4 (Kd = 21 and 45 μM, respectively). PS-1 and PS-2 peptides are highly flexible and cannot maintain in native active conformation when splitting from the interfacial context, and thus would incur a considerable entropy penalty upon rebinding to the interface. Cyclization does not influence the direct interaction between PS-2 peptide and TEAD4 protein, but can largely reduce the intrinsic disorder of PS-2 peptide in free state and considerably minimize indirect entropy effect upon the peptide binding.


Prevalence of human papillomavirus in young Italian women with normal cytology: how should we adapt the national vaccination policy?
Human Papillomavirus (HPV) is the most common sexually transmitted infection. In Italy, HPV vaccination is now offered free of charge to 12-year-old females. However, some regional health authorities have extended free vaccination to other age-groups, especially to girls under 18 years of age. We conducted a multicentre epidemiological study to ascertain the prevalence of different genotypes of HPV in young Italian women with normal cytology, with the aim of evaluating the possibility of extending vaccination to older females. The study was performed in 2010. Women aged 16-26 years with normal cytology were studied. Cervical samples were analyzed to identify the presence of HPV by PCR amplification of a segment of ORF L1 (450 bp). All positive HPV-DNA samples underwent viral genotype analysis by means of a restriction fragment length polymorphism assay. Positivity for at least one HPV genotype was found in 18.2% of the 566 women recruited: 48.1% in the 16-17 age-class, 15.4 in the 18-20 age-class, 21.9% in the 21-23 age-class, and 15.5% in the 24-26 age-class; 10.1% of women were infected by at least one high-risk HPV genotype. HPV-16 was the most prevalent genotype. Only 4 (0.7%), 4 (0.7%) and 3 (0.5%) women were infected by HPV-18, HPV-6 and HPV-11, respectively. Of the HPV-DNA-positive women, 64.1% presented only one viral genotype, while 24.3% had multiple infections. The HPV genotypes most often involved in multiple infections were high-risk. A high prevalence was noted in the first years of sexual activity (48.1% of HPV-DNA-positive women aged 16-17 years); HPV prevalence subsequently declined and stabilized.The estimate of cumulative proportions of young women free from any HPV infection at each age was evaluated; 93.3% and 97.1% of 26 year-old women proved free from HPV-16 and/or HPV-18 and from HPV-6 and/or HPV-11, respectively. Our findings confirm the crucial importance of conducting studies on women without cytological damage, in order to optimise and up-date preventive interventions against HPV infection, and suggest that vaccinating 26-year-old females at the time of their first pap-test is to be recommend, though this issue should be further explored.


Performance of an image analysis processing system for hen tracking in an environmental preference chamber.
Image processing systems have been widely used in monitoring livestock for many applications, including identification, tracking, behavior analysis, occupancy rates, and activity calculations. The primary goal of this work was to quantify image processing performance when monitoring laying hens by comparing length of stay in each compartment as detected by the image processing system with the actual occurrences registered by human observations. In this work, an image processing system was implemented and evaluated for use in an environmental animal preference chamber to detect hen navigation between 4 compartments of the chamber. One camera was installed above each compartment to produce top-view images of the whole compartment. An ellipse-fitting model was applied to captured images to detect whether the hen was present in a compartment. During a choice-test study, mean ± SD success detection rates of 95.9 ± 2.6% were achieved when considering total duration of compartment occupancy. These results suggest that the image processing system is currently suitable for determining the response measures for assessing environmental choices. Moreover, the image processing system offered a comprehensive analysis of occupancy while substantially reducing data processing time compared with the time-intensive alternative of manual video analysis. The above technique was used to monitor ammonia aversion in the chamber. As a preliminary pilot study, different levels of ammonia were applied to different compartments while hens were allowed to navigate between compartments. Using the automated monitor tool to assess occupancy, a negative trend of compartment occupancy with ammonia level was revealed, though further examination is needed.


