Severe intravascular hemolysis after transcatheter closure of a large patent ductus arteriosus using the Amplatzer duct occluder: successful resolution by intradevice coil deployment.
A 21-year-old female developed severe unremitting intravascular hemolysis following closure of a large patent ductus arteriosus using an Amplatzer duct occluder. Percutaneous deployment of fibered platinum coils within the nitinol wire cage of the Amplatzer duct occluder abolished the residual shunt through the device and resulted in cessation of intravascular hemolysis and reversal of its adverse sequelae.


An ortho-carbonyl substituted hydroquinone derivative is an anticancer agent that acts by inhibiting mitochondrial bioenergetics and by inducing G₂/M-phase arrest in mammary adenocarcinoma TA3.
Tumor cells present a known metabolic reprogramming, which makes them more susceptible for a selective cellular death by modifying its mitochondrial bioenergetics. Anticancer action of the antioxidant 9,10-dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one (HQ) on mouse mammary adenocarcinoma TA3, and its multiresistant variant TA3-MTXR, were evaluated. HQ decreased the viability of both tumor cells, affecting slightly mammary epithelial cells. This hydroquinone blocked the electron flow through the NADH dehydrogenase (Complex I), leading to ADP-stimulated oxygen consumption inhibition, transmembrane potential dissipation and cellular ATP level decrease, without increasing ROS production. Duroquinol, an electron donor at CoQ level, reversed the decrease of cell viability induced by HQ. Additionally, HQ selectively induced G₂/M-phase arrest. Taken together, our results suggest that the bioenergetic dysfunction provoked by HQ is implicated in its anticancer action.


H2O2 signals via iron induction of VL30 retrotransposition correlated with cytotoxicity.
The impact of oxidative stress on mobilization of endogenous retroviruses and their effects on cell fate is unknown. We investigated the action of H2O2 on retrotransposition of an EGFP-tagged mouse LTR-retrotransposon, VL30, in an NIH3T3 cell-retrotransposition assay. H2O2 treatment of assay cells caused specific retrotranspositions documented by UV microscopy and PCR analysis. Flow cytometric analysis revealed an unusually high dose- and time-dependent retrotransposition frequency induced, ∼420,000-fold at 40 μM H2O2 compared to the natural frequency, which was reduced by ectopic expression of catalase. Remarkably, H2O2 moderately induced the RNA expression of retrotransposon B2 without affecting the basal expression of VL30s and L1 and significantly induced the expression of various endogenous reverse transcriptase genes. Further, whereas treatment with 50 μM FeCl2 alone was ineffective, cotreatment with 10 μM H2O2 and 50 μM FeCl2 caused a 6-fold higher retrotransposition induction than H2O2 alone, which was associated with cytotoxicity. H2O2- or H2O2/FeCl2-induced retrotransposition was significantly reduced by the iron chelator DFO or the antioxidant NAC, respectively. Furthermore, both H2O2-induced retrotransposition and associated cytotoxicity were inhibited after pretreatment of cells with DFO or the reverse transcriptase inhibitors efavirenz and etravirine. Our data show for the first time that H2O2, acting via iron, is a potent stimulus of retrotransposition contributing to oxidative stress-induced cell damage.


A survey of scholarly literature databases for clinical laboratory science.
This article reviews the use of journal literature databases including CINAHL, EMBASE, and Web of Science; summarizing databases including Cochrane Database of Systematic Reviews, online textbooks, and clinical decision-support tools; and the Internet search engines Google and Google Scholar. The series closes with a practical example employing a cross-section of the knowledge and skills gained from all three articles.


Central corneal thickness measurement in clinical practice.
To determine if a single measurement of central corneal thickness (CCT) is an adequate sample to aid in glaucoma risk assessment in clinical practice. Central corneal thickness was measured by ultrasound pachymetry (mean of 15 measurements for each eye) on two separate occasions at least one month apart (range, 33 to 610 days). Eyes with a history of prior incisional surgery or corneal pathology were excluded. Ninety-eight eyes of 98 patients (43 male, 55 female) were enrolled. Mean age was 61.2 +/- 15.5 years. Mean inter-test period was 276 +/- 124 days. No significant difference in mean CCT was observed between the two visits (549 +/- 41 microm versus 548 +/- 42 microm, P = 0.4, two-tailed, paired t test). Measured CCT values differed by more than 20 microm in 20 eyes (20.4%), whereas CCT difference of at least 40 microm was seen in 5 eyes (5.1%). There was no correlation between the measured or absolute difference in CCT and IOP (r = -0.016, P > 0.43), inter-test time period (r = 0.072, P > 0.23), and glaucoma diagnosis. Central corneal thickness measurements in this study differed by at least 20 microm in 20% of eyes. This has important implications for risk assessment, management, and follow-up of patients with glaucoma and related disorders. Factors affecting CCT measurement, such as examiner error or true alterations in corneal thickness, require continued investigation.


Neuropathological correlates of reversible posterior leukoencephalopathy.
The pathogenesis and neuropathology of reversible posterior leukoencephalopathy (RPLE; a clinical and radiographical syndrome linked to malignant hypertension, eclampsia, immunosuppressive drugs, and chemotherapy) remain poorly understood. Autopsies on patients with hypertensive encephalopathy have demonstrated arteriolar fibrinoid necrosis with micro-infarcts and failed to show brain edema; nonetheless, magnetic resonance imagings (MRIs) of patients with RPLE generally show findings most consistent with vasogenic edema. This article reports a patient with RPLE in whom brain biopsy revealed edematous white matter with no evidence of vessel wall damage or infarction. This supports the concept that the imaging changes on MRI represent vasogenic edema and suggests that the changes observed on autopsy in malignant hypertension may be an epiphenomenon.


Electric Field Based Therapies in Cancer Treatment.
Enormous progress has been made in pulsed electric field-based therapies since J [...].


Building infrastructures of abortion care in an un-caring state: acompañante's carework and abortion access in Peru.
For abortion seekers, Peru is an uncaring state where legal and policy interventions have resulted in violence, persecution, and neglect. This state of abortion uncare is set within historic and ongoing denials of reproductive autonomy, coercive reproductive care, and the marginalisation of abortion. Abortion is not supported, even where legally permissible. Here we explore abortion care activism within the Peruvian context, foregrounding a key mobilisation that has emerged against a state of un-care - acompañante carework. Through interviews with people involved in abortion access and activism in Peru, we argue that acompañantes have constructed an infrastructure of abortion care in Peru through the bringing together of actors, technologies, and strategies. This infrastructure is shaped by a feminist ethic of care that differs from minority world care assumptions regarding high quality abortion care in three key ways: (i) care is provided beyond the state; (ii) care is holistic; and (iii) care is collective. We argue that US feminist debates relating to the emerging hyperrestrictive state of abortion un-care as well as broader research on feminist care can learn from acompañante activism strategically and conceptually.


Sliding indirect hernia containing both ovaries.
Although sliding indirect inguinal hernias containing the ipsilateral ovary and fallopian tube are not uncommon in infant girls, sliding hernias containing both ovaries are rare. This report describes a large indirect inguinal hernia in a 1-year-old infant girl that contained the left uterine fundus, left bladder ear, as well as both ovaries and fallopian tubes.


Development of a program teaching laparoscopic sterilization using local anesthesia.
A program teaching laparoscopic sterilization using local anesthesia was developed and implemented in a large residency program in which sterilization using general anesthesia was already being taught in a traditional fashion. Important steps for the development of such a program included the designation of an individual with overall responsibility for the program, identification of potential obstacles along with feasible solutions, and training of residents and staff in the new techniques. The major obstacles to implementation included opposition from anesthesia personnel, the need for additional training in the new techniques for both residents and faculty, nursing staff resistance, and the uncertainty of patient acceptance. Solutions included involving anesthesia personnel in program planning as well as in the ultimate performance of the procedures, practicing local techniques during cases under general anesthesia, limiting initial cases to candidates anticipated to be uncomplicated, and using nondirective counseling of patients. Similar strategies can be useful both to other residency programs and individuals wishing to offer local anesthesia as an option for laparoscopic sterilization at their hospitals.


Geographic Atrophy Progression Is Associated With Choriocapillaris Flow Deficits Measured With Optical Coherence Tomographic Angiography.
The purpose of this study was to assess the associations between baseline choriocapillaris (CC) flow deficits and geographic atrophy (GA) progression. In this prospective cohort study, patients with GA underwent 3 × 3-mm macular spectral-domain optical coherence tomographic angiography (OCTA) at baseline and follow-up visits. Annual GA enlargement rate was defined as change of square root of GA area in 12 months. Shadow areas due to iris, media opacity, retinal vessels, and drusen were excluded. CC vessel density (CC-VD) in non-GA areas was measured using a validated machine-learning-based algorithm. Low perfusion area (LPA) was defined as capillary density below the 0.1 percentile threshold of the same location of 40 normal healthy control eye. Focal perfusion loss (FPL) was defined as percentage of CC loss within LPA compared with normal controls. Ten patients with GA were enrolled and followed for 26 months on average. At baseline, the mean GA area was 0.84 ± 0.70 mm2. The mean CC-VD was 44.5 ± 15.2%, the mean LPA was 4.29 ± 2.6 mm2, and the mean FPL was 50.4 ± 28.2%. The annual GA enlargement rate was significantly associated with baseline CC-VD (r = -0.816, P = 0.004), LPA (r = 0.809, P = 0.005), and FPL (r = 0.800, P = 0.005), but not with age (r = 0.008, P = 0.98) and GA area (r = -0.362, P = 0.30). Baseline CC flow deficits were significantly associated with a faster GA enlargement over the course of 1 year, suggesting the choriocapillaris perfusion outside of a GA area may play a role in GA progression.


High adsorption capacity of ammonia nitrogen on hexagonal porous aluminosilicate derived from solid-waste bagasse bottom ash.
This study investigates the use of a hexagonal-porous aluminosilicate (HAS) adsorbent derived from bagasse bottom ash (BBA), an agricultural solid waste, for the adsorption of ammonia nitrogen (NH3-N)-a key water pollutant from agricultural and farming activities. Sodium silicate derived from BBA via the alkaline fusion method was employed, resulting in energy savings due to a synthesis temperature 1.53 times lower than that of commercial sodium silicate synthesis. The sol-gel method was utilized to successfully synthesize HAS featuring a high surface area and porosity using the sodium silicate prepared from BBA. However, an increase in aluminum content resulted in a decrease in surface area and hexagonal porosity. In performance tests, the HAS(5) adsorbent exhibited the most efficient NH3-N removal, outperforming other adsorbents by 4.54-25.19 times across all initial concentrations. This enhanced efficiency can be attributed to its numerous acidic surface sites, enabling the bonding of NH3-N molecules through monolayer adsorption on the HAS surface.


