Parathyroid hormone (1-84) and treatment of osteoporosis.
To present the chemistry, pharmacology, and pharmacokinetics of parathyroid hormone (PTH) (1-84) and review the available clinical trials that evaluate its efficacy and safety; clinical applicability of this agent and its relationship to other Food and Drug Administration (FDA)-approved medications for treatment of osteoporosis are also discussed. A MEDLINE search (1996-December 2004) was completed, along with a review of information obtained from the manufacturer, NPS Pharmaceuticals. Key search terms included parathyroid hormone, PTH (1-84), and ALX 111. Studies were selected based on their relevance and availability. Pertinent information, including objectives, design, demographics, outcomes, adverse events, dosing strategies, and therapeutic controversies, was extracted. PTH (1-84) is being developed for treatment of osteoporosis. Recent studies have shown that, when administered intermittently as a subcutaneous injection, PTH (1-84) produces an increase in bone mineral density and prevents vertebral fractures. The fact that this agent contains the C-terminal region of PTH may differentiate it from PTH (1-34), teriparatide, which is approved by the FDA for treatment of osteoporosis. Further trials are necessary to determine the role of PTH (1-84) in combination with other treatments for osteoporosis and/or the order in which PTH (1-84) is given with these other agents. There are currently no comparative trials with other osteoporosis treatment modalities. PTH (1-84), when given intermittently as a subcutaneous injection, appears to be a safe and efficacious treatment option for osteoporosis. Further trials are needed to determine its specific place in therapy compared with other treatment options.


Progression of coronary artery calcification in black and white women: do the stresses and rewards of multiple roles matter?
Black women experience higher rates of cardiovascular disease (CVD) than white women, though evidence for racial differences in subclinical CVD is mixed. Few studies have examined multiple roles (number, perceived stress, and/or reward) in relation to subclinical CVD, or whether those effects differ by race. The aim of this study was to investigate the effects of multiple roles on 2-year progression of coronary artery calcium. Subjects were 104 black and 232 white women (mean age 50.8 years). Stress and reward from four roles (spouse, parent, employee, caregiver) were assessed on five-point scales. Coronary artery calcium progression was defined as an increase of ≥10 Agatston units. White women reported higher rewards from their multiple roles than black women, yet black women showed cardiovascular benefits from role rewards. Among black women only, higher role rewards were related significantly to lower progression of coronary artery calcium, adjusting for body mass index, blood pressure, and other known CVD risk factors. Blacks reported fewer roles but similar role stress as whites; role number and stress were unrelated to coronary artery calcium progression. Rewarding roles may be a novel protective psychosocial factor for progression of coronary calcium among black women.


Diagnostic Assessment Strategies and Disease Subsets in Giant Cell Arteritis: Data From an International Observational Cohort.
Diagnostic assessment in giant cell arteritis (GCA) is rapidly changing as vascular imaging becomes more available. This study was undertaken to determine if clinical GCA subsets have distinct profiles or reflect differential diagnostic assessments. Patients were recruited from an international cohort and divided into 4 subsets based on a temporal artery (TA) abnormality (positive TA biopsy [TAB] or halo sign on TA ultrasound [TA-US]) and/or evidence of large vessel (LV) involvement on imaging: 1) both TA abnormality and LV involvement (TA+/LV+ GCA); 2) TA abnormality without LV involvement (TA+/LV- GCA); 3) LV involvement without TA abnormality (TA-/LV+ GCA); and 4) clinically diagnosed GCA without LV involvement or TA abnormality (TA-/LV- GCA). Nine hundred forty-one patients with GCA were recruited from 72 international study sites. Most patients received multiple forms of diagnostic assessment, including TAB (n = 705 [75%]), TA-US (n = 328 [35%]), and LV imaging (n = 534 [57%]). Assessment using TAB, TA-US, and LV imaging confirmed the diagnosis of GCA in 66%, 79%, and 40% of cases, respectively. GCA subsets had distinct profiles independent of diagnostic assessment strategies. TA+/LV- were the most common subset (51%), with a high burden of cranial ischemia. Those in the TA-/LV- subset (26%) had a high prevalence of cranial ischemia and musculoskeletal symptoms. Patients in the TA-/LV+ subset (12%) had prevalent upper extremity vascular abnormalities and a low prevalence of vision loss, and those in the TA+/LV+ subset (11%) were older and had a high prevalence of cranial ischemia, constitutional symptoms, and elevated acute-phase reactant levels. Vascular imaging is increasingly incorporated into the diagnostic assessment of GCA and identifies clinical subsets of patients based on involvement of temporal and extracranial arteries.


Use of cyclodextrins in isotachophoresis. VII. Resolution of structurally related and chiral phenothiazines.
Commercially available phenothiazine derivatives were used for the study of cyclodextrin complex formation by cationic isotachophoresis with alpha-, beta- and gamma-cyclodextrin and methylated analogues of beta-cyclodextrin as leading electrolyte additives. The relationships between the type of solute substituent in the 10- and/or 2-position and the stability of the created cyclodextrin complex were studied and the results were utilized for the optimization of isotachophoretic conditions suitable for the resolution of the studied phenothiazine derivatives. Successful resolution of three racemic solutes was achieved.


One stage procedure in the management of acute sigmoid volvulus without colonic lavage.
There is a growing acceptance of one-stage primary resection and anastomosis of left-sided colon obstruction with on-table antegrade colonic lavage to reduce the risk of post-operative infectious complications and anastomotic dehiscence. The purpose of this study was to evaluate the safety of single-stage resection and anastomosis for acute left-sided colonic obstruction due to acute sigmoid volvulus, without intraoperative colonic lavage, in a consecutive series of patients admitted to our department. Emergency resection of acute sigmoid volvulus was performed by an experienced senior surgeon (consultant grade). This was followed by primary anastomosis without on-table colonic lavage after a manual decompression. A total of 21 patients underwent bowel decompression, resection and primary colorectal anastomosis. Two of the patients who had ileosigmoid knotting and gangrenous bowel had double resection with primary ileoileal and colorectal anastomosis. There were two superficial wound infections. No death or clinical anastomotic failure were recorded in this series. The mean hospital stay was 10.3 days. Our results suggest that resection of acute sigmoid volvulus and primary anastomosis after decompression alone can be carried out safely in reasonably fit patients.


Visualizing exertional dyspnea in a post-COVID patient using electrical impedance tomography.
Many post-COVID patients suffer from dyspnea on exertion. To visualize exercise-induced dyspnea, a post-COVID patient and a healthy volunteer underwent an exercise test on a treadmill under stress relevant to everyday life monitored by electrical impedance tomography (EIT). The lung-healthy volunteer showed an even ventilation distribution throughout the assessment, a large ventilated area, and a butterfly-like lung shape with a convex lung rim. The post-COVID patient showed clear differences in the ventilated area compared to the control subject. During exercise, a constantly changing picture of differently ventilated areas is shown. However, especially the anterior regions were under-ventilated and larger areas were partially absent from ventilation. Overall, uncoordinated breathing and an uneven distribution of ventilation dominated the findings. EIT is suitable for visualizing disturbed ventilation of the lungs, both at rest and under stress. The potential as a diagnostic tool in dyspnea assessment should be investigated.


Connectivity and cytoarchitecture of telencephalic centers in the fire-bellied toad Bombina orientalis.
In the fire-bellied toad Bombina orientalis, the connectivity and cytoarchitecture of telencephalic structures were studied by intracellular, anterograde and retrograde biocytin labelling in order to elucidate the neuronal basis of fear conditioning and context learning in amphibians. Our findings suggest the existence of a central amygdala-bed nucleus of the stria terminalis complex in the caudal mid-ventral telencephalon, a vomeronasal amygdala in the caudolateral ventral telencephalon, an olfactory amygdala in the caudal pole of the telencephalon lateral of the vomeronasal amygdala, and a ventromedially situated "medial" amygdala, which is assumed to be functionally equivalent to the basolateral amygdala of mammals. A ventromedial cellular column forms a nucleus accumbens rostrally and continues caudally into a shell-like ventral pallidum. A lateral column constitutes a dorsal striatum proper rostrally, a dorsal pallidum caudally, and a mixed striato-pallidum at intermediate levels. We conclude that the caudal mediolateral complex consisting of an extended central, vomeronasal and olfactory amygdala of anurans represents the ancestral equivalent of the amygdaloid complex of tetrapods. During the evolution of the mammalian telencephalon, this complex apparently was shifted medially and involuted.


Optical tweezers for drug discovery.
The time taken and the cost of producing novel therapeutic drugs presents a significant burden - a typical target-based drug discovery process involves computational screening of drug libraries, compound assays and expensive clinical trials. This review summarises the value of dynamic conformational information obtained by optical tweezers and how this information can target 'undruggable' proteins. Optical tweezers provide insights into the link between biological mechanisms and structural conformations, which can be used in drug discovery. Developing workflows including software and sample preparation will improve throughput, enabling adoption of optical tweezers in biopharma. As a complementary tool, optical tweezers increase the number of drug candidates, improve the understanding of a target's complex structural dynamics and elucidate interactions between compounds and their targets.


Apical transportation with different root canal preparation techniques using edgEEvolve rotary instruments.
This study aimed to investigate the extent of apical transportation following instrumentation with EdgeEvolve rotary instruments applying single-length and crown-down techniques. In this experimental in-vitro study, 60 mandibular molars with mesiobuccal curvatures of 20°-40° were selected, and digital radiographic images were taken. Teeth were randomly assigned into two groups of single-length and crown-down preparation techniques. In both mentioned groups, EdgeEvolve rotary system was used. After preparation, the same as the previous ones, digital radiographic images were taken from the canals. The data were analyzed using Student' t-test and ShapiroWilk normality test (P = 0.05). The mean standard deviation (SD) for apical transportation in the single-length and the crown-down group was 4.42 (2.9) and 7.48 (3.9) degrees, respectively (P < 0.05). The mean SD of the preparation time in the single-length and crown-down group was 135.07 (30.8) and 109.07 (20.8), respectively (P < 0.05). The apical transportation and the time of preparation between the two groups were significant. Using EdgeEvolve rotary instruments canal preparation with both single-length and crown-down techniques led to some degrees of apical transportation.