Facilitating the development of cross-platform mHealth applications for chronic supportive care and a case study.
Mobile health (mHealth) apps have received increasing attention, due to their abilities to support patients who suffer from various conditions. mHealth apps may be especially helpful for patients with chronic diseases, by providing pertinent information, tracking symptoms, and inspiring adherence to medication regimens. To achieve these objectives, researchers need to prototype mHealth apps with dedicated software architectures. In this paper, a cloud-based mHealth application development concept is presented for chronic patient supportive care apps. The concept integrates existing software platforms and services for simplified app development that can be reused for other target applications. This developmental method also facilitates app portability, through the use of common components found across multiple mobile platforms, and scalability, through the loose coupling of services. The results are demonstrated by the development of native Android and cross-platform web apps, in a case study that presents an mHealth solution for endocrine hormone therapy (EHT). A performance analysis methodology, an app usability evaluation, based on focus group responses, and alpha and pre-beta testing results are provided.


Human-animal chimeras for vaccine development: an endangered species or opportunity for the developing world?
In recent years, the field of vaccines for diseases such as Human Immunodeficiency Virus (HIV) which take a heavy toll in developing countries has faced major failures. This has led to a call for more basic science research, and development as well as evaluation of new vaccine candidates. Human-animal chimeras, developed with a 'humanized' immune system could be useful to study infectious diseases, including many neglected diseases. These would also serve as an important tool for the efficient testing of new vaccine candidates to streamline promising candidates for further trials in humans. However, developing human-animal chimeras has proved to be controversial. Development of human-animal chimeras for vaccine development has been slowed down because of opposition by some philosophers, ethicists and policy makers in the west-they question the moral status of such animals, and also express discomfort about transgression of species barriers. Such opposition often uses a contemporary western world view as a reference point. Human-animal chimeras are often being created for diseases which cause significantly higher morbidity and mortality in the developing world as compared to the developed world. We argue in our commentary that given this high disease burden, we should look at socio-cultural perspectives on human-animal chimera like beings in the developing world. On examination, it's clear that such beings have been part of mythology and cultural descriptions in many countries in the developing world. To ensure that important research on diseases afflicting millions like malaria, HIV, Hepatitis-C and dengue continues to progress, we recommend supporting human-animal chimera research for vaccine development in developing countries (especially China and India which have growing technical expertise in the area). The negative perceptions in some parts of the west about human-animal chimeras can be used as an opportunity for nurturing important vaccine development research in the developing world.


Emergency department visits by older adults receiving postacute care in skilled nursing facilities.
Skilled nursing facilities (SNF) represent a common postdischarge destination for hospitalized older adults. The goals of SNF care include the completion of extended skilled nursing care and physical rehabilitation to enable patients to safely return home. However, nearly one in four older adults discharged to SNF are rehospitalized and one in five seek care in the emergency department (ED) but are discharged back to SNF. Our aim was to measure the national prevalence and costs to Medicare of ED visits by SNF patients. Of the 1,551,703 Medicare beneficiaries discharged to SNF in 2019, 16.3% had an ED visit within 14 days (n = 253,104). Of those ED visits, 25.5% resulted in a same-day discharge back to SNF (n = 64,472), costing Medicare $24.6 million. Novel care models that can leverage SNF staff and resources while providing rapid diagnostic services are urgently needed.


Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trial.
BACKGROUND : Endoscopic papillary large balloon dilation (EPLBD) has been increasingly used for the management of large common bile duct (CBD) stones. Although EPLBD is often preceded by endoscopic sphincterotomy (EST), EPLBD alone without EST has been increasingly reported as an alternative to EST for large CBD stones. METHODS : This multicenter randomized trial was conducted at 19 Japanese institutions to compare the efficacy and safety of EPLBD alone versus EST for the removal of large (≥ 10 mm) CBD stones. The primary end point was complete stone removal in a single session. The secondary end points included: overall complete stone removal, lithotripsy use, procedure time, adverse events, and cost. RESULTS: 171 patients with large CBD stones were included in the analysis. The rate of single-session complete stone removal was significantly higher in the EPLBD-alone group than in the EST group (90.7 % vs. 78.8 %; P = 0.04). Lithotripsy use was significantly less frequent in the EPLBD group than in the EST group (30.2 % vs. 48.2 %; P = 0.02). The rates of early adverse events were comparable between the two groups: rates of overall adverse events were 9.3 % vs. 9.4 % and of pancreatitis were 4.7 % vs. 5.9 % in the EPLBD and EST groups, respectively. The procedure costs were $1442 vs. $1661 in the EPLBD and EST groups, respectively (P = 0.12). CONCLUSION : EPLBD without EST for the endoscopic treatment of large CBD stones achieved a significantly higher rate of complete stone removal in a single session compared with EST, without increasing adverse events.


