Effects of trees, gardens, and nature trails on heat index and child health: design and methods of the Green Schoolyards Project.
Latinx children in the United States are at high risk for nature-deficit disorder, heat-related illness, and physical inactivity. We developed the Green Schoolyards Project to investigate how green features-trees, gardens, and nature trails-in school parks impact heat index (i.e., air temperature and relative humidity) within parks, and physical activity levels and socioemotional well-being of these children. Herein, we present novel methods for a) observing children's interaction with green features and b) measuring heat index and children's behaviors in a natural setting, and a selection of baseline results. During two September weeks (high temperature) and one November week (moderate temperature) in 2019, we examined three joint-use elementary school parks in Central Texas, United States, serving predominantly low-income Latinx families. To develop thermal profiles for each park, we installed 10 air temperature/relative humidity sensors per park, selecting sites based on land cover, land use, and even spatial coverage. We measured green features within a geographic information system. In a cross-sectional study, we used an adapted version of System for Observing Play and Recreation in Communities (SOPARC) to assess children's physical activity levels and interactions with green features. In a cohort study, we equipped 30 3rd and 30 4th grade students per school during recess with accelerometers and Global Positioning System devices, and surveyed these students regarding their connection to nature. Baseline analyses included inverse distance weighting for thermal profiles and summing observed counts of children interacting with trees. In September 2019, average daily heat index ranged 2.0 °F among park sites, and maximum daily heat index ranged from 103.4 °F (air temperature = 33.8 °C; relative humidity = 55.2%) under tree canopy to 114.1 °F (air temperature = 37.9 °C; relative humidity = 45.2%) on an unshaded playground. 10.8% more girls and 25.4% more boys interacted with trees in September than in November. We found extreme heat conditions at select sites within parks, and children positioning themselves under trees during periods of high heat index. These methods can be used by public health researchers and practitioners to inform the redesign of greenspaces in the face of climate change and health inequities.


Maternal sucrose-rich diet and fetal programming: changes in hepatic lipogenic and oxidative enzymes and glucose homeostasis in adult offspring.
Nutritional insults during pregnancy and lactation (P + L) are often associated with offspring health risks. We investigated the effect of maternal exposure to a sucrose-rich diet (SRD) during P + L on glucose and lipid metabolism of adult offspring regardless of post-weaning diet. Dams were fed an SRD or a control diet (CD) during P + L. After weaning, male offspring from SRD and CD dams were divided into two groups and fed a CD or SRD until 150 days old forming CD-CD, CD-SRD, SRD-SRD and SRD-CD groups. Offspring where SRD was fed at any period of life showed: (1) increased adipose tissue weight without changes in the final body weight; (2) dyslipidemia as a result of increased very low density lipoprotein triglyceride secretion rate and decreased triglyceride clearance; (3) hepatic steatosis associated with increased activity of key enzymes involved in liver de novo lipogenesis and significant decrease of the activity of mitochondrial fatty acid oxidation enzyme. These results were more pronounced in CD-SRD and SRD-SRD groups. (4) Hyperglycemia without changes in insulin levels, plus a deterioration of intravenous glucose tolerance and intraperitoneal insulin tolerance test. We hypothesized that SRD during P + L could be associated with a programming effect on glucose homeostasis and hepatic lipid metabolism that predispose offspring to develop later-life insulin resistance and metabolic disorders, regardless of post-natal diet.


Silver colloidal pastes for dye analysis of reference and historical textile fibers using direct, extractionless, non-hydrolysis surface-enhanced Raman spectroscopy.
Surface-enhanced Raman spectroscopy (SERS) is an ideal tool for analyzing dyes on historical textiles because it requires very little sample compared to other available analytical methods and analysis can be done directly on the fiber. This paper reports on the first systematic study of the use of citrate-reduced silver colloidal pastes for the direct, extractionless, non-hydrolysis detection of dyes directly on wool, silk, cotton, and flax fibers. This type of study provides greater insight into the optimal conditions required for accurate analysis of dyes in historical samples. In this work, Ag colloidal pastes were characterized using localized surface plasmon resonance and scanning electron microscopy. The pastes were then employed for SERS analysis of twelve reference samples of different vegetal and animal fibers dyed with cochineal and eleven dyed with brazilwood. Furthermore, six historical textiles from an important collection of Mariano Fortuny (1871-1949) textiles at the Art Institute of Chicago were also examined, to test the efficacy of the paste on aged samples, and to shed light on Fortuny's fascinating production techniques. A mixture of cochineal and brazilwood was detected in some of the historical samples demonstrating, for the first time, simultaneous identification of these colorants used in combination. In addition, the findings give substance to the claim that Fortuny kept using natural dyes at a time when many new and attractive synthetic products became available.


Acute gout precipitated by total parenteral nutrition.
Hypouricemia is seen in a variety of clinical situations. Although precipitation of gout is well known following initiation of uricosuric therapy, it has been reported rarely following the institution of total parenteral nutrition (TPN), despite its known uricosuric effect. We describe a patient who developed polyarticular gout on 2 occasions after a sudden decline in serum uric acid after initiation of purine-free TPN. Potential etiologies include increased urate clearance due to the infusion of glycine or amino acids. Monitoring of serum uric acid concentrations in patients with a history of gout may help predict a gout attack. Prophylactic treatment or alternative TPN formulations may be indicated.


A Scalable ECG Identification System Based on Locality-Sensitive Hashing.
Electrocardiograms (ECGs) have the inherent property of being intrinsic and dynamic and are shown to be unique among individuals, making them promising as a biometric trait. Although many ECG biometric recognition approaches have demonstrated accurate recognition results in small enrollment sets, they can suffer from performance degradation when many subjects are enrolled. This study proposes an ECG biometric identification system based on locality-sensitive hashing (LSH) that can accommodate a large number of registrants while maintaining satisfactory identification accuracy. By incorporating the concept of LSH, the identity of an unknown subject can be recognized without performing vector comparisons for all registered subjects. Moreover, a kernel density estimator-based method is used to exclude unregistered subjects. The ECGs of 285 subjects from the PTB dataset were used to evaluate the proposed scheme's performance. Experimental results demonstrated an IR and EER of 99% and 4%, respectively, when Nen/Nid = 15/3.