Anti-proliferative effect of metformin on a feline injection site sarcoma cell line independent of Mtor inhibition.
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8.0mM. Using flow cytometry, the mechanism of cell death was determined to be apoptosis or necrosis. To evaluate the role of mTOR inhibition in metformin-induced cell death, Western blot was performed. No inhibition of mTOR or phosphorylated mTOR was found. Although metformin treatment leads to apoptotic or necrotic cell death in feline injection site sarcoma cells, the mechanism does not appear to be mediated by mTOR inhibition.


Analysis of multi-exponential relaxation data with very short components using linear regularization.
Linear regularization is a common and robust technique for fitting multi-exponential relaxation decay data to obtain a distribution of relaxation times. The regularization algorithms employed by the Uniform-Penalty inversion (UPEN) and CONTIN computer programs have been compared using simulated transverse (T2) relaxation data derived from a typical bimodal distribution observed in cartilage tissue which contain a component shorter than t(0), the time of the first decay sample. We examined the reliability of detecting sub-t(0) relaxation components and the accuracy of statistical estimates of T2 distribution parameters. When the integrated area of the sub-t(0) component relative to that of the total distribution was greater than 0.25, our results indicated a signal-to-noise threshold of about 300 for detecting the presence of the sub-t(0) component with a probability of 0.9 or greater. This threshold was obtained using both the UPEN and CONTIN algorithms. In addition, when using the second-derivative-squared regularizer, UPEN solutions provided statistical estimates of T2 distribution parameters which were substantially free of the biasing effect of the regularizer observed in analagous CONTIN solutions.


Vitamin D in Adolescents: A Systematic Review and Narrative Synthesis of Available Recommendations.
Practical guidelines help clinicians make their preventive and therapeutic choices and improve care management. Our purpose was to collect and synthesize available recommendations concerning vitamin D in adolescents (aged 10-19 years). We searched PubMed, EMBASE, and Cochrane databases from inception to February 5, 2019, for guidance published by different professional associations and governments. We also searched the reference lists of identified recommendations and explored the gray literature using Web search engines. We organized documents by theme: dietary requirements, thresholds, prophylactic supplementation, and treatment of deficiency. A total of 32 documents were identified. Most of them targeted the general population and not specifically the age group of adolescents. There is a general agreement that adolescents should not have serum 25-hydroxyvitamin D concentrations below 25-30 nmol/L to avoid poor bone health. However, there is lack of consensus on the optimal concentration to aim for, levels varying between 25 nmol/L and 150 nmol/L. Adequate nutritional requirements of vitamin D are also subject to debate with values ranging between 200 IU/d and 1,000 IU/d. The upper tolerable intake is estimated at 4,000 IU/d by all study groups. Certain associations recommend routine vitamin D supplementation in adolescents. The recommended daily preventive doses vary between 400 IU and 4,000 IU, depending on season, skin pigmentation, sun exposure, consumption of vitamin D-fortified foods, body mass index, and coexistence of certain medical conditions. In case of deficiency, different therapeutic regimens of oral vitamin D are proposed depending on the presence of illness and/or the baseline serum 25-hydroxyvitamin D concentrations. Duration of the treatment varies between 4 weeks and 3 months. A maintenance dose is generally recommended after treatment. At present, there is no consensus among the different societies about vitamin D needs during adolescence. Stronger, evidence-based guidance is needed to inform clinical practice.


Italian consumers' attitudes towards entomophagy: Influence of human factors and properties of insects and insect-based food.
Studies on consumers' perceptions towards entomophagy have recently gained popularity. However, the use of the general term "insect" represents a limitation of previous research, due to the need for more precise terminology. This study assessed attitudes towards specific insects, their gastronomic preparations, their relationships with human factors and the characteristics of insects as a food source. Using a survey, socio-demographics, personality traits, willingness to eat (WTE) six edible insects and their relative insect-based products or dishes (IBPD) and the emotions associated with entomophagy were collected from 400 Italians. Compared with females, males were found to be more positive towards insects, less influenced by the species and level of processing of insects and more willing to eat insects for reasons of taste. Eating insects evoked adventurous, daring and wild emotions, while disgust and food neophobia represented the main factors in refusal to eat insects. WTE was: crickets > bee larvae and grasshoppers > mealworms and silkworms > giant water bugs. A similar result was obtained considering the respective IBPD. On average, adult insects were preferred over larvae. Three subject groups, namely "In favour of eating insects" (41%), "Picky towards eating insects" (32%) and "Against eating insects" (27%) were found. A sensory evaluation performed on three cricket-based samples with 52 Italians revealed that a low level of insect visibility was preferred. This study gives new insights into the variables related to the acceptance of entomophagy by determining the characteristics of a potential consumer and of a probable insect product for the market.


CD4+Foxp3+ regulatory T cells in the control of autoimmunity: in vivo veritas.
The immune system requires a homeostatic equilibrium between the mechanisms that assure self-tolerance, those that control the capacity to mount life-long immunity to pathogenic microbes, and those that attenuate effector mechanisms from inducing immune pathology [Sakaguchi S, Yamaguchi T, Nomura T, Ono M: Regulatory T cells and immune tolerance. Cell 2008, 133 (5):775-87; Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4+CD25+regulatory T cells. Trends Immunol 2004, 25:374-80]. In the past decade, an overwhelming body of literature showed that CD4+Foxp3+ regulatory T (Treg) cells are a dominant mechanism regulating the decision fate of these different immunological outcomes. Indeed, CD4+Foxp3+ Treg cells develop largely in the thymus but can be induced in the periphery throughout the course of immune responses [Sakaguchi S, Yamaguchi T, Nomura T, Ono M: Regulatory T cells and immune tolerance. Cell 2008, 133 (5):775-87; Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4+CD25+regulatory T cells. Trends Immunol 2004, 25:374-80]. Treg cells have emerged as a central control point in the regulation of autoimmune responses. Despite progress made in various in vitro and in vivo models, much uncertainty exists over their mechanism of action in vivo. Here, we summarize research characterizing the functional dynamics of CD4+Foxp3+ Treg cells in the control of autoimmunity in rodents and humans.


Associations between cooking fuels and hypertension prevalence in Chinese adults: A prospective cohort analysis focusing on fuel transitioning.
Using polluting cooking fuels is a suggested risk factor for hypertension. Transitioning to clean cooking fuels has occurred widely in China in the past 30 years. This provides an opportunity to examine whether the transition could reduce hypertension risk and to ascertain the inconsistent literature on the relationship between cooking fuels and hypertension prevalence. Initiated in 1989, the China Health and Nutrition Survey (CHNS) enrolled participants from 12 provinces in China. By 2015, nine waves of follow-up have been conducted. Based on self-reported cooking fuels, participants were classified into persistent clean fuel users, persistent polluting fuel users and those who transitioned from polluting fuels to clean fuels. Hypertension was defined as having systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or self-reported current use of antihypertension medication. Among 12,668 participants, 3963 (31.28%) were persistent polluting fuel users; 4299 (33.94%) transitioned to clean fuels; and 4406 (34.78%) were persistent clean fuel users. During the period of follow-up (7.8 ± 6.1 years), hypertension was diagnosed in 4428 participants. Compared to persistent clean fuel users, persistent polluting fuel users had a higher risk for hypertension (hazard ratio [HR] 1.69, 95%CI 1.55-1.85), while those transitioned to clean fuels did not. The effects were consistent by gender and urbanicity, respectively. The HRs for hypertension were 1.99 (95%CI 1.75-2.25), 1.55 (95%CI 1.32-1.81) and 1.36 (95%CI 1.13-1.65) among those persistent polluting fuel users aged 18-44, 45-59 and ≥60 years old, respectively. Transitioning from using polluting fuels to clean fuels prevented an increase in hypertension risk. The finding highlights the importance of promoting the fuel transition as a risk-reduction strategy for reducing the disease burden from hypertension.


Estimation of intake of zinc, copper and iron in the diet of patients with chronic renal failure treated by haemodialysis.
The aim of this study was to analyse the dietary zinc, copper and iron intakes in haemodialysis patients and in healthy controls. A statistically significant lower intake of these elements was observed in the patients group. In particular, the copper intake was extremely low in that group, not reaching 40% of the recommended value.


United States rural residence is associated with increased acute maternal end-organ injury or mortality after birth: a retrospective multi-state analysis, 2007-2018.
Geographic-based healthcare determinants and choice of anesthesia have been shown to be associated with maternal morbidity and mortality. We explored whether differences in maternal outcomes based on maternal residence, and anesthesia type for cesarean and vaginal birth, exist. This study was a retrospective multi-state analysis; patient residence was the predictor variable of interest and a composite binary measure of maternal end-organ injury or inpatient mortality was the primary outcome. Our secondary outcomes included a binary measure of anesthesia type for cesarean birth (general vs. neuraxial [NA]) and NA analgesia for vaginal birth (no NA vs. NA). Our predictor variable of interest was patient residency (reference category central metropolitan areas of >1 million population), fringe large metropolitan county, medium metropolitan, small metropolitan, micropolitan, and non-metropolitan or micropolitan county. Women residing in micropolitan (OR 1.17; 95% CI 1.09 to 1.27) and non-metropolitan or micropolitan counties (OR 1.14; 95% CI 1.04 to 1.24) had the highest adjusted increased odds of adverse maternal outcomes. Those residing in suburban, medium, and small metropolitan areas underwent general anesthesia less often during cesarean births than those residing in urban areas. Patients residing in micropolitan rural (OR 2.07; 95% CI 2.02 to 2.12) and non-metropolitan or micropolitan (2.25; 95% CI 2.16 to 2.34) counties underwent vaginal births without NA analgesia more than twice as often as those residing in urban areas. Rural-urban disparities in maternal end-organ damage and mortality exist and anesthesia choice may play an important role in these disparate outcomes.


Stable isotope labeling with amino acids in cell culture-based proteomic analysis of ethanol-induced protein expression profiles in microglia.
Ethanol exposure causes neurotoxicity, where neuroinflammation has been proposed to contribute to ethanol neurotoxicity. In addition to astroglia, microglia, as resident immune cells in the central nervous system, have been implicated as a key contributor to the neuroimmune and inflammatory processes. However, little is known regarding the role of microglia in alcohol-induced neuronal dysfunction. In this chapter, we describe a method that provides an effective and unbiased global-scale analysis for relative quantitation of protein expression in microglial cells to elucidate the molecular mechanisms underlying microglial activation after ethanol exposure. The approach involves stable isotope labeling with amino acids in cell culture followed by mass spectrometric analysis of stable isotope-labeled proteins derived from cultured microglial cells and represents a powerful tool that can be used for general assessment of microglial response at the protein level.