The effect of animal versus plant protein on muscle mass, muscle strength, physical performance and sarcopenia in adults: protocol for a systematic review.
The evidence base for the role of dietary protein in maintaining good muscle health in older age is strong; however, the importance of protein source remains unclear. Plant proteins are generally of lower quality, with a less favourable amino acid profile and reduced bioavailability; therefore, it is possible that their therapeutic effects may be less than that of higher quality animal proteins. This review aims to evaluate the effectiveness of plant and animal protein interventions on muscle health outcomes. A robust search strategy was developed to include terms relating to dietary protein with a focus on protein source, for example dairy, meat and soy. These were linked to terms related to muscle health outcomes, for example mass, strength, performance and sarcopenia. Five databases will be searched: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Embase and Web of Science. Studies included will be randomised controlled trials with an adult population (≥ 18) living in the community or residential homes for older adults, and only English language articles will be included. Two independent reviewers will assess eligibility of individual studies. The internal validity of included studies will be assessed using Cochrane Risk of Bias 2.0 tool. Results will be synthesised in narrative format. Where applicable, standardised mean differences (SMD) (95% confidence interval [CI]) will be combined using a random-effects meta-analysis, and tests of homogeneity of variance will be calculated. Dietary guidelines recommend a change towards a plant-based diet that is more sustainable for health and for the environment; however, reduction of animal-based foods may impact protein quality in the diet. High-quality protein is important for maintenance of muscle health in older age; therefore, there is a need to understand whether replacement of animal protein with plant protein will make a significant difference in terms of muscle health outcomes. Findings from this review will be informative for sustainable nutritional guidelines, particularly for older adults and for those following vegan or vegetarian diets. PROSPERO CRD420201886582.


Iron Overload Is Associated With Oxidative Stress and Nutritional Immunity During Viral Infection in Fish.
Iron is a trace element, essential to support life due to its inherent ability to exchange electrons with a variety of molecules. The use of iron as a cofactor in basic metabolic pathways is essential to both pathogenic microorganisms and their hosts. During evolution, the shared requirement of micro- and macro-organisms for this important nutrient has shaped the pathogen-host relationship. Infectious pancreatic necrosis virus (IPNv) affects salmonids constituting a sanitary problem for this industry as it has an important impact on post-smolt survival. While immune modulation induced by IPNv infection has been widely characterized on Salmo salar, viral impact on iron host metabolism has not yet been elucidated. In the present work, we evaluate short-term effect of IPNv on several infected tissues from Salmo salar. We observed that IPNv displayed high tropism to headkidney, which directly correlates with a rise in oxidative stress and antiviral responses. Transcriptional profiling on headkidney showed a massive modulation of gene expression, from which biological pathways involved with iron metabolism were remarkable. Our findings suggest that IPNv infection increase oxidative stress on headkidney as a consequence of iron overload induced by a massive upregulation of genes involved in iron metabolism.


The Escherichia coli FadR transcription factor: Too much of a good thing?
Escherichia coli FadR is a transcription factor regulated by acyl-CoA thioester binding that optimizes fatty acid (FA) metabolism in response to environmental FAs. FadR represses the fad genes of FA degradation (β-oxidation) and activates the fab genes of FA synthesis thereby allowing E. coli to have its cake (acyl chains for phospholipid synthesis) and eat it (degrade acyl chains to acetyl-CoA). Acyl-CoA binding of FadR derepresses the transcription of the fad genes and cancels fab gene transcriptional activation. Activation of fab genes was thought restricted to the fabA and fabB genes of unsaturated FA synthesis, but FadR overproduction markedly increases yields of all FA acyl chains. Subsequently, almost all of the remaining fab genes were shown to be transcriptionally activated by FadR binding, but binding was very weak. Why are the low-affinity sites retained? What effects on cell physiology would result from their conversion to high-affinity sites (thereby mimicking FadR overproduction)? Investigations of E. coli cell size determinants showed that FA synthesis primarily determines E. coli cell size. Upon modest induction of FadR, cell size increases, but at the cost of growth rate and accumulation of intracellular membranes. Greater induction resulted in further growth rate decreases and abnormal cells. Hence, too much FadR is bad. FadR is extraordinarily conserved in γ-proteobacteria but has migrated. Mycobacterium tuberculosis encodes FadR orthologs one of which is functional in E. coli. Strikingly, the FadR theme of acyl-CoA-dependent transcriptional regulation is found in a different transcription factor family where two Bacillus species plus bacterial and archaeal thermophiles contain related proteins of similar function.