Validation of the Tenon breast cancer score for predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastasis: a prospective multicenter study.
Axillary lymph node dissection (ALND) is the standard treatment for patients with sentinel node (SN) metastasis, but most of these patients have negative non-sentinel nodes (non-SN). We have developed a scoring system (the Tenon score) to help identify a subgroup of patients who have a low risk of having non-SN metastases and who may thus forgo ALND. Here we validated the Tenon score in an independent cohort of SN-positive patients. We tested the accuracy of the Tenon score for predicting non-SN status in a prospective multicenter study of 226 SN-positive breast cancer patients. We calculated the false-negative rate, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). Receiver operating characteristics (ROC) curves were constructed and the areas under the curve (AUC) were calculated as a measure of discriminatory capacity. At least one non-SN was positive in 63 patients (27.9%). One hundred and twenty (53.1%) of the 226 patients had a Tenon score of 3.5 or less. Among these 120 patients, five had at least one positive non-SN. With a score cut-off of 3.5, the negative predictive value was 95.8% and the false-negative rate was 4.2%. Overall, the Tenon score accurately predicted non-SN status, with an AUC of 0.82 (95% confidence interval, 0.77-0.88). In this multicenter study of an independent patient population, the Tenon score was accurate and reproducible for predicting non-SN status in breast cancer patients. The simplicity and reliability of the variables on which the Tenon score is based may be an advantage over other scoring systems.


Pediatric dysphagia.
Feeding and swallowing disorders during childhood are on the increase and typically occur in conjunction with multiple and complex medical, health, and developmental conditions. A multidisciplinary approach is essential for the evaluation of these disorders and the prompt initiation of appropriate treatment. Following a brief description of the terms feeding and swallowing, this article provides an overview of the available epidemiologic data on dysphagia and its common diagnostic conditions, impact, evaluation, and management in the pediatric population.


[Psychosomatic aspects of chronic pelvic pain syndrome. Psychometric results from the pilot phase of an interdisciplinary outpatient clinic].
Chronic pelvic pain syndrome (CPPS) presents as a multicausal disorder. Complex interactions of psychological factors with somatic dysfunctions are crucial to the development and maintenance of CPPS. This study characterized the patient cohort from a psychosomatic perspective. Subjects with CPPS were recruited from an interdisciplinary CPP outpatient clinic. Sociodemographic data, symptoms (National Institutes of Health Chronic Prostatitis Symptom Index, NIH-CPSI) and pain-related factors (Short Form of the McGill Pain Questionnaire, SF-MPQ) as well as depressive symptoms (Patient Health Questionnaire 9, PHQ-9), anxiety [Generalized Anxiety Disorder 7-item (GAD-7) Scale], the severity of somatic symptoms (PHQ-15) and quality of life (Short Form-12, SF-12) were measured. Additional socioeconomic data were obtained. A total of 50 men and women with a mean disease duration of 5.8 years were included in the study. The disease-related symptom severity and healthcare utilization were high. All psychometric scales showed significantly lower values compared with the general population. A high symptom burden was associated with high psychopathological findings and reduced quality of life. The psychopathological comorbidities in subjects with CPPS require specific evidence-based diagnostic and treatment methods to reduce psychopathology and improve quality of life.


Dental material allergies and oral soft tissue reactions.
Dental materials can cause reactions to the oral mucosa and present to the general dental practitioner. These are often referred to as 'allergies' but are frequently lichenoid reactions. Most of these are related to dental amalgam restorations and can be remedied by replacing the restoration with another suitable material. Other metals, including gold, palladium, nickel and chrome, have also been reported to trigger mucosal changes. Less commonly, issues arise from other restorative materials, including denture acrylics, composites and glass polyalkenoates. Reactions are also reported due to endodontic and sealing materials. It is unclear what role skin 'patch' testing has in managing dental material allergies. This article aims to give the practitioner a clearer picture of dental material allergy issues and how they should be approached in primary dental practice.


Activation of the alternative pathway of complement by human serum IgA.
In order to study the activation of complement by soluble aggregates of human polyclonal serum IgA, lysis of sheep erythrocytes (E) coated with several IgA preparations was used as a model. A complement nonactivating monoclonal mouse IgG1 against IgA was used to coat the cells. IgA, isolated from normal human serum, was aggregated by either N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP), glutaraldehyde, carbodiimide or heating. Depending on the size of the aggregates, and on the method of aggregation, E coated with aggregated IgA (E gamma 1.AIgA) could be lysed. The alternative pathway of complement appeared to mediate the lysis because the latter was observed in the presence of EGTA containing 5 mM Mg2+ (MgEGTA) and properdin (P) was deposited on the cells. Furthermore, no lysis was observed in C3-deficient serum. In the absence of AIgA the cells were not lysed, and no P deposition was observed. In another set of experiments E gamma 1.AIgA were first reacted with purified C3, B, D and P for 30 min at 30 degrees C, and subsequently in rat serum EDTA at 37 degrees C. Lysis occurred when E gamma 1.AIgA were prepared using SPDP-, glutaraldehyde- or carbodiimide-AIgA. Incubation of 100 micrograms/ml SPDP-AIgA with normal human serum for 30 min at 37 degrees C in the presence or absence of MgEGTA also induced consumption of total complement. The other soluble AIgA preparations were less effective in activating complement. These results suggest that polymeric serum IgA is capable of activating the alternative pathway of complement.


Dexamethasone and Statins in Patients Undergoing Primary Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Propensity-Matched Study in the TriNetX Research Network.
Middle meningeal artery embolization (MMAE) is an effective minimally invasive option for chronic subdural hematoma (cSDH). Dexamethasone and statins have been reported to improve the resolution of cSDH and reduce its recurrence. However, only 1 study has investigated the role of statins in patients treated with MMAE, and there is no such study on dexamethasone. Thus, we used the TriNetX research network to determine whether adding dexamethasone or statin along with primary MMAE is associated with a benefit in outcomes. We queried all primary MMAE cases for cSDH between January 1st, 2012, and July 1st, 2022, in the TriNetX research network. We included patients greater than or equal to 18 years old and separated them regarding statin and dexamethasone use around the time of MMAE. Outcomes were evaluated within 6 months and 3 years after MMAE, and analyses were performed before and after propensity score matching. The study included 372 patients with chronic subdural hematoma who underwent MMAE and were on dexamethasone, 339 not on dexamethasone, 391 on statins, and 278 not on statins. After propensity score matching, the dexamethasone cohorts included 250 patients each and only headache remained more prevalent in the dexamethasone cohort at both 6 months (21.2% vs. 10.0%, P = 0.001) and 3 years (23.6% vs. 12.4%, P = 0.001). After propensity score matching, the statin cohorts included 150 patients each and no differences in outcomes were found at both 6 months and 3 months after MMAE. Patients treated with primary MMAE and were on dexamethasone or statins had no differences in mortality and functional/provider dependence compared to those who were not on dexamethasone or statins. Patients on dexamethasone had a higher prevalence of headaches.


Angiosarcoma after tylectomy and radiation therapy for carcinoma of the breast.
Angiosarcoma (AS) is an uncommon tumor that rarely develops after external beam radiation therapy (EBRT). Thirty-six cases have been reported in the literature. The authors present two additional cases. Each of these patients received breast-conserving treatment for breast carcinoma that consisted of tylectomy and EBRT. In each case, AS developed in the field of prior irradiation. Currently, seven cases of AS after radiation therapy for breast-conserving treatment of breast carcinoma have been reported. The average time interval between the administration of radiation therapy and the development of AS is 8.6 years. This complication is rare and should not influence the decision to offer breast-conserving therapy to patients. However, patients should be informed that AS may develop as a result of radiation therapy.


Antigenic characterization of an abnormal isoform of prion protein using a new diverse panel of monoclonal antibodies.
We established a panel of monoclonal antibodies (mAbs) against prion protein (PrP) by immunizing PrP gene-ablated mice with the pathogenic isoform of prion protein (PrPSc) or recombinant prion protein (rPrP). The mAbs could be divided into at least 10 groups by fine epitope analyses using mutant rPrPs and pepspot analysis. Seven linear epitopes, lying within residues 56-90, 119-127, 137-143, 143-149, 147-151, 163-169, and 219-229, were defined by seven groups of mAbs, although the remaining three groups of mAbs recognized discontinuous epitopes. We attempted to examine whether any of these epitopes are located on the accessible surface of PrPSc. However, no mAbs reacted with protease-treated PrPSc purified from scrapie-affected mice, even when PrPSc was dispersed into a detergent-lipid protein complex, to reduce the size of PrPSc aggregates. In contrast, denaturation of PrPSc by guanidine hydrochloride efficiently exposed all of the epitopes. This suggests that any epitope recognized by this panel of mAbs is buried within the PrPSc aggregates. Alternatively, if the corresponding region(s) are on the surface of PrPSc, the region(s) may be folded into conformations to which the mAbs cannot bind. The reactivity of a panel of mAb also showed that the state of PrPSc aggregation influenced the denaturation process, and the sensitivity to denaturation appeared to vary between epitopes. Our results demonstrate that this new panel of well-characterized mAbs will be valuable for studying the biochemistry and biophysics of PrP molecules as well as for the immuno-diagnosis of prion diseases.


Attitudes: Mediators of the Relation between Health and Driving in Older Adults.
We examined the relations between perceived health (e.g., self-perceived health status) and driving self-regulatory practices (e.g., frequency of driving, avoiding challenging driving situations) as mediated by driving attitudes and perceptions (i.e., driving comfort, positive and negative attitudes towards driving) in data collected for 928 drivers aged 70 and older enrolled in the Candrive II study. We observed that specific attitudes towards driving (e.g., driving comfort, negative attitudes towards driving) mediate the relations between health symptoms and self-regulatory driving behaviours at baseline and over time. Only negative attitudes towards driving fully mediated the relationships between changes in perceived health symptoms and changes in driving behavior. Perceived health symptoms apparently influence the likelihood of avoiding challenging driving situations through both initial negative attitudes towards driving as well as changes in negative attitudes over time. Understanding influences on self-regulatory driving behaviours will be of benefit when designing interventions to enhance the safety of older drivers.