Facile synthesis of nanostructured cobalt pigments by Co- A zeolite thermal conversion and its application in porcelain manufacture.
An innovative and facile synthesis of cobalt based inorganic pigment was carried out by means of a low energy thermal conversion of a cobalt-exchanged zeolite. The Na-A [LTA] zeolite was used, since it is a low cost and easily available raw material. The ion exchange mechanism allowed to control, at microscopic level, the composition of the zeolitic precursor. Several chromatic effects could be obtained by varying the treatment temperature and/or the cobalt concentration in the contact solution. The reliability of these new zeolite-based pigments was tested in porcelain manufacture, in collaboration with the Institute for the Capodimonte porcelain "Giovanni Caselli". The developed cobalt pigments were successfully tested either in the porcelain mixture to obtain a coloured product or in the decoration step (such as ingobbio, colored glazes and "third fire decoration").


Chilled storage of semen from Atlantic halibut, Hippoglossus hippoglossus L. I: optimizing the protocol.
Asynchrony in gamete production between females and males, and decrease in semen quality towards the end of reproductive season make chilled short-term storage of Atlantic halibut, Hippoglossus hippoglossus, semen a desirable method to apply for artificial propagation of this fish species. The goal of the present study was to determine the critical physiochemical factors that affect the success of chilled storage of halibut spermatozoa, and to develop a reliable, simple and efficient protocol for the storage. The presence and type of gaseous atmosphere, dilution and type of diluent, dilution ratio, and additional factors including spermatozoa sedimentation and replenishing the storage medium were tested in relation to spermatozoa motility parameters. Also, fertilization tests were performed with stored semen. Normoxia (air atmosphere) conditions were superior to both hyperoxia (pure oxygen) and no gaseous atmosphere for chilled storage. Dilution of semen with a diluent was superior to incubating undiluted semen. A dilution factor of between 6 and 10 times the original semen volume resulted in the longest viability of stored spermatozoa. Preventing spermatozoa sedimentation through daily swirling of the samples was superior to weekly swirling, however the effect was negligible for the first month of storage. Replenishing the storage medium showed no advantage to incubating in unchanged medium. Semen diluted in modified Hanks' balanced salt solution 1:5-1:9, supplemented with antibiotics, and kept at 0-1 degrees C in Ziploc bag filled with air retained its viability for exceptionally long time. A decrease in the percentage of motile spermatozoa was observed after 43 days of storage, and a decrease in curvilinear velocity occurred after 15 days. Samples remained motile for at least 79 days of storage and the fertilization ability was retained for at least 70 days of storage. The results demonstrate a high potential of application of chilled storage of semen into reproduction programs in Atlantic halibut aquaculture.


Quantitative analysis of nasal tip projection.
Previously described methods for quantifying nasal tip projection were evaluated. Fifty-one nasal profiles were analyzed and scored by expert rhinoplastic surgeons. The noses and faces were then evaluated quantitatively using several methods. The methods were found to vary widely in their correlation with the experts' subjective analyses. Several helpful relationships and guides were obtained: 1. Aesthetic tip projection does not correlate well with upper lip length. 2. A new method described in this paper showed the best correlation with the experts' opinions (regression, r value = 0.8132). This method related tip projection to total nasal length (including upper lip length). 3. The second new method tested in this report yielded helpful data by comparing tip projection with overall facial length. 4. After slight modification the method previously described by Goode proved useful as nasal length and desired tip projection formed a 3:4:5 right triangle.


Crash narrative classification: Identifying agricultural crashes using machine learning with curated keywords.
Traditionally, structured or coded data fields from a crash report are the basis for identifying crashes involving different types of vehicles, such as farm equipment. However, using only the structured data can lead to misclassification of vehicle or crash type. The objective of the current article is to examine the use of machine learning methods for identifying agricultural crashes based on the crash narrative and to transfer the application of models to different settings (e.g., future years of data, other states). Different data representations (e.g., bag-of-words [BoW], bag-of-keywords [BoK]) and document classification algorithms (e.g., support vector machine [SVM], multinomial naïve Bayes classifier [MNB]) were explored using Texas and Louisiana crash narratives across different time periods. The BoK-support vector classifier (SVC), BoK-MNB, and BoW-SVC models trained with Texas data were better predictive models than the baseline rule-based algorithm on the future year test data, with F1 scores of 0.88, 0.89, 0.85 vs. 0.84. The BoK-MNB trained with Louisiana data performed the closest to the baseline rule-based algorithm on the future year test data (F1 scores, 0.91 baseline rule-based algorithm vs. 0.89 BoK-MNB). The BoK-SVC and BoK-MNB models trained with Texas and Louisiana data were better productive models for Texas future year test data with F1 scores 0.89 and 0.90 vs. 0.84. The BoK-MNB model trained with both states' data was a better predictive model for the Louisiana future year test data, F1 score 0.94 vs. 0.91. The findings of this study support that machine learning methodologies can potentially reduce the amount of human power required to develop key word lists and manually review narratives.


Effects of nutrients on crude oil biodegradation in the upper intertidal zone.
To enhance biodegradation, nutrients in the form of slow-release fertilizer (SRF) were applied to oil-contaminated microcosms (3%, v/v) which simulated intertidal environmental systems. Although nutrient concentrations in the interstitial water were not proportional to those in amended SRF, microbial activity, growth of oil-degrading microorganisms, and oil-degradation rate were closely related to the concentration of nutrients in the interstitial water. Adding nutrients at higher dose (microcosm I, 144.4 mg C/kg sand/day, versus microcosm II, 8.5 mg C/kg sand/day) had a positive effect on oil degradation rate, which was especially obvious during the early phase of treatment. Use of pristane, phytane, and nor-hopane as biomarkers enabled the detection of significant treatment differences in hydrocarbon biodegradation, which were not reliable enough when the data were normalized to sand mass.


Putative serotonergic bipolar and amacrine cells in the chicken retina.
Four populations of putative serotonergic cells could be detected in the chicken retina by histofluorescence and immunohistochemistry. Numerous (10,000/mm2) small (6 micron diameter) bipolar cells were located towards the middle of the inner nuclear layer, as were sparser (1000/mm2) larger (12 micron diameter) amacrine cells. Very sparse large (greater than 30 micron diameter) and more numerous small (12 micron diameter) ganglion cells were also detected. Prominent fibre plexuses were detected in the inner plexiform layer, close to the inner nuclear and ganglion cell layers, and appeared to be formed by the processes of the bipolar cells, amacrine cells and at least the large ganglion cells. Exogenous serotonin (5-HT) was detected in the chicken retina. From the effects of neurotoxins on 5-HT levels and 5-HT-like immunoreactivity (5-HTLI), most of this appeared to be associated with the amacrine cells. 5-HTLI bipolar cells were selectively destroyed by intravitreal injections of 5-10 nmol of kainic acid, while 5-HTLI amacrine cells were destroyed by N-methyl-D,L-aspartic acid and 5,7-dihydroxytryptamine. The sensitivity of the bipolar cells to kainic acid indicates that they are OFF-cells.


Working well: Mitigating the impact of menopause in the workplace - A narrative evidence review.
In recent years there has been a much greater recognition by some employers of the need to support female employees experiencing the menopause. However, despite an increased awareness of the need to reduce the impact of menopause on the workforce, employers rarely have the opportunity to implement evidence-based interventions. This evidence review aims to provide an insight into the effectiveness of workplace programmes supporting women experiencing menopause symptoms, and to identify knowledge gaps as drivers for future research. A search for papers published in English between 2012 and 2023 was carried out on the PsycINFO, Medline, and Embase databases. Abstract review was used to screen initial returns before a subsequent full-text review determined the final studies included. Twelve studies were selected for in-depth review: four conducted in the UK, seven in continental Europe and one in South America. The findings of the papers fell into five categories: work ability, improved symptom management, mental wellbeing and empowerment, increased openness about menopause in the workplace, and the impact of management/leadership. None of the included interventions were reported to give a significant improvement in measures of work ability. However, there were improvements in women's wellbeing, and their ability to manage symptoms. Interventions to improve workplace openness and managers' skills were well received by participants. The evidence for effective workplace interventions for women experiencing menopause symptoms is currently lacking. There is considerable need for further high-quality evaluations of interventions designed to support women in the workplace.


Usefulness of the phage display technology for the identification of a hepatitis C virus NS4A epitope recognized early in the course of the disease.
A dodecapeptide phage-displayed library was screened with the mouse monoclonal antibody (mAb) 2E3C2 which competed with human antibodies for the binding to the HCV c100 recombinant protein. Four mimotopes shared a consensus motif with the HCV 1701-1707 sequence corresponding to the carboxyl-terminal domain of the non-structural protein NS4A. However, these mimotopes reacted with 2E3C2 only, whereas the corresponding NS4 epitope defined at the sequence 1698-1709 and displayed on phage was recognized by both 2E3C2 and sera from HCV infected patients. Using the Spot method of multiple peptide synthesis and alanine replacement analysis, the respective reactivities of mAb 2E3C2 and anti-NS4A human antibodies against NS4 were shown to be directed against two slightly different overlapping minimal linear sequences and to involve different critical residues. The phage clone displaying the NS4 epitope was used to study the specific recognition of this epitope by different individual HCV positive sera as well as by two seroconversion panels of sera from HCV infected patients. Compared with the detection by RIBA of the different HCV antigens and c100 particularly, these results indicated that the antibodies directed against the NS4 (1698-1709) epitope were produced early during the course of the disease and decreased later.


Evolution of large Aβ16-22 aggregates at atomic details and potential of mean force associated to peptide unbinding and fragmentation events.
Atomic characterization of large nonfibrillar aggregates of amyloid polypeptides cannot be determined by experimental means. Starting from β-rich aggregates of Y and elongated topologies predicted by coarse-grained simulations and consisting of more than 100 Aβ16-22 peptides, we performed atomistic molecular dynamics (MD), replica exchange with solute scaling (REST2), and umbrella sampling simulations using the CHARMM36m force field in explicit solvent. Here, we explored the dynamics within 3 μs, the free energy landscape, and the potential of mean force associated with either the unbinding of one single peptide in different configurations within the aggregate or fragmentation events of a large number of peptides. Within the time scale of MD and REST2, we find that the aggregates experience slow global conformational plasticity, and remain essentially random coil though we observe slow beta-strand structuring with a dominance of antiparallel beta-sheets over parallel beta-sheets. Enhanced REST2 simulation is able to capture fragmentation events, and the free energy of fragmentation of a large block of peptides is found to be similar to the free energy associated with fibril depolymerization by one chain for longer Aβ sequences.