Giardia taxonomy, phylogeny and epidemiology: Facts and open questions.
Giardia duodenalis (synonymous Giardia lamblia and Giardia intestinalis) is a flagellated protozoan parasite that reproduces in the small intestine causing giardiasis. It is a cosmopolitan pathogen with a very wide host range, including domestic and wild animal species, as well as human beings. In this paper the current knowledge about the taxonomy and phylogeny of G. duodenalis is summarized from the international literature and data on the detection and epidemiology are also reviewed concentrating on the last 20 years. Authors highlighted the current knowledge and some aspects on G. duodenalis in particular, water transmission and in vitro cultivation. The review sheds light on the difficulties of the strain differentiation and multilocus molecular analysis of Giardia strains especially when applied to water samples containing low numbers of cysts and components complicating the problem of tracking sources of contamination. Genetic elements determining or conferring traits such as infectivity, pathogenicity, virulence, and immune interaction contributing to clearance are currently not well established, if at all. These should be useful and important topics for future research.


[Perfusion microfilter for blood].
The authors have developed a variant of microfilters for extracorporal perfusions possessing the following functional characteristics: square surface of filtrating elements 150 cm2, volume of filling 80 ml, efficiency not less than 6 1/min, filtration of micro-aggregates 30 mkm and more in 70-98%. The microfilter may be used in the arterial line and in the line of the cardiotomic suction.


ASAS Centennial Paper: Development of a corn-based beef industry.
The development of a beef industry, heavily dependent on corn utilization, began to occur in the 1940s. Begun as a means to add value to the grain while improving consumer acceptance of beef, corn has become an integral part of beef production. Developments in the 21st century including unprecedented cattle prices, changes in beef demand, bovine spongiform encephalopathy, surge in energy costs, pricing differentiation of cattle prices based on quality, and industry consolidation have dramatically changed the price of corn and cost of beef production. The future of the beef industry will be dependent on our ability to continue producing high-quality beef for a global market through effective use of genetics, new technologies, and economic management strategies.


[Anti-dementia drugs for dementia syndromes--just unkept promises?].
The present study situation confirms the efficacy of donepezil, galantamine, ginkgo biloba EGb 761, memantine and rivastigmine for Alzheimer's disease. These substances neither cure the disease nor halt its progression. However, they do improve the symptoms for a substantial portion of the patients for a significant length of time and, thus, increase the options for treatment and facilitate the care. Hence, these substances afford many patients and their caregivers a relevant therapeutic success. More transparency must be demanded of reviews, meta-analyses, guidelines or assessments undertaken by governmental bodies; otherwise their conclusions remain equivocal. Transparency must mean that it is clear who prepares the document, to whom it applies and which connections exist to science, media, politics, health insurance companies, pharmaceutical manufacturers and other interest groups.


Magnitude, Diversity, and Antibiograms of Bacteria Isolated from Patient-Care Equipment and Inanimate Objects of Selected Wards in Arba Minch General Hospital, Southern Ethiopia.
Patient-care equipment and inanimate objects contaminated with bacteria are a persistent problem in countries like Ethiopia, and remain overlooked. This study aimed to elucidate the magnitude of contaminations, diversity, and antimicrobial-susceptibility patterns of bacterial isolates from selected wards of Arba Minch General Hospital, Ethiopia. Samples were inoculated into bacteriological media and identified by biochemical characterization, followed by antimicrobial-susceptibility tests. Of the 99 inanimate objects and items of patient-care equipment examined, 71 (71.7%) showed contamination: 26 (76.4%) from the surgical ward and 22 (66.6%) and 23 (71.8%), respectively, from the pediatric ward and neonatal intensive care unit. In the case of Gram-positive bacteria, coagulase-negative staphylococci (CoNS; 52.2%) were predominant, followed by Staphylococcus aureus (47.7%), whereas common Gram-negative counterparts were Acinetobacter spp. (28.5%) and Klebsiella spp. (23.8%). Antibiograms of S. aureus and CoNS showed 100% and 78% resistance, respectively, against penicillin. Isolates of Acinetobacter spp. showed 100% resistance to ceftriaxone and ampicillin, whereas those of Klebsiella spp. displayed complete resistance against ampicillin and trimethoprim-sulfamethoxazole. All isolates of Citrobacter spp., Enterobacter spp., Salmonella spp., Escherichia coli, and Serratia spp. exhibited 100% resistance to amoxicillin, ampicillin, and trimethoprim-sulfamethoxazole. Overall prevalence of multidrug-resistant bacteria was 57.7%. A stringent infection-vigilance program comprising routine sampling from equipment and inanimate objects combined with antimicrobial-resistance surveillance and decontamination efforts must be instituted promptly.