Kinetics of iron hexacyanide release from the ferric hemes of partially oxidized intermediates of human deoxy hemoglobin.
A new experiment is presented in which the kinetics of iron hexacyanide release is measured from partially oxidized intermediates of human deoxy hemoglobin (T state). The intermediates were generated by briefly exposing a solution of hemoglobin and dithionite to various concentrations of ferricyanide at 6 degrees C in 0.1 M phosphate buffer, pH 7. The reaction of the residual dithionite with the partially oxidized intermediates was limited by the release of ferrocyanide and was strongly biphasic with about 75% fast phase and 25% slow and with the two phases differing in rate by a factor of 26. The predominance of rapid over slow phase is the result of a wide (approx. factor of 5) difference in the kinetics of oxidation of the alpha and beta chains by ferricyanide and is not due to heme-heme interaction. This experimental approach appears to offer a clear example of wide kinetic differences between the two types of subunits within the deoxy quaternary structure of human hemoglobin, uncomplicated by strong cooperative effects.


The non-selective adenosine antagonist theophylline reverses the effects of dopamine antagonism on tremor, motor activity and effort-based decision-making.
Considerable evidence indicates that adenosine and dopamine systems interact in the regulation of basal ganglia function. Nonselective adenosine antagonists such as the methylxanthine caffeine as well as selective adenosine A2A antagonists have been shown to produce antiparkinsonian and antidepressant effects in animal models. The present studies were conducted to assess if another methylxantine, theophylline, can reverse motor and motivational impairments induced by dopamine antagonism in rats. RESULTS: Theophylline (3.75-30.0 mg/kg, IP) reversed tremulous jaw movements (TJMs), catalepsy, and locomotor suppression induced by the dopamine D2 antagonist pimozide. It also reversed TJMs induced by the muscarinic receptor agonist pilocarpine, which is a well-known tremorogenic agent. Parallel studies assessed the ability of theophylline (5.0-20.0 mg/kg, IP) to reverse the changes in effort-related choice behavior induced by the dopamine D1 antagonist ecopipam (0.2 mg/kg, IP) and the D2 antagonist haloperidol (0.1 mg/kg, IP). Rats were tested on two different operant choice tasks which assess the tendency to work for a preferred reinforcer by lever pressing (for palatable pellets or a high 5% sucrose solution) vs. approaching and consuming a less preferred reinforcer (freely available lab chow or a less concentrated 0.3% sucrose solution). Theophylline restored food and sucrose-reinforced lever pressing in animals treated with the D2 antagonist. However, it was unable to reverse the effects of the D1 antagonist. Overall, the effects of theophylline resembled those previously reported for adenosine A2A antagonists, and suggest that theophylline could be clinically useful for the treatment of motor and motivational symptoms in humans.


Assessing mammal fence crossing and local fence management in relation to classical swine fever spread in Japan.
Infectious diseases at the wildlife-livestock-human interface have become a crucial issue, and evidence-based measures are growing increasingly important. One countermeasure against animal diseases in wildlife is using fencing to contain and reduce disease spread and transmission rates between wild populations; however, quantitative assessments on fencing are rare. Moreover, existing research on fencing has highlighted knowledge gaps on the social and ecological aspects relevant to the use and design of fences. To control the spread of classical swine fever, fences were installed from the east to west in Gifu Prefecture, Japan, by March 2019, with the aim of restricting wild boar movement. To clarify the process of installation and maintenance of the fences, we conducted semi-structured interviews with prefectural government officers in Gifu Prefecture. Additionally, we installed infrared-triggered cameras at fence locations with and without gaps to evaluate the fence permeability of mammals. We used a generalized linear mixed model to evaluate the relationship between the presence of gaps and the relative abundance and permeability of each mammal. Our findings showed that the occurrence of gaps was inevitable during the installation and management of wide-area perimeter fence in Japan, partly because of social factors. For example, fences could not be installed on roads that were frequently used by residents and were not adequately maintained owing to budgetary reasons in some cases. Analysis of footage from the infrared-triggered cameras revealed that several mammal species crossed the fence at gaps and even had the ability to cross the gapless parts of the fences. Wild boars crossed through the gaps regularly. It is possible that Sika deer, Japanese serows, raccoons, Japanese badgers, raccoon dogs, Japanese macaques, and feral cats crossed through fence gaps because their relative abundance was high at gap locations. In contrast, Japanese hares slipped through the fence mesh rather than crossing through the gaps. In conclusion, we suggest that coordination and collaboration among related parties, a sufficient supply of fence materials, and securing a budget for fence maintenance are important for fence installation and maintenance. Furthermore, as fence gaps are inevitable, technical development of countermeasures for these gaps could be effective.


Factors associated with verbal fluency in older adults living with HIV in West Africa: A longitudinal study.
Verbal fluency decline, observed both in aging and HIV infection, has been related to lower quality of life. This study aimed to evaluate the factors associated with categorical fluency in people living with HIV (PLHIV) aged ≥60 years living in West Africa. In this longitudinal study, PLHIV aged ≥60 years, on antiretroviral therapy (ART) for ≥6 months were included in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. Categorical fluency was evaluated with the Isaacs Set Test at 60 s at baseline and 2 years later. Factors associated with verbal fluency baseline performance and annual rates of changes were evaluated using multivariate linear regression models. Ninety-seven PLHIV were included with 41 of them (42%) having a 2-year follow-up visit. The median age was 64 (62-67), 45.4% were female, and 89.7% had an undetectable viral load. The median annual change in categorical fluency scores was -0.9 (IQR: -2.7 to 1.8). Low baseline categorical fluency performance and its decline were associated with older age and being a female. Low educational level was associated with low baseline categorical fluency performance but not with its decline. Categorical fluency decline was also associated with marital status and hypertension. Among older West African PLHIV, usual socio-demographic variables and hypertension were the main factors associated with low categorical fluency performance and/or its decline. Interventions that focus on supporting cardiometabolic health are highly recommended to prevent cognitive disorders in PLHIV.


Theoretical Applications of Positive Psychology to Vocational Rehabilitation After Traumatic Brain Injury.
Traumatic brain injury (TBI) produces broad-reaching and often persistent challenges that impact an individual's ability to engage in vocational productivity. Return to work (RTW) rates after TBI are markedly poor and the efficacy of current TBI vocational rehabilitation (VR) practices is unclear. Positive psychology, the practice of fostering positive emotions and traits, offers novel approaches that might enhance the effectiveness of existing TBI VR practices. This article assesses the potential relevance of positive psychology principles and practices to VR for clients recovering from TBI. A literature search was conducted using the database resources of a large university hospital, including PubMed, ProQuest, PsycINFO, and Web of Science. Content from this search was reviewed and synthesized, including literature on VR for TBI, vocational applications of positive psychology, and general rehabilitation applications of positive psychology. Ten guiding principles for positively-informed TBI VR are proposed. Specific positive psychology measures and interventions for improving emotional, social, and cognitive functioning are identified and discussed as they might be applied to TBI VR. Theoretically, positive psychology principles and practices appear to be well suited to improving VR outcomes for individuals with TBI. In addition to examining the feasibility of incorporating positive psychology techniques, future research should examine the impact of positive psychology interventions on RTW rates, job satisfaction, job stability, and other vocational outcomes. With additional investigation, positive psychology measures and interventions may prove to be a beneficial compliment to existing VR practices.


Alantolactone and Isoalantolactone Prevent Amyloid β25-35 -induced Toxicity in Mouse Cortical Neurons and Scopolamine-induced Cognitive Impairment in Mice.
Given the evidence for detoxifying/antioxidant enzyme-inducing activities by alantolactone (AL) and isoalantolactone (IAL), the purpose of this study was to investigate the effects of AL and IAL on Aβ25-35 -induced cell death in mouse cortical neuron cells and to determine their effects on scopolamine-induced amnesia in mice. Our data demonstrated that both compounds effectively attenuated the cytotoxicity of Aβ25-35 (10 μM) in neuronal cells derived from the mouse cerebral cortex. It was also found that the production of intracellular reactive oxygen species, including superoxide anion induced by Aβ25-35 , was inhibited. Moreover, the administration of the sesquiterpenes reversed scopolamine-induced cognitive impairments as assessed by Morris water, Y-maze, and the passive avoidance tests, and the compounds decreased acetylcholinesterase (AChE) activities in a dose-dependent manner. Interestingly, AL and IAL did not improve scopolamine-induced cognitive deficit in Nrf2-/- mice, suggesting that memory improvement by sesquiterpenes was mediated not only by the activation of the Nrf2 signaling pathway but also by their inhibitory activity against AChE. In conclusion, our results showed that AL and IAL had neuroprotective effects and reversed cognitive impairments induced by scopolamine in a mouse model. Therefore, AL and IAL deserve further study as potential therapeutic agents for reactive oxygen species-related neurodegenerative diseases. Copyright © 2017 John Wiley & Sons, Ltd.


A novel aminotransferase gene and its regulator acquired in Saccharomyces by a horizontal gene transfer event.
Horizontal gene transfer (HGT) is an evolutionary mechanism of adaptive importance, which has been deeply studied in wine S. cerevisiae strains, where those acquired genes conferred improved traits related to both transport and metabolism of the nutrients present in the grape must. However, little is known about HGT events that occurred in wild Saccharomyces yeasts and how they determine their phenotypes. Through a comparative genomic approach among Saccharomyces species, we detected a subtelomeric segment present in the S. uvarum, S. kudriavzevii, and S. eubayanus species, belonging to the first species to diverge in the Saccharomyces genus, but absent in the other Saccharomyces species. The segment contains three genes, two of which were characterized, named DGD1 and DGD2. DGD1 encodes dialkylglicine decarboxylase, whose specific substrate is the non-proteinogenic amino acid 2-aminoisobutyric acid (AIB), a rare amino acid present in some antimicrobial peptides of fungal origin. DGD2 encodes putative zinc finger transcription factor, which is essential to induce the AIB-dependent expression of DGD1. Phylogenetic analysis showed that DGD1 and DGD2 are closely related to two adjacent genes present in Zygosaccharomyces. The presented results show evidence of an early HGT event conferring new traits to the ancestor of the Saccharomyces genus that could be lost in the evolutionary more recent Saccharomyces species, perhaps due to loss of function during the colonization of new habitats.