A Comparison of Time to Treatment between an Emergency Department Focused Stroke Protocol and Mobile Stroke Units.
San Francisco (California USA) is a relatively compact city with a population of 884,000 and nine stroke centers within a 47 square mile area. Emergency Medical Services (EMS) transport distances and times are short and there are currently no Mobile Stroke Units (MSUs). This study evaluated EMS activation to computed tomography (CT [EMS-CT]) and EMS activation to thrombolysis (EMS-TPA) times for acute stroke in the first two years after implementation of an emergency department (ED) focused, direct EMS-to-CT protocol entitled "Mission Protocol" (MP) at a safety net hospital in San Francisco and compared performance to published reports from MSUs. The EMS times were abstracted from ambulance records. Geometric means were calculated for MP data and pooled means were similarly calculated from published MSU data. From July 2017 through June 2019, a total of 423 patients with suspected stroke were evaluated under the MP, and 166 of these patients were either ultimately diagnosed with ischemic stroke or were treated as a stroke but later diagnosed as a stroke mimic. The EMS and treatment time data were available for 134 of these patients with 61 patients (45.5%) receiving thrombolysis, with mean EMS-CT and EMS-TPA times of 41 minutes (95% CI, 39-43) and 63 minutes (95% CI, 57-70), respectively. The pooled estimates for MSUs suggested a mean EMS-CT time of 35 minutes (95% CI, 27-45) and a mean EMS-TPA time of 48 minutes (95% CI, 39-60). The MSUs achieved faster EMS-CT and EMS-TPA times (P <.0001 for each). In a moderate-sized, urban setting with high population density, MP was able to achieve EMS activation to treatment times for stroke thrombolysis that were approximately 15 minutes slower than the published performance of MSUs.


Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention.
People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n-3 PUFAs have been observed. We aimed to assess the impact of APOE genotype on peripheral blood mononuclear cell whole genome gene expression at baseline and following a fish-oil intervention. Participants received 6 months of fish-oil supplementation containing 1800 mg of eicosapentaenoic acid and docosahexaenoic acid per day. APOE genotype and peripheral blood mononuclear cell whole genome gene expression before and after supplementation were measured. We characterized the differences in gene expression profiles in carriers of APOE4 (N = 8) compared to noncarriers (N = 15). At baseline, 1320 genes were differentially expressed and the fish-oil supplementation differentially regulated 866 genes between APOE4 carriers and noncarriers. Gene set enrichment analysis showed that carriers had a higher gene expression of cholesterol biosynthesis and IFN signaling pathways. Fish-oil supplementation reduced expression of IFN-related genes in carriers only. The increased expression of IFN signaling and cholesterol biosynthesis pathways might explain part of the association between APOE4 and CVD. Fish-oil supplementation may particularly benefit APOE4 carriers by decreasing expression of IFN-related genes.


A case study of community-based distribution and use of Misoprostol and Chlorhexidine in Sokoto State, Nigeria.
The United States Agency for International Development/Targeted States High Impact Project supported Sokoto State, Nigeria government in the development of a community-based intervention aimed at preventing post-partum haemorrhage (PPH) and cord infection among women and children, respectively. This paper describes the innovative intervention within the Nigeria health delivery system. It then explains the case study approach to assessing this intervention and summarises findings. Ultimately, the intervention was received well in communities and both drugs were added to the procurement list of all health facilities providing maternity services in the State. Key factors leading to such success include early advocacy efforts at the state-level, broad stakeholder engagement in designing the distribution system, early community engagement about the value of the drugs and concerted efforts to monitor and ensure availability of the drugs. Implementation challenges occurred in some areas, including shortage of community-based health volunteers (CBHVs) and drug keepers, and socio-cultural barriers. To maximise and sustain the effectiveness of such interventions, state government needs to ensure constant drug supply and adequate human resources at the community level, enhance counselling and mobilisation efforts, establish effective quality improvement strategies and implement a strong M&E system.


[The treatment of newborns with gastroschisis].
Gastroschisis is considered by the authors to be an embryopathy. The main principles of management of newborns with gastroschisis are: warming of the newborn, rehydration, measures against pseudoobstruction of the intestine. An effective method which could be recommended for all kinds of operations for defects of the anterior abdominal wall is a "manual enlargement of the abdominal cavity" during operation.


[Effect of acupoint irradiation with Q-wave millimeter microwave on peripheral white blood cells in post-operational treatment with chemotherapy in stomach and colorectal cancer patients].
To explore the biological effect of Q-wave millimeter microwave (QWMM). The QWMM was used to irradiate the acupoints Xuehai (Sp10) and Geshu (B17) in treating post-operational and chemotherapy treated stomach cancer and colorectal cancer patients. The effect of irradiation on chemotherapy affected peripheral white blood cells was observed. 62 cases (stomach cancer 42, colorectal cancer 20) in total were divided into two groups: group A, 21 cases (stomach cancer 15, colorectal cancer 6) the irradiation began 10 days after operation, and on the 16th day the chemotherapy combined with irradiation started. Group B had 41 cases (stomach cancer 27, colorectal cancer 14), in which the irradiation began immediately after the occurrence of chemotherapy induced peripheral WBC reduction, which persisted for at least 12 days. The effective rate for the group A and B was 85.7% (18/21) and 73.2% (30/41) respectively. The total effective rate of the two groups was 77.4% (48/62). The effective rate of group A was significantly higher than that of group B, P < 0.01. GWMM irradiation at acupoints could promote the hematopoietic function of bone marrow, and the irradiation performed 1 week before chemotherapy yielded even better protection on bone marrow.