Cabergoline in the Management of Residual Nonfunctioning Pituitary Adenoma: A Single-Center, Open-Label, 2-Year Randomized Clinical Trial.
Complete tumor removal by transsphenoidal surgery is usually difficult for large nonfunctioning pituitary adenomas (NFPAs). A validated medical treatment may be useful for their management. This study evaluates the clinical efficacy of the dopaminergic agonist cabergoline for residual NFPA. We conducted a randomized, parallel, open-label clinical trial that compared cabergoline with nonintervention in patients with residual NFPA after transsphenoidal surgery over 2 years. The primary outcome was clinical efficacy (tumor reduction). The secondary outcome was the relationship between tumor dopamine D2 receptor (D2R) expression and clinical responsiveness. Tumor measurements and clinical evaluations were performed every 6 months. In total, 59 and 57 individuals were randomly assigned to the study and control groups, respectively. At the end of the study, residual tumor shrinkage, stabilization, and enlargement were observed in 28.8%, 66.1%, and 5.1% of patients, respectively, in the medical-therapy group and in 10.5%, 73.7%, and 15.8% of patients, respectively, in the control group (P=0.01). The progression-free survival rate was 23.2 and 20.8 months for the study and control groups, respectively (P=0.01). D2R was not associated with cabergoline responsiveness. No major side effects were related to cabergoline use. Cabergoline was an effective drug for treating residual NFPA, and its use was associated with a high rate of tumor shrinkage (ClinicalTrials.gov NCT03271918).


The molecular and genetic analysis of mouse development.
This review describes some recent advances in the molecular-genetic analysis of mouse development. Reversed genetics and gene assignment have been used to isolate genes affected in developmental mutations. The establishment of a high-density molecular-genetic map promises to facilitate cloning of additional genes with developmental functions. Based on molecular, biochemical or other biological criteria many mouse genes that code for transcriptional regulators, growth-factor-like molecules and their receptors have been isolated. The role of these genes during development can be analysed in vivo after producing targeted mutations. Mutations can be generated by homologous recombination in the genome of embryonic stem cells and can then be introduced into the mouse germ line by means of germ-line chimaeras. Additional approaches employing stem cells to identify and mutate putative developmental genes are coming into use.


Rec dependence of mu transposition from P22-transduced fragments.
Derivatives of bacteriophage Mu carrying a lac operon and a selectable drug resistance element (Mu d phages) are frequently used tools of bacterial genetics. Mu d prophages used in this way can be treated as transposons, in that the inserted material can be transduced from one strain to another by general transducing phages, such as P1 and P22. When a Mu d prophage is transduced into a new recipient by P1 or P22, the Mu d element can transpose from the transduced fragment into the bacterial chromosome. Transposition of the Mu d element from a P22-transduced fragment shows several striking differences from transposition of a Mu d genome injected by a Mu virion. First, the frequency of transposition from a transduced fragment is greatly enhanced by a P22 helper genome. Second, transposition requires the host recA, B, and C functions. Transposition of Mu following injection by a Mu virion is rec independent. While the basis of these observations is not understood, we suggest that the Mu X protein, a 65-kilodalton protein injected by a Mu virion and required for Mu transposition, may not be packaged by P22. We suggest that the effects seen reflect the behavior of a Mu genome in the absence of the X protein.