Favorable long-term results of primary pterygium removal by bare sclera extirpation followed by a single 90Strontium application.
To describe and compare long-term (> or = 36 months) effects of patients with 86 primary pterygia treated with bare sclera extirpation (BSE) followed by Beta-RT or by sham irradiation. Prospective, multicenter, randomized, double-blind study. After BSE of their pterygium, patients were randomized to either Beta-RT or sham irradiation. In the case of Beta-RT, within 24 hours after the operation, a 90Sr eye applicator was used to deliver 2500 cGy to the sclera surface at a dose rate of between 200 and 250 cGy/min. Sham irradiation was given using the same type of applicator without the 90Sr layer. After treatment, both a masked ophthalmologist and a radiation oncologist performed follow-up examinations. These were continued until either a relapse occurred or at least 36 months had elapsed. Adequate follow-up was available of 86 pterygia in 81 patients, treated between February 1998 and September 2002. Fifty-two (60%) patients were male. The mean age of the patients was 50 years (range: 24-77). After a follow-up of at least 36 months (mean: 40 months, SD:13.9 months), 5 out of 44 eyes (11%) treated with Beta-RT showed a recurrence versus 32 out of 42 eyes (76%) treated with sham-RT (after a mean follow-up of 22 months) (p<0.001). In the Beta-RT group, 80% were satisfied with the cosmetic result, whereas in the sham group this percentage was 41% (p<0.001). In the Beta-RT group, no scar or a white scar could be detected in 86% of the treated eyes, versus in 24% of the sham irradiated eyes (p<0.001). A change of keratometry (Javal) was seen in 5 patients (12%) following Beta-RT compared to 16 (38%) after sham irradiation (p=0.002). Complications were few: a granuloma was seen in three patients after sham irradiation, mild limitation of abduction in two Beta-RT patients versus in five after sham irradiation, and mild scleromalacia in one Beta-RT patient. Bare sclera extirpation of a pterygium without adjuvant treatment has an unacceptably high recurrence rate and therefore should be considered obsolete. Bare sclera extirpation of a primary pterygium followed by a single-dose Beta-RT is a simple, effective, and safe treatment with lasting results and very few complications.


Psychophysiological correlates of induced headaches.
The psychophysiological correlates of induced headaches were examined. Subjects with frequent muscle-contraction headaches, frequent migraine headaches, or infrequent headaches were exposed to a 1-h cognitive stressor while multiple electromyographic and cardiovascular measures were monitored. The stressor was associated with significant changes in all psychophysiological measures. Eleven of 16 headache subjects and 2 of 8 control subjects developed headaches. Significant associations between several psychophysiological variables and headache occurrence were found and individual differences in the association between psychophysiological variables and headaches intensity were examined. The results were consistent with the hypothesized role of cardiovascular factors in the pathophysiology of muscle-contraction headache. This was the first controlled demonstration of headaches occurring as a function of environmental stressors.


Endoplasmic reticulum-plasma membrane junctions: structure, function and dynamics.
Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are contact sites between the ER and the PM; the distance between the two organelles in the junctions is below 40 nm and the membranes are connected by protein tethers. A number of molecular tools and technical approaches have been recently developed to visualise, modify and characterise properties of ER-PM junctions. The junctions serve as the platforms for lipid exchange between the organelles and for cell signalling, notably Ca(2+) and cAMP signalling. Vice versa, signalling events regulate the development and properties of the junctions. Two Ca(2+) -dependent mechanisms of de novo formation of ER-PM junctions have been recently described and characterised. The junction-forming proteins and lipids are currently the focus of vigorous investigation. Junctions can be relatively short-lived and simple structures, forming and dissolving on the time scale of a few minutes. However, complex, sophisticated and multifunctional ER-PM junctions, capable of attracting numerous protein residents and other cellular organelles, have been described in some cell types. The road from simplicity to complexity, i.e. the transformation from simple 'nascent' ER-PM junctions to advanced stable multiorganellar complexes, is likely to become an attractive research avenue for current and future junctologists. Another area of considerable research interest is the downstream cellular processes that can be activated by specific local signalling events in the ER-PM junctions. Studies of the cell physiology and indeed pathophysiology of ER-PM junctions have already produced some surprising discoveries, likely to expand with advances in our understanding of these remarkable organellar contact sites.


Adsorption and separation of proteins by collagen fiber adsorbent.
The separation of proteins is a key step in biomedical and pharmaceutical industries. In the present investigation, the collagen fiber adsorbent (CFA) was exploited as column packing material to separate proteins. Bovine serum albumin (BSA), bovine hemoglobin (Hb) and lysozyme (LYS) that have different isoelectric points (pIs) were selected as model proteins to investigate the separation ability of CFA to proteins. In batch adsorption, the adsorption behaviors of these proteins on CFA under different pHs and ionic strengths indicated that the electrostatic interaction plays a predominant role in the adsorption of proteins on CFA. CFA exhibited high adsorption capacity to Hb and LYS. In column separation, the proteins were completely separated by adjusting pH and ionic strength of the eluent. The increase of flow rate could reduce the separation time with no influence on the recovery of protein in the experimental range. The protein recovery was higher than 90% even when the CFA column was re-used for 4 times in separation of BSA and LYS, and the retention time of BSA or LYS was almost constant during the repeated applications. In addition, as a practical application, LYS was successfully separated from chicken egg white powder by CFA column.


Effect on in vitro cell response of the statistical insertion of N-(2-hydroxypropyl) methacrylamide on linear pro-dendronic polyamine's gene carriers.
Statistical copolymers of N-(2-hydroxypropyl) methacrylamide (HPMA) and the dendronic methacrylic monomer 2-(3-(Bis(2-(diethylamino)ethyl)amino)propanamido)ethyl methacrylate (TEDETAMA, derived from N,N,N',N'-tetraethyldiethylenetriamine, TEDETA), were synthesized through radical copolymerization and evaluated in vitro as non-viral gene carriers. Three copolymers with nominal molar percentages of HPMA of 25%, 50% and 75% were prepared and studied comparatively to the positive controls poly-TEDETAMA and hyperbranched polyethyleneimine (PEI, 25kDa). Their ability to complex DNA at different N/P molar ratios, from 1/1 up to 8/1, was determined through agarose gel electrophoresis and Dynamic Light Scattering. The resulting complexes (polyplexes) were characterized and evaluated in vitro as possible non-viral gene carriers for Swiss-3T3 fibroblasts, using luciferase as reporter gene and a calcein cytocompatibility assay. All the copolymers, except the one with highest HPMA proportion (75 molar %) at the lowest N/P ratio, condensed DNA to a particle size between 100 and 300 nm. The copolymers with 25 and 50 molar % of HPMA displayed higher transfection efficiency and cytocompatibility than the positive controls poly-TEDETAMA and PEI. A higher proportion of HPMA (75 molar %) led to copolymers that displayed very low transfection efficiency, despite their full cytocompatibility even at the highest N/P ratio. These results indicate that the statistical combination of TEDETAMA and HPMA and its fine compositional tuning in the copolymers may fulfill the fine balance of transfection efficiency and cytocompatibility in a superior way to the control poly-TEDETAMA and PEI.


Discoid lupus erythematosus with secondary amyloidosis.
Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes. To characterize the amyloid deposition observed incidentally within lesional biopsies from three patients with discoid lupus erythematosus (DLE), and retrospectively to study the phenomenon within DLE skin samples. Localized amyloid deposition was observed in three cases of DLE by immunofluorescence studies, and these cases were further studied by histology and immunohistochemistry using a monoclonal anticytokeratin antibody. Retrospective histological review of DLE tissue specimens archived over 12 months was performed to look for evidence of previously undetected amyloid. Amyloid deposition was confirmed histologically in the three index cases by staining with Congo red and thioflavin T. Positive staining with an anticytokeratin antibody demonstrated the epidermal origin of the amyloid protein. Of the 18 archived cases reviewed amyloid was retrospectively detected in one sample. Secondary cutaneous amyloidosis of keratinocyte origin can be seen in DLE lesions. It may be a not infrequent occurrence and may remain under-reported. We discuss the possible role of disease chronicity and colloid body degradation in the pathogenesis of amyloidosis.


Circulating IL-18 concentration is associated with insulin sensitivity and glucose tolerance through increased fat-free mass.
Knowledge of the factors which simultaneously contribute to insulin-resistance-related inflammation may contribute to early therapeutic targeting. IL-18 has recently been described as one of the factors which, in addition to insulin resistance, may also contribute to atherosclerosis. However, the source of IL-18 is not well characterised. We aimed to study body composition (bioelectric impedance), glucose tolerance (OGTT) and insulin sensitivity (minimal model method) in relation to serum IL-18 (ELISA) concentration in 144 otherwise healthy men aged 51.9+/-12.5 years. In contrast to previous observations in women, circulating IL-18 was not significantly associated with BMI (r=0.12, p=0.1) or WHR (r=0.08, p=0.3). IL-18 was also not associated with absolute or percent fat mass (bioelectric impedance, p>0.20) but, interestingly, it was significantly linked to fat-free mass (p=0.03). Serum IL-18 increased with each quartile of fat-free mass, corresponding to values of < or = 64.2; >64.2 to < or = 71.6; >71.6 to < or = 80.9; and > or = 80.9 kg (ANOVA, p<0.0001). IL-18 was more closely associated with postload glucose during an OGTT (p=0.04) rather than with fasting glucose (p=0.1). HbA1c (p=0.03), HDL-cholesterol (p=0.04) and serum triglycerides (p=0.03) and parameters of systemic inflammation (C-reactive protein, p=0.02) were also significantly associated with circulating IL-18. Insulin sensitivity (minimal model analysis) was linked to circulating IL-18 (p=0.01). In a multiple linear regression analysis this relationship remained significant after controlling for BMI, age and glucose tolerance status. In another model, both fat-free mass and insulin sensitivity contributed to 10% of IL-18 variance. Fat mass does not seem to influence circulating IL-18, as initially proposed. In contrast, the fat-free mass compartment (a well-known confounder in the evaluation of insulin sensitivity) may significantly contribute to the relationship between IL-18 and insulin action.


