Inter-individual discount factor differences in reward prediction are topographically associated with caudate activation.
In general, humans tend to devalue a delayed reward. Such delay discounting is a theoretical and computational concept in which the discount factor influences the time scale of the trade-off between delay of reward and amount of reward. The discount factor relies on the individual's ability to evaluate the future reward. Using functional magnetic resonance imaging, we investigated brain mechanisms for reward valuation at different individual discount factors in a delayed reward choice task. In the task, participants were required to select small/immediate or large/delayed rewards to maximize the total reward over time. The discount factor for each participant individually was calculated from the behavioral data based on an exponential discounting model. The estimated value of a future reward increases as the expected delivery approaches, so the time course of these estimated values was computed based on each individual's discount factor; each was entered into the regression analysis as an explanatory (independent) variable. After the region of interest was narrowed anatomically to the caudate, a peak coordinate was detected in each individual. A correlation analysis revealed that the location of the peak along the dorsal-ventral axis in the right caudate was positively correlated with the discount factor. This implies that individuals who showed a larger discount factor had peak activations in a more dorsal part of the right caudate associated with future reward prediction. This evidence also suggests that a higher ability to delay reward prediction might be related to activation of the more dorsal caudate.


Natural progression of bilateral maxillary silent sinus syndrome: A metachronous case report.
Silent sinus syndrome refers to a constellation of spontaneous and progressive enophthalmos and hypoglobus in the setting of asymptomatic ipsilateral maxillary sinus atelectasis. Although its exact etiopathogenesis is not completely understood, obstruction of the ostiomeatal complex appears to be the inciting event. Most of the reported cases of silent sinus syndrome involve one maxillary sinus. Only a handful of true bilateral silent sinus syndrome cases have been reported in the literature. The aim of this report is to present a case of metachronous bilateral maxillary silent sinus syndrome and its natural progression. Also included is a review of the literature on ethmoidal, frontal, and bilateral maxillary silent sinus syndrome.


Addition and correction: the NF-kappa B-like DNA binding activity observed in Dictyostelium nuclear extracts is due to the GBF transcription factor.
We have previously reported that a NF-kappa B transduction pathway was likely to be present in the cellular slime mold Dictyostelium discoideum. This conclusion was based on several observations, including the detection of developmentally regulated DNA binding proteins in Dictyostelium nuclear extracts that bound to bona fide kappa B sequences. We have now performed additional experiments which demonstrate that the protein responsible for this NF-kappa B-like DNA binding activity is the Dictyostelium GBF (G box regulatory element binding factor) transcription factor. This result, along with the fact that no sequence with significant similarity to components of the mammalian NF-kappa B pathway can be found in Dictyostelium genome, now almost entirely sequenced, led us to reconsider our previous conclusion on the occurrence of a NF-kappa B signal transduction pathway in Dictyostelium.


[Anterior pelvic exenteration. Report of a case].
Anterior pelvic exenteration is the last opportunity to control disease in a patient with cervical cancer in an advanced stage with a vesico-vaginal fistula, or in a patient with persistence of the disease and the need of improving the quality of life. In this case we present the cause of a 62 year old patient, with IVa stage cervical cancer, with bladder spread and a vesico-vaginal fistula treated with an anterior pelvic exenteration with Bricker technique and adjuvant treatment with radiotherapy.


A Chemical Role for Trichloromethane: Room-Temperature Removal of Coordinated Solvents from Open Metal Sites in the Copper-Based Metal-Organic Frameworks.
Open coordination sites (OCSs) in metal-organic frameworks (MOFs) have shown potential in applications such as molecular separation, sorption, catalysis, and sensing. Thus, the removal of coordinated solvent has been viewed as an essential step that needs to be performed prior to the use of the MOFs in the above applications. To date, a thermal method that is normally performed by applying heat and vacuum has been the most commonly employed activation method despite its negative influence on the structural integrity of the MOFs. In this report, we demonstrate that commonly inert trichloromethane (TCM) can activate OCSs; the TCM treatment process serves as an alternative chemical route to activation that does not require the external thermal energy. On the basis of the Raman study, we suggest a possible mechanism for the chemical activation process where TCM may weakly coordinate to the OCSs and then spontaneously dissociate. In addition, we prove that the chemical activation behavior is substantially boosted when a small amount of external heat energy (55 °C, 2.6 meV) is supplied during the TCM treatment. Using an HKUST-1-polyvinylidene fluoride (PVDF) mixed matrix (MM), we also demonstrate that this chemical activation strategy is a safe way to activate thermally deformable MOF-polymer mixed matrices.


The Effect of Clenching and Occlusal Instability on Body Weight Distribution, Assessed by a Postural Platform.
The purpose of this research project was to investigate whether or not clenching and occlusal instability of Angle's Class I malocclusion have an effect on body weight distribution in healthy adult subjects. Twenty adults (fourteen males and six females, ages 27-40, mean age 31.7 years, SD 3.32) were included in this study. The MatScan (Tekscan Inc., Boston, MA) system was used to measure the body weight distribution changes of the subjects. Four body weight distribution measurements were taken for each subject while (1) the mandible was in the rest position (no tooth contact) (RES), (2) subject was clenching (maximum intercuspation of the teeth with heavy occlusal forces) (CL), (3) subject was clenching on the right side (with 1 mm disocclusion on the left side) (CLR), and (4) subject was clenching on the left side (with 1 mm disocclusion on the right side) (CLL). The lateral and the anteroposterior body weight distribution changes during the different clenching conditions (both sides, right, and left) were compared to those at which the mandible was at the rest position. The statistical significance of these results was tested with a Chi-Squared test (p<0.05). Based on the findings of the present study it was concluded that clenching and occlusal instability are associated with lateral body weight distribution changes.


Balancing local order and long-ranged interactions in the molecular theory of liquid water.
A molecular theory of liquid water is identified and studied on the basis of computer simulation of the TIP3P model of liquid water. This theory would be exact for models of liquid water in which the intermolecular interactions vanish outside a finite spatial range, and therefore provides a precise analysis tool for investigating the effects of longer-ranged intermolecular interactions. We show how local order can be introduced through quasichemical theory. Long-ranged interactions are characterized generally by a conditional distribution of binding energies, and this formulation is interpreted as a regularization of the primitive statistical thermodynamic problem. These binding-energy distributions for liquid water are observed to be unimodal. The Gaussian approximation proposed is remarkably successful in predicting the Gibbs free energy and the molar entropy of liquid water, as judged by comparison with numerically exact results. The remaining discrepancies are subtle quantitative problems that do have significant consequences for the thermodynamic properties that distinguish water from many other liquids. The basic subtlety of liquid water is found then in the competition of several effects which must be quantitatively balanced for realistic results.


High energy ion beams from the plasma focus.
Instability development in the pinch induces a locally enhanced electric field that accelerates the charged particles to extraordinary high energies. Rapid discharge is the singular state of the ion source confirming high plasma impedance. High energy ion beam is correlated to the electrical discharge parameters and consequently the ion acceleration potential is directly related to the mean ion energy. Multi-MeV ions have been measured by magnetic spectrometry and nuclear activation yield-ratio to obtain the ion energy spectra and critically analyze the ion spectrum. A set of magnetic lens arranged in an optimized coil configuration results in medical grade radioactivity of 0.5GBq for a low energy plasma focus. High energy proton beams enables evaluating the sensitivity of link-board components and the error structure identification, with a significant probability of 0.1perproton.


Proposition of a New POLA Index to Assess the Immunomodulatory Properties of the Diet and Its Relationship with the Gut Microbiota, Using the Example of the Incidence of COVID-19 in a Group of People without Comorbidities.
A rise in the incidence of infections with severe acute respiratory syndrome coronavirus 2 has sparked the search for protective strategies against the new pathogen. It is known that individual food components can interact with different immune cells, modulating the immune response of the body. The aim of this study was to develop an index assessing the immunomodulatory potential of diet (POLA index) and to test its utility for the prediction of coronavirus disease 2019 (COVID-19) in a group of healthy young people following a traditional or vegetarian diet. Data on body composition, anthropometric measurements, physical activity, dietary intake, and gut microbiota were obtained from 95 adults (mean age, 34.66 ± 5.76 years). There was a strong correlation between the dietary inflammatory index and the POLA index (r = 0.90; p < 0.0001). Based on Cohen's kappa statistic, there was a good agreement in qualitative interpretation between the two indices (kappa = 0.61; p < 0.0001). People on a diet with beneficial immunomodulatory effects had a lower risk of COVID-19 of approximately 80%, as compared with those on a diet with highly unbeneficial immunomodulatory effects. In daily practice, the POLA index might serve as a useful tool for dietitians to identify individuals whose diet is deficient in ingredients for optimal immune system function and change their dietary behavior to ensure optimal immune function that reduces the risk of infection.


Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes.
Aneuploidy is the leading genetic abnormality causing early miscarriage and pregnancy failure in humans. Most errors in chromosome segregation that give rise to aneuploidy occur during meiosis in oocytes, but why oocyte meiosis is error-prone is still not fully understood. During cell division, cells prevent errors in chromosome segregation by activating the spindle assembly checkpoint (SAC). This control mechanism relies on detecting kinetochore (KT)-microtubule (MT) attachments and sensing tension generated by spindle fibers. When KTs are unattached, the SAC is activated and prevents cell-cycle progression. The SAC is activated first by MPS1 kinase, which triggers the recruitment and formation of the mitotic checkpoint complex (MCC), composed of MAD1, MAD2, BUB3, and BUBR1. Then, the MCC diffuses into the cytoplasm and sequesters CDC20, an anaphase-promoting complex/cyclosome (APC/C) activator. Once KTs become attached to microtubules and chromosomes are aligned at the metaphase plate, the SAC is silenced, CDC20 is released, and the APC/C is activated, triggering the degradation of Cyclin B and Securin, thereby allowing anaphase onset. Compared to somatic cells, the SAC in oocytes is not as effective because cells can undergo anaphase despite having unattached KTs. Understanding why the SAC is more permissive and if this permissiveness is one of the causes of chromosome segregation errors in oocytes still needs further investigation. The present protocol describes the three techniques to comprehensively evaluate SAC integrity in mouse oocytes. These techniques include using nocodazole to depolymerize MTs to evaluate the SAC response, tracking SAC silencing by following the kinetics of Securin destruction, and evaluating the recruitment of MAD2 to KTs by immunofluorescence. Together these techniques probe mechanisms needed to produce healthy eggs by providing a complete evaluation of SAC integrity.