A facile isoelectric focusing of myoglobin and hemoglobin used as markers for screening of chicken meat quality in China.
A novel analytical protocol was developed for general quality screening of chicken meat based on IEF and protein extraction. To demonstrate the developed protocol, 24 chickens were divided into three groups; each had eight chickens. The chickens in Group 1 were slaughtered by exsanguination, Group 2 asphyxiated in water, and that in Group 3 were infected by new castle disease virus. Proteins were extracted from the meat samples by using pure water as an extractant, separated by IEF, verified by western blot, and quantified via imaging analysis. The relevant experiments demonstrated that two myoglobin (Mb) bands were detected at pI 6.8 and 7.04 for all samples of Groups 1, 2, and 3, but there were additional hemoglobin (Hb) bands at pI 7.09 and 7.13 (P < 0.05) for the samples of Groups 2 and 3. The results implied that Hb bands might be a potential biomarker for the screening of chicken meat quality. The RSD values of two Mb bands (pI 6.8 and 7.04) in Group 1 were respectively 4.08 and 3.63%, the ones of two Hb bands (pI 7.09 and 7.13) in Group 2 were 3.66 and 2.10%, and those in Group 3 were 2.17% and 2.77%, respectively. All the RSD values indicated high stability and reliability of the developed protocol. Additionally, the protocol had a direct readout of protein bands in IEF without staining. However, it was time-consuming and had high cost. Even so, the relevant general method and finding have potential for screening of chicken meat quality.


The comparative investigation of morphology of papillary muscles of left ventricle in different species.
The papillary muscles of the heart are conical projections into the respective chamber of myocardium covered by endocardium. Functionally, the papillary muscles are important part of the respective valve complex. They prevent the cusps of a valve from being everted when the ventricle contracts. Our study was conducted on papillary muscles in left ventricle of 135 normal adult hearts (20 humans, 25 dogs, 60 sheep and 30 goats). The length (L), width (W), head number (HN), angle with ventricular wall (A degrees ), distance with annulus (AnD) and apex (ApD), and the shapes of the anterior and posterior papillary muscles were observed. The tendinous chords (CTN) attached to each papillary muscle were counted at their origin. The values of both anterior and posterior papillary muscles were not statistically significant (p > 0.05) in measurements of L, W, HN, A degrees and AnD of all species, but those of CTN and ApD were significant (p < 0.05) between human and animal hearts, while the difference was not significant (p > 0.05) between sheep and goat hearts. Knowledge of morphology of papillary muscles in different species will be of much use to clinical investigators in their studies.


Chondrocyte gene expression in osteoarthritis: Correlation with disease severity.
Osteoarthritis is characterized by a progressive degradation of cartilage structure and function. This study tests the hypothesis that disease severity is characterized by alterations in expression of cartilage-specific genes for aggrecan and collagen type II. Cartilage, discarded from six subjects undergoing knee replacement, was subdivided into homogeneous portions by the surgeon according to the Outerbridge classification. For four subjects, it was possible to separate the tissue into two or three fractions with different disease severity. Portions of each sample were prepared either for histological analysis and ranking according to the Mankin system or for RNA extraction. Quantitative, competitive RT-PCR assays were used for measurement of mRNA for aggrecan, collagen type II, and glyceraldehyde-3-phosphate dehydrogenase. Clinical grading was correlated with histological score (Spearman r = 0.60, p = 0.043). There was a striking decrease in expression of aggrecan and collagen II that was correlated with increase in the grade in regions of cartilage within an individual subject. In the series of 12 samples, there was an inverse correlation between aggrecan expression and osteoarthritis grade (Spearman r = -0.59, p = 0.042). In conclusion, there was an inverse relationship between regional disease severity in osteoarthritis and expression of aggrecan. Use of quantitative, competitive RT-PCR is practical for assessment of chondrocyte gene signatures.


Cerebrospinal fluid bombesin and calcitonin in patients with central nervous system metastases from small-cell lung cancer.
To determine whether levels of mammalian bombesin (MB) or calcitonin would be useful in detecting CNS metastases in patients with small-cell lung cancer (SCLC), we measured their concentrations in the CSF of 94 patients who underwent lumbar puncture for suspected CNS involvement. The MB concentration was significantly elevated in the 51 patients with definite CNS metastases as compared with the 30 patients without apparent CNS involvement (P less than .01). This significance was due to increased levels of MB in 18 patients with meningeal carcinomatosis. Whereas CSF MB was detectable (greater than 10 fmol/mL) in only 7% of patients without apparent CNS involvement, CSF MB was detectable in 21% with parenchymal CNS metastases and in 78% of those with meningeal carcinomatosis. Interestingly, 93% of patients having MB concentrations above 20 fmol/mL had meningeal metastases. The calcitonin concentration was significantly elevated in 42 patients with CNS metastases as compared with 27 patients without CNS involvement (P less than .01). Both the 15 patients with meningeal carcinomatosis and the 27 patients with only parenchymal metastases had significantly elevated levels of CSF calcitonin as compared with those without CNS metastases. Fifty-three percent of patients with meningeal carcinomatosis and 48% with parenchymal metastases had a CSF calcitonin level above 18 fmol/mL, whereas only 7% without apparent CNS metastases exceeded this level. Sixty-seven percent of all patients with CNS metastases had increased CSF levels of one of the two hormonal markers. Thus, in SCLC patients, an elevated CSF calcitonin strongly suggested CNS metastases and an elevated MB was very suggestive of the presence of meningeal carcinomatosis. However, only the latter observation seems of clinical importance due to the difficulties in establishing this diagnosis with current diagnostic measures.