Characteristic pattern of chromosomal imbalances in posttransplantation lymphoproliferative disorders: correlation with histopathological subcategories and EBV status.
Posttransplantation lymphoproliferative disorders (PTLDs) are a spectrum of lymphoid proliferations, occurring in immunosuppressed organ transplant recipients. They comprise early lesions, polymorphic (P-PTLD), monomorphic (M-PTLD), and Hodgkin/Hodgkin-like lymphoma PTLD (HL-PTLD) lesions. Most of them are associated with Epstein-Barr virus (EBV). Little is known about their genetic changes. We have studied 35 PTLDs[7 P-PTLDs (3/7 polyclonal IgH), 26 M-PTLDs (22 B-cell PTLD, 4 T-cell PTLD), 2 HL-PTLDs], using comparative genomic hybridization (CGH), a DNA-based technique allowing a screening of chromosomal imbalances without needing cultured cells. RESULTS.: Overall incidence of chromosomal imbalances: 51.5 %. The most frequent gains involved 8q24, 3q27 [4 cases each]; 2p24p25, 5p, 9q22q34, 11, 12q22q24, 14q32, 17q, 18q21 [2 cases each]. Nonrandom losses were 17p13 [4 cases]; 1p36, 4q [3 cases each]; 17q23q25, Xp [2 cases each]. Three high-level amplifications were detected: 4p16, 9p22p24, 18q21q23. In this latter imbalance, involvement of Bcl2 has been confirmed by FISH. The nonrandom CGH imbalances occurring in M-PTLD are usually described in lymphomas of immunocompetent patients and contain genes known to be involved in lymphomagenesis, while genomic abnormalities detected in half cases of EBV positive P-PTLD are mostly unknown. This study reported nonrandom chromosomal imbalances in PTLD and also identified early genomic alterations in EBV positive P-PTLD. These results raise two questions: the role of such lesions in the development and progression of those EBV induced-lymphoproliferations and their clinical significance especially in P-PTLD.


Duodenal diverticulitis accompanied by abscess formation treated successfully using an endoscopic nasobiliary drainage catheter: a case report.
Diverticulitis and diverticular abscesses are rare and potentially serious complications of duodenal diverticulum. These conditions often lead to perforation of the diverticulum, necessitating surgical treatment. There have been few reported cases of duodenal diverticulitis with or without perforation treated by endoscopic drainage. Here, we present a case of duodenal diverticulitis accompanied by abscess formation that was treated successfully with an endoscopic nasobiliary drainage catheter. We suggest this treatment could be an acceptable option for selected patients with a localized abscess that is resistant to conservative treatment.


Protein binding of salicylate in cutaneous hepatic porphyria.
(1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltrations. (2) Albumin and haemoglobin levels were significantly reduced in patients with CHP, and salicylate binding by ultrafiltration/centrifugation was 65% compared with 84% in normal subjects. (3) Plasma porphyrin levels were raised, but did not correlate with salicylate binding, and protoporphyrin or uroporphyrin added to plasma did not alter the amount of drug bound. (4) Palmitate added to plasma reduced salicylate binding by 9 to 20% but a crossover of patient and normal plasma proteins and ultrafiltrates confirmed that no other ultrafiltrable metabolites present in patient plasma appeared to cause decreased binding. (5) Scatchard plots obtained by continuous ultrafiltration for normal and patient plasma showed a reduction in the number of primary and secondary binding sites and an increase in the intrinsic association constants for both these sites. (6) It was concluded that the decreased salicylate binding in CHP was due to a reduced albumin concentration and altered salicylate albumin interaction.


Correlation of pre-operative circulating inflammatory cytokines with restenosis and rapid angiographic stenotic progression risk in coronary artery disease patients underwent percutaneous coronary intervention with drug-eluting stents.
This study aimed to explore the associations of common inflammatory cytokine levels with restenosis and rapid angiographic stenotic progression (RASP) risk in coronary artery disease (CAD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Two hundred and ten CAD patients underwent PCI with DES were consecutively recruited, then pre-operative serum levels of TNF-α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, and IL-23 were determined by ELISA. The 12-month in-stent restenosis and RASP of non-intervened lesion were assessed by quantitative coronary angiography analysis. The pre-operative TNF-α, IL-6, IL-17A, and IL-23 expressions were increased while IL-4 expression was decreased in restenosis patients compared with non-restenosis patients. Further analysis revealed that IL-6, IL-8, hypercholesteremia, diabetes mellitus, and HsCRP could independently predict restenosis risk, and subsequent ROC curve revealed that their combination was able to differentiate restenosis patients from non-restenosis patients with an AUC of 0.951 (95%CI: 0.925-0.978). Meanwhile, the pre-operative TNF-α, IL-6, IL-17A, IL-21, and IL-23 expressions were increased whereas IL-4 level was decreased in RASP patients compared with non-RASP patients. Further analysis revealed that TNF-α, IL-6, IL-23, hypercholesteremia, SUA, HsCRP, and multivessel artery lesions could independently predict RASP risk, and subsequent ROC curve disclosed that their combination could discriminate RASP patients from non-RASP patients with an AUC of 0.886 (95%CI: 0.841-0.931). This study unveils the potentiality of pre-operative circulating inflammatory cytokines as markers for predicting restenosis and RASP risk in CAD patients underwent PCI with DES.


Post Earthquake Equilibrium Disturbance: A Study After Nepal-India Earthquake 2015.
Nepal and adjoining areas of India suffered a series of massive earthquakes in April-May 2015. This was followed by a remarkable increase in the patient presenting with vague dizziness like features which could not be attributed to any defined variant of vestibular disorder. Extensive search of literature revealed only scarce information about ambiguous post-earthquake vestibular symptoms and their management. We performed a detailed epidemiological analysis of these patients to analyse the presentation, underlying mechanism and optimal management. The results were scrutinised in light of existing international literature. We observed that earthquake precipitated a psychological stress like event that provoked features of disequilibrium and the neuroanatomical basis of the proposition was explored. We renounce the hypothesis of Secondary BPPV precipitated by earthquake leading to symptoms. The results were interpreted from the perspective of Indian scenario and its utility in post-earthquake disaster management in our country has been highlighted.


Zero-valent iron coupled calcium hydroxide: A highly efficient strategy for removal and magnetic separation of concentrated fluoride from acidic wastewater.
The removal of concentrated fluoride in acidic wastewater by the conventional Ca(OH)2 method is challenged by the insufficient efficiency and difficult separation of fine CaF2 precipitate. Herein, we construct a strategy to tackle these challenges by coupling zero-valent iron (ZVI) with Ca(OH)2. ZVI reduces fluoride concentration from 12,000 to 3980 mg L-1 under optimal conditions primarily through the in-situ growth of porous FeF2·4H2O shell on its surface, which simultaneously assists fluoride removal via adsorption. The residual fluoride after ZVI treatment then decreases to 6.74 mg L-1 via precipitation with Ca(OH)2. Interestingly, the iron ions dissolved from ZVI also participate in the precipitation to form magnetite. This co-precipitation reinforces the fluoride removal and meanwhile endows the resulted precipitates with magnetism, thus enabling the perfect solid-liquid separation by the magnetic field before discharge. The application prospect of this coupling strategy is further verified by its ability in decreasing the concentrations of fluoride and other coexisting heavy metals (Zn2+, Cd2+ and Pb2+) in real smeltery wastewater below their discharge limitations. This study provides a promising strategy for the treatment of concentrated fluoride in acidic wastewater and also highlights ZVI as a good candidate to couple with conventional methods for enhanced pollution control.


Experimental set up for the irradiation of biological samples and nuclear track detectors with UV C.
In this work we present a methodology to produce an "imprint" of cells cultivated on a polycarbonate detector by exposure of the detector to UV C radiation. The distribution and concentration of (10)B atoms in tissue samples coming from BNCT (Boron Neutron Capture Therapy) protocols can be determined through the quantification and analysis of the tracks forming its autoradiography image on a nuclear track detector. The location of boron atoms in the cell structure could be known more accurately by the simultaneous observation of the nuclear tracks and the sample image on the detector. A UV C irradiator was constructed. The irradiance was measured along the lamp direction and at different distances. Melanoma cells were cultured on polycarbonate foils, incubated with borophenylalanine, irradiated with thermal neutrons and exposed to UV C radiation. The samples were chemically attacked with a KOH solution. A uniform irradiation field was established to expose the detector foils to UV C light. Cells could be seeded on the polycarbonate surface. Both imprints from cells and nuclear tracks were obtained after chemical etching. It is possible to yield cellular imprints in polycarbonate. The nuclear tracks were mostly present inside the cells, indicating a preferential boron uptake.


Inhibition of HIV Entry by Targeting the Envelope Transmembrane Subunit gp41.
The transmembrane subunit of the HIV envelope protein, gp41 is a vulnerable target to inhibit HIV entry. There is one fusion inhibitor T20 (brand name: Fuzeon, generic name: enfuvirtide) available by prescription. However, it has several drawbacks such as a high level of development of drug resistance, a short-half life in vivo, rapid renal clearance, low oral bioavailability, and it is only used as a salvage therapy. Therefore, investigators have been studying a variety of different modalities to attempt to overcome these limitations. Comprehensive literature searches were performed on HIV gp41, inhibition mechanisms, and inhibitors. The latest structural information was collected, and multiple inhibition strategies targeting gp41 were reviewed. Many of the recent advances in inhibitors were peptide-based. Several creative modification strategies have also been performed to improve inhibitory efficacy of peptides and to overcome the drawbacks of T20 treatment. Small compounds have also been an area of intense research. There is a wide variety in development from those identified by virtual screens targeting specific regions of the protein to natural products. Finally, broadly neutralizing antibodies have also been important area of research. The inaccessible nature of the target regions for antibodies is a challenge, however, extensive efforts to develop better neutralizing antibodies are ongoing. The fusogenic protein, gp41 has been extensively studied as a promising target to inhibit membrane fusion between the virus and target cells. At the same time, it is a challenging target because the vulnerable conformations of the protein are exposed only transiently. However, advances in biochemical, biophysical, structural, and immunological studies are coming together to move the field closer to an understanding of gp41 structure and function that will lead to the development of novel drugs and vaccines.