Anaemia status of preconception young married women in India.
The early detection of anaemia is important for its subsequent control and incidence among women of childbearing age. This study aimed to assess the anaemia status of preconception young married women in India using National Family Health Survey-4 data collected in 2015-16. A total 65,238 sample preconception young married women were analysed using univariate, bivariate and multivariate techniques. A majority belonged to the Hindu religion (81.7%), lived in rural areas (64.5%) and had secondary level education (51.8%), and 41.7% had not yet given birth. The percentage suffering from anaemia was 51.3%. The prevalence of anaemia was higher among younger women (55.3%), those from Scheduled Tribes (59.0%), those living in rural areas (52.8%), the non-educated (55.9%), those in the poorest wealth quintile (56.9%), those from the East region (57.0%) and those with a low body mass index (BMI) (58.4%). The adjusted odds ratios indicated that, after controlling for significant background factors, Hindu, Scheduled Tribe, Scheduled Caste, East region, already having a child, too thin for their height and poorer and poorest wealth quintiles had higher odds of suffering from anaemia compared with the reference groups. The odds of suffering from anaemia decreased with age and education. The study showed a high burden of anaemia and associated risk factors among preconception young married women in India. The finding will inform decision-makers when planning interventions to decrease anaemia among women of childbearing age in India.


A Latent Variable Approach to Differentiating Neural Mechanisms of Irritability and Anxiety in Youth.
Comorbidity is ubiquitous in psychiatry, but it is unclear how to differentiate neural mechanisms of co-occurring symptoms. Pediatric irritability and anxiety symptoms are prevalent and frequently co-occur. Threat orienting is pertinent to both phenotypes and is an ideal context in which to examine their unique and common neural mechanisms. To decompose the unique and shared variances of pediatric irritability and anxiety symptoms and to determine neural correlates of these differentiated phenotypes during threat orienting. This investigation was a cross-sectional functional magnetic resonance imaging study. The setting was a research clinic at the National Institute of Mental Health. Participants were youth aged 8 to 18 years spanning multiple diagnostic categories (141 youth with disruptive mood dysregulation disorder, anxiety disorder, and/or attention-deficit/hyperactivity disorder and 56 healthy youth). This combination provided wide variation in levels of irritability and anxiety symptoms. Data were acquired between June 30, 2012, and June 28, 2016. Participants and parents rated youth's irritability on the Affective Reactivity Index and anxiety on the Screen for Child Anxiety Related Emotional Disorders. Bifactor analysis decomposed the unique and shared variances. A functional magnetic resonance imaging dot-probe task assessed attention orienting to angry (ie, threat) vs neutral faces. Whole-brain analyses examined associations between the bifactor-derived phenotypes and both neural activity and amygdala functional connectivity. Among 197 participants included in the final analysis, the mean (SD) age was 13.1 (2.7) years, and 91 (46.2%) were female. The best-fit bifactor model (Comparative Fit Index, 0.959; Root Mean Square Error of Approximation, 0.066) included unique factors of parent-reported irritability, youth-reported irritability, and anxiety, as well as a common factor of negative affectivity. When the task required attention away from threat, higher parent-reported irritability was associated with increased activity in the insula, caudate, dorsolateral and ventrolateral prefrontal cortex, and inferior parietal lobule (t189≥4.15 for all, P < .001 for all). In contrast, higher anxiety was associated with decreased amygdala connectivity to the cingulate, thalamus, and precentral gyrus (t189≤-4.19 for all, P < .001 for all). These distinctive neural correlates did not emerge using a diagnostic approach. A latent variable approach to parsing co-occurring symptom dimensions revealed a novel double dissociation. During orientation away from threat, only irritability was associated with neural activity, whereas only anxiety was associated with amygdala connectivity. Despite the challenges of symptom co-occurrence for clinical neuroscience, data-driven phenotyping may facilitate a path forward.


Non-steroidal anti-inflammatory drugs and paracetamol in self-therapy of various disorders in students of different fields of study.
Over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are most commonly the first-line pharmacotherapy in combating different pain and inflammatory disorders and fever. Unfortunately, those drugs might have serious side effects, especially when they are used in an inappropriate way. The aim of the study was to explore various aspects of NSAIDs and paracetamol use in the self-therapy of miscellaneous disorders in young adults. The questionnaire-based survey comprised 250 consecutive students aged 22.1 ± 1.9 years (189 women) of diverse fields of study. The drugs were applied in clinical conditions in which they should be avoided including asthma attack (1.2%), vomiting (2.4%), malaise and depression (3.6%), in autumn and winter as a preventive measure against infections (14.0%), heart-burn (2.0%) and during food poisoning (16.0%). As many as 6.0% of the students claimed that studied medications are ultimately free of adverse reactions. Men more frequently than women used NSAIDs and paracetamol during alcohol consumption (49.2% vs 30.7%, p = 0.009, respectively) but less often were aware that there are maximum doses of medications which should not be exceeded (57.4% vs 76.7%, p = 0.003, respectively). The students of medical-related degree courses (n = 82) compared with individuals of other subjects (n = 168) declared they more often have the custom of always reading medications' leaflets (46.3% vs 31.0%, p = 0.017, respectively). Side effects of medicines were reported by 65 participants - 26.0%. In conclusion, students' knowledge about NSAIDs and paracetamol is low. Participants do not search for information on drug related endangerments, the medication group choice for the given disorder is often inappropriate and the drugs are applied in conditions in which they are contraindicated.


Alazami syndrome: the first case of papillary thyroid carcinoma.
Alazami syndrome (MIM#615071) is a rare developmental disorder caused by biallelic variants in the LARP7 gene. Hallmark features include short stature, global developmental delay, and distinctive facial features. To date, 23 patients from 11 families have been reported in the literature. Here we describe a 19-year-old man who, in association with the typical features of Alazami syndrome, was diagnosed at the age of 14 years with papillary thyroid carcinoma, harboring the somatic BRAF V600E mutation. Whole exome sequencing revealed two novel LARP7 variants in compound heterozygosity, whereas only common variants were detected in genes associated with familial nonmedullary thyroid cancer (MIM#188550). LARP7 acts as a tumor suppressor in breast and gastric cancer, and possibly, according to recent studies, in thyroid tumors. Since thyroid cancer is rare among children and adolescents, we hypothesize that the LARP7 variants identified in our patient are responsible for both Alazami syndrome and tumor susceptibility. We also provide an overview of the clinical findings in all Alazami syndrome patients reported to date and discuss the possible pathogenetic mechanism that may underlie this condition, including the role of LARP7 in tumor susceptibility.


The shared risk of diabetes between dog and cat owners and their pets: register based cohort study.
To investigate whether dog and cat owners and their pets share a risk of developing diabetes. Cohort study. Register based longitudinal study, Sweden. 208 980 owner-dog pairs and 123 566 owner-cat pairs identified during a baseline assessment period (1 January 2004 to 31 December 2006). Type 2 diabetes events in dog and cat owners and diabetes events in their pets, including date of diagnosis during the follow-up period (1 January 2007 to 31 December 2012). Owners with type 2 diabetes were identified by combining information from the National Patient Register, the Cause of Death Register, and the Swedish Prescribed Drug Register. Information on diabetes in the pets was extracted from veterinary care insurance data. Multi-state models were used to assess the hazard ratios with 95% confidence intervals and to adjust for possible shared risk factors, including personal and socioeconomic circumstances. The incidence of type 2 diabetes during follow-up was 7.7 cases per 1000 person years at risk in dog owners and 7.9 cases per 1000 person years at risk in cat owners. The incidence of diabetes in the pets was 1.3 cases per 1000 dog years at risk and 2.2 cases per 1000 cat years at risk. The crude hazard ratio for type 2 diabetes in owners of a dog with diabetes compared with owners of a dog without diabetes was 1.38 (95% confidence interval 1.10 to 1.74), with a multivariable adjusted hazard ratio of 1.32 (1.04 to 1.68). Having an owner with type 2 diabetes was associated with an increased hazard of diabetes in the dog (crude hazard ratio 1.28, 1.01 to 1.63), which was attenuated after adjusting for owner's age, with the confidence interval crossing the null (1.11, 0.87 to 1.42). No association was found between type 2 diabetes in cat owners and diabetes in their cats (crude hazard ratio 0.99, 0.74 to 1.34, and 1.00, 0.78 to 1.28, respectively). Data indicated that owners of a dog with diabetes were more likely to develop type 2 diabetes during follow-up than owners of a dog without diabetes. It is possible that dogs with diabetes could serve as a sentinel for shared diabetogenic health behaviours and environmental exposures.