Phospholipid biosynthesis in myelin: presence of CTP:phosphoethanolamine cytidylyltransferase in purified myelin of rat brain.
Highly purified myelin from rat brain was previously shown to contain the ethanolaminephosphotransferase which completes the synthesis of phosphatidyl ethanolamine. We have now obtained evidence for the presence in myelin of CTP:phosphoethanolamine cytidylyltransferase, the enzyme catalyzing formation of CDP-ethanolamine. Myelin was isolated by two different procedures, one based on the Norton-Poduslo method and the other involving repetitive gradients with osmotic shocking deferred to the end. The fact that activity remained constant through all but the earliest steps suggested that the enzyme is intrinsic to myelin. Comparison of subcellular fractions revealed that approximately half the total activity was in the supernatant, the remainder being distributed among the particulate fractions. Relative specific activity of myelin was 27-31% that of microsomes, thus eliminating the possibility of appreciable contamination by the latter. The possibility of adsorption of the soluble enzyme by myelin was rendered unlikely by retention of activity after washing the myelin with buffered sodium chloride or sodium taurocholate. Furthermore, relative specific activity of the cytidylyltransferase was 10-fold higher than that of lactate dehydrogenase (a cytosolic marker) in myelin. The apparent Km for CTP was approximately the same for myelin and microsomes, but that for phosphoethanolamine was significantly higher for myelin.


Risk of hypertension from exposure to road traffic noise in a population-based sample.
To assess the association between hypertension and traffic noise. The prevalence and incidence of hypertension were examined in a Swedish municipality partly affected by noise from a highway (20,000 vehicles/24 h) and a railway (200 trains/24 h). A-weighed 24 h average sound levels (L(Aeq,24h)) from road and railway traffic were calculated at each residential building using a geographical information system and a validated model. Physician-diagnosed hypertension, antihypertensive medication and background factors were evaluated in 1953 individuals using postal questionnaires (71% response rate). Prevalence ratios and odds ratios (ORs) were calculated for different noise categories. Based on year of moving into the residence and year of diagnosis, person-years and incidence rates of hypertension were estimated, as well as relative risks including covariates, using Poisson and Cox regression. When road traffic noise, age, sex, heredity and body mass index were included in logistic regression models, and allowing for >10 years of latency, the OR for hypertension was 1.9 (95% CI 1.1 to 3.5) in the highest noise category (56-70 dBA) and 3.8 (95% CI 1.6 to 9.0) in men. The incidence rate ratio was increased in this group of men, and the relative risk of hypertension in a Poisson regression model was 2.9 (95% CI 1.4 to 6.2). There were no clear associations in women or for railway noise. The study shows a positive association between residential road traffic noise and hypertension among men, and an exposure-response relationship. While prevalence ratios were increased, findings were more pronounced when incidence was assessed.


Song structure without auditory feedback: emendations of the auditory template hypothesis.
Motor patterns of songs of swamp and song sparrows, Melospiza georgiana and M. melodia, deafened early in life display a significant degree of species-specific structure. Normal songs of the two species differ in the degree to which they are segmented. Swamp sparrow song consists of a single segment, and song sparrow songs are multisegmental. Song and swamp sparrows were deafened at 17 to 23 days, prior to the onset of song or subsong. The song sparrows developed more segments in their singing than the swamp sparrows. Species-specific trends were also evident in song durations and frequency characteristics. Abnormalities were found, however, in the morphology of the notes and syllables from which songs of early deafened sparrows are constructed. These results require emendation of the auditory template hypothesis of song learning in birds.


Genetics of dyslexia: the evolving landscape.
Dyslexia is among the most common neurodevelopmental disorders, with a prevalence of 5-12%. At the phenotypic level, various cognitive components that enable reading and spelling and that are disturbed in affected individuals can be distinguished. Depending on the phenotype dimension investigated, inherited factors are estimated to account for up to 80%. Linkage findings in dyslexia are relatively consistent across studies in comparison to findings for other neuropsychiatric disorders. This is particularly true for chromosome regions 1p34-p36, 6p21-p22, 15q21 and 18q11. Four candidate genes have recently been identified through systematic linkage disequilibrium studies in linkage region 6p21-p22, and through cloning approaches at chromosomal breakpoints. Results indicate that a disturbance in neuronal migration is a pathological correlate of dyslexia at the functional level. This review presents a summary of the latest insights into the genetics of dyslexia and an overview of anticipated future developments.