Nutrient Sensing and the Oxidative Stress Response.
The simplicity and effectiveness of calorie restriction (CR) in lifespan and healthspan extension have fascinated generations searching for the Fountain of Youth. CR reduces levels of oxidative stress and damage, which have been postulated in the free radical theory of aging as a major cause of aging and diseases of aging. This reduction has long been viewed as a result of passive slowing of metabolism. Recent advances in nutrient sensing have provided molecular insights into the oxidative stress response and suggest that CR triggers an active defense program involving a cascade of molecular regulators to reduce oxidative stress. Physiological studies have provided strong support for oxidative stress in the development of aging-associated conditions and diseases but have also revealed the surprising requirement for oxidative stress to support normal physiological functions and, in some contexts, even slow aging and prevent the progression of cancer. Deciphering the molecular mechanisms and physiological implications of the oxidative stress response during CR will increase our understanding of the basic biology of aging and pave the way for the design of CR mimetics to improve healthspan.


Coupling bending and shear effects on liposome deformation.
Cell membrane deformation induced by external mechanical stimuli has been studied extensively over the past three decades. The present study focuses on the coupling of in-plane shear H and out-of-plane bending B of liposome membrane and its influences on the deformation of a single vesicle subjected to (i) external compressive load via two parallel platens and (ii) contact forces caused by a rigid substrate. Our results show that the increase of membrane resultant stress in both loading configurations causes the liposome to become more rigid and the degree of vesicle deformation decreases when the in-plane shearing effect is dominant. A theoretical approach is developed to facilitate cell membrane characterization under different biomechanical stimuli.


Quantitative density-time measurements in the lungs of children with suspected airway obstruction using ultrafast CT.
Fourteen children under 3 years of age with possible airway obstruction were evaluated with an ultrafast CT scanner, Imatron C-100. Serial 0.05-second multilevel scans were obtained through the chest at rates of 17 images per second. No patient sedation or contrast medium was used. Time-density curves generated over each lung and specific pulmonary zones were compared to characterize the normal variation of density during inspiration and expiration and to determine abnormal patterns associated with airway obstruction. There was a high, positive correlation value (r greater than 0.79) between time/density curves over those pulmonary regions in which there was no focal bronchial obstruction and a low, negative correlation value (r = less than -0.58) with bronchial obstruction. Three studies with reconstruction artifacts were excluded. Furthermore, the results indicate that young children generally have denser lungs, particularly in expiration, than older children or adults. This preliminary study suggests that ultrafast CT offers a promising, unique, rapid and noninvasive approach for diagnosing airway obstruction in childhood.


Administration of Valproic Acid Improves the Survival of Patients with Glioma Treated with Postoperative Radiotherapy.
The aim of this study was to investigate the impact of valproic acid (VPA) on survival and prognosis of patients with glioma who underwent postoperative radiotherapy. We obtained the case data with brain glioma who underwent postoperative radiotherapy from January 2012 to December 2019. This cohort was heterogeneous. We conducted single-factor analysis and multiple-factors analysis of the basic features, pathological classification, therapies of all 185 patients using Kaplan-Meier survival curve, log-rank survival significance test, and Cox regression analysis model. By the end of the last follow-up, 94 patients had died and 96 had recurred in all 185 cases. The median follow-up time of this study was 47 months. The median overall survival (OS) and progression-free survival (PFS) times were 34 and 27 months, respectively. The 1-, 3-, and 5-year OS rates were 86.49%, 48.11%, and 14.60%, respectively. The 1-, 3-, and 5-year PFS rates were 80.00%, 43.78%, and 12.97%, respectively. Univariate analysis revealed that age, pathological grade, and VPA administration were all associated with patients' prognosis (p < 0.05). A Cox multivariate analysis revealed that being 47 years or older, having a high pathological grade (WHO grades III and IV), and not taking VPA were all adverse prognostic factors for OS and PFS in patients with glioma. Age, pathological grade, and VPA administration are the influencing factors for the prognosis of glioma patients with postoperative radiotherapy. Patients with glioma who received VPA had a more favorable prognosis and a lower recurrence rate.


Multiple conduction defects with markedly prolonged ventricular depolarization in cardiomyopathy.
Electrophysiologic investigation of a diffuse and bizarre conduction abnormality in a patient with cardiomyopathy revealed profound slowing of the impulse in the right ventricular outflow region. The resultant 220 msec QRS duration is the longest reported in right bundle branch block.


Vascular and Chronological Age in Men With Erectile Dysfunction: A Longitudinal Study.
Impaired penile color Doppler ultrasound predicts major adverse cardiovascular (CV) events (MACE), particularly in men at low-risk. However, penile color Doppler ultrasound is not recommended in routine clinical checkups. To evaluate whether the difference between vascular and chronological age (Δage), as derived from the SCORE algorithm, is a predictor of MACE in subjects consulting for erectile dysfunction (ED) independently from other CV risk factors, including penile color Doppler ultrasound parameters. A consecutive series of 1687 male patients attending the Outpatient Clinic for ED for the first time was retrospectively studied. Among them, the SCORE was applicable in 49.9% (n = 841) men, of whom 87.9% (n = 739) were free from previous MACE and were analyzed. Vascular age was derived from the SCORE algorithm and the Δage was considered. Information on MACE was obtained through the City of Florence Registry Office. MACE were identified using the International Classification of Diseases, and fatal and nonfatal MACE were coded as 410-414 (ischemic heart disease), 420-429 (other heart diseases), or 798-799 (sudden death from cardiac diseases), 430-434 or 436-438 (cerebrovascular disease), and 440 (peripheral arterial disease). Δage was associated with incident MACE. When dividing the population according to the median age (56 years), family history of CV diseases, and the presence of metabolic syndrome, the association between Δage and MACE was maintained only in low-risk subjects, even after adjusting for confounders [HR = 1.09(1.03-1.16), 1.05(1.01-1.10) and 1.08(1.01-1.16) for younger men, without CV family history or metabolic syndrome, respectively, all P < .05], including penile color Doppler ultrasound parameters. In subjects consulting for ED, Δage is associated with incident MACE, in particular in low-risk men. The prediction of MACE by Δage is independent from other risk factors including penile color Doppler ultrasound parameters, so it can be used as a costless and safe surrogate marker of penile vascular damage.


Molecular cloning and gonadotropin-dependent regulation of equine prostaglandin F2alpha receptor in ovarian follicles during the ovulatory process in vivo.
The progressive rise in gonadotropins prior to ovulation triggers a marked increase in intrafollicular levels of prostaglandin F(2alpha)(PGF(2alpha)), which is known to interact with PGF(2alpha) receptor (FP). Little is known about the regulation of FP during ovulation. This study was undertaken to characterize the equine FP and its gonadotropin-dependent regulation in preovulatory follicles prior to ovulation. The full-length equine FP encodes a 366-amino acid protein that is 82-93% homologous to other species. Using semi-quantitative RT-PCR/Southern blot, we showed that FP mRNA expression was low in follicles obtained before hCG treatment (0h) and at 24, but increased at 12 and 36h post-hCG (P<0.05). This expression was regulated in both follicular cells, with high levels of the transcript at 33 and 36h post-hCG in granulosa cells, and at 12, 30 and 33h post-hCG in theca cells (P<0.05). Immunohistochemistry confirmed the induction of FP protein in both follicular cells after hCG, and immunoblotting revealed the increase of FP protein in preovulatory follicles 36h post-hCG. High levels of FP mRNA were detected in the corpora lutea and heart, but very low or undetectable in other tissues. This study reports for the first time the expression of FP and its up-regulation by hCG in preovulatory follicles prior to ovulation. FP regulation was occurred in different pattern than that observed in other species, suggesting a distinct and species-specific follicular control of FP expression during ovulation, and a potential involvement of PGF(2alpha), acting on granulosa and theca cells, in the ovulatory process.


Edge-to-edge repair with mitral annuloplasty for Barlow's disease.
The purpose of this study was to define the early and midterm results obtained after the use of edge-to-edge repair with mitral annuloplasty in the setting of Barlow's disease. Between 1998 and 2004, 41 patients having Barlow's disease had an edge-to-edge repair creating a double-lumen mitral valve orifice in our unit. In 38 patients (93%), an annuloplasty band was also inserted. Preoperatively, all patients had severe mitral regurgitation (MR), 12 were in New York Heart Association (NYHA) class I, 15 in class II, and 14 in class III. One patient died in hospital (2.4%) and 5 experienced complications (12.5%). There were no late deaths. At follow-up, 2 patients had severe MR and underwent valve replacement, 1 exhibited moderate MR, and 5 had mild MR. Kaplan-Meier 5-year survival, freedom from reoperation and recurrent moderate-severe MR was 97.6% +/- 2.4%, 94% +/- 4.4%, and 90.6% +/- 5.1%, respectively. At latest echocardiographic evaluation (mean 35 +/- 12 months) the mean left ventricular end-systolic and end-diastolic diameters, and the mitral valve area decreased (p = 0.0001) compared with baseline. The mean mitral valve gradient increased (p = 0.001) without clinical evidence of mitral stenosis whereas ejection fraction did not change. Currently, 35 patients are in NYHA class I and 5 are in class II. In the setting of Barlow's disease, use of edge-to-edge repair with mitral annuloplasty is safe and provides lasting restoration of mitral valve competence with measurable hemodynamic and clinical benefits. In our unit, it is the procedure of choice for correction of MR in patients having Barlow's disease.


Multimodality Chamber for coregistered anatomical and molecular imaging of small animals.
Modern imaging methods are applied extensively in translational animal research, and combined analysis of anatomical and functional imaging results is of increasing importance. Many imaging centers handle multiple independent animal colonies and use several imaging modalities, often in combination. The authors have developed and successfully tested a two-piece acrylic Multimodality Chamber that enables investigators to coregister images from two or more modalities, including microMR, microCT, microPET and optical imaging.