Acute toxicity and safety profile evolution of aqueous extracts of Sanren decoction using in vivo models.
Sanren decoction (SRD) is a well-known traditional Chinese medicine prescription containing eight kinds of materials. SRD has been used mainly in China for more than 200 years for the treatment of respiratory disorders that co-occur with a bad fever after midday. To evaluate the acute and 28-day subacute toxicity of an aqueous extract of SRD using in vivo methods. To determine acute toxicity, SRD was administered by gavage at a dosage of 58.5 g/kg/day to male and female mice for 7 days. To determine subacute toxicity, SRD was administered at 3.3, 6.5, or 13 g/kg/day to male and female rats for 28 days. The general behavior, body weight, biochemical and hematological parameters, organ coefficients and pathological morphology of the treated animals were analyzed. Neither acute nor subacute concentrations of SRD caused significant changes in the body weights, general behavior, hematology and biochemical parameters, organ weights, or histopathological appearances of the liver, kidney, spleen, brain, lung or heart in mice or rats. The administration of SRD can be considered safe within the conditions of this study.


The awesome burden upon the child who must keep a family secret.
This paper describes a series of young patients hospitalized in a psychiatric facility because they presented symptoms indicative of a psychotic disorder when, in fact, the youngsters were dealing with the strain of keeping a family secret hidden. Case presentation oriented to how the burden prohibited proper psychological development and the manner of how these secrets came to light are offered. The commonality of patients exhibiting this phenomenon is discussed.


Optimization of Cyclic Peptide Property Using Chromatographic Capacity Factor on Permeability of Passive Cell Membrane and Human Induced Pluripotent Stem Cell-Derived Intestinal Membrane.
Cyclic peptides have attracted increasing attention as a privileged class of molecules addressing undruggable targets. Cell permeability of cyclic peptides has remained a challenging issue owing to their molecular properties. Various efficiency metrics have emerged to assess this issue. Among them, the lipophilic permeability efficiency (LPE) metric is the difference between an experimental 1,9-decadiene-water partition coefficient at pH 7.4 (log Ddec/w) and calculated octanol/water partition coefficients (ALogP). This metric provides insight into how structural changes affect permeability. Here, we demonstrate the chromatographic capacity factor (log k') of cyclic peptides using reversed-phase liquid chromatography as an alternative to log Ddec/w, which enables efficient and reliable experimental lipophilicity for the adoption of LPE in early drug discovery. The log k' indicates the passive membrane permeability of cyclic peptides and can be used to optimize passive membrane permeability in combination with other parameters. In addition, intestinal membrane permeability of cyclic peptides on human induced pluripotent stem cell-derived intestinal epithelial cells was achieved with log k' and high passive membrane permeability, although cyclic peptides are P-glycoprotein substrates. These approaches could facilitate optimization of properties of cyclic peptides for oral administration and contribute to the successful discovery and development of cyclic peptides.


Vascular Endothelial Growth Factor Signaling in Models of Oxygen-Induced Retinopathy: Insights Into Mechanisms of Pathology in Retinopathy of Prematurity.
Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide. Blindness can occur from retinal detachment caused by pathologic retinal angiogenesis into the vitreous, termed intravitreal neovascularization (IVNV). Although agents that interfere with the bioactivity of vascular endothelial growth factor (VEGF) are now used to treat IVNV, concerns exist regarding the identification of optimal doses of anti-VEGF for individual infants and the effect of broad VEGF inhibition on physiologic angiogenesis in external organs or in the retina of a preterm infant. Therefore, it is important to understand VEGF signaling in both physiologic and pathologic angiogenesis in the retina. In this manuscript, we review the role of receptors that interact with VEGF in oxygen-induced retinopathy (OIR) models that represent features of ROP pathology. Specifically, we discuss our work regarding the regulation of VEGFR2 signaling in retinal endothelial cells to not only reduce severe ROP but also facilitate physiologic retinal vascular and neuronal development.


The risk of adenomatous polyps in asymptomatic first-degree relatives of persons with colon cancer.
Increasing evidence indicates that inherited susceptibility is important in the pathogenesis of colorectal neoplasia. The aim of this study was to clarify whether having only one first-degree relative with colorectal cancer increases the risk of developing adenomatous polyps and whether total colonoscopy is an appropriate screening measure in these patients. The frequency of such a history was evaluated in 397 asymptomatic patients who underwent total colonoscopy. Of these patients, 155 had colorectal polyps and the remaining 242 did not have polyps. Among polyp cases, 27 of 155 (17.4%) had a positive history; among those without polyps, 12 of 242 (5.0%) had a positive history. Alternatively expressed, 27 of 39 patients (69%) with family history and 128 of 358 patients (36%) without family history had adenomas. The estimated risk for polyps associated with family history was 1.9. Among polyp cases, 14 of 27 patients (51.9%) with family history and 32 of 128 patients (25.0%) without family history had only proximal polyps (chi 2 test; P = 0.006; odds ratio, 3.2), In the same groups, frequency of high-grade dysplasia was 8 of 27 patients (29.6%) and 16 of 128 patients (12.5%), respectively (chi 2 test; P = 0.04; odds ratio, 2.9). Relative to subjects with no family history, asymptomatic patients with one first-degree relative with colorectal cancer had nearly double the risk of developing adenomatous polyps, greater frequency of severely dysplastic lesions, and significantly higher frequency of proximal polyp location. This suggests that total colonoscopy screening is indicated in these subjects.


The importance of Asn47 for structure and reactivity of azurin from Alcaligenes denitrificans as studied by site-directed mutagenesis and spectroscopy.
To study the importance of a rigid copper site for the structure and function of azurin, a mutant with a reduced number of internal hydrogen bonds around the copper has been prepared and characterized. To this purpose, the previously cloned azu gene from Alcaligenes denitrificans (Hoitink, C. W. G., Woudt, L. P., Turenhout, J. C. M., Van de Kamp, M., and Canters, G. W. (1990) Gene (Amst.) 90, 15-20) was expressed in Escherichia coli and an isolation and purification procedure for the azurin was developed. The azurin obtained after heterologous expression in E. coli appears spectroscopically indistinguishable from azurin derived from A. denitrificans. The hydrogen bonding network around the copper site was altered by replacing Asn47 by a leucine by means of site-directed mutagenesis. Asn47 is a conserved residue in all blue copper proteins of which the primary structure has been reported. Characterization of the mutant protein with UV-visible, electron spin resonance, and NMR spectroscopy, and comparison with the wild type azurin revealed that the structure of the copper site as well as the overall structure of the protein have been largely retained. The redox activity as measured by the electron self-exchange rate appears not to have changed either. However, the mutant differs from the wild type azurin with respect to stability and midpoint potential. Midpoint potentials of mutant and wild type azurin amount to 396 and 286 mV, respectively. The difference is due to sizable entropic and enthalpic contributions which to a large extent cancel. Possible explanations for the outcome of these experiments are discussed.


A comparison of H1N1 influenza among pediatric inpatients in the pandemic and post pandemic era.
The novel influenza A H1N1 (A[H1N1]pdm09) strain emerged in 2009, contributing to significant morbidity and mortality. It is not known whether illness associated with A(H1N1) pdm09 in the post-pandemic era exhibits a similar disease profile. The objectives of this study were to compare the burden of disease of A(H1N1) pdm09 influenza from the 2009 pandemic year to the post-pandemic years (2010-2014), and to explore potential reasons for any differences. We conducted a retrospective cohort study of inpatients admitted to Children's Hospital Colorado with a positive respiratory specimen for influenza from May-December, 2009 and December, 2010-April, 2014. Univariate and multivariate analyses were conducted to compare the demographics and clinical characteristics of patients with H1N1 during the two periods. There were 388 inpatients with influenza A(H1N1) pdm09 in 2009, and 117 during the post-pandemic years. Ninety-four percent of all H1N1 during the post-pandemic era was observed during the 2013-2014 influenza season. Patients with A(H1N1) pdm09 during the post-pandemic year were less likely to have an underlying medical condition (P<0.01). Patients admitted to the ICU during the post-pandemic year had a lower median age (5 vs 8 years, P=0.01) and a lower proportion of patients were intubated, had mental status changes, and ARDS compared with the pandemic years, (P<0.01 for all), with decreased mortality (P=0.02). Patients with influenza A(H1N1) pdm09 during the post-pandemic years appeared to have less severe disease than patients with A(H1N1) pdm09 during the pandemic year. The reasons for this difference are likely multifactorial.


Effect-directed analysis of a hospital effluent sample using A-YES for the identification of endocrine disrupting compounds.
An effect-directed analysis (EDA) approach was used to identify the compounds responsible for endocrine disruption in a hospital effluent (Basque Country). In order to facilitate the identification of the potentially toxic substances, a sample was collected using an automated onsite large volume solid phase extraction (LV-SPE) system. Then, it was fractionated with a two-step orthogonal chromatographic separation and tested for estrogenic effects with a recombinant yeast (A-YES) in-vitro bioassay. The fractionation method was optimized and validated for 184 compounds, and its application to the hospital effluent sample allowed reducing the number of unknowns from 292 in the raw sample to 35 after suspect analysis of the bioactive fractions. Among those, 7 of them were confirmed with chemical standards. In addition, target analysis of the raw sample confirmed the presence of mestranol, estrone and dodemorph in the fractions showing estrogenic activity. Predictive estrogenic activity modelling using quantitative structure-activity relationships indicated that the hormones mestranol (5840 ng/L) and estrone (128 ng/L), the plasticiser bisphenol A (9219 ng/L) and the preservative butylparaben (1224 ng/L) were the main contributors of the potential toxicity. Derived bioanalytical equivalents (BEQs) pointed mestranol and estrone as the main contributors (56 % and 43 %, respectively) of the 50 % of the sample's explained total estrogenic activity.