Sustainability Evaluation of Polyhydroxyalkanoate Production from Slaughterhouse Residues Utilising Emergy Accounting.
High raw material prices and rivalry from the food industry have hampered the adoption of renewable resource-based goods. It has necessitated the investigation of cost-cutting strategies such as locating low-cost raw material supplies and adopting cleaner manufacturing processes. Exploiting waste streams as substitute resources for the operations is one low-cost option. The present study evaluates the environmental burden of biopolymer (polyhydroxyalkanoate) production from slaughtering residues. The sustainability of the PHA production process will be assessed utilising the Emergy Accounting methodology. The effect of changing energy resources from business as usual (i.e., electricity mix from the grid and heat provision utilising natural gas) to different renewable energy resources is also evaluated. The emergy intensity for PHA production (seJ/g) shows a minor improvement ranging from 1.5% to 2% by changing only the electricity provision resources. This impact reaches up to 17% when electricity and heat provision resources are replaced with biomass resources. Similarly, the emergy intensity for PHA production using electricity EU27 mix, coal, hydropower, wind power, and biomass is about 5% to 7% lower than the emergy intensity of polyethylene high density (PE-HD). In comparison, its value is up to 21% lower for electricity and heat provision from biomass.


The distinct translational landscapes of gram-negative Salmonella and gram-positive Listeria.
Translational control in pathogenic bacteria is fundamental to gene expression and affects virulence and other infection phenotypes. We used an enhanced ribosome profiling protocol coupled with parallel transcriptomics to capture accurately the global translatome of two evolutionarily distant pathogenic bacteria-the Gram-negative bacterium Salmonella and the Gram-positive bacterium Listeria. We find that the two bacteria use different mechanisms to translationally regulate protein synthesis. In Salmonella, in addition to the expected correlation between translational efficiency and cis-regulatory features such as Shine-Dalgarno (SD) strength and RNA secondary structure around the initiation codon, our data reveal an effect of the 2nd and 3rd codons, where the presence of tandem lysine codons (AAA-AAA) enhances translation in both Salmonella and E. coli. Strikingly, none of these features are seen in efficiently translated Listeria transcripts. Instead, approximately 20% of efficiently translated Listeria genes exhibit 70 S footprints seven nt upstream of the authentic start codon, suggesting that these genes may be subject to a novel translational initiation mechanism. Our results show that SD strength is not a direct hallmark of translational efficiency in all bacteria. Instead, Listeria has evolved additional mechanisms to control gene expression level that are distinct from those utilised by Salmonella and E. coli.


Characterization of surrogate parameters for blood pressure regulation in neurally-mediated syncope.
Neurally Mediated Syncope (NMS) is often cited as the most common cause of syncope. It can lead to severe consequences such as injuries, high rates of hospitalization and reduced quality of life, especially in elderly populations. Therefore, information about the syncope triggers and reflex mechanisms would be of a great value in the development of a cost-effective p-health system for the prediction of syncope episodes, by enhancing patients' quality of life and reducing the incidence of syncope related disorders/conditions. In the present paper we study the characterization of syncope reflex mechanisms and blood pressure changes from the analysis of several non-invasive modalities (ECG, ICG and PPG). Several parameters were extracted in order to characterize the chronotropic, inotropic and vascular tone changes. Thus, we evaluate the ability of parameters such as Heart Rate (HR), Pre-Ejection Period (PEP) and Left Ventricular Ejection Time (LVET) to characterize the physiological mechanisms behind the development of reflex syncope and their potential syncope prediction capability. The significant parameter changes (e.g. HR from 12.9% to -12.4%, PEP from 14.9% to -3.8% and LVET from -14.4% to 12.3%) found in the present work suggest the feasibility of these surrogates to characterize the blood pressure regulation mechanisms during impending syncope.


Transcutaneous pressure at which the internal jugular vein is collapsed on ultrasonic imaging predicts easiness of the venous puncture.
Even though we use ultrasound guidance for central venous puncture, we sometimes experience difficulties. We infer that in such cases the vein is collapsed and that the transcutaneous ultrasound probe pressure at which the vein is collapsed (P (tc)) may predict the easiness of the venous puncture. We measured P (tc) and the diameter of the internal jugular vein in 47 adult patients in our ICU. After successful puncture, we also measured venous pressure (P (v)). The patients were divided into two groups based on the number of puncture attempts: ≥3 attempts constituted the "difficult group" and <3 attempts was considered the "easy group:" 33 patients were in the easy group and 14 patients were in the difficult group. The easy group showed significantly higher P (tc) value (9.3 ± 3.8 vs. 3.5 ± 0.9 cmH(2)O, P < 0.0001) and larger vertical diameter (9.2 ± 3.1 vs. 6.8 ± 2.2 mm, P = 0.013) than the difficult group. We observed a clear border between the minimum P (tc) in the easy group (6 cmH(2)O) and the maximum value in the difficult group (5 cmH(2)O). In conclusion, venous collapsibility and vertical diameter determine difficulty in performing venous puncture.


A Randomized Controlled, Treat-to-Target Study Evaluating the Efficacy and Safety of Insulin Glargine 300 U/mL (Gla-300) Administered Using Either Device-Supported or Routine Titration in People With Type 2 Diabetes.
The efficacy/safety of device-supported versus routine titration with Gla-300 in type 2 diabetes (T2DM) was evaluated. AUTOMATIX was a 16-week, randomized, open-label, parallel-group, multicenter, noninferiority trial in insulin-treated or insulin-naïve people with T2DM. The fasting self-monitored plasma glucose (FSMPG) target was 90-130 mg/dL (5.0-7.2 mmol/L). Primary endpoint: proportion of participants achieving target FSMPG at week 16 without severe hypoglycemia. Secondary endpoints included: proportion reaching FSMPG target without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia; time to first achieve FSMPG target; mean FSMPG and HbA1c change (baseline to week 16). Safety endpoints included hypoglycemia and adverse events. Patient-reported outcomes (PROs) were also assessed. Participants were randomized to device-supported (n = 75) or routine titration (n = 76); 17 participants in the device-supported group discontinued device use. Noninferiority was achieved for the primary endpoint (device-supported: 45.9%, routine: 36.8%; weighted difference: 9.04 [95% CI: -6.75, 24.83]), but not superiority (P = .262). The proportion reaching FSMPG target range without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia was 34.3% vs 14.5%, respectively. The time at which 50% of the participants achieved the FSMPG target was less in the device-supported than routine titration arm (10 vs 13 weeks). Least squares mean HbA1c reduction, safety profiles, and PROs were similar in both arms. Mean "ease of use" score for the device, assessed by healthcare professionals and participants on a scale of 1-7, was ≥6. Device-supported self-titration had a good safety/efficacy profile, and was noninferior to routine titration and well accepted by diabetes specialists and patients.