Management outcomes in pubic diastasis: our experience with 19 patients.
Pubic diastasis, a result of high energy antero-posterior compression (APC) injury, has been managed based on the Young and Burguess classification system. The mode of fixation in APC II injury has, however, been a subject of controversy and some authors have proposed a need to address the issue of partial breach of the posterior pelvic ring elements in these injuries. The study included a total of 19 patients with pubic diastasis managed by us from May 2006 to December 2007. There was a single patient with type I APC injury who treated conservatively. Type II APC injuries (13 patients) were treated surgically with symphyseal plating using single anterior/superior plates or double perpendicularly placed plates. Type III injuries (5 patients) in addition underwent posterior fixation using plates or percutaneous sacro-iliac screws. The outcome was assessed clinically (Majeed score) and radiologically. The mean follow-up was for 2.9 years (6 months to 4.5 years). Among the 13 patients with APC II injuries, the clinical scores were excellent in one (7.6%), good in 6 (46.15%), fair in 4 (30.76%) and poor in 2 (15.38%). Radiological scores were excellent in 2 (15.38%), good in 8 (61.53%), fair in 2 (15.38%) and poor in one patient (7.6%). Among the 5 patients with APC III injuries, there were 2 patients each with good (50%) and fair (50%) clinical scores while one patient was lost on long term follow up. The radiological outcomes were also similar in these. Complications included implant failure in 3 patients, postoperative infection in 2 patients, deep venous thrombosis in one patient and bladder herniation in one of the patients with implant failure. There is no observed dissimilarity in outcomes between isolated anterior and combined symphyseal (perpendicular) plating techniques in APC II injuries. Single anterior symphyseal plating along with posterior stabilisation provides a stable fixation in type III APC injuries. Limited dissection ensuring adequate intactness of rectus sheath is important to avoid long term post-operative complications.


Factors Associated with Caregiver Burden in Caregivers of Older Patients with Dementia in Indonesia.
This cross-sectional study aimed to identify caregiver burden and its determinants in the informal caregivers of older patients with dementia (PWDs) aged ≥ 60 years in Java, Indonesia. Data were collected from 207 caregivers of older PWDs using self-administered questionnaires. The dependent variable was caregiver subjective burden, assessed using the Zarit Burden Interview (ZBI). The independent variables included the socio-demographic characteristics of PWDs and caregivers, the caregiver's perceived social support, and the behavioural and psychological symptoms of dementia (BPSD). Linear regression with a stepwise elimination method was used to identify the factors associated with caregiver burden. This study found that four factors were associated with the caregiver burden, such as the gender of PWDs, the educational level of caregivers, social support, and BPSD (R-squared = 27.78%). Higher burden was reported among the caregivers of female PWDs (β = 5.58; 95%CI = 2.16; 8.99) and PWDs with higher scores of BPSD (β = 0.34; 95%CI = 0.25; 0.43). Meanwhile, the caregivers with higher perceived social support (β = -0.26; 95%CI = -0.42; -0.10) and who completed high school education and above (β = -6.41; 95%CI = -10.07; -2.74) tended to have lower scores of subjective burden. These findings suggest that BPSD management and maintaining the resources of support may provide an opportunity to minimise caregiver burden and improve the quality of life of caregivers and PWDs.


Rice endosperm produces an underglycosylated and potent form of the HIV-neutralizing monoclonal antibody 2G12.
Protein microbicides against HIV can help to prevent infection but they are required in large, repetitive doses. This makes current fermenter-based production systems prohibitively expensive. Plants are advantageous as production platforms because they offer a safe, economical and scalable alternative, and cereals such as rice are particularly attractive because they could allow pharmaceutical proteins to be produced economically and on a large scale in developing countries. Pharmaceutical proteins can also be stored as unprocessed seed, circumventing the need for a cold chain. Here, we report the development of transgenic rice plants expressing the HIV-neutralizing antibody 2G12 in the endosperm. Surprisingly for an antibody expressed in plants, the heavy chain was predominantly aglycosylated. Nevertheless, the heavy and light chains assembled into functional antibodies with more potent HIV-neutralizing activity than other plant-derived forms of 2G12 bearing typical high-mannose or plant complex-type glycans. Immunolocalization experiments showed that the assembled antibody accumulated predominantly in protein storage vacuoles but also induced the formation of novel, spherical storage compartments surrounded by ribosomes indicating that they originated from the endoplasmic reticulum. The comparison of wild-type and transgenic plants at the transcriptomic and proteomic levels indicated that endogenous genes related to starch biosynthesis were down-regulated in the endosperm of the transgenic plants, whereas genes encoding prolamin and glutaredoxin-C8 were up-regulated. Our data provide insight into factors that affect the functional efficacy of neutralizing antibodies in plants and the impact of recombinant proteins on endogenous gene expression.