Fat distribution, endocrine and metabolic profile in obese women with and without hirsutism.
The relationship between adipose tissue distribution, androgen levels, and metabolic complications of obesity was studied in 20 hirsute and 20 nonhirsute obese premenopausal women. The group of hirsute women showed preferentially an upper body type of obesity as assessed by the waist-to-hip ratio (0.902 + 0.017 v 0.778 +/- 0.015, P less than .01). They had higher serum concentrations of total testosterone (100.4 + 11.7 v 48.8 +/- 4.5 ng/dL, P less than .01) and lower levels of serum sex-hormone-binding globulin (28.1 +/- 3.6 v 44.0 + 4.2 nmol/L, P less than .05) exhibiting an increased androgenic activity as compared to the nonhirsute women. Serum glucose and insulin levels after an oral glucose load were significantly higher in the hirsute women. In addition, the group of hirsute females has significantly higher fasting concentrations of total cholesterol (5.82 +/- 0.28 v 4.75 +/- 0.14 mmol/L, P less than .05) and triglycerides (2.51 +/- 0.38 v 1.14 +/- 0.10 mmol/L, P less than .01). The hirsute group also showed higher systolic (166.7 +/- 5.1 v 142.1 +/- 4.5 mm Hg, P less than .01) and diastolic (100.9 +/- 3.6 v 85.2 +/- 2.5 mm Hg, P less than .01) blood pressure values than the nonhirsute women. Analysis of correlation revealed that an increasing waist-to-hip ratio was accompanied by increasing testosterone levels (r = .39, P less than .05) and by decreasing sex-hormone-binding globulin levels (r = .37, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Flow cytometric quantitation of the c-myc oncoprotein in archival neoplastic biopsies of the colon.
The c-myc oncogene encoded protein product, p62c-myc, was assayed simultaneously with DNA in populations of individual nuclei extracted from archival biopsies of colonic neoplasia. Both the protein and DNA were assayed fluorimetrically using flow cytometry with a synthetic peptide induced monoclonal antibody (MYC 1-6E10) for the protein and propidium iodide for DNA. The nuclear p62c-myc levels increased progressively from normal mucosa through polyps to carcinomas. However, there was a trend for the more poorly differentiated carcinomas to exhibit lower levels than moderately and well-differentiated tumours, p = 0.085. These results agree with those published previously with the same antibody using Western blotting for protein extracted from fresh frozen tissue and immunocytochemical assessment. Furthermore, flow cytometry is able to effect discriminations between subsets in heterogeneous populations using DNA as a second parameter which Western blot bulk studies cannot.


Partitioning of mesophyll conductance for CO2 into intercellular and cellular components using carbon isotope composition of cuticles from opposite leaf sides.
We suggest a new technique for estimating the relative drawdown of CO2 concentration (c) in the intercellular air space (IAS) across hypostomatous leaves (expressed as the ratio cd/cb, where the indexes d and b denote the adaxial and abaxial edges, respectively, of IAS), based on the carbon isotope composition (δ13C) of leaf cuticular membranes (CMs), cuticular waxes (WXs) or epicuticular waxes (EWXs) isolated from opposite leaf sides. The relative drawdown in the intracellular liquid phase (i.e., the ratio cc/cbd, where cc and cbd stand for mean CO2 concentrations in chloroplasts and in the IAS), the fraction of intercellular resistance in the total mesophyll resistance (rIAS/rm), leaf thickness, and leaf mass per area (LMA) were also assessed. We show in a conceptual model that the upper (adaxial) side of a hypostomatous leaf should be enriched in 13C compared to the lower (abaxial) side. CM, WX, and/or EWX isolated from 40 hypostomatous C3 species were 13C depleted relative to bulk leaf tissue by 2.01-2.85‰. The difference in δ13C between the abaxial and adaxial leaf sides (δ13CAB - 13CAD, Δb-d), ranged from - 2.22 to + 0.71‰ (- 0.09 ± 0.54‰, mean ± SD) in CM and from - 7.95 to 0.89‰ (- 1.17 ± 1.40‰) in WX. In contrast, two tested amphistomatous species showed no significant Δb-d difference in WX. Δb-d correlated negatively with LMA and leaf thickness of hypostomatous leaves, which indicates that the mesophyll air space imposes a non-negligible resistance to CO2 diffusion. δ13C of EWX and 30-C aldehyde in WX reveal a stronger CO2 drawdown than bulk WX or CM. Mean values of cd/cb and cc/cbd were 0.90 ± 0.12 and 0.66 ± 0.11, respectively, across 14 investigated species in which wax was isolated and analyzed. The diffusion resistance of IAS contributed 20 ± 14% to total mesophyll resistance and reflects species-specific and environmentally-induced differences in leaf functional anatomy.


Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist.
Solid organ transplant recipients (SOTRs) are at increased risk for the development of skin cancer compared with the general population, which requires consistent monitoring and management from a multidisciplinary team. The aim of this review is to provide a comprehensive overview for nondermatologist clinicians, outlining skin cancer diagnosis, treatment pearls, and skin cancer prevention strategies as they relate to SOTRs. A comprehensive search of the literature was conducted through the MEDLINE database with search terms including organ transplantation, transplant recipient, skin cancer, cutaneous neoplasms, management, and therapies. The search was limited to the English language and dates ranging from January 1, 2011, to December 28, 2021. All studies were reviewed for inclusion. Skin cancer will develop in more than half of SOTRs at some point in their life, most often nonmelanoma skin cancer such as basal cell carcinoma or squamous cell carcinoma. Melanoma and rarer cutaneous malignant neoplasms, such as Merkel cell carcinoma and Kaposi sarcoma, are also more frequent among SOTRs. A multidisciplinary effort at skin cancer screening and patient education is invaluable to prevent skin cancer-related morbidity and mortality in this population of patients. Reduction in immunosuppressive medications and surgical intervention are effective therapeutic approaches, and more novel systemic therapies including G protein-coupled receptor inhibitors and immune checkpoint inhibitors are possible options when traditional treatment approaches are not feasible. Checkpoint inhibitor therapy, however, comes with the risk of allograft rejection. With a growing and aging SOTR population, it is essential that SOTRs have support from dermatologists and nondermatologists alike in skin cancer prevention and treatment.


Interaction of neocuproine, 1,10-phenanthroline and 2,2'-dipyridyl with human ceruloplasmin.
1. Neocuproine binding to ceruloplasmin markedly increases the chlorpromazine-ceruloplasmin-catalyzed oxidation of NADH. 2. 1,10-Phenanthroline and 2,2'-dipyridyl inhibit neocuproine activation in a competitive manner. 3. The order of enzyme chelator complex stability was: phenanthroline greater than dipyridyl greater than neocuproine.


A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma.
This study was undertaken to evaluate safety and pharmacokinetics and to determine treatment doses of vorinostat plus bortezomib in Japanese patients with relapsed or refractory multiple myeloma (MM). Of 9 originally enrolled patients, 2 were refractory to bortezomib, and both experienced dose-limiting toxicity (DLT), prompting a protocol amendment to exclude bortezomib-refractory individuals. Patients not considered bortezomib refractory (N = 7) received 21-day cycles of 1.3 mg/m(2) intravenous bortezomib (Days 1, 4, 8, and 11) and oral vorinostat 400 mg (Days 1 through 14) and were further evaluated. Vorinostat and bortezomib treatment doses were determined by DLT and safety, tolerability, and treatment response were assessed. Of 7 enrolled patients, 6 were evaluated, and one developed DLTs. The most common adverse events were leukopenia, neutropenia, thrombocytopenia, diarrhea, nausea, decreased appetite, and vomiting. Combination of vorinostat plus bortezomib did not increase vorinostat exposure at Day 11 [AUC0-24 h ratio (95% CI) = 1.08 (0.80, 1.45)]; geometric mean AUC0-24 h ratio for bortezomib (90% CI) was 1.96 (1.24-3.12). Objective therapeutic response occurred in 3 patients, including 1 complete response and 2 partial responses. Vorinostat 400 mg plus bortezomib 1.3 mg/m(2) was safe and well-tolerated in Japanese patients with relapsed or refractory MM not considered bortezomib refractory (NCT00858234).


The estimation of mean duration from stage frequency data.
A simple method of estimating duration from stage frequency data is derived. A simulation model of the passage of individuals through a particular stage in the life-cycle is presented, together with results from the model on the influence of recruitment, development and mortality on the parameters used in the estimation of stage duration. The application of the method to field data is described and a test example, using simulated data, is given.


Memory impairment in Parkinson's disease: The retrieval versus associative deficit hypothesis revisited and reconciled.
Our study explored the retrieval deficit and the associative deficit hypotheses of memory impairments in Parkinson's disease (PD). The former supports a memory deficit mediated by attention/executive dysfunctions, whereas the latter hypothesizes a hippocampal memory impairment in PD. We studied 31 controls and 34 PD patients classified as PD with normal cognition (PD-NC; n = 18) and PD with mild cognitive impairment (PD-MCI; n= 16). To test the retrieval deficit hypothesis, we measured the performance in encoding, retention, and recognition in verbal and visual domains; to test the associative deficit hypothesis, we used a specific associative binding measure. Using resting-state functional-MRI, we compared the functional connectivity of different hippocampal subfields between PD patients and controls, and we related it to memory performance. Consistently with the retrieval deficit hypothesis, PD-MCI, and PD-NC, were impaired in free recall encoding and retention in comparison to controls, especially in the visual domain. However, as predicted by the associative deficit hypothesis, PD-MCI and, to a lesser extent, PD-NC, showed also significant associative and binding deficits in cued recall. Notably, PD patients compared to controls did not show structural differences, although they had lower connectivity between the anterior hippocampi and the precuneus/superior parietal cortex. Worse performance in memory was associated with a more severe disruption of the hippocampal connectivity. The pervasive pattern of memory impairment in PD supports both hypotheses. The interplay between the hippocampus, related to associative memory deficits, and the precuneus, related to attentional control, provides a neural signature that reconciles them. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Comparison of the antioxidant potential in urine, saliva and skin.
Free radicals, oxidative stress and their possible consequences for health are becoming increasingly important in modern medicine. Reactive species influence the organism, potentially causing oxidative cell damage. They can be produced by exogenous sources, or be a product of a variety of not only physiological metabolic processes, such as immune response, but also pathological processes. The antioxidant protection system protects the organism from oxidative damage caused by reactions producing an excess of free radicals. The analysis of antioxidant potential (AOP) is therefore becoming increasingly important for the diagnosis of individual vitality. The photochemoluminescence method was used to measure the AOP in urine and saliva, spectrometry was employed to measure the β-carotene content of the skin. In addition, it was investigated whether the AOP(saliva) correlated with the AOPU(urine) (uric-acid independent AOP) as well as the β-carotene content of the skin. The AOP was significantly higher in urine than in saliva, and both values were significantly positively correlated with each other. However, there was no significant correlation to the β-carotene content of the skin. The components of the AOPU(urine) are accumulated over time (night), whereas AOP measurement in saliva is like a snapshot, which explains why AOPU(urine) was significantly higher than AOP(saliva), although the two parameters are correlated with each other. β-carotene is a fat-soluble antioxidant, whereas in our study, only water-soluble antioxidants were determined in the urine. This explains why there is no positive correlation between β-carotene of the skin and AOP. For the characterization of the AOP in epidemiological studies, we recommend determining the AOPU(urine) and parallel to this, the β-carotene content of the skin.