Clinical effectiveness and safety of montelukast in asthma. What are the conclusions from clinical trials and meta-analyses?
Asthma is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for this disease, treatment relies on avoidance of triggers such as food and aeroallergens, the use of inhaled bronchodilators/corticosteroids and antiallergic or immunomodulating therapies. Inhaled corticosteroids (ICSs) and bronchodilators have been the mainstay. However, in Asia, myths and fallacies regarding Western medicine and corticosteroids are prevalent and lead to nonadherence to treatment. Also, use of traditional and proprietary herbal medicines is popular. In the past decades, a novel class of nonsteroidal immunomodulating montelukasts has become available. This article reviews the evidence for the effectiveness and clinical efficacy of these medications. A number of randomized and controlled trials have been performed over the years. The majority of studies confirm the usefulness of montelukast as monotherapy and add-on therapy to ICS in mild to moderate childhood asthma across all age groups. ICSs are generally superior to montelukasts for asthma management. However, montelukast has a place in the treatment of young children with viral-triggered wheezing diseases, exercise-induced asthma, and in children whose parents are steroid-phobic and find ICS unacceptable.


[Spatial distribution and ecological risk assessment of heavy metals in the estuaries surface sediments from the Haihe River Basin].
It is well known that the rivers in the Haihe River Basin have been seriously polluted. However, what is the present condition of the estuary pollution and how the polluted inland rivers affect the estuary areas are not clear. 10 main estuaries of the Haihe River Basin were selected to measure the contents of typical heavy metals (Pb, Cu, Zn, Cd, Cr and Ni) in the surface sediments and to analyze the spatial distribution of these heavy metals. The potential ecological risk index was used to assess the ecological risk of the six heavy metals in the estuaries. The results showed that the contents of Pb, Cu, Zn, Cd, Cr and Ni in the surface sediments of the 10 estuaries were all higher than their background values in the main local soil types and the contents of Cu, Ni and Pb were 2.3-2.6 times as high as their background values, which indicated that the estuaries were contaminated by the six heavy metals. The results also indicated that the contents of the six heavy metals in surface sediment varied from one estuary to another. The four heavy metals of Cr, Cu, Ni and Zn had bigger spatial differences than Pb and Cd in the contents in sediment from different estuaries. The contents of Cr, Cu, Ni and Zn in sediment were higher in the estuaries of the Yongdingxin River, Ziyaxin River and Beipai River than those in the other estuaries, and there were significant correlations between each other (R(Cu-Zn) = 0.891, R(Cu-Cr) = 0.927, R(Cu-Ni) = 0.964, R(Zn-Cr) = 0.842, R(Zn-Ni) = 0.939, and R(Cr-Ni) = 0.879, P < 0.01), which indicated that they possibly came from the same sources. Moreover, the contents of Cr, Cu, Ni and Zn in sediment also had significant correlations with the populations of sub-river basins with correlation coefficients of 0.855, 0.806, 0.867 and 0.855 (P < 0.01), respectively. The contents of Cd and Pb had smaller spatial differences in sediment from different estuaries than the other heavy metals, with the values ranged 23.3-95.8 mg x kg(-1) and 0.051-0.200 mg x kg(-1). Contents of the two heavy metals had no significant correlation with the other heavy metals or with the populations of sub-river basins, indicating that Cd and Pb had little connection with the in-land polluted sources. The results of ecological risk assessment showed that estuaries of the Haihe River Basin had the potential ecological risk at lower levels (RI were 33.7-116) and the most important contaminating element was Cd with a middle-level potential ecological risk (Er(i) were 18.0-48.9).


Pulpal response to intraligamentary injection in the cynomologus monkey.
The objective of this study was to determine if intraligamentary injection causes qualitative histopathologic changes in the dental pulp of a Cynomologus monkey. In as much as the pulp and periapical tissues of the monkey are similar to that of humans, nonresolving damage to the pulp would contraindicate periodontal ligament injection in procedures where the tooth would not be extracted or the pulp extirpated. Periodontal ligament injection in this study did not produce any histopathological pulpal changes when compared to the pulps of uninjected teeth.


Immune Responses in Malaria.
Evidence accumulated through the years clearly indicates that antiparasite immune responses can efficiently control malaria parasite infection at all development stages, and under certain circumstances they can prevent parasite infection. Translating these findings into vaccines or immunotherapeutic interventions has been difficult in part because of the extraordinary biological complexity of this parasite, which has several developmental stages expressing unique sets of stage-specific genes and multiple antigens, most of which are antigenically diverse. Nevertheless, in the last 30 years major advances have resulted in characterization of a number of vaccine candidates, exploration of the repertoire of host immune responses to the various parasite stages, and also identification of significant hurdles that need to be overcome. Most important, these advances strengthened the concept that the induction of host immune responses that target all developmental stages of Plasmodium can efficiently control or abrogate Plasmodium infections and strongly support the notion that an effective vaccine can be developed. This vaccine would be a critical component for programs aimed at controlling or eradicating malaria.


Impact of dispersion on amplitude and frequency noise in a Yb-fiber laser comb.
We describe a Yb-fiber-based laser comb, with a focus on the relationship between the net-cavity dispersion and frequency noise on the comb. While tuning the net-cavity dispersion from anomalous to normal, we measure the relative intensity noise, offset frequency (f(CEO)) linewidth, and the resulting frequency noise spectrum on the f(CEO). We find that the laser operating at zero net-cavity dispersion has many advantages, including an approximately 100× reduction in free-running f(CEO) linewidth and frequency noise power spectral density when compared to the normal-dispersion regime. At the zero-dispersion point, we demonstrate a phase-locked f(CEO) beat with low residual noise.