Prospective assessment of the impact of feedback on colonoscopy performance.
Colonoscopy is an operator-dependent procedure. The medical literature describes disparity in colonoscopy performance with respect to polyp detection, caecal intubation rates and procedural times. To assess prospectively the impact of feedback among a large cohort of colonoscopists on three performance parameters: caecal intubation rate, insertion time and withdrawal time. In a prospective clinical study, procedural data from all out-patient colonoscopies performed by attending gastroenterologists at our institution were recorded routinely in a computerized database. Enhanced serial feedback was provided on a quarterly basis for three procedure parameters: intubation to caecum, insertion time and withdrawal time. Feedback (absolute value, % rank and group distribution) was sent by email every 3 months beginning with January 2005 feedback for all of 2004, and subsequently quarterly in April 2005 (for January-March 2005), July 2005 (for April-June 2005) and October 2005 (for July-September 2005). Feedback was provided to 58 endoscopists with a median experience level of 8 years. There was a relative decline of 19% in incomplete procedures, with median caecal non-intubation rates decreasing from 4.7% to 3.8% following the introduction of feedback while median insertion times declined from 10.6 to 9.5 mins, P = 0.02. Median withdrawal times did not change significantly, 9.1-8.9 mins, P = 0.6. Feedback by email appears to improve colonoscopy performance, enhancing completion rates and shortening insertion times without compromising withdrawal times.


Interpersonal relationships and drug use over time among homeless people: a qualitative study.
Homelessness is one of the most severe forms of social exclusion and is an important public health issue. It is characterized by processes of weakening of interpersonal bonds. The objective of this study was, therefore, to elucidate how interpersonal relationships change over the life cycle of homeless drug and alcohol users. We used a qualitative methodology. The participants were adults who had a history of homelessness and use of alcohol and other drugs. The interviews were semi structured and used a timeline instrument. All interview were audio recorded, transcribed, and submitted to thematic analysis. Twenty individuals participated in the study. Reports on social exclusion over time stood out in respect of four main themes and their respective subthemes: Theme 1 - Childhood: instability upbringing, abuse, violence, and an absent or not very present father figure; Theme 2 - Adolescence: school dropout and failure; acceptance of gender and sexual orientation; birth of first child, living with a partner or getting married: Theme 3 - Adulthood: estrangement or conflicting relationship with family; health problems; drug trafficking and prostitution; Theme 4 - Cross-cutting factors: death of relatives and substance use. The results suggest that interpersonal relationships are permeated by successive breakups, conflicts and other events that start in childhood and can have a cumulative effect in later stages of life, and cross the subsequent phases. Substance abuse and dependence are mentioned as cross-cutting factors that intensify social exclusion in all stages of life.


Clinical results after the multidisciplinary treatment of spinal arteriovenous fistulas.
We retrospectively evaluated the clinical outcome after multidisciplinary treatment of spinal arteriovenous fistulas (AVFs) in terms of the Aminoff-Logue grading scale (ALS) to depict the outcome in a perspective pertinent to the quality of everyday living. Twenty-six spinal AVFs in 25 patients were angiographically diagnosed from April 1998 through April 2012 and treated by endovascular embolization or surgery. When both treatment procedures seemed feasible, embolization was undertaken as the initial treatment. Motor and gait disturbance at follow-up was retrospectively graded according to ALS. All lesions were localized at the thoracolumbar or sacral levels and include six epidural AVFs with intradural venous reflux, 14 dural AVFs, and six perimedullary AVFs. Embolization was performed as the initial treatment for 17 lesions, while open surgery was performed for the others as well as for residual or recurrent lesions after embolization. All lesions were completely occluded except three perimedullary AVFs. At clinical follow-up of 1-153 months (mean 53.3), amelioration of gait disturbance with reduction of ALS scores was noted for 13 lesions and amelioration of micturition for 13 lesions as well. Clinical functional status was improved for half of the lesions after the multidisciplinary treatment.


Fecal constituents of a high-risk North American and a low-risk Finnish population for the development of large bowel cancer.
Feces collected in Kuopio, Finland, a low-risk population for colon cancer, and in the New York metropolitan area, a high-risk population for colon cancer, were compared. The dietary intake of fat and protein were the same in the two populations, but the sources of fat were different, a greater portion coming from meat in New York, and from dairy products in Kuopio. The daily stool output was higher in Kuopio due to the high intake of cereal products rich in fiber. The concentration of fecal secondary bile acids and the bacterial beta-glucuronidase activity were lower in Kuopio, but the daily output of these constituents was the same in the two groups. The daily fecal excretion of neutral sterols was higher in Kuopio than in New York. Our data suggest that the greater fecal bulk in Kuopio may dilute tumorigenic compounds which come in direct contact with the colon mucosa.


Gender dimorphism of tumor growth: role of gonadal hormones in differential regulation of apoptosis of a murine T cell lymphoma.
The present investigation was undertaken to study if a gender-dependent differential induction of tumor cell apoptosis is responsible for the manifestation of gender dimorphism observed in the growth of a transplantable murine T cell lymphoma, designated as Dalton's lymphoma (DL). Tumor cell samples obtained from male tumor-bearing mice showed a higher number of cells with apoptotic morphology compared to that observed in female tumor-bearing mice. In this report we demonstrate that male hormone androgen and female hormone estrogen can differentially modulate tumor cell proliferation and apoptosis through alteration in the expression pattern of cell death regulating genes: p53 and CAD. DL cells were shown to express mRNA for androgen and estrogen receptors. Further these gonadal hormones also induced tumor cells to produce tumor growth regulating proteins: VEGF, TGF-beta, IL-2, IL-2R, SOCS, Hsp-70 and IFN-gamma which in turn either through autocrine action on tumor cells or via TAM-derived NO were observed to regulate tumor cell apoptosis leading to gender dimorphism of tumor growth. This study also discusses the possible mechanism involved. The study has clinical significance as these results will helps in understanding the mechanism of gender dimorphism with respect to the progression of T-cells tumors.


Can COVID 2019 induce a specific cardiovascular damage or it exacerbates pre-existing cardiovascular diseases?
A novel coronavirus SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) with cardiovascular and multiple organ failure till death. The main mechanisms of virus internalization and interaction with the host are down-regulation or upregulation of the ACE2 receptor, the surface glycoprotein competition mechanism for the binding of porphyrin to iron in heme formation as well as interference with the immune system. The interference on renin-angiotensin-aldosterone system (RAAS) activation, heme formation, and the immune response is responsible for infection diffusion, endothelial dysfunction, vasoconstriction, oxidative damage and releasing of inflammatory mediators. The main pathological findings are bilateral interstitial pneumonia with diffuse alveolar damage (DAD). Because ACE receptor is also present in the endothelium of other districts as well as in different cell types, and as porphyrins are transporters in the blood and other biological liquids of iron forming heme, which is important in the assembly of the hemoglobin, myoglobin and the cytochromes, multiorgan damage occurs both primitive and secondary to lung damage. More relevantly, myocarditis, acute myocardial infarction, thromboembolism, and disseminated intravasal coagulation (DIC) are described as complications in patients with poor outcome. Here, we investigated the role of SARSCoV-2 on the cardiovascular system and in patients with cardiovascular comorbidities, and possible drug interference on the heart.


Estimation of fetal weight using Hadlock's formulas: Is head circumference an essential parameter?
To test the equivalence of two fetal weight estimation formulas generated by Hadlock, a formula that includes head circumference parameter (H1), and another (H2) which excludes this parameter. A secondary aim was to identify the patients in which H2 formula is less reliable to use. This retrospective cohort study included a total of 1220 sonographic fetal weight estimations performed within seven days of delivery and recorded at a single medical center from January 2014 to December 2016. Estimated fetal weight was calculated using H1 and H2 formulas. Their accuracies were compared using percentage error, the proportion of weight estimations falling within ±15% error interval and by Bland-Altman analysis. Multivariate regression was performed to evaluate factors affecting weight estimation by H2 formula. The mean birth weight was 3288.92 ± 641.27gr. The H2 formula presented with statistically significant higher value of systemic mean percent error comparing to H1 (3.19% vs. 1.87%, p < 0.001 respectively). H2 formula had a lower accuracy compared to H1 in predicting fetal weight within ±15% of birth weight (90.49% vs. 93.44%, p < 0.01 respectively). Using Bland-Altman analysis, the 95% limits of agreement between both formulas were (-142.03) to 231.79gr with a mean of 44.88gr. Factors found to influence significantly on H2 formula were long femur length (OR 1.144, p < 0.0001) and low maternal age (OR 0.947, p < 0.01). H1formula was more accurate than H2 formula in predicting fetal weight at term. However, the accuracy difference was found to be small. Therefore, if ultrasonographic evaluation of HC is technically difficult, Hadlock formula that excludes head circumference can be used with confidence. Caution should be paid with higher values of femur length and lower maternal age.


The 16S rRNA and mcrA gene based comparative diversity of methanogens in cattle fed on high fibre based diet.
In the present study, the diversity of rumen methanogens in crossbred Karan Fries cattle was determined by constructing 16S rRNA and mcrA (methyl coenzyme-M reductase α subunit) gene libraries using specific primers. All thirteen OTUs or phylotypes from 16S rRNA library clustered with order Methanobacteriales, twelve of which aligned with Methanobrevibacter spp., whereas one OTU resemble with Methanosphaera stadtmanae. Out of eighteen OTUs identified from mcrA gene library, fifteen clustered with order Methanobacteriales, two resemble with Methanomicrobiales and remaining one grouped with Methanosarcinales. These results revealed that Methanobrevibacter phylotype was predominantly present in Karan Fries crossbred cattle fed on high fibrous diet containing wheat straw. Compared to 16S rRNA gene, mcrA gene OTUs clustered in three orders providing better insights of rumen methanogens diversity in cattle.


Antimetastasis effect of anthraquinones from marine fungus, Microsporum sp.
This chapter discusses about obtaining natural products which have anticancer metastasis activities from selected marine-derived fungus (Microsporum sp.) and investigates their biological activities such as cytotoxicity on viability cell lines, anticancer cell migration and invasion, protease inhibition, and expression of matrix metalloproteinase (MMP-2 and -9). Moreover, the correlative mechanisms behind these activities were studied.