Management of amyotrophic lateral sclerosis (ALS) by the family nurse practitioner: a timeline for anticipated referrals.
This article reviews characteristics of amyotrophic lateral sclerosis (ALS) and appropriate timing of referrals by the nurse practitioner (NP). Selected research and clinical articles. Management of patients with ALS by the NP requires anticipation of needed referrals based on symptom assessment and knowledge of the common timeline of ALS progression. Close collaboration with specialists such as neurologists, pulmonologists, and a palliative care team provides patients and families with much needed support and improves outcomes. Anticipating and initiating appropriate and timely referrals for patients with ALS may improve quality of life for patients with this devastating condition.


Anisakiasis and gastroallergic reactions associated with Anisakis pegreffii infection, Italy.
Human cases of gastric anisakiasis caused by the zoonotic parasite Anisakis pegreffii are increasing in Italy. The disease is caused by ingestion of larval nematodes in lightly cooked or raw seafood. Because symptoms are vague and serodiagnosis is difficult, the disease is often misdiagnosed and cases are understimated.


Universal newborn hearing screening--the Colorado story.
The Colorado State Public Health Department inaugurated a state-wide program of universal newborn hearing screening in 1992. A preliminary report covers the screening of 14,494 infants. 95% passed the screening tests, 5% failed. Of the failures, 6% were found with confirmed hearing losses. The average cost per test was $25.00. Research from the University of Colorado confirms that children receiving intervention by 3 months perform significantly higher at 40 months than those identified later.


Automatic dirt trail analysis in dermoscopy images.
Basal cell carcinoma (BCC) is the most common cancer in the US. Dermatoscopes are devices used by physicians to facilitate the early detection of these cancers based on the identification of skin lesion structures often specific to BCCs. One new lesion structure, referred to as dirt trails, has the appearance of dark gray, brown or black dots and clods of varying sizes distributed in elongated clusters with indistinct borders, often appearing as curvilinear trails. In this research, we explore a dirt trail detection and analysis algorithm for extracting, measuring, and characterizing dirt trails based on size, distribution, and color in dermoscopic skin lesion images. These dirt trails are then used to automatically discriminate BCC from benign skin lesions. For an experimental data set of 35 BCC images with dirt trails and 79 benign lesion images, a neural network-based classifier achieved a 0.902 are under a receiver operating characteristic curve using a leave-one-out approach. Results obtained from this study show that automatic detection of dirt trails in dermoscopic images of BCC is feasible. This is important because of the large number of these skin cancers seen every year and the challenge of discovering these earlier with instrumentation.


Neoadjuvant vismodegib in the management of locally advanced periocular basal cell carcinoma.
Vismodegib, a hedgehog pathway inhibitor, has been used in the management of locally advanced basal cell carcinoma (BCC) not suitable for surgery or radiation therapy. We report our experience using neoadjuvant vismodegib for locally advanced periocular BCC, followed by surgical excision. Our aim was to assess the effect on the extent of surgical excision and histological response. A retrospective case series of patients treated with neoadjuvant vismodegib, for the management of locally advanced periocular BCC prior to surgical excision, with intraoperative margin control. Patients were treated until a maximum clinical response was seen. The difference between the estimated surgical margins prior to vismodegib and the eventual margins used was compared. Fine (1 mm) vertical sections through the excised tumour were performed to assess the histological response and look for a multifocal tumour. Eight Caucasian patients had neoadjuvant treatment with vismodegib for a median duration of 6 months. Some clinical response was seen in all cases but was only partial in 6/8 patients. Histological evaluation of the excised specimen showed residual BCC in 6/8 cases and thus 2/8 showed complete histological regression. Two cases showed squamous differentiation. Side effects occurred in 7/8 patients all which resolved on cessation of therapy. The mean follow-up was 13.4 ± 5.2 months. Neoadjuvant treatment of periocular BCC showed a mixed clinical and histological response. Final surgical excision achieved clear margins in all patients with no recurrence at 13 months and a reduction in predicted defect size, but possible squamous differentiation in two cases.


Intraspecific variation in the population dynamics and growth of the limpet, Cellana tramoserica.
Populations of the limpet Cellana tramoserica (Sowerby) from high, mid, and low intertidal regions, and from a subtidal zone, were studied at Cape Banks (N.S.W.), Australia. Individuals from the subtidal population had the largest mean and maximum shell size, the low and high shore populations were intermediate, while the midshore population had both the smallest mean and maximum size. The density of adults showed the reverse trend: the midshore region had the greatest adult population density while the subtidal population had the smallest density. The density of juveniles and recruits was negatively correlated with tidal height in the intertidal areas, but the density of both age-classes was smallest in the subtidal region. The rate of growth of individuals was negatively correlated to the adult density of a site; individuals from the subtidal population grew the fastest, while those from the midshore region grew the slowest. The level of adult mortality of the four populations was similar, with an annual rate of between 50-60%. Juvenile mortality did, however, differ among populations; reduced percentages of juveniles reached adult size in the mid and low shore populations than in the highshore and subtidal populations.The expected lifetime fecundity of individual females differed among the four populations. Subtidal individuals were expected to spawn 40 times the amount of gonad material during their life than were individuals from the midshore population. Individuals from the high and low populations probably spawn 10 times more than those from the midshore region. Differences in the fecundities of individuals were not likely to be the result of genetic differences because experimental transplants and manipulations of density showed that individuals from all the intertidal populations could increase their growth rate to match that of subtidal individuals. The implications of the difference in lifetime fecundity among populations are discussed.


[Pulmonary re-expansion in metastatic pleural effusions after thoracentesis: A pilot study].
Metastatic pleural effusion is a cause of dyspnea. The American thoracic society has strongly suggested that studies evaluating thoracic ultrasonography as potentially predictive of improvment of dyspnea are needed. We conducted a prospective monocentric observational study to assess chest ultrasound predictors of response to thoracentesis. Fifteen patients with metastatic pleural effusion were included. The initial mean VAS score was5 ± 2,9 cm. The majority of patients had pleural effusions equal to or greater than 5 intercostal spaces (EIC) in height, while 7 patients had an abnormal curvature of the hemidiaphragm (flattened or inverted). The volume removed was greater in the group with anechoic pleurisy compared to the group with sonographic septation, notwithstanding complex pleural effusion (non-septated, relatively hyperechoic, with some spots in the effusion). The patients with complex pleural effusions had an higher score of dyspnea. The 7 patients with abnormal diaphragmatic curvature presented significant dyspnea with a pain score of approximately 7 and profuse pleurisy occupying 8 intercostal spaces in height. The effusions of those who could not normalize their curvature had a complex aspect and the volume removed was lower. The ultrasound characteristics of pleural effusions seem to be predictors of improvment of dyspnea after thoracentesis. The septated and complex aspects are probably predictors of non improvment of dyspnea.


Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer.
Tissue transglutaminase (TG2), an enzyme involved in cell proliferation, differentiation and apoptosis is overexpressed in ovarian carcinomas, where it modulates epithelial-to-mesenchymal transition (EMT) and promotes metastasis. Its regulation in ovarian cancer (OC) remains unexplored. Here, we show that transforming growth factor (TGF)-β, a cytokine involved in tumor dissemination is abundantly secreted in the OC microenvironment and induces TG2 expression and enzymatic activity. This is mediated at transcriptional level by SMADs and by TGF-β-activated kinase 1-mediated activation of the nuclear factor-κB complex. TGF-β-stimulated OC cells aggregate as spheroids, which enable peritoneal dissemination. We show that TGF-β-induced TG2 regulates EMT, formation of spheroids and OC metastasis. TG2 knock-down in OC cells decreases the number of cells harboring a cancer stem cell phenotype (CD44+/CD117+). Furthermore, CD44+/CD117+ cells isolated from human ovarian tumors express high levels of TG2. In summary, TGF-β-induced TG2 enhances ovarian tumor metastasis by inducing EMT and a cancer stem cell phenotype.


Treatment of osteoporotic vertebral compression fractures with percutaneous vertebroplasty under local anesthesia: clinical and radiological results.
Vertebroplasty (VP) is a commonly used method for the treatment of osteoporotic vertebral fractures (OVF). The aim of this study is to analyze retrospectively the efficacy of PV in symptomatic osteoprotic spine fractures. Patients with symptomatic osteoporotic spine fractures were included in our study. Visual analog scale and demographic characteristics were used for clinical examination, local wedge angle and the central height of the vertebral body were measured preoperatively and postoperatively. 95 patients (72 female, 23 male) were included and 118 level vertebroplasty were performed. There was statistical significance in the differences of preoperative VAS scores compared to postoperative first day, first month and sixth month. The radiologic assessment of the mean local wedge angle correction at the postoperative sixth month, was 13.9 and mean increase of mid height of vertebral body was 7.9 mm, but it was not statistically significant. VP is at an important point as a minimally invasive method, that provides rapid pain relief in symptomatic osteoporotic vertebral fractures and that prevents the patient being bed-dependent. It is a reliable surgical method, being an alternative to open surgery with minimal complications in patients with comorbidities, which can be arapidley applied and decreases the potential spinal deformity after the fracture and prevents the progression of deformity.


BRN-103, a novel nicotinamide derivative, inhibits VEGF-induced angiogenesis and proliferation in human umbilical vein endothelial cells.
Anti-angiogenesis is regarded as an effective strategy for cancer treatment, and vascular endothelial growth factor (VEGF) plays a key role in the regulations of angiogenesis and vasculogenesis. In the present study, the authors synthesized five novel nicotinamide derivatives which structurally mimic the receptor tyrosine kinase inhibitor sunitinib and evaluated their anti-angiogenic effects. Transwell migration assays revealed that 2-(1-benzylpiperidin-4-yl) amino-N-(3-chlorophenyl) nicotinamide (BRN-103), among the five derivatives most potently inhibited VEGF-induced human umbilical vein endothelial cells (HUVECs). In addition, BRN-103 dose-dependently inhibited VEGF-induced migration, proliferation, and capillary-like tube formation of HUVECs and vessel sprouting from mouse aortic rings. To understand the molecular mechanisms responsible for these activities, the authors examined the effect of BRN-103 on VEGF signaling pathways in HUVECs. BRN-103 was found to suppress the VEGF-induced phosphorylation of VEGF receptor 2 (VEGR2) and the activations of AKT and eNOS. Taken together, these results suggest that BRN-103 inhibits VEGF-mediated angiogenesis signaling in human endothelial cells.