A decreased response of cyclic adenosine monophosphate concentrations to glucagon in liver slices from streptozotocin-induced diabetic rats.
Responses to glucagon from the adenylate cyclasecyclic adenosine monophosphate (cAMP) system in liver slices from control and streptozotocin-induced diabetic rats were compared. Tissue cAMP levels were similar in the basal state but responded poorly to glucagon (20 pg/ml-2 microgram/ml) in diabetic rats. Insulin treatment of diabetic rats in vivo led to a reversal of the glucagon stimulation towards the values in the control rats. The basal and glucagon-stimulated activities of adenylate cyclase in crude membrane fractions were similar in both groups. Plasma immunoreactive glucagon levels in diabetic rats were approximately three times higher than those in normal rats. Liver slices obtained from normal rats, which were injected with glucagon (0.2 mg, i.m.) 45 min previously, also showed an impaired responsiveness to glucagon of tissue cAMP levels, while no significant difference in adenylate cyclase activity was observed between the normal and glucagon-treated rats. These results suggest that the responsiveness of liver slices from the streptozotocin-induced diabetic rat has been modified by the preceding hyperglucagonemia. The reason for the observed differences between slices and crude membranes is not known.


Attack rates of acute nephritis after type 49 streptococcal infection of the skin and of the respiratory tract.
Prospective studies in a population of American Indian children during an outbreak of acute nephritis associated with the Type 49 Group A streptococcus permitted a comparison of attack rates of renal complications after infection at different sites and at different ages. Acute nephritis or unexplained hematuria developed in 10 of 42 children (23.8%) with Type 49 streptococcal skin infection, in 2 of 44 (4.5%) with Type 49 throat infection, and in 3 of 16 (18.8%) with simultaneous Type 49 infection at both sites. The higher attack rate of nephritis and hematuria in children with pyoderma indicates that skin lesions played a direct and quantitatively greater role than respiratory infection in the pathogenesis of acute nephritis during this outbreak. Skin infections with the Type 49 strain were followed by evidence of renal complications more often in children younger than 6.5 yr (9 of 21 or 43%) than in older children (1 of 21 or 5%). Attack rates of renal complications after Type 49 skin infection were approximately equal in males and females.


Ambulatory arterial stiffness index and its role in assessing arterial stiffness in dialysis patients.
Ambulatory arterial stiffness index (AASI) is a parameter derived from ambulatory blood pressure (ABP) readings. It is calculated as 1 minus the linear slope of DBP on SBP. We tested its value in assessing arterial stiffness in dialysis patients. We performed a cross-sectional analysis of the baseline data from a cohort study. A total of 344 patients on maintenance hemodialysis from six tertiary hospitals were included. All patients underwent ABP monitoring and carotid-femoral pulse wave velocity (cfPWV) measurement. Clinical determinants of AASI were analyzed, and the ability of AASI for assessing arterial stiffness was compared with ambulatory pulse pressure (PP). Multiple regression analysis revealed that ambulatory PP (β = 0.003), current smoker (β = -0.069), age (β = 0.003) and ambulatory SBP (β = 0.001) were independent determinants of AASI. Ambulatory PP correlates better with cfPWV than AASI (r = 0.28 for AASI and 0.59 for PP; P for difference: <0.001). When cfPWV was treated as a categorical variable, receiver operating characteristic curve analysis also showed a more potent predictive value of PP over AASI (area under the curve: 0.64 for AASI, 0.80 for PP; P for difference: <0.001). Net reclassification improvement and integrated discrimination improvement analysis demonstrated no added predictive value of AASI to PP (net reclassification improvement = -2.2%, P = 0.26; integrated discrimination improvement = 0.001, P = 0.51). Sensitivity analysis in patients with more ABP readings (≥49) yielded similar results. For dialysis patients, AASI has very limited value in assessing arterial stiffness, whether used alone or added to PP. Our results suggest that this index should not be used as a surrogate marker of arterial stiffness for dialysis patients in future practice and studies.


Clinical innovation for promoting family care in paediatric intensive care: demonstration, role modelling and reflective practice.
To explore family caregiving problems in paediatric crisis care and methods that could be applied to move the abstraction of family care to development of specific family interventions. Family centred care has been accepted as the ideal philosophy for holistic health care of children, but methods for its implementation are not well established. In paediatric health crises, family care requires special sensitivity to family needs and a type of complex nursing care for which many practitioners are not sufficiently prepared. Developing family sensitive models of intervention and finding a strategy for transfer of this knowledge to clinical practice is an important challenge facing family nursing today. Social learning theory provides a rich background to explore these issues. Specific techniques of role modelling and reflective practice are suggested as effective approaches to teach family sensitive care in clinical settings where families are part of the care environment.


Presenting Features in 269 Patients With Clinically Nonfunctioning Pituitary Adenomas Enrolled in a Prospective Study.
Clinically nonfunctioning pituitary adenomas (CNFPAs) typically remain undetected until mass effect symptoms develop. However, currently, head imaging is performed commonly for many other indications, which may increase incidental discovery of CNFPAs. Since current presentation and outcome data are based on older, retrospective series, a prospective characterization of a contemporary CNFPA cohort was needed. To determine the prevalence of incidental presentation and hypopituitarism and its predictors in a CNFPA cohort that spanned 6 to 9 mm micro- to macroadenoma included observational and surgical therapy. At enrollment in a prospective, observational study, 269 patients with CNFPAs were studied by history, examination, blood sampling, and pituitary imaging analysis and categorized into incidental or symptoms presentation groups that were compared. Presentation was incidental in 48.7% of patients and due to tumor symptoms in 51.3%. In the symptoms and incidental groups, 58.7% and 27.4% of patients had hypopituitarism, respectively, and 25% of patients with microadenomas had hypopituitarism. Many had unappreciated signs and symptoms of pituitary disease. Most tumors were macroadenomas (87%) and were larger in the symptoms than incidental and hypopituitary groups than in the eupituitary groups. The patients in the incidental group were older, and males were older and had larger tumors in both the incidental and symptoms groups. Patients with CNFPAs commonly present incidentally and with previously unrecognized hypopituitarism and symptoms that could have prompted earlier diagnosis. Our data support screening all large micro and macro-CNFPAs for hypopituitarism. Most patients with CNFPAs still have mass effect signs at presentation, suggesting the need for more awareness of pituitary disease. Our ongoing, prospective observation of this cohort will assess outcomes of these CNFPA groups.