A BEt3-Base Catalyst for Amide Reduction with Silane.
Reported herein is the development of a simple but practical catalytic system for the selective reduction of amides with hydrosilane or hydrosiloxane. Low-cost and readily available triethylborane (1.0 M in THF), in combination with a catalytic amount of an alkali metal base, was found to catalyze the reduction of all three amide classes (tertiary, secondary, and primary amides) to form amines under mild conditions. In addition, the selective transformation of secondary amides to aldimines and primary amides to nitriles can also be achieved by using a proper combination of BEt3 and base. The scope of these BEt3-base-catalyzed amide hydrosilylation reactions has been explored in depth. Preliminary results of mechanistic studies suggest a modified Piers' silane Si-H···B activation mode wherein the hydride abstraction by BEt3 is promoted by the coordination of an alkoxide or hydroxide anion to the Si center.


Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.
Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30+ 1 (23+ 2-33+ 5) weeks and median postmenstrual age at scan was 42+ 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury.


[Study of X-irradiation to enhance the functional and structural recovery of the injured spinal cord of rat].
To explore whether X-irradiation can enhance the functional and structural recovery of the injured spinal cord of rats. Seventy Sprague-Dawley rats received spinal cord injury by clip compression at the T2 level were randomly divided into two groups. The experimental group received X-irradiation at 14 days after injury, the control group did not receive X-irradiation. The functional tests were performed at day 3, 7, 14, 21, 28, 35, and 42 after irradiation including open field movement, inclined plane and pain withdrawal test. All injured rats were sacrificed at 43 days after injury and the injured spinal cords were taken out for histological tests. Sixty-two rats met the experimental requirements among 70 injured rats, 32 rats in experimental group and 30 rats in control group. Statistically significant difference was achieved between two groups in open field movement and inclined plane (P < 0.01), but not for the pain withdrawal test. The edema and necrosis area of injured spinal cords of experimental group were less than those in control group, and the number of axons of experimental group were more than those in control group. X-irradiation can enhance the functional recovery by improving and restoring structural integrity of the injured spinal cord.


Estimation of lateral water flow and bromide transport in a subsurface seepage irrigation system.
Subsurface seepage irrigation is a common method used by growers in the Tri-County Agricultural Area (TCAA), Florida, USA, owing to its cost-effectiveness and low maintenance requirements. This study investigated the lateral flow of the perched water and the lateral transport of bromide (Br-) in this irrigation system in the TCAA and estimated the potential discharge of Br- into the drainage canals at the edges of the field, using the Visual MODFLOW/ MT3DMS models in conjunction with field experiments. Simulations showed that the perched water flowed from the northeast to the southwest of the field. Migration of the Br- plume from the source areas toward the canals was very slow and varied depending on the selection of the outer Br- concentration contour levels. However, the lateral transport of Br- from the perched water into the canals occurred after about 61 days. The simulations further revealed that the rate of perched water Br- discharge into the canals averaged 8.6 g day(-1) during a 30-day discharge period (from 61 to 91 days). This rate is very important for estimating Br- discharge into the canals and could also provide useful information for evaluating dissolved nutrient discharge into canals from the subsurface seepage irrigation system.


Factors influencing quality of life (QOL) amongst elderly caregivers of people living with HIV/AIDS in Phayao province, Thailand: a cross-sectional study.
Background: There are many impacts on quality of life among elderly people living with HIV patients. This study aimed to assess factors influencing quality of life among elderly people living with HIV/AIDS in a northern province of Thailand. Methods: This cross-sectional study was conducted in Phayao province, Thailand. A systematic sampling technique was employed to select study participants. 152 elderly participants aged 60 years and older with a family member living with HIV/AIDS were recruited to the study. They were interviewed using the World Health Organization Quality of Life-Older Adults Module (WHOQOL-OLD) questionnaire. Stepwise multiple regression analysis was performed to determine the factors influencing quality of life among elderly people affected by family member living with HIV/AIDS. Results: The results of the study showed the mean age of elderly participants was 67.20 + 52 years, most of which were female (97 persons, 63.8%). The mean time taking care of HIV/AIDS patients was 6.61 + 4.96 years. In term of health status among the elderly participants, the majority did not have chronic diseases (61.4%), amongst those with chronic diseases (38.6%), hypertension and diabetes were the most common. The average quality of life score was at a fair level. The time taking care of HIV/AIDS patients and health status were significant predictors of quality of life among participants 8.1 % ( R 2 =.081; p < .05). Conclusion: In order to improve quality of life among elderly caregivers to family member living with HIV/AIDS, time taking care of HIV/AIDS patients and health status should be focused on, amongst other factors. Help and support from the government, community, health organizations, academic research, and family members can help improve quality of life amongst the elderly.


[Studies on male infertility--acrosome reaction of the human sperm incubated in vitro].
In 1981, P. Talbot developed a triple-stain technique to estimate the number of human sperm undergoing normal acrosome reaction in fixed smears. In this method, live and dead sperm are first differentiated using the vital stain trypan blue. Sperm are then fixed in glutaraldehyde, dried onto slides, and the postacrosomal region and acrosome are differentiated using Bismark brown and Rose Bengal. Slides are examined at 1,000x with a bright-field microscope and assessed for the percentage of sperm that have undergone the normal acrosome reaction. Using this method we examined the time course of the acrosome reaction of human sperm incubated in mBWW the influence of human serum albumin, the calcium concentration of incubation media, Ca ionophore A 23187, and trypsin on the acrosome reaction of human sperm and the difference between the percentage of sperm undergoing normal acrosome reaction of fertile and infertile males. We got the following results: The percentage of human sperm undergoing acrosome reaction increased for the first six hours of incubation. Without human serum albumin the acrosome reaction did not occur. Ca ion could be one of the triggers of the acrosome reaction. Ca ionophore A23187 and trypsin induced the acrosome reaction in vitro. Sperm from oligozoospermic males, especially poorly motile sperm, could not undergo acrosome reaction so easily as sperm from fertile males could.


Vestibular Sclerosis: Is This a New, Distinct Clinicopathological Entity?
The aims of this case series were to present a series of patients with clinical and histopathological findings consistent with a recently described condition vestibular sclerosis (VS) and to contribute to the current discussion of whether VS is a subset of lichen sclerosus (LS) or a distinct entity. This case series of 6 women for a 12-month period was initiated from an ongoing collaboration between a gynecological dermatologist and an anatomical pathologist specializing in gynecological dermatopathology. We describe 6 women with white, hyperkeratotic patches and plaques confined to the vulvar vestibule with stromal sclerosis and an absence of inflammation on histology. All our patients were either perimenopausal or postmenopausal. The condition was either asymptomatic or characterized by mild to moderate dyspareunia. No patient had LS elsewhere on the vulva. There was no response to estrogen or topical corticosteroid therapy in symptomatic patients. Vestibular sclerosis may be a new distinct clinicopathologial entity, which is in the differential diagnosis of white plaques and patches in the vulvar vestibule. The characteristic siting in the anterior vestibule only, in the presence of an otherwise normal vulva and absence of inflammation on histology, is a reason to separate this condition from LS.


Notch1-dependent lymphomagenesis is assisted by but does not essentially require pre-TCR signaling.
Overexpression of intracellular Notch plays an important role in the generation of human acute lymphoblastic T cell leukemia (T-ALL). In mouse models, it was shown that Notch-dependent T-ALL required pre-TCR signaling. Here we show that pre-TCR signaling is required to condition mice for Notch-dependent transformation but that it is not required to sustain malignant growth of T-ALL. In contrast to previous studies, we found that disease development does not require pre-TCR but that it can be accelerated in Rag2(-/-) mice by transient mimicking of pre-TCR signals.


Pregnancy-specific beta 1-glycoprotein messenger ribonucleic acid and immunoreactive protein in the rat testis.
Human pregnancy-specific beta 1-glycoprotein (PS beta G) is synthesized in large quantities by syncytiotrophoblasts of the placenta. Recent studies using a partial cDNA of PS beta G isolated from human term placenta detected the presence of mRNA highly homologous to placental PS beta G in a number of extraplacental tissues, including human and rat testis. The present study determined in the rat that the amount of PS beta G mRNA based on percentage of total tissue RNA was greatest in the testis of mature rats, followed by senescent and prepubertal rats. In experiments using rats with testicular feminization syndrome (Tfm) which exhibit end-organ insensitivity to androgen stimulation, slot blot analysis of testicular RNA showed reduced levels of PS beta G mRNA in Tfm rats compared to normal rats. Northern blot analysis of rat testicular RNA probed with a human placental PS beta G cDNA demonstrated the presence of a single mRNA species of 1.65 kilobases. Subsequent studies investigated whether proteins immunologically similar to PS beta G were present in the testes from normal and Tfm rats. The rat testes were perfused with fixative, and sections from paraffin-embedded tissues were treated with rabbit anti-human PS beta G, followed by the avidin-biotin-peroxidase complex. Testes from the normal rat showed intense immunostaining in late spermatids (steps 16, 17, 18, and 19 of spermiogenesis), residual bodies, as well as cytoplasm of Leydig cells. Spermatozoa within the epididymis also demonstrated intense immunolabeling. Paraffin sections of the testes from the Tfm rat showed light diffuse cytoplasmic immunostaining in cells of the seminiferous tubules. Since spermiogenesis does not proceed normally, and no spermatids were seen, it was not possible to accurately stage the seminiferous tubules of the Tfm rat. The Leydig cells of the Tfm testes stained intensely, however, as was observed in the testes of the normal rat. These data suggest that the rat may provide an animal model for the investigation of the biological function and regulation of PS beta G in the testis.


Lasers in dermatology: a review.
The revolution in laser technology has had a significant impact on medicine in general and dermatology in particular and has piqued the interest of physicians, the lay public, and the media. Advances in laser therapy have dramatically improved the clinicians' ability to treat cosmetic and noncosmetic skin lesions safely and effectively. The number and variety of skin problems amenable to laser treatment continues to grow. We will provide a review of the major cosmetic and therapeutic applications of laser therapy.