Academic surgeons, take heart: the story of a student, his mentor, and the discovery of the etiology of angina pectoris.
Edward Jenner is renowned for developing a vaccination for smallpox. He trained as a surgeon and was an ardent anatomist and naturalist. Part of his formal training was directed by John Hunter, the father of scientific surgery. Jenner diagnosed Hunter as suffering from angina pectoris and correctly identified the cause of angina pectoris from a series of autopsies he conducted. After Hunter died during an altercation in committee, his postmortem examination proved Jenner correct. Jenner can be recognized as the first to correctly ascribe the etiology of angina pectoris to coronary atherosclerosis.


GSM-900MHz at low dose temperature-dependently downregulates α-synuclein in cultured cerebral cells independently of chaperone-mediated-autophagy.
The expanding use of GSM devices has resulted in public concern. Chaperone-mediated autophagy (CMA) is a way for protein degradation in the lysosomes and increases under stress conditions as a cell defense response. α-synuclein, a CMA substrate, is a component of Parkinson disease. Since GSM might constitute a stress signal, we raised the possibility that GSM could alter the CMA process. Here, we analyzed the effects of chronic exposure to a low GSM-900MHz dose on apoptosis and CMA. Cultured cerebral cortical cells were sham-exposed or exposed to GSM-900MHz at specific absorption rate (SAR): 0.25W/kg for 24 h using a wire-patch cell. Apoptosis was analyzed by DAPI stain of the nuclei and western blot of cleaved caspase-3. The expression of proteins involved in CMA (HSC70, HSP40, HSP90 and LAMP-2A) and α-synuclein were analyzed by western blot. CMA was also quantified in situ by analyzing the cell localization of active lysosomes. 24 h exposure to GSM-900MHz resulted in ∼0.5°C temperature rise. It did not induce apoptosis but increased HSC70 by 26% and slightly decreased HSP90 (<10%). It also decreased α-synuclein by 24% independently of CMA, since the localization of active lysosomes was not altered. Comparable effects were observed in cells incubated at 37.5°C, a condition that mimics the GSM-generated temperature rise. The GSM-induced changes in HSC70, HSP90 and α-synuclein are most likely linked to temperature rise. We did not observe any immediate effect on cell viability. However, the delayed and long term consequences (protective or deleterious) of these changes on cell fate should be examined.


Effect of acute alcohol administration on erythrocyte aldehyde dehydrogenase activity in man.
The acute oral administration of ethanol to normal subjects resulted in an increase in erythrocyte aldehyde dehydrogenase activity. Incubation of blood with ethanol at 37 degrees C for 2 hr also increased the enzyme activity. By contrast, addition of ethanol directly to the enzyme after its partial purification had no effect on the enzyme activity. The increase in erythrocyte aldehyde dehydrogenase activity following acute ethanol administration is directly opposite to the effect of chronic ethanol consumption in decreasing the enzyme activity in alcoholics. The mechanism for this effect is unknown but may be related to alterations in the erythrocyte membrane and its interaction with the enzyme.


[Musca osiris--a new intermediate host of Thelazia gulosa].
Musca osiris Wd. was first recorded as an intermediate host of the nematode Th. gulosa. In Tadjikistan Musca autumnalis Deg. was first recorded as an intermediate host of Th. gulosa and Th. skrjabini. The flies are suggested to be used as indicators of thelaziasis infection by using a key suggested for the first time for the definition of species of larvae belonging to the genus Thelazia during differentiation of infected larvae from flies.