Long-term effects of weight loss on pharmaceutical costs in obese subjects. A report from the SOS intervention study.
Although intentional weight reduction improves obesity-related comorbidities, the associations between weight reduction, medication and related costs are rarely studied. This study investigates the long-term effects of weight change on medication for diabetes and cardiovascular disease (CVD) in severely obese subjects. In the intervention study Swedish Obese Subjects, 510 surgically and 455 conventionally treated obese patients have so far been followed for 6 y. Changes in the use and costs of medication were analyzed in relation to treatment and weight change. In comparison with controls, larger fraction of surgically treated patients discontinued the use of medication for CVD and diabetes at 2 and 6 y (risk ratios 0.56-0.77). Among subjects not initially on medication, surgery reduced the frequency of started treatments (risk ratios 0.08-0.80). Relative weight loss >or=10% was necessary to reduce costs of medication for CVD and diabetes among subjects with such treatment at baseline. To reduce initiation of new treatment against the two conditions, weight loss >or=15% was required. Over 6 y, the average annual cost for diabetes and CVD medication increased by 463 SEK (96%) in subjects with weight loss <5%, and decreased by 39 SEK(8%) in the weight loss group >or=15%. Long-term intentional weight loss is associated with reduced medication and medication costs for diabetes and CVD. The effects appear to be more marked among subjects who are initially on medication for these conditions, whereas greater weight reduction is needed to prevent new subjects from starting on medication.


Can restricting while-in-bed smartphone use improve sleep quality via decreasing pre-sleep cognitive arousal among Chinese undergraduates with problematic smartphone use? Longitudinal mediation analysis using parallel process latent growth curve modeling.
Problematic smartphone use (PSU) has become a global public health problem. Excessive while-in-bed smartphone use may result in poor sleep quality. The present study aimed to examine whether restricting while-in-bed smartphone use can improve sleep quality and the mediating role of pre-sleep cognitive arousal in this process. A total 152 Chinese undergraduates with symptoms of PSU (Smartphone Addiction Scale-Short Version [SAS-SV] > 31) were recruited and randomly assigned to the intervention group (N = 76) and the control group (N = 76) for a 4-week follow-up experiment. Sleep quality (assessed by the Pittsburgh Sleep Quality Index) and pre-sleep cognitive arousal (assessed by the Pre-sleep Arousal Scale-Cognitive Arousal) were measured at baselime, Week1, Week2, Week3, and Week4. The longitudinal mediation model was analyzed using parallel process latent growth curve modeling. The significance of indirect effect was tested by 95% biascorrected accelerated confidence intervals on the basis of 5000 bootstrap samples. The initial level of sleep quality was positively associated with the initial level of pre-sleep cognitive arousal. The intervention decreased pre-sleep cognitive arousal and increased sleep quality. The slope of pre-sleep cognitive arousal was positively associated with the slope of sleep quality. The mediating effect of pre-sleep cognitive arousal was significant. Restricting while-in-bed smartphone use can improve sleep quality via decreasing pre-sleep cognitive arousal among Chinese undergraduates with symptoms of PSU. These results suggests that restricting while-in-bed smartphone use is a potential remedy for sleep disturbance induced by PSU.


Advanced strategies for metabolic engineering of Bacillus to produce extracellular polymeric substances.
Extracellular polymeric substances are mainly synthesized via a variety of biosynthetic pathways in bacteria. Bacilli-sourced extracellular polymeric substances, such as exopolysaccharides (EPS) and poly-γ-glutamic acid (γ-PGA), can serve as active ingredients and hydrogels, and have other important industrial applications. However, the functional diversity and widespread applications of these extracellular polymeric substances, are hampered by their low yields and high costs. Biosynthesis of extracellular polymeric substances is very complex in Bacillus, and there is no detailed elucidation of the reactions and regulations among various metabolic pathways. Therefore, a better understanding of the metabolic mechanisms is required to broaden the functions and increase the yield of extracellular polymeric substances. This review systematically summarizes the biosynthesis and metabolic mechanisms of extracellular polymeric substances in Bacillus, providing an in-depth understanding of the relationships between EPS and γ-PGA synthesis. This review provides a better clarification of Bacillus metabolic mechanisms during extracellular polymeric substance secretion and thus benefits their application and commercialization.


Cannabinoid receptors are involved in the protective effect of a novel curcumin derivative C66 against CCl4-induced liver fibrosis.
Liver fibrosis is one of the major causes of morbidity and mortality worldwide and lacks efficient therapy. Recent studies suggest the curcumin protects liver from fibrosis. However, curcumin itself is in low bioavailable concentration when administered orally, and the protective mechanism remains poorly understood. The current study aimed to investigate whether a more stable derivative of curcumin, C66, protects against CCl4-inudced liver fibrosis and examine the underlying mechanism involving cannabinoid receptor (CB receptor). At a dose lower than curcumin itself, C66 displayed a superior anti-fibrotic effect. C66 significantly reduced collagen deposition, pro-inflammatory cytokine expression, and liver enzyme activities. Mechanistic study revealed that C66 treatment decreased CCl4-induced cannabinoid receptor 1 (CB1 receptor) expression and increased cannabinoid receptor 2 (CB2 receptor) expression, along with an inhibition of JNK/NF-κB-mediated inflammatory signaling. In conclusion, this curcumin derivative attenuates liver fibrosis likely involving a CB/JNK/NF-κB-mediated pathway.


Investigation of in vitro antileishmanial activity of moxifloxacin, linezolid and caspofungin on Leishmania tropica promastigotes.
This study aimed to evaluate the potential in vitro anti-leishmanial activities of moxifloxacin, linezolid and caspofungin against Leishmania tropica. In vitro effects of all agents were studied by using the microdilution method. For this purpose, serial dilutions of the aforementioned agents were prepared in concentrations between 4096 μg/mL-0.008 μg/mL. Afterwards, promastigotes incubated in suitable medium were counted with the hemocytometer and adjusted as having a last concentration of 2.5 x 10(6) cells/mL in wells containing medium+antibiotic or antifungal. After incubation live promastigotes were counted with the hemocytometer and inhibitor concentrations (IC(50)) were determined by comparing with the control that contained no antibiotics or antifungal. IC(50) values of moxiloxacin, linezolid and caspofungin were found as 194.7 μg/mL, 896 μg/mL and 235.7 μg/mL, respectively. As a result, moxifloxacin was found to be effective in lower concentrations than the other studied agents against L. tropica promastigotes.


Evaluation of an alternative biotreatment for the extraction of harmful iron and sulfur species from waterlogged wood.
An innovative bioextraction method was tested and compared to common chemical extraction for the preservation of waterlogged archeological wood (WAW) artifacts. During burial, WAW artifacts accumulate iron and sulfur species forming iron sulfides. These compounds are harmless in the burial environment, where the oxygen content is low. But upon excavation, the WAW undergoes the oxidation of these compounds, and thus, irreversible physical and chemical damages occur. Fresh and archeological oak and pine samples were selected as representative species of WAW artifacts. Fresh samples were previously artificially contaminated to ascertain the presence of iron and sulfur. Thiobacillus denitrificans and natural iron chelators, called siderophores, were investigated to extract iron and sulfur as a 2-step biological treatment (BT) and compared to sodium persulfate-EDTA as chemical treatment (CT). Consolidation and freeze-drying were performed on the samples after BT and CT as traditional conservation protocols. BT and CT efficiency was evaluated through Raman, inductively coupled plasma-optical emission (ICP-OES), and Fourier transformed infrared (FTIR) spectroscopies. Raman and ICP showed that most of the iron and sulfur was extracted after BT, while some sulfur species remained present on CT samples. None of the extraction methods resulted in a degradation of the wood, as ascertained by FTIR analyses. Yet, all samples presented visual modifications after conservation. Pine samples treated with BT illustrated the oxidation of the species. Present principal component analysis (PCA) and analysis of variance (ANOVA) which were selected as statistical approaches and validated BT as a promising alternative extraction method, with encouraging extraction rates and less alteration of the sample appearance.


[Neo-natal neutropenia induced by anti-NA 2 allo-immunization. Serological and clinical study of 2 cases in a family].
A severe neutropenia in a 2 day old newborn drew attention to anti-HLA and NA 2 antigranulocytic antibodies in the maternal serum. Close supervision from birth of a younger sibling demonstrated a neutropenia on the 5th day of life. Serological investigation showed the anti-NA 2 antibody to be responsible in both cases. A good result with total blood replacement of leucocyte-free blood in the second case would advocate this treatment in cases of severe immunological neutropenia.


A multicenter, prospective, randomized study of selective bile duct cannulation performed by multiple endoscopists: the BIDMEN study.
Wire-guided cannulation (WGC) with a sphincterotome (S) for selective bile duct cannulation (SBDC) has been reported to have a higher success rate and lower incidence of post-ERCP pancreatitis (PEP) than conventional methods in some randomized, controlled trials (RCTs) that were both single center and limited to only a few endoscopists. To estimate the difference in SBDC according to the method and catheter used in a multicenter and multiendoscopist study. A prospective, multicenter RCT with a 2 × 2 factorial design. Fifteen referral endoscopy units. In total, 400 consecutive patients with naive papillae who were candidates for ERCP were enrolled and randomized. Patients were assigned to 4 groups according to combined catheter (S or catheter [C]) and method (with/without guidewire [GW]). Success rate of SBDC performed in 10 minutes, SBDC time, fluoroscopy time, and incidence of complications. There was no significant difference in the SBDC success rate between the groups with and without GW, between C and S, or among the 4 groups (C+GW, C, S+GW, S). WGC had a tendency to significantly shorten cannulation and fluoroscopy times only in approximately 70% of patients in this study in whom SBDC was achieved in 10 minutes or less (P = .036 and .00004, respectively). All 4 groups resulted in similar outcomes in PEP (4%, 5.9%, 2%, and 2.1%, respectively). Non-double-blind study. WGC appears to significantly shorten cannulation and fluoroscopy times. However, neither the method nor type of catheter used resulted in significant differences in either SBDC success rate or incidence of PEP in this RCT. ( UMIN000002572.).