Effect of Ketogenic Diets on Body Composition and Metabolic Parameters of Cancer Patients: A Systematic Review and Meta-Analysis.
A ketogenic diet characterized by high fat and low carbohydrate can drive the body to produce a large number of ketone bodies, altering human metabolism. Unlike normal cells, tumor cells have difficulty in consuming ketone bodies. Therefore, the application of ketogenic diets in cancer therapy is gaining attention. However, the effect of ketogenic diets on body parameters of cancer patients is not well established. This meta-analysis aimed to summarize the effects of ketogenic diets on cancer patients in earlier controlled trials. PubMed, Embase, and Cochrane Library were searched for clinical trials that enrolled cancer patients who received ketogenic diets intervention. Ten controlled trials were included in this meta-analysis. Data were extracted and checked by three authors independently. Pooled effect sizes revealed a significant effect of ketogenic diets on body weight (SMD −1.83, 95% CI −2.30 to −1.35; p < 0.00001) and fat mass (SMD −1.52, 95% CI −1.92 to −1.07; p < 0.00001). No significant effect on blood glucose, insulin, or lipid profile except triglycerides was found in the analysis. It had no effect on liver and kidney function except that GGT were decreased a little. There were no significant changes in IGF-1 and TNF-α related to tumor growth. Mental health improvement of cancer patients was supported by several trials. Taken together, findings in this study confirmed that the ketogenic diet was a safe approach for cancer patients reducing body weight and fat mass. In addition, cancer treatment-related indicators changed insignificantly. Ketogenic diets may be beneficial to the quality of life of cancer patients. However, intervention duration in most studies is shorter than 6 months, and the effect of a long-term ketogenic diet is still required further validation. More trials with a larger sample size are necessary to give a more conclusive result; PROSPERO registration number: CRD42021277559.


Cognitive control of orofacial motor and vocal responses in the ventrolateral and dorsomedial human frontal cortex.
In the primate brain, a set of areas in the ventrolateral frontal (VLF) cortex and the dorsomedial frontal (DMF) cortex appear to control vocalizations. The basic role of this network in the human brain and how it may have evolved to enable complex speech remain unknown. In the present functional neuroimaging study of the human brain, a multidomain protocol was utilized to investigate the roles of the various areas that comprise the VLF-DMF network in learning rule-based cognitive selections between different types of motor actions: manual, orofacial, nonspeech vocal, and speech vocal actions. Ventrolateral area 44 (a key component of the Broca's language production region in the human brain) is involved in the cognitive selection of orofacial, as well as, speech and nonspeech vocal responses; and the midcingulate cortex is involved in the analysis of speech and nonspeech vocal feedback driving adaptation of these responses. By contrast, the cognitive selection of speech vocal information requires this former network and the additional recruitment of area 45 and the presupplementary motor area. We propose that the basic function expressed by the VLF-DMF network is to exert cognitive control of orofacial and vocal acts and, in the language dominant hemisphere of the human brain, has been adapted to serve higher speech function. These results pave the way to understand the potential changes that could have occurred in this network across primate evolution to enable speech production.


[The usefulness of SNP markers for analyses of highly degraded biological materials].
The most common cause of problems associated with analyzing DNA extracted from forensic samples is their high level of degradation. Such difficulties are caused by the fact that STR markers have too large amplicon sizes to be amplified in degraded DNA samples. Thus, it is necessary to employ more efficient markers for analyzing evidential samples. SNPs are ideal tools for such purposes, for the SNP genotyping method does not require large amplicon size, and thus increases the possibility of amplifying degraded DNA samples. Although single SNP is not polymorphic enough, we can obtain sufficient results by examining several SNPs. The aim of this study was to examine the usefulness of the SNP-pentaplex (rs2294067, rs2282160, rs2070764, rs2277216, rs1063739) for forensic applications by analysing several forensic cases, which were impossible to solve in a range of STR markers because of highly degraded DNA. DNA fragments were amplified in one multiplex PCR reaction, which contained 5 primer pairs. SNPs were subsequently identified in a minisequencing reaction and gel electrophoresis in an ABI Prism 377 Sequencer. The research confirmed the usefulness of SNP-pentaplex for forensic applications. Despite employing mainly degraded and low copy number DNA, full genetic profiles were obtained in almost every sample. Although the discrimination power of SNP-pentaplex is not sufficient for obtaining adequate evidential value, it seems to be an ideal screening method for forensic applications.


Dewetting-induced formation and mechanical properties of synthetic bacterial outer membrane models (GUVs) with controlled inner-leaflet lipid composition.
The double-membrane cellular envelope of Gram-negative bacteria enables them to endure harsh environments and represents a barrier to many clinically available antibiotics. The outer membrane (OM) is exposed to the environment and is the first point of contact involved in bacterial processes such as signaling, pathogenesis, and motility. As in the cytoplasmic membrane, the OM in Gram-negative bacteria has a phospholipid-rich inner leaflet and an outer leaflet that is predominantly composed of lipopolysaccharide (LPS). We report on a microfluidic technique for fabricating monodisperse asymmetric giant unilamellar vesicles (GUVs) possessing the Gram-negative bacterial OM lipid composition. Our continuous microfluidic fabrication technique generates 50-150 μm diameter water-in-oil-in-water double emulsions at high-throughput. The water-oil and oil-water interfaces facilitate the self-assembly of phospholipid and LPS molecules to create the inner and outer leaflets of the lipid bilayer, respectively. The double emulsions have ultrathin oil shells, which minimizes the amount of residual organic solvent that remains trapped between the leaflets of the GUV membrane. An extraction process by ethanol and micropipette aspiration of the ultrathin oil shells triggers an adhesive interaction between the two lipid monolayers assembled on the water-oil and oil-water interfaces (i.e., dewetting transition), forcing them to contact and form a lipid bilayer membrane. The effect of different inner-leaflet lipid compositions on the emulsion/vesicle stability and the dewetting transition is investigated. We also report on the values for bending and area expansion moduli of synthetic asymmetric model membranes with lipid composition/architecture that is physiologically relevant to the OM in Pseudomonas aeruginosa bacteria.


Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data.
Parkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. Cross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. Our multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. Three distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.


Effects of 2% ibopamine on pupil, refraction, anterior segment anatomy and intraocular pressure.
The aim of the study was to determine the effects of a dopaminergic drug, 2% ibopamine, on the pupil, intraocular pressure and other ocular and ultrasound biometric variables. Thirty healthy subjects and 15 patients with primary open-angle glaucoma, aged from 40 to 78 years (mean age: 59.2 +/- 11), were included in two prospective open controlled trials. In the first, the mydriatic effect of 2% ibopamine and its inhibition and reversibility were evaluated in 15 healthy subjects using the alpha1-adrenergic drug, 0.5% dapiprazole. In the second, refraction, visual acuity, pupil diameter, intraocular pressure and 5 A-scan ultrasound biometric variables were evaluated in 15 healthy subjects and in 15 glaucoma patients. As early as forty min after administration of 2% ibopamine, a marked mydriatic effect (7.3 vs 3.9 mm; P < 0.0001), which was completely inhibited or reversed by 0.5% dapiprazole, was detected. The drug induced no changes in refraction, visual acuity or A-scan ultrasound biometric variables in any of the subjects examined. In healthy subjects, the intraocular pressure values were not changed to a statistically significant extent (13.8 vs 14.8 mm Hg; P = 0.668), whereas a slight, though significant, hypertensive effect (24 vs 22.2 mm Hg; P = 0.002) was observed in the glaucoma patients. The study confirms the intense mydriatic effect of 2% ibopamine with no changes in refraction, visual acuity or A-scan ultrasound biometric variables. The drug has no effect on intraocular pressure in healthy subjects, but induces a significant hypertensive effect in patients with initial glaucoma. This characteristic could be used for early diagnosis of primary open-angle glaucoma.


A subpopulation of allospecific cytotoxic T-cell precursors with phenotypic characteristics of natural killer cells.
We have proposed that natural killer (NK) cells are germ-line V-gene encoded prothymocytes specific for either self or non-self histocompatibility antigens. This hypothesis predicts that at least some precursors of allospecific cytotoxic T cells (allo-CTL) are NK cells. To test this we examined the effect of depleting NK cells and/or T cells (by complement lysis with anti-asialo GM1 and/or anti-Thy 1) on the development of allo-CTL induced during mixed lymphocyte culture (MLC). Removal of Thy 1+ cells from MLC responder populations prevented development of allo-CTL. This was partially reversed by addition of concanavalin A-conditioned medium (Con A-CM) to the MLC at day 0. Removal of asialo GM1+ cells eliminated NK activity measured at day 0, but failed to prevent development of allo-CTL of otherwise intact responder cells. However, removal of asialo GM1+ cells did prevent the Con A-CM dependent development of allo-CTL by responder cells depleted of Thy 1+ cells. These findings indicate that a subpopulation of allo-CTL precursors has the phenotypic characteristics of NK cells: absence or low density of Thy 1, and susceptibility to complement lysis by anti-asialo GM1.


The erythroid membrane skeleton: expression and assembly during erythropoiesis.
One aspect of erythropoiesis entails the biogenesis of a membrane skeleton. Analysis of the expression and assembly of the various components of this multisubunit structure illustrates the problem of spatial and temporal regulation of cytoskeletal morphogenesis, departures from simple self-assembly, and the various levels of regulation that might be operative in this aspect of cellular morphogenesis in development. Additionally, it reveals a new insight into the mechanisms underlying the molecular defects in certain hereditary hemolytic anemias.