Individualized treatment of NSCLC: from research to clinical practice.
The exact clinical significance of EGFR mutation status in NSCLC at the time of initial diagnosis remains disputable. The gene expression module in NSCLC for chemotherapy outcome prediction needs to be developed. We analyzed 56 patients with NSCLC received chemotherapy either with (n=20) or without EGFR-TKIs (n=36) between 2008 and 2012 in China. EGFR mutation test and gene expression profiling were performed in samples obtained before medication treatment by liquidchip platform. Significant association (P = 0.028) was seen between EGFR mutation status before first-line chemotherapy and EGFR-TKIs treatment outcomes, which even can be found from the status before second- or third-line treatment. A14-gene expression profiling had been studied. Patients with low mRNA expression of ERCC1 or TYMS preferred higher DCR to cisplatin and pemetrexed than those with high expression (P = 0.39 and P= 0.11). Highly co-expression of TUBB3 and STMN1 gene has associated with the resistance to antimicrotubule drugs (P = 0.03). Our data suggest the EGFR mutations status, even at the time of initial diagnosis, is predictive of outcomes of TKIs treatment after chemotherapy. The mRNA expression profiling investigated in this study has a predictive value in NSCLC treatment, but further research with expanded samples is still required.


Three-dimensional computerized tomography angiography in the diagnosis of cerebrovascular disease.
Computer-generated three-dimensional reconstruction of the intracranial vascular system obtained by contrast-enhanced computerized tomography (CT) has been used in the diagnosis of 20 patients with known or suspected intracranial cerebrovascular disease. This technique allows visualization of the intracranial vasculature without exposing patients to the risks associated with intra-arterial angiography. The color prints and videotape images generated have been used to diagnose the presence of intracranial aneurysms, arteriovenous malformations, and venous angiomas. They have also been used to rule out structural abnormalities in patients with suspected intracranial vascular pathology and to screen patients with a strong family history of intracranial aneurysm. In 11 patients who underwent both three-dimensional CT angiography and intra-arterial angiography, the diagnostic correlation was 100%. No complications from the procedures or from incorrect diagnosis have been encountered. Although this technique requires further development and clinical evaluation, the authors' early experience with three-dimensional CT angiography suggests that this may become a valuable tool in the diagnosis of patients with cerebrovascular disease.


Success rates and adverse events during neonatal intubation: Lessons learned from an international registry.
Neonatal endotracheal intubation is a challenging procedure with suboptimal success and adverse event rates. Systematically tracking intubation outcomes is imperative to understand both universal and site-specific barriers to intubation success and safety. The National Emergency Airway Registry for Neonates (NEAR4NEOS) is an international registry designed to improve neonatal intubation practice and outcomes that includes over 17,000 intubations across 23 international sites as of 2023. Methods to improve intubation safety and success include appropriately matching the intubation provider and situation and increasing adoption of evidence-based practices such as muscle relaxant premedication and video laryngoscope, and potentially new interventions such as procedural oxygenation.


Protecting quantum anomalous Hall state from thermal fluctuation via the giant magnetic anisotropy of Os-based dimers.
To protect the quantum anomalous Hall state from thermal fluctuation, it is necessary to search for magnetic topological insulators with giant magnetic anisotropy. We have investigated the magnetic and topological properties of Os-based dimers adsorbed onto graphene by density-functional calculations plus the Wannier-function technique. Our results reveal that the systems of Os-Fe@G, Os-Ru@G, and Os-Rh@G possess both giant magnetic anisotropy, typically larger than 100 meV, and a large nontrivial topological band gap. Both the magnetic anisotropy and the band gap can be effectively tuned by the electric field. The dimers prefer ferromagnetic coupling and are stable against thermal fluctuation. The topological band-gap opening can be attributed to the intrinsic spin-orbital coupling of the dimer rather than Rashba spin-orbital coupling. These Chern insulators are found to be [script C] = ±2 with two conducting edge states crossing the Fermi level.


Relation between serum quantitative HBsAg, ALT and HBV DNA levels in HBeAg negative chronic HBV infection.
In this study, we aimed to investigate whether quantitative HBsAg and alanine aminotransferase (ALT) levels correlated with Hepatitis B Virus (HBV) DNA levels in patients with HBeAg negative chronic HBV infection. Ninetynine patients were divided into two groups; inactive HBsAg carriers (IC) and active carriers (AC) with HBV DNA>2000 IU/mL. These two groups were compared in terms of ALT and HBsAg levels. Quantitative HBsAg measurements were performed with Elecsys HBsAg II Quant assay (Roche Diagnostic). Mean age of patients was 43.11±14.79 years. HBsAg and ALT values of IC and AC patients were 2.47±1.35 log10 IU/mL, 3.59±0.97 log10 IU/mL (p=0.0001), and 25.94±13.06 IU/mL, 55.54±82.38 IU/mL (p=0.015), respectively and the difference was significant. When ROC analysis was performed to determine the most appropriate quantitative HBsAg value to define inactive carrier patients, the area under the ROC curve for HBsAg was 0.738 (95% CI:0.637-0.840). A cut-off of 2147 IU/mL revealed sensitivity of 76% and specificity of 70% for diagnosing the IC. Also, a significant correlation was also found between levels of HBV DNA (log) and HBsAg (log) (r: 0.503, p=0.0001). It has been concluded that quantitative measurements of HBsAg could be used to differentiate between IC and AC patients.