Evaluating the clinical implementation of structured exercise: A randomized controlled trial among non-insulin dependent type II diabetics.
The American Diabetes Association (ADA) currently recommends 150 min of moderate-intensity aerobic exercise per week and resistance exercise at least twice per week in individuals with type 2 diabetes (T2DM) to improve overall health [1]. However, approximately 38% of patients with T2DM do not exercise at recommended levels and 31% do not exercise at all [2]. The efficacy of structured exercise interventions has been proven effective in reducing glycosylated hemoglobin A1c (HbA1c) levels in patients, but practical approaches are needed to translate these findings into the clinical setting [3-7]. The Initiate and Maintain Physical Activity in Clinics (IMPACT) Study aims to compare structured group exercise within the clinic to usual care in T2DM patients. The main purpose of the study is to determine the optimal and feasible level and weekly frequency of structured contact in a clinical setting needed to initiate and maintain physical activity recommendations long-term. IMPACT is a longitudinal, randomized-controlled study designed to track study participants over 30 months. Once study participants have met eligibility and enrollment criteria, they are randomized and enrolled into one of three arms: 1× per week exercise, 3× per week exercise, or the usual care control group. After randomization, participants begin Phase 1: Initiate lasting 6 months. Over the course of Phase 1, participants in the exercise groups will attend instructor led group training at a Stanford approved physical fitness facility. At the end of 6 months, participants enter Phase 2: Maintain lasting 24 months. Over the course of Phase 2, participants in all three arms will attend periodic follow-up visits for clinical measurements and survey administration for their final two years of participation. These findings will enable the clinical implementation of a structured exercise regimen designed to specifically address the aerobic and resistance training recommendations for patients with T2DM.


Embodied choices bypass narratives under radical uncertainty.
Johnson et al. suggest that we rely on narratives to make choices under radical uncertainty. We argue that in its current version Conviction Narrative Theory (CNT) does not account for embodied, direct sensorimotor influences on choices under radical uncertainty that may bypass narratives, particularly in highly time-constrained situations. We therefore suggest to extend CNT by an embodied choice perspective.


Preparation of cobalt nanoparticles from polymorphic bacterial templates: A novel platform for biocatalysis.
Nanoparticles have gathered significant research attention as materials for enzyme immobilization due to their advantageous properties such as low diffusion rates, ease of manipulation, and large surface areas. Here, polymorphic cobalt nanoparticles of varied sizes and shapes were prepared using Micrococcus lylae, Bacillus subtilis, Escherichia coli, Paracoccus sp., and Haloarcula vallismortis as bacterial templates. Furthermore, nine lipases/carboxylesterases were successfully immobilized on these cobalt nanoparticles. Especially, immobilized forms of Est-Y29, LmH, and Sm23 were characterized in more detail for potential industrial applications. Immobilization of enzymes onto cobalt oxide nanoparticles prepared from polymorphic bacterial templates may have potential for efficient hydrolysis on an industrial-scale, with several advantages such as high retention of enzymatic activity, increased stability, and strong reusability.


Mitochondrial 16S ribosomal RNA gene for forensic identification of crocodile species.
All crocodilians are under various threats due to over exploitation and these species have been listed in Appendix I or II of CITES. Lack of molecular techniques for the forensic identification of confiscated samples makes it difficult to enforce the law. Therefore, we herein present a molecular method developed on the basis on 16S rRNA gene of mitochondrial DNA for identification of crocodile species. We have developed a set of 16S rRNA primers for PCR based identification of crocodilian species. These novel primers amplify partial 16S rRNA sequences of six crocodile species which can be later combined to obtain a larger region (1290 bp) of 16S rRNA gene. This 16S rRNA gene could be used as an effective tool for forensic authentication of crocodiles. The described primers hold great promise in forensic identification of crocodile species, which can aid in the effective enforcement of law and conservation of these species.


Automated Quantification of Compartmental Blood Volumes Enables Prediction of Delayed Cerebral Ischemia and Outcomes After Aneurysmal Subarachnoid Hemorrhage.
The role of hemorrhage volume in risk of vasospasm, delayed cerebral ischemia (DCI), and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH) is well established. However, the relative contribution of blood within individual compartments is unclear. We present an automated technique for measuring not only total but also volumes of blood in each major compartment after SAH. We trained convolutional neural networks to identify compartmental blood (cisterns, sulci, and ventricles) from baseline computed tomography scans of patients with SAH. We compared automated blood volumes against traditional markers of bleeding (modified Fisher score [mFS], Hijdra sum score [HSS]) in 190 SAH patients for prediction of vasospasm, DCI, and functional status (modified Rankin Scale) at hospital discharge. Combined cisternal and sulcal volume was better correlated with mFS and HSS than cisternal volume alone (ρ = 0.63 vs. 0.58 and 0.75 vs. 0.70, P < 0.001). Only blood volume in combined cisternal plus sulcal compartments was independently associated with DCI (OR 1.023 per mL, 95% CI 1.002-1.048), after adjusting for clinical factors while ventricular blood volume was not. Total and specifically sulcal blood volume was strongly associated with poor outcome (OR 1.03 per mL, 1.01-1.06, P = 0.006 and OR 1.04, 1.00-1.08 for sulcal) as was HSS (OR 1.06 per point, 1.00-1.12, P = 0.04), while mFS was not (P = 0.24). An automated imaging algorithm can measure the volume of bleeding after SAH within individual compartments, demonstrating cisternal plus sulcal (and not ventricular) blood contributes to risk of DCI/vasospasm. Automated blood volume was independently associated with outcome, while qualitative grading was not.


A theoretical analysis of the effects of sonication on differential absorption flattening in suspensions of membrane sheets.
A theoretical analysis is presented for the flattening of absorption and circular dichroic spectra of suspensions of membrane sheets containing proteins. Equations are presented to describe the dependence of this artifact on the size of the sheets. Values for the flattening coefficients QA and QB are calculated both as a function of absorptivity and sheet size. These studies show that sonication in an inadequate procedure for eliminating flattening in these samples.


Angiogenic factors as diagnostic tests for preeclampsia: a performance comparison between two commercial immunoassays.
Placental growth factor and soluble Fms-like tyrosine kinase-1 may be potential diagnostic markers of preeclampsia. We compared performances of 2 immunoassays, the Triage placental growth factor assay and the Elecsys soluble Fms-like tyrosine kinase-1/placental growth factor ratio in diagnosing preeclampsia. A single site, case-control study of 44 patients with preeclampsia and 84 matched normal pregnant controls. Samples were collected at the time of diagnosis. Assays were performed according to product inserts. Both assays had optimal performance in diagnosing early-onset preeclampsia with area under the receiver operating characteristic curves of 0.99 (Triage: 100% sensitivity, 96% specificity; Elecsys: 64% sensitivity, 100% specificity for early-onset preeclampsia). Reassignment of the Elecsys cutoff for a positive test based on receiver operating characteristic curves increased sensitivity to 92%. Using product insert cutoffs, Triage appears to have greater sensitivity at only a small reduction in specificity compared with Elecsys in the diagnosis of early-onset preeclampsia. A different cutoff may improve Elecsys sensitivity.


Neonatal heavy metals levels are associated with the severity of neonatal respiratory distress syndrome: a case-control study.
This case-control study aimed to compare lead (Pb), cadmium (Cd), and arsenic (As) levels in neonates with respiratory distress syndrome (NRDS) with those levels in normal neonates and tested their associations with the severity of NRDS indicated by the levels of serum surfactant protein D (SP-D) and cord blood cardiac troponin I (CTnI), and high-sensitive C-reactive protein (hs-CRP). The study included two groups: G1 (60 healthy neonates) and G2 (100 cases with NRDS). Cord blood Pb, erythrocytic Cd (E-Cd), neonatal scalp hair As (N-As), maternal urinary Cd (U-Cd), and arsenic (U-As) were measured by a Thermo Scientific iCAP 6200, while CTnI, hs-CRP, and SP-D by their corresponding ELISA kits. The levels of cord blood Pb, E-Cd, N-As, U-Cd, U-As, SP-D, CTnI, and hs-CRP were significantly higher in G2 than G1 (p = 0.019, 0.040, 0.003, 0.010, 0.011, < 0.001, 0.004, < 0.001, respectively). While the birth weight, and APGAR score at 1, 5 and 10 min were significantly lower in G2 than G1 (p = 0.002, < 0.001, < 0.001, < 0.001, respectively). The levels of the studied heavy metals correlated positively with the levels of SP-D, CTnI, and hs-CRP. Heavy metals toxicity may be accused to be one of the causes of NRDS especially if other apparent causes are not there. Measuring and follow-up of heavy metal levels should be considered during pregnancy.


Valsalva retinopathy with double ring sign: Laser membranotomy for twin bleeds.
This report describes the case of a 27-year-old lady who presented with sudden decrease in vision in the right eye for one week. She was suffering from constipation and had a history of straining while passing stools. She was found to have two large sub-internal limiting membrane haemorrhages with the classical double ring sign, which were drained using laser membranotomy, following which her vision rapidly improved. This case of two sub-internal limiting membrane haemorrhages is reported for its rarity and also highlights the usefulness of laser hyaloidotomy or membranotomy in large haemorrhages of recent onset. The literature was also reviewed to discuss the other treatment options in brief.


Apolipoprotein A1 Baltimore (Arg10----Leu), a new ApoA1 variant.
A new apolipoprotein A1 (APOA1) gene variant has been identified in a family ascertained through a proband undergoing coronary angiography. The variant, ApoA1 Baltimore, was due to a mutation at codon 34 of the third exon of the APOA1 gene (CGA to CTA) that resulted in an arginine-to-leucine substitution at the tenth amino acid of the mature ApoA1 and a change in charge of -1. The mutation abolishes a TaqI restriction site and it is easily detectable after polymerase chain reaction amplification of genomic DNA. The proband was heterozygous for the mutation. Eight other members of the pedigree had the same ApoA1 variant. Cosegregation of the variant with hypoalphalipoproteinemia could not be demonstrated and the association of this mutation with hypoalphalipoproteinemia was confined to three affected members of the nuclear family. No effect of the mutant on any lipoprotein phenotype could be established.