Serologic and animal inoculation studies of a communal outbreak of viral hepatitis, type A.
Sera from individuals in an outbreak of viral hepatitis in a multifamily household, probably spread by contaminated food, were studied for antibodies to hepatitis A virus (anti-HAV), and selected acute phase sera were inoculated into marmosets. Significant rises in anti-HAV titers between acute and convalescent sera occurred in all of 15 individuals in the outbreak who experienced serum enzyme elevations and in one of 14 individuals whose serum enzyme levels remained normal. The remaining 13 individuals in the latter group had antibody levels in both early and late sera compatible with residual immunity from prior HAV infections and correlating with resistance to reinfection. Groups of marmosets were infected with acute phase sera from two of the cases; in both instances the inoculated sera contained substantial levels of anti-HAV. The marmosets developed specific anti-HAV seroconversions as well as enzyme elevations.


[A microangiographic study of the damaged liver in acute radiation sickness].
Microangiographic investigation with intravital filling up of the vessels was used to study a course and regeneration of a liver lesion in rats irradiated at a dose of 6 Gy. A traumatic liver lesion is characterized by severe local disorders of blood circulation, sharp vasoconstriction and depletion of the entire liver microcirculatory network. Combined radiation injuries result in phase changes: parenchymal edema, liver microcirculatory depletion in the early posttraumatic period change into relative normalization of the blood circulation of uninjured liver tissue in the latent period. Parenchymal edema, vasodilation and hypostasis reappear at the height of a lesion, followed by rarefaction of the network and vasoconstriction of the microcirculatory bed. Necrotic mass resorption in the period of combined radiation injury is as active as that in unirradiated animals. However at the height of a radiation injury capillary regeneration and necrotic mass resorption cease resulting in retarded regeneration of injured tissues.


Peroxisome Proliferator-Activated Receptors and their Ligands in Cancer Drug- Resistance: Opportunity or Challenge.
Development of resistance in cancer cells results in a high failure rate in cancer chemotherapy in the clinic. Therefore, investigating the mechanisms by which cancer cells acquire the capability to avoid cell death upon exposure to antineoplastic agents is of great significance in cancer research. In this review article, we will provide an overview of the mechanisms and molecular machinery of drug resistance in cancer cells which include but may not be limited to altered membrane transport and drug metabolizing enzymes, genetic response, enhanced DNA repair and alternation in the target molecules. A special focus will be on describing the strategies and the rationale for exploitation of peroxisome proliferator-activated receptors for overcoming the observed resistance in cancer cells.


Systemic consequences of ventricular assist devices: alterations of coagulation, immune function, inflammation, and the neuroendocrine system.
Implantable ventricular assist devices have proven efficacious as a bridge to transplantation and as a bridge to recovery. Although current indications for use of assist devices are somewhat limited, they are likely to expand in the upcoming years, including their use as destination therapy for end-stage heart failure. Recipients of assist devices, however, are prone to certain device-specific complications, including excessive postoperative bleeding, late propensity for thromboembolism, infections, and systemic inflammation, which may contribute to end-organ dysfunction. This article reviews the systemic biochemical alterations underlying these clinical phenomena. As assist devices are increasingly used, better understanding of these systemic perturbations is imperative.


Deletion of calcineurin and myocyte enhancer factor 2 (MEF2) binding domain of Cabin1 results in enhanced cytokine gene expression in T cells.
Cabin1 binds calcineurin and myocyte enhancer factor 2 (MEF2) through its COOH-terminal region. In cell lines, these interactions were shown to inhibit calcineurin activity after T cell receptor (TCR) signaling and transcriptional activation of Nur77 by MEF2. The role of these interactions under physiological conditions was investigated using a mutant mouse strain that expresses a truncated Cabin1 lacking the COOH-terminal calcineurin and MEF2 binding domains. T and B cell development and thymocyte apoptosis were normal in mutant mice. In response to anti-CD3 stimulation, however, mutant T cells expressed significantly higher levels of interleukin (IL)-2, IL-4, IL-9, IL-13, and interferon gamma than wild-type T cells. The enhanced cytokine gene expression was not associated with change in nuclear factor of activated T cells (NF-AT)c or NF-ATp nuclear translocation but was preceded by the induction of a phosphorylated form of MEF2D in mutant T cells. Consistent with the enhanced cytokine expression, mutant mice had elevated levels of serum immunoglobulin (Ig)G1, IgG2b, and IgE and produced more IgG1 in response to a T cell-dependent antigen. These findings suggest that the calcineurin and MEF2 binding domain of Cabin1 is dispensable for thymocyte development and apoptosis, but is required for proper regulation of T cell cytokine expression probably through modulation of MEF2 activity.


First Intrashot Observation of Runaway-Electron-Driven Instabilities at the Lower-Hybrid Frequency Range under ITER-Relevant Plasma-Wave Dispersion Conditions.
Kinetic instabilities driven by runaway electrons (REs) have recently received attention in the fusion community as a means to control and diagnose REs in a tokamak. Experiments aimed at studying such kinetic instabilities have been performed at the Frascati Tokamak Upgrade (FTU), where different families of waves have been identified, from wide-band bursting emissions to quasi-monochromatic waves and sharp lines, in the presence of REs with energies from a few to tens of MeV. A specific family of waves with intense kinetic drive was directly observed for the first time, during both the early Ohmic plasma start-up and the current ramp-up. A clear wave frequency scaling with respect to the electron density was demonstrated. This scaling, with the complementary analysis of signals observed at different magnetic fields, allowed the identification of these instabilities as lower-hybrid waves. The relevant analysis shown in this Letter is based on a continuous intrashot detection of the RE-driven wave, which is reported for the first time for this kind of instability. We demonstrated that unstable waves are excited already at the very beginning of a tokamak discharge, opening the way to new possible research on the exploitation of this kind of measurement for monitoring seed REs formation at the early plasma stage, while most diagnostics still have limited capabilities. The conditions for plasma wave dispersion at the early phase of the FTU discharge are very similar to the ones expected during the ITER start-up, when analogous instabilities might, hence, come to light, in case of formation of suprathermal populations.


Mitochondrial Pharmaceutics: A New Therapeutic Strategy to Ameliorate Oxidative Stress in Alzheimer's Disease.
Association between amyloid-β (Aβ) toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage has been demonstrated in the pathophysiology of Alzheimer's disease (AD). In the early stages of the disease, the defect in energy metabolism was found to be severe. This may probably due to the Aβ and ROS-induced declined activity of complexes in electron transport chain (ETC) as well as damages to mitochondrial DNA. Though clinically inconclusive, supplementation with antioxidants is reported to be beneficial especially in the early stages of the disease. A mild to moderate improvement in dementia is possible with therapy using antioxidants viz coenzyme Q10 (ubiquinone), α -lipoic acid, selenium, omega-3 fatty acids and vitamin E, emphasize their possible role as an adjuvant with the existing conventional treatment. Since mitochondrial dysfunction has been observed, a new therapeutic strategy called as 'Mitochondrial Medicine' which is aimed to maintain the energy production as well as to ameliorate the enhanced apoptosis of nerve cells, has been developed. Mitochondrial CoQ10, Szeto-Schiller peptide-31 and superoxide dismutase/ catalase mimetic, EUK-207 were the mitochondrial targeted agents demonstrated in experimental studies. This article discusses the mitochondrial impairment and the possible mitochondria targeted therapeutic intervention in AD.


[Intestinal parasitosis in the inhabitants of a suburban zone in which the groundwater is polluted by nitrates of fecal origin (Yeumbeul, Senegal)].
This study was carried out in 1997 to 1998, to determine the prevalence of intestinal parasite infestations due to groundwater pollution at Yeumbeul, Senegal, and to follow the progression of parasite infestations following anti-parasite treatment. The study included 705 people living in a suburban zone in which the water table was polluted with nitrates of fecal origin. These individuals consumed either well water or water from springs. The overall prevalence of parasite infestation was 42.26%, but varied significantly with age (p < 0.001). Individuals who consumed well water were more frequently infested than those who consumed spring water, but the difference was not significant (p > 0.3). Giardia and Entamoeba coli were the most frequently isolated parasites, with Giardia predominating in the 0 to 9 year age-group. There was no significant correlation between the prevalence of the various parasites and indicators of water pollution (R2 = 0.0566 for nitrates and 0.1086 for fecal coliform bacteria). Similarly, no correlation was found with water pollution factors such as the depth of the water table (R2 = 0.027) and the distance between the wells and the latrines (R2 = 0.00007). Following specific treatment, the prevalence of parasite infestation fell to 30.81%. This indicates the limitations of drug treatment, which is always used alone to combat intestinal parasites, in the face of possible reinfestation.


Genetic screening of the canine connexin 40 gene in dogs with inherited cardiac conduction defects.
Connexin 40 (Cx40) is a gap-junction protein expressed in the heart where it mediates the coordinated electrical activation of the atria and ventricular conduction tissues, facilitates cell-to-cell adhesion, and provides pathways for direct intercellular communication. Recent studies have shown that Cx40 null mice have cardiac conduction abnormalities with a very high incidence of cardiac malformations in heterozygous (18%) and homozygous (33%) animals, indicating that Cx40 plays a vital role in cardiomorphogenesis. Since several inherited cardiac conduction defects have also been found in dogs, we hypothesized that the clinical findings are genetically linked to a tissue-specific mutation or mutations in the canine Cx40 gene. We therefore screened the Cx40 gene in dogs with inherited cardiac conduction defects for mutations. In this study, we have identified three heterozygous base changes (C384G, C402T, C837T) in the dogs screened and determined them to be synonymous mutations. These mutations, however, have recently been found in an unrelated group of normal dogs.