Atypical functional brain connectivity during rest in autism spectrum disorders.
Connectivity atypicalities in autism spectrum disorders (ASD) have been extensively proposed. The default mode network (DMN) is critical in this study, given the insight it provides for long-distance connectivity, and the importance of regions in this network for introspection and social emotion processing, areas affected in ASD. However, study of this network has largely been limited to adults; research earlier in development is lacking. The objective of this study was to examine DMN connectivity in children/adolescents with ASD. A total of 115 children/adolescents, aged 6 to 17 years (71 males with ASD and 44 group age-matched TD males) were included in these analyses. We examined group differences in (1) functional connectivity between the posterior cingulate cortex and regions across the brain, (2) connectivity within the DMN as a function of age and intelligence quotient (IQ), and (3) the association between DMN connectivity and empathic accuracy. Individuals with ASD, relative to controls, showed either stronger or weaker connectivity between the posterior cingulate cortex (PCC) and DMN regions, depending on the region, but also showed stronger connectivity with non-DMN regions. A significant group-by-age interaction was observed in functional connectivity between the PCC and medial prefrontal cortex; connectivity increased with age in controls, but decreased in individuals with ASD. No effects of IQ were found. There was a significant group difference in the relation between DMN connectivity and empathic accuracy. Differences in functional connectivity may suggest the presence of neural atypicalities that impact the development of typical connectivity in ASD. In addition to affecting DMN dynamics, these atypicalities may also impact social-cognitive abilities.


High Adherence of Oral Streptococcus to Polylactic Acid Might Explain Implant Infections Associated with PLA Mesh Implantation.
The aim of this study was to evaluate and compare the biofilm formation properties of common pathogens associated with implant-related infections on two different implant material types. Bacterial strains tested in this study were Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Escherichia coli. Implant materials tested and compared were PLA Resorb × polymer of Poly DL-lactide (PDLLA) comprising 50% poly-L-lactic acid and 50% poly-D-lactic acid) and Ti grade 2 (tooled with a Planmeca CAD-CAM milling device). Biofilm assays were done with and without saliva treatment to evaluate the effect of saliva on bacterial adhesion and to mimic the intraoral and extraoral surgical routes of implant placement, respectively. Five specimens of each implant type were tested for each bacterial strain. Autoclaved material specimens were first treated with 1:1 saliva-PBS solution for 30 min, followed by washing of specimens and the addition of bacterial suspension. Specimens with bacterial suspension were incubated for 24 h at 37 °C for biofilm formation. After 24 h, non-adhered bacteria were removed, and specimens were washed, followed by removal and calculation of adhered bacterial biofilm. S. aureus and E. faecalis showed more attachment to Ti grade 2, whereas S. mutans showed higher adherence to PLA in a statistically significant manner. The salivary coating of specimens enhanced the bacterial attachment by all the bacterial strains tested. In conclusion, both implant materials showed significant levels of bacterial adhesion, but saliva treatment played a vital role in bacterial attachment, therefore, saliva contamination of the implant materials should be minimized and considered when placing implant materials inside the body.


Appearance of non-specific suppressor T cells during in vitro culture.
It was found that when normal mouse spleen cells were cultured for 4 days they were capable of non-specifically suppressing the in vitro antibody response of non-precultured spleen. The suppression was mediated by a subpopulation of viable, non-adherent, T lymphocytes with the surface phenotype Ly-1+, Ly-2- and Ia-. Furthermore, it appeared that the suppressor cells were responding to foetal calf serum antigens present in the tissue culture medium and were subsequently inactivating either B lymphocytes or accessory cells required for antibody formation, which had passively absorbed these antigens.


Different effects of prenatal stress on ERK2/CREB/Bcl-2 expression in the hippocampus and the prefrontal cortex of adult offspring rats.
It has become increasingly evident that prenatal stress and its psychological and physiological concomitants are associated with the pathophysiology of mood disorders. However, the mechanisms underlying the prenatal stress-induced offspring's anxiety disorders remain unknown. We recently reported that prenatal stress enhanced anxiety-like behavior in adult offspring rat, and involved N-methyl-D-aspartate receptor subunits, including NR1 and NR2A. In the present research, using the same prenatal stress model, we measured the ERK2/CREB/Bcl-2 mRNA levels by real-time PCR. Our findings indicated that prenatal stress decreased ERK2 and CREB mRNA levels in the hippocampus and the prefrontal cortex and Bcl-2 mRNA levels in the hippocampus of offspring rat. The results showed that the abnormal ERK2, CREB, and Bcl-2 mRNA levels may be involved in the anxiety-like behavior of adult rats with prenatal stress.


The Hadropithecus conundrum reconsidered, with implications for interpreting diet in fossil hominins.
The fossil 'monkey lemur' Hadropithecus stenognathus has long excited palaeontologists because its skull bears an astonishing resemblance to those of robust australopiths, an enigmatic side branch of the human family tree. Multiple lines of evidence point to the likelihood that these australopiths ate at least some 'hard', stress-limited food items, but conflicting data from H. stenognathus pose a conundrum. While its hominin-like craniofacial architecture is suggestive of an ability to generate high bite forces, details of its tooth structure suggest that it was not well equipped to withstand the forces imposed by cracking hard objects. Here, we use three-dimensional digital reconstructions and finite-element analysis to test the hard-object processing hypothesis. We show that Archaeolemur sp. cf. A. edwardsi, a longer-faced close relative of H. stenognathus that lacked hominin convergences, was probably capable of breaking apart large, stress-limited food items, while Hadropithecus was better suited to processing small, displacement-limited (tougher but more compliant) foods. Our suggestion that H. stenognathus was not a hard-object feeder has bearing on the interpretation of hominin cranial architecture; the features shared by H. stenognathus and robust australopiths do not necessarily reflect adaptations for hard-object processing.


Effect of cell cycle inhibition on Cisplatin-induced cytotoxicity.
Pharmacological inhibitors of cyclin-dependent kinase (CDK)2 are currently in preclinical and clinical development. The purpose of our work was to evaluate a series of guanine derivatives for their