Hematopoietic neoplasms in Prkar2a-deficient mice.
Protein kinase A (PKA) is a holoenzyme that consists of a dimer of regulatory subunits and two inactive catalytic subunits that bind to the regulatory subunit dimer. Four regulatory subunits (RIα, RIβ, RIIα, RIIβ) and four catalytic subunits (Cα, Cβ, Cγ, Prkx) have been described in the human and mouse genomes. Previous studies showed that complete inactivation of the Prkar1a subunit (coding for RIα) in the germline leads to embryonic lethality, while Prkar1a-deficient mice are viable and develop schwannomas, thyroid, and bone neoplasms, and rarely lymphomas and sarcomas. Mice with inactivation of the Prkar2a and Prkar2b genes (coding for RIIα and RIIβ, respectively) are also viable but have not been studied for their susceptibility to any tumors. Cohorts of Prkar1a (+/-) , Prkar2a (+/-) , Prkar2a (-/-) , Prkar2b (+/-) and wild type (WT) mice have been observed between 5 and 25 months of age for the development of hematologic malignancies. Tissues were studied by immunohistochemistry; tumor-specific markers were also used as indicated. Cell sorting and protein studies were also performed. Both Prkar2a (-/-) and Prkar2a (+/-) mice frequently developed hematopoietic neoplasms dominated by histiocytic sarcomas (HS) with rare diffuse large B cell lymphomas (DLBCL). Southern blot analysis confirmed that the tumors diagnosed histologically as DLBCL were clonal B cell neoplasms. Mice with other genotypes did not develop a significant number of similar neoplasms. Prkar2a deficiency predisposes to hematopoietic malignancies in vivo. RIIα's likely association with HS and DLBCL was hitherto unrecognized and may lead to better understanding of these rare neoplasms.


A repackaged CRISPR platform increases homology-directed repair for yeast engineering.
Inefficient homology-directed repair (HDR) constrains CRISPR-Cas9 genome editing in organisms that preferentially employ nonhomologous end joining (NHEJ) to fix DNA double-strand breaks (DSBs). Current strategies used to alleviate NHEJ proficiency involve NHEJ disruption. To confer precision editing without NHEJ disruption, we identified the shortcomings of the conventional CRISPR platforms and developed a CRISPR platform-lowered indel nuclease system enabling accurate repair (LINEAR)-which enhanced HDR rates (to 67-100%) compared to those in previous reports using conventional platforms in four NHEJ-proficient yeasts. With NHEJ preserved, we demonstrate its ability to survey genomic landscapes, identifying loci whose spatiotemporal genomic architectures yield favorable expression dynamics for heterologous pathways. We present a case study that deploys LINEAR precision editing and NHEJ-mediated random integration to rapidly engineer and optimize a microbial factory to produce (S)-norcoclaurine. Taken together, this work demonstrates how to leverage an antagonizing pair of DNA DSB repair pathways to expand the current collection of microbial factories.


Testing an Instrument for Assessing Nursing Intensity in Perioperative Settings: Construct Validity.
To test the construct validity of an instrument to assess nursing intensity in perioperative settings. A survey based on 24 core elements of perioperative nursing was used. A total of 652 assessments were performed on 308 patients. Principal component analysis was used. A model with four principal components was suggested. Patients' care needs appear to vary as they progress along the perioperative continuum. Thus, a given instrument's content differs from the intraoperative to postoperative phases. More testing is needed to achieve a valid tool for allocating nursing staff in operating departments. Reliable tools are needed to match patients' care needs with available nursing resources.


Epidemiology of gastroesophageal reflux disease in Iran: a systematic review and meta-analysis.
Gastroesophageal reflux disease (GERD), which leads to acid reflux into the esophagus, is a common gastrointestinal disorder. Several studies have shown the prevalence of GERD in Iranian population, but their evidence is contradictory. Therefore, the present study was conducted to investigate the epidemiology of GERD in Iran. The entire steps of this systematic review and meta-analysis were based on the MOOSE protocol, and the results were reported accordance with the PRISMA guideline. This review is registered on PROSPERO (registration number: CRD42020142861). To find potentially relevant published articles, comprehensive search was done on international online databases Scopus, Science Direct, EMBASE, PubMed/Medline, CINAHL, EBSCO, Cochrane Library, Web of Science, Iranian online databases and the Google Scholar search engine in June 2019. Cochran test and I2 index were used to assess the heterogeneity of the studies. Data were analyzed using Comprehensive Meta-Analysis software ver. 2. The significance level of the test was considered to be P < 0.05. The daily, weekly, monthly, and overall prevalence of GERD symptoms in Iranian population was 5.64% (95%CI [confidence interval]: 3.77-8.35%; N = 66,398), 12.50% (95%CI: 9.63-16.08%; N = 110,388), 18.62% (95%CI: 12.90-26.12%; N = 70,749) and 43.07% (95%CI: 35.00-51.53%; N = 73,189), respectively. The daily, weekly, monthly, and overall prevalence of heartburn in Iranian population was 2.46% (95%CI: 0.93-6.39%; N = 18,774), 9.52% (95%CI: 6.16-14.41%; N = 54,125), 8.19% (95%CI: 2.42-24.30%; N = 19,363) and 23.20% (95%CI: 13.56-36.79%; N = 26,543), respectively. The daily, weekly, monthly, and overall prevalence of regurgitation in Iranian population was 4.00% (95%CI: 1.88-8.32%; N = 18,774), 9.79% (95%CI: 5.99-15.60%; N = 41,140), 13.76% (95%CI: 6.18-44.31%; N = 19,363) and 36.53% (95%CI: 19.30-58.08%; N = 21,174), respectively. The sensitivity analysis for prevalence of all types GERD, heartburn and regurgitation symptoms by removing a study showed that the overall estimate is still robust. The present meta-analysis provides comprehensive and useful information on the epidemiology of GERD in Iran for policy-makers and health care providers. This study showed a high prevalence of GERD in Iran. Therefore, effective measures on GERD-related factors such as lifestyle can be among the health policies of Iran.


Outcomes of mature primiparas in an out-of-hospital birth center.
This is a retrospective chart review of perinatal outcomes of all primiparas over the age of 24 delivering at Maternity Center Associates, an out-of-hospital birth center, from January 1985 through May 1988 (N = 228). Chi-square analysis was used to determine whether mature primiparas, aged 35 to 43 (n = 27), had significantly more adverse outcomes than younger primiparas, aged 25 to 34 (n = 201). There was a significant difference between the groups in rate of transfer to hospital; however, there were no significant differences in rate of cesarean section, infant birth weight, apgar scores, and length of second stage labor. Implications for practice and future study are examined.


What are American children eating? Implications for public policy.
As the health and demographic profile of the U.S. population changes, the food consumption patterns of American children have also changed. This review is organized around a series of policy issues looking at these new food consumption patterns, their relationship to the Dietary Guidelines, and their impact on children's health.


Commentary: Using potential outcomes causal methods to assess whether reductions in PM2.5 result in decreased mortality.
Causal inference regarding exposures to ambient fine particulate matter (PM2.5) and mortality estimated from observational studies is limited by confounding, among other factors. In light of a variety of causal inference frameworks and methods that have been developed over the past century to specifically quantify causal effects, three research teams were selected in 2016 to evaluate the causality of PM2.5-mortality association among Medicare beneficiaries, using their own selections of causal inference methods and study designs but the same data sources. With a particular focus on controlling for unmeasured confounding, two research teams adopted an instrumental variables approach under a quasi-experiment or natural experiment study design, whereas one team adopted a structural nested mean model under the traditional cohort study design. All three research teams reported results supporting an estimated counterfactual causal relationship between ambient PM2.5 and all-cause mortality, and their estimated causal relationships are largely of similar magnitudes to recent epidemiological studies based on regression analyses with omitted potential confounders. The causal methods used by all three research teams were built upon the potential outcomes framework. This framework has marked conceptual advantages over regression-based methods in addressing confounding and yielding unbiased estimates of average treatment effect in observational epidemiological studies. However, potential violations of the unverifiable assumptions underlying each causal method leave the results from all three studies subject to biases. We also note that the studies are not immune to some other common sources of bias, including exposure measurement errors, ecological study design, model uncertainty and specification errors, and irrelevant exposure windows, that can undermine the validity of causal inferences in observational studies. As a result, despite some apparent consistency of study results from the three research teams with the wider epidemiological literature on PM2.5-mortality statistical associations, caution seems warranted in drawing causal conclusions from the results. A possible way forward is to improve study design and reduce dependence of conclusions on untested assumptions by complementing potential outcomes methods with structural causal modeling and information-theoretic methods that emphasize empirically tested and validated relationships.


Copper deprivation modulates CTR1 and CUP1 expression and enhances cisplatin cytotoxicity in Saccharomyces cerevisiae.
Saccharomyces cerevisiae has been established as a model system for cancer studies, due to the widely conserved family of genes involved in cell cycle progression, proliferation and apoptosis. In the current study, we sought to determine whether copper deprivation modulates sensitivity of yeast to cisplatin. Yeast cultures grown in low copper medium and exposed to bathocuproiene disulfate (BCS) resulted in significant reduction of intracellular copper. We report here that low copper medium rendered BY4741 hypersensitive to cisplatin (CDDP). Yeast grown in low copper medium exhibited ∼2.0 fold enhanced cytotoxicity in survival and colony-forming ability, compared to copper adequate control cells grown in YPD. The effect of copper restriction on CDDP sensitivity appeared to be associated with the up regulation of CTR1, facilitating enhanced uptake and accumulation of CDDP. Also, CDDP further lowered copper deprivation-induced changes in CUP1 metallothionein levels, SOD activity and GSH levels. These changes were associated with increased protein oxidation and lipid peroxidation induced by CDDP. These results thus suggest that cisplatin cytotoxicity is potentiated under low copper conditions due to enhanced uptake and accumulation of cisplatin and also in part due to lowered antioxidant defense and increased oxidative stress imposed by copper deprivation.


Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.
Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined. We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non-transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion. We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non-transplantable lungs, while CHIT-1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non-transplantable lungs (AUC .81). Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.


Treatment of lichen planus with griseofulvin. Report of seven cases.
Seven patients with lichen planus of the oral mucosa (four with erosive and three with reticular types of the disease) were studied; they were treated with 500 mg of griseofulvin twice daily for 2 1/2 months. In no case was improvement observed; on the contrary, in four patients (two with erosive and two with reticular forms) the condition worsened.


Glutamate receptors: RNA editing and death of motor neurons.
The aetiology of sporadic amyotrophic lateral sclerosis (ALS), a fatal paralytic disease, is largely unknown. Here we show that there is a defect in the editing of the messenger RNA encoding the GluR2 subunit of glutamate AMPA receptors in the spinal motor neurons of individuals affected by ALS. This failure to swap an arginine for a glutamine residue at a crucial site in the subunit, which occurs normally in the affected brain areas of patients with other neurodegenerative diseases, will interfere with the correct functioning of the glutamate receptors and may be a contributory cause of neuronal death in ALS patients.