A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125% bupivacaine with fentanyl during labor.
We previously found that the extent of an epidural motor block produced by 0.125% ropivacaine was clinically indistinguishable from 0.125% bupivacaine in laboring patients. By adding fentanyl to the 0. 125% ropivacaine and bupivacaine solutions in an attempt to reduce hourly local anesthetic requirements, we hypothesized that differences in motor block produced by the two drugs may become apparent. Fifty laboring women were randomized to receive either 0. 125% ropivacaine with fentanyl 2 microg/mL or an equivalent concentration of bupivacaine/fentanyl using patient-controlled epidural analgesia (PCEA) with settings of: 6-mL/hr basal rate, 5-mL bolus, 10-min lockout, 30-mL/h dose limit. Analgesia, local anesthetic use, motor block, patient satisfaction, and side effects were assessed until the time of delivery. No differences in verbal pain scores, local anesthetic use, patient satisfaction, or side effects between groups were observed; however, patients administered ropivacaine/fentanyl developed significantly less motor block than patients administered bupivacaine/fentanyl. Ropivacaine 0.125% with fentanyl 2 microg/mL produces similar labor analgesia with significantly less motor block than an equivalent concentration of bupivacaine/fentanyl. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the PCEA technique remains to be determined. By using a patient-controlled epidural analgesia technique, ropivacaine 0.125% with fentanyl 2 microg/mL produces similar analgesia with significantly less motor block than a similar concentration of bupivacaine with fentanyl during labor. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the patient-controlled epidural analgesia technique remains to be determined.


[Clozapine-induced cholestatic jaundice: a case report].
We report on a patient who became jaundiced during treatment with clozapine (Leponex). Histologically, cholestatic hepatitis with single-cell necroses of hepatocytes and infiltration of the portal zones with eosinophilic granulocytes were found. The patient recovered after discontinuation of clozapine, and liver function tests returned to normal within 4 weeks. This adverse effect of clozapine suggests that this "atypical" tricyclic neuroleptic resembles the phenothiazines both with regard to therapeutic spectrum and side effects.


Expression of a homeostatic regulator, Wip1 (wild-type p53-induced phosphatase), is temporally induced by c-Jun and p53 in response to UV irradiation.
Wild-type p53-induced phosphatase (Wip1) is induced by p53 in response to stress, which results in the dephosphorylation of proteins (i.e. p38 MAPK, p53, and uracil DNA glycosylase) involved in DNA repair and cell cycle checkpoint pathways. p38 MAPK-p53 signaling is a unique way to induce Wip1 in response to stress. Here, we show that c-Jun directly binds to and activates the Wip1 promoter in response to UV irradiation. The binding of p53 to the promoter occurs earlier than that of c-Jun. In experiments, mutation of the p53 response element (p53RE) or c-Jun consensus sites reduced promoter activity in both non-stressed and stressed A549 cells. Overexpression of p53 significantly decreased Wip1 expression in HCT116 p53(+/+) cells but increased it in HCT116 p53(-/-) cells. Adenovirus-mediated p53 overexpression greatly decreased JNK activity. Up-regulation of Wip1 via the p38 MAPK-p53 and JNK-c-Jun pathways is specific, as demonstrated by our findings that p38 MAPK and JNK inhibitors affected the expression of the Wip1 protein, whereas an ERK inhibitor did not. c-Jun activation occurred much more quickly, and to a greater extent, in A549-E6 cells than in A549 cells, with delayed but fully induced Wip1 expression. These data indicate that Wip1 is activated via both the JNK-c-Jun and p38 MAPK-p53 signaling pathways and that temporal induction of Wip1 depends largely on the balance between c-Jun and p53, which compete for JNK binding. Moreover, our results suggest that JNK-c-Jun-mediated Wip1 induction could serve as a major signaling pathway in human tumors in response to frequent p53 mutation.


Contraction frequency after administration of misoprostol in obese versus nonobese women.
Objective: To examine impact of obesity on contraction frequency following misoprostol. Our hypothesis is that an increased volume of distribution reduces the bioavailability of misoprostol and may be an explanation for reduced efficacy. We examined the contraction frequency as a surrogate marker for bioavailability of misoprostol. Study design: We compared the rate of contractions at five time intervals in 313 subjects: prior to administration, and at four intervals post administration. We compared number of contractions in obese versus nonobese. As a planned secondary analysis, we then compared the rate of change in contractions per hour at four time intervals: a repeated measures analysis to compare the rate of change in contractions per hour over the 5-hour window controlling for race (White versus non-White) and parity (primiparous versus multiparous). General linear model and repeated measures analysis were conducted to report the parameter estimates, least square means, difference of least square means, and p values. Results: Nonobese women presented with more contractions at baseline, 7 ± 5 versus 4 ± 5 c/h, p < .001. At all four time intervals after misoprostol administration obese women had fewer contractions per hour. The rate of change in contraction frequency after administration found obese women had a lower rate of increase in contraction frequency over the course of all four hours. We found a least squares means estimate (c/h): first hour (-0.87), p = .08, second hour (-2.43), p = .01, third hour (-1.80), p = .96, and fourth hour (-2.98), p = .007. Conclusions: Obese women have a lower rate of contractions per hour at baseline and at four intervals after misoprostol administration. In addition, the rate of change in the increase in contractions/hour also was reduced in obese women versus nonobese women. This suggests a lower bioavailability of misoprostol in women with a larger volume of distribution which would likely impact the efficacy of misoprostol in obese women when given the same dose of misoprostol. It is unknown if higher misoprostol dosing would increase efficacy of misoprostol in obese women.


Limited sampling strategies for the estimation of atazanavir daily exposure in HIV-infected patients.
Stepwise multiple regression analyses were applied to 44 atazanavir pharmacokinetic profiles from 44 HIV-1 infected patients concomitantly treated with raltegravir with the goal of identifying limited sampling strategies for the prediction of drug AUC(0-12) . Atazanavir trough-based equations failed to reliably predict daily drug exposure in patients with low drug bioavailability. Conversely, different algorithms based on few samples and associated with good correlation, acceptable bias and imprecision with the measured atazanavir AUC(0-12) were identified. These models could be used to predict atazanavir exposure for clinic or research purposes.


Acute vertebral-basilar thrombosis. Angiologic-clinical comparison and therapeutic implications.
The clinical-angiologic data and the clinical outcome in 66 patients with acute vertebro-basilar thrombosis treated with antiplatelet agents, anticoagulants, or fibrinolytic agents are presented. Forty-three patients were treated with local intraarterial infusion of streptokinase or urokinase proximal to the thrombotic occlusion; 14 patients in this group (33%) survived, only one of whom was in deep coma when therapy was started. Twenty-three patients did not receive fibrinolytic therapy; 4 of these patients (17%) who exhibited mild brainstem-related symptoms survived. This study implies that early diagnosis and treatment in vertebrobasilar stroke in progression may achieve improved survival.


Reactions of nurses to the use of electronic health record alert features in an inpatient setting.
While studies have been conducted to assess nurse perception of electronic health records, once electronic health record systems are up and running, there is little to guide the use of features within the electronic health record for nursing practice. Alerts are a promising tool for implementing best practice for patient care in inpatient settings. Yet the use of alerts for inpatient nursing is understudied. This study examined nurse attitudes and reactions to alerts in the inpatient setting. Focus groups were conducted at three hospitals with 50 nurses. Nurses were asked about five different alert features. For each alert, participants were asked about their feelings and reactions to the alert, how alerts help or hinder work, and suggestions for improvements. Findings include clear preferences for alert types and content. Nurses preferred a dashboard style alert with functions included to accomplish tasks directly in the alert. While nurses reported positive reactions to certain alert pages, they also reported low use of those features and occasional distrust of the data included in alerts. Findings provide guidance for future use of alerts and design of new alerts. Findings also identify the important challenge of designing and implementing alerts for integration with nursing workflow.


Hindrance demands as a boundary condition to the appraisal of challenge demands.
Studies show that prototypical challenge demands can be appraised as challenging, hindering and threatening. Yet, to date there exists no clear reasoning as to why these different appraisals occur. Drawing on transactional stress theory, we propose that co-occurring hindrance demands likely affect the day-specific appraisal of challenge demands (i.e., time pressure and complexity). To test this proposition we conducted a daily diary study with 432 employees. We tested our hypotheses using multi-level latent interaction analyses at the within-person level. Results revealed that on days when individuals experienced more hindrance demands, they were less likely to appraise time pressure and complexity as challenging and more likely to appraise them as hindering or threatening. The results outline the need to consider co-occurring hindrance demands when assessing appraisal patterns associated with challenge demands.


Bilateral thoracic radiographs increase lesion detection in horses with pneumonia or pulmonary neoplasia but do not bring any additional benefit for inflammatory or diffuse pulmonary disease.
Published studies describing the effects of bilateral radiographic projections on the detection of equine pulmonary lesions are currently lacking. The objectives of this retrospective, single center, observational study were to compare unilateral and bilateral thoracic radiographic projections for the detection of pulmonary lesions in a group of horses. Based on their clinical diagnosis, 167 adults and foals with bilateral thoracic radiographs were classified as having pneumonia (n = 88), inflammatory or diffuse pulmonary disease (n = 72), and pulmonary masses (n = 7). After an initial interrater repeatability test, right-to-left and left-to-right projections were anonymized and independently interpreted by a radiologist blinded to the clinical diagnosis. Scores were attributed for each pattern/lesion (alveolar, interstitial, bronchial, nodules/masses, cavitary lesions) and each quadrant. Agreement between scores from each projection was evaluated with Bland-Altman plots. Lesions identified on one side but not on the contralateral projection were considered discordant. There was no preferential lateralization of pulmonary lesions. The prevalence of discordance was 14.4%, 9.0%, and 4.2% for alveolar pattern, nodules/masses, and cavitary lesions, respectively. Up to nine horses (10.2%) with pneumonia could have been misdiagnosed. A pulmonary mass would have been missed in one case. For inflammatory or diffuse disease, discordance was slight, and the addition of contralateral projections had no impact on radiographic interpretation. In conclusion, in horses with pneumonia or neoplasia, bilateral projections, or adding at least one contralateral caudoventral view, increased the probability of identifying pulmonary lesions. In horses with inflammatory or diffuse disease, bilateral thoracic radiography provided no additional benefit.


Computed tomography for staging bronchogenic carcinoma.
One hundred and fourty patients with a primary lung neoplasm underwent transmission computed tomography (TCT) for staging prior to therapy. TCT results were compared with the post-operative T- and N-stage. The preoperative TCT examination correctly classified 70% of all tumors. 73% of T1, 63% of T2 and 74% of T3 tumors did not require restaging after surgery. TCT correctly staged 80% of the patients with respect to the N-stage. Ninety-seven percent of the patients with N0, 42% with N1 and 79% with N2 tumors were correctly classified. Serious over- and understaging was observed in patients with centrally located bronchogenic carcinoma. This was due to the difficulty of distinguishing tumor tissue from enlarged lymph nodes and atelectasis.


New Aspects Towards a Molecular Understanding of the Allicin Immunostimulatory Mechanism via Colec12, MARCO, and SCARB1 Receptors.
The allicin pleiotropic effects, which include anti-inflammatory, anti-oxidant, anti-tumoral, and antibacterial actions, were well demonstrated and correlated with various molecular pathways. The immunostimulatory mechanism of allicin has not been elucidated; however, there is a possible cytokine stimulation from immunoglobulin release caused by allicin. In this study, when Wistar female rats and CD19+ lymphocytes were treated with three different doses of allicin, immunoglobulins, glutathione, and oxidative stress markers were assayed. Molecular docking was performed between S-allylmercaptoglutathione (GSSA)-a circulating form of allicin in in vivo systems formed by the allicin interaction with glutathione (GSH)-and scavenger receptors class A and B from macrophages, as well as CD19+ B lymphocytes. Our data demonstrated a humoral immunostimulatory effect of allicin in rats and direct stimulation of B lymphocytes by S-allyl-mercapto-glutathione, both correlated with decreased catalase (CAT) activity. The molecular docking revealed that S-allyl-mercapto-glutathione interacting with Colec12, MARCO (class A), and SCARB1 (class B) scavenger receptors in in vitro tests demonstrates a direct stimulation of immunoglobulin secretion by GSSA in CD19+ B lymphocytes. These data collectively indicate that GSSA stimulates immunoglobulin secretion by binding on scavenger receptors class B type 1 (SCARB1) from CD19+ B lymphocytes.


Checkpoint Kinase 2 Inhibition Can Reverse Tamoxifen Resistance in ER-Positive Breast Cancer.
Breast cancer is a heterogeneous disease. Tamoxifen is frequently used to treat ER-positive breast cancer. Our team has identified a novel splice variant of NCOR2, BQ323636.1 (BQ), that mediates tamoxifen resistance. However, the upstream factors that modulate BQ expression are not apparent. This study reveals that tamoxifen treatment causes induction of DNA damage which can enhance BQ expression. We show that DNA damage can activate the ATM/CHK2 and ATR/CHK1 signalling cascades and confirm that ATM/CHK2 signalling is responsible for enhancing the protein stability of BQ. siRNA or a small inhibitor targeting CHK2 resulted in the reduction in BQ expression through reduced phosphorylation and enhanced poly-ubiquitination of BQ. Inhibition of CHK2 by CCT241533 could reverse tamoxifen resistance in vitro and in vivo. Using clinical samples in the tissue microarray, we confirmed that high p-CHK2 expression was significantly associated with high nuclear BQ expression, tamoxifen resistance and poorer overall and disease-specific survival. In conclusion, tamoxifen treatment can enhance BQ expression in ER-positive breast cancer by activating the ATM/CHK2 axis. Targeting CHK2 is a promising approach to overcoming tamoxifen resistance in ER-positive breast cancer.


Localization of electrons due to orbitally ordered bi-stripes in the bilayer manganite La(2-2x)Sr(1+2x)Mn2O7 (x ~ 0.59).
Electronic phases with stripe patterns have been intensively investigated for their vital roles in unique properties of correlated electronic materials. How these real-space patterns affect the conductivity and other properties of materials (which are usually described in momentum space) is one of the major challenges of modern condensed matter physics. By studying the electronic structure of La(2-2x)Sr(1+2x)Mn(2)O(7) (x ∼ 0.59) and in combination with earlier scattering measurements, we demonstrate the variation of electronic properties accompanying the melting of so-called bi-stripes in this material. The static bi-stripes can strongly localize the electrons in the insulating phase above T(c) ∼ 160 K, while the fraction of mobile electrons grows, coexisting with a significant portion of localized electrons when the static bi-stripes melt below T(c). The presence of localized electrons below T(c) suggests that the melting bi-stripes exist as a disordered or fluctuating counterpart. From static to melting, the bi-stripes act as an atomic-scale electronic valve, leading to a "colossal" metal-insulator transition in this material.


Endoscopic transnasal repair of cerebrospinal fluid leaks with and without an encephalocele in pediatric patients: from infants to children.
The diagnosis and management of pediatric cerebrospinal fluid (CSF) leak and encephalocele are challenging. The current study aimed to identify patient characteristics, review operative techniques, and evaluate the efficacy and safety of endoscopic endonasal repair in a pediatric population. We retrospectively reviewed the records of pediatric patients who underwent transnasal endoscopic repair of CSF leak with or without a meningocele or an encephalocele at Beijing Tongren Hospital, Capital Medical University, between July 2003 and May 2014. All patients had preoperative radiological evaluations and underwent endoscopic endonasal repair of their skull base defects. Altogether, 23 children (mean age 7.0 years) underwent the procedures. Sixteen cases were congenital, and 7 patients had trauma history. The herniations or defects included meningoencephaloceles in 15 cases, meningoceles in 4 cases, and CSF leak in 4 cases (2 patients had bilateral leaks). The leak or herniation sites were ethmoid roof in 10 patients (one was bilateral), cribriform plate in 5, lateral to the foramen cecum in 3, posterior wall of the frontal sinus in 1, sphenoid sinus in 2, lateral recess of the sphenoid sinus in 1, and sella turcica base in 2. All subjects had favorable clinical outcomes without recurrence during a follow-up of 6-123 months (mean 61.1 months). The endoscopic endonasal approach was the preferred method for repairing CSF leaks with or without an encephalocele in pediatric patients. Compared to traditional operations, this endoscopic procedure is minimally invasive, efficient, and safe.


SSDOnt: An Ontology for Representing Single-Subject Design Studies.
Single-Subject Design is used in several areas such as education and biomedicine. However, no suited formal vocabulary exists for annotating the detailed configuration and the results of this type of research studies with the appropriate granularity for looking for information about them. Therefore, the search for those study designs relies heavily on a syntactical search on the abstract, keywords or full text of the publications about the study, which entails some limitations. To present SSDOnt, a specific purpose ontology for describing and annotating single-subject design studies, so that complex questions can be asked about them afterwards. The ontology was developed following the NeOn methodology. Once the requirements of the ontology were defined, a formal model was described in a Description Logic and later implemented in the ontology language OWL 2 DL. We show how the ontology provides a reference model with a suitable terminology for the annotation and searching of single-subject design studies and their main components, such as the phases, the intervention types, the outcomes and the results. Some mappings with terms of related ontologies have been established. We show as proof-of-concept that classes in the ontology can be easily extended to annotate more precise information about specific interventions and outcomes such as those related to autism. Moreover, we provide examples of some types of queries that can be posed to the ontology. SSDOnt has achieved the purpose of covering the descriptions of the domain of single-subject research studies.


Mini-Review: PDPK1 (3-phosphoinositide dependent protein kinase-1), An Emerging Cancer Stem Cell Target.
Cancer stem cells (CSCs) are subpopulations of tumor cells that possess abilities for self-renewal, differentiation, and tumor initiation. These rare but therapy-recalcitrant cells are assumed to repopulate tumors following administration of systemic chemotherapy driving therapy failure, tumor recurrence, and disease progression. In early clinical trials, anti-CSC therapies have found limited success to-date possibly due to the inherent heterogeneity and plasticity of CSCs and the incomplete characterization of essential CSC targets. Here, we review the role of 3-phosphoinositide dependent protein kinase-1 (PDPK1) as an emerging CSC target. While most previous studies have relied on CSC models which are based on lineage and tissue-specific marker profiles to define the relationships between putative target and CSC traits, this review discusses PDPK1 and its role in CSC biology with an emphasis on CSC systems which are based on proposed function like label-retaining cancer cells (LRCCs).


Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis.
Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a gluten-free diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 (or, about 4.3%) was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.


Long-term clinical evaluation of fracture and pulp injury following glass-ionomer cement or composite resin applied as a base filling in teeth restored with amalgam.
The aim of this research was to analyse the long-term clinical behaviour of two dental materials applied as filling under silver amalgam restorations: glass-ionomer cement (GIC) and composite resin with adhesive system (CR). In this study, 117 posterior teeth (29 premolars and 88 molars) were selected with carious lesions which resulted in great loss of dentin and cusps with unsupported enamel. After caries removal, cavities were prepared and totally filled with GIC or with CR. In a following visit, new cavities were prepared, leaving the employed filling material as a base and support for the enamel, which were then restored with silver amalgam. Restorations were evaluated periodically after 6 months and up to 5 years. Both fracture and pulpal involvement rates were low. Although differences could be observed in the behaviour of the materials, statistical survival estimation showed that the performances of GIC and CR as filling material were similar. There was a significant association both between kind of tooth (molar or premolar) and long-term survival of the restorations; and between degree of unsupported enamel and the same long-term survival. Our results confirmed that the technique in which GIC or CR are used as filling under silver amalgam restorations is clinically acceptable.


Design and Development of a THOR Based Small Female Crash Test Dummy.
This paper describes the design and development of a small female crash test dummy, results of biofidelity tests, and preliminary results from full scale 3 point belt and airbag type sled tests. The small female THOR was designed using the anthropometric data developed by Robbins for the 5(th) percentile female and biomechanical requirements derived from scaling the responses of the 50(th) percentile male. While many of the mechanical components of the NHTSA THOR 50(th) percentile male dummy were scaled according to the appropriate anthropometric data, a number of improved design features have been introduced in the new female THOR. These include; improved neck design, new designs for the head and neck skins: and new designs for the upper and lower abdomen. The lower leg, ankle and foot, known as THOR-FLx, were developed in an earlier effort and have been included as a standard part of the new female dummy. The instrumentation on the dummy is generally the same as in the male THOR-Alpha dummy. A few sensors, which were thought to be of secondary importance, were eliminated because of the limited volume within the female dummy. Scaled versions of the biofidelity tests defined for the male THOR were used to test the response of the new dummy.


Biomechanics of Vertical Posture and Control with Referent Joint Configurations.
Our study compared the results of two methods of analysis of postural sway during human quiet standing, the rambling-trembling (Rm-Tr) decomposition and the analysis of the point of intersection of the ground reaction forces (zIP analysis). Young, healthy subjects were required to stand naturally and with an increased level of leg/trunk muscle co-activation under visual feedback on the magnitude of a combined index of muscle activation (muscle mode). The main findings included the shift of zIP toward higher frequencies and strong correlations between Tr and zIP when the subjects stood with increased muscle co-activation. We interpret the results within the idea of whole-body control with a set of primitives associated with referent coordinates in the joint configuration space.


Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release.
Histone deacetylase inhibitors (HDACi) target abnormal epigenetic states associated with a variety of pathologies, including cancer. Here, the development of a prodrug of the canonical broad-spectrum HDACi suberoylanilide hydroxamic acid (SAHA) is described. Although hydroxamic acids are utilized universally in the development of metalloenzyme inhibitors, they are considered to be poor pharmacophores with reduced activity in vivo. We developed a prodrug of SAHA by appending a promoiety, sensitive to thiols, to the hydroxamic acid warhead (termed SAHA-TAP). After incubation of SAHA-TAP with an HDAC, the thiol of a conserved HDAC cysteine residue becomes covalently tagged with the promoiety, initiating a cascade reaction that leads to the release of SAHA. Mass spectrometry and enzyme kinetics experiments validate that the cysteine residue is covalently appended with the TAP promoiety. SAHA-TAP demonstrates cytotoxicity activity against various cancer cell lines. This strategy represents an original prodrug design with a dual mode of action for HDAC inhibition.


The Association between Primary Care Practices' Structural Capabilities and Hospitalizations among Persons Living with Dementia.
Background: Persons living with dementia (PLWD) are more likely to be hospitalized than individuals without dementia. Little is known about key features (i.e., structural capabilities) in primary care practices where PLWD receive care. This study assessed the relationship between structural capabilities (i.e., care coordination, community integration, and reminder systems) and hospitalizations among PLWD. Methods: We conducted a secondary analysis of cross-sectional data from 5001 PLWD in 192 practices and used three datasets: nurse practitioner surveys, Medicare claims, and Minimum Data Set. Using generalized estimating equations, we evaluated the association between structural capabilities and hospitalizations. Results: PLWD who received care from practices with care coordination were less likely to have hospitalizations (OR = 0.62, p < .05). No statistically significant associations were observed between community integration and reminder systems and hospitalizations. Conclusion: Primary care practices need to tailor structural capabilities to address the needs of PLWD to reduce hospitalizations.


Registration accuracy enhancement of a surgical navigation system for anterior cruciate ligament reconstruction: A phantom and cadaveric study.
Recently, surgical navigation systems have been widely used to improve the results of various orthopaedic surgeries. However, surgical navigation has not been successful in anterior cruciate ligament reconstruction, owing to its inaccuracy and inconvenience. This study investigated the registration of preoperative and intraoperative data, which are the key components in improving accuracy of the navigation system. An accurate registration method was proposed using new optical tracking markers and landmark retake. A surgical planning and navigation system for anterior cruciate ligament reconstruction was developed and implemented. The accuracy of the proposed system has been evaluated using phantoms and eight cadaveric knees. The present study investigated only the registration accuracy excluding the errors of optical tracking hardware and surgeon. The target registration errors of femoral tunnelling for anterior cruciate ligament reconstruction in phantoms were found to be 0.24±0.03mm and 0.19±0.10° for the tunnel entry position and tunnel direction, respectively. The target registration errors measured using cadavers were 0.9mm and 1.94°, respectively. The preclinical experimental results showed that the proposed methods enhanced the registration accuracy of the developed system. As the system becomes more accurate, surgeons could more precisely position and orient the femoral and tibial tunnels to their original anatomical locations.


Percutaneous absorption of hydrocortisone increases with long-term administration. In vivo studies in the rhesus monkey.
This study compares percutaneous absorption of hydrocortisone after short and long-term administration. The experimental design was to first apply 14C-hydrocortisone. This was followed by long-term administration of nonradioactive hydrocortisone. Then 14C-hydrocortisone was applied again when urinary excretion of radioactivity from the first application reached minimum detectable levels. Short- (first 14C-hydrocortisone application) and long-term (second 14C-hydrocortisone application) penetrations were compared. The level of absorption of hydrocortisone significantly increased during long-term administration, whether applied in an acetone vehicle or in a 0.9% emulsion ointment base (Eucerin). A placebo study in which only an acetone vehicle was applied for a long period followed by 14C-hydrocortisone application showed no enhanced penetration. It is suggested that long-term application of hydrocortisone alters the penetration barrier, resulting in enhanced penetration. The relevance of this long-term corticosteroid use in man is possibly of great importance.


Bio-concentration potential and associations of heavy metals in Amanita muscaria (L.) Lam. from northern regions of Poland.
Fruiting bodies of Amanita muscaria and topsoil beneath from six background areas in northern regions of Poland were investigated for the concentration levels of Ag, Al, Ba, Ca, Cd, Co, Cu, Fe, Hg, K, Mg, Mn, Na, Rb, Sr, and Zn. In addition, the bioconcentration factors (BCF values) were studied for each of these metallic elements. Similar to studies from other basidiomycetes, A. muscaria showed species-specific affinities to some elements, resulting in their bioconcentration in mycelium and fruiting bodies. This mushroom growing in soils with different levels of the geogenic metallic elements (Ag, Al, Ba, Ca, Co, Cu, Fe, Hg, K, Mg, Mn, Na, Rb, Sr, and Zn) showed signs of homeostatic accumulation in fruiting bodies of several of these elements, while Cd appeared to be accumulated at a rate dependent of the concentration level in the soil substrate. This species is an efficient bio-concentrator of K, Mg, Cd, Cu, Hg, Rb, and Zn and hence also contributes to the natural cycling of these metallic elements in forest ecosystems.


Scene-Motion Thresholds During Head Yaw for Immersive Virtual Environments.
In order to better understand how scene motion is perceived in immersive virtual environments, we measured scene-motion thresholds under different conditions across three experiments. Thresholds were measured during quasi-sinusoidal head yaw, single left-to-right or right-to-left head yaw, different phases of head yaw, slow to fast head yaw, scene motion relative to head yaw, and two scene illumination levels. We found that across various conditions 1) thresholds are greater when the scene moves with head yaw (corresponding to gain < 1:0) than when the scene moves against head yaw (corresponding to gain > 1:0), and 2) thresholds increase as head motion increases.


Ostomy-Related Quality of Life in Puerto Ricans Living With Inflammatory Bowel Disease: A Prospective Cohort Study.
The aim of this study was to determine ostomy-related quality of life (QOL) in Hispanic Puerto Ricans living with an enteral stoma and inflammatory bowel disease (IBD). We analyzed possible associations between QOL and sex, diagnosis, and type and duration of stoma. Prospective cohort study. The sample comprised 102 adults living with IBD and an ostomy; 60 of 101 (59.4%) were males, 44 of 102 (43.1%) had Crohn's disease, and 60 of 102 (58.9%) had an ileostomy. Participants were receiving care at the Center for IBD of the University of Puerto Rico in San Juan, Puerto Rico, between January 2012 and December 2014. One-hundred two adults Puerto Ricans with IBD completed the Stoma Quality of Life (Stoma-QOL) questionnaire. Data were analyzed using frequency distributions for categorical variables and summary statistics for continuous variables. Independent-group t test and one-way analysis of variance, with the post hoc Tukey test, were used to determine group differences for the variables of age, sex, civil status, time living with an ostomy, type of ostomy, and IBD diagnosis. Results were analyzed according to the number of responses to each variable; the denominator varied for some variables. Having an ostomy for more than 40 months was significantly associated with a higher QOL score (59.0 vs 50.7; P = .05). Males had significantly higher scores than females (59.94 vs 50.23; P = .0019). Age, IBD diagnosis, and type of ostomy were not associated with the Stoma-QOL scores. The achievement (over 40 months) to attain improved ostomy-related QOL suggests that early training in the care of the ostomy and advanced planning when leaving home may enhance ostomy-related QOL. Lower QOL in women may represent an opportunity for a sex-specific educational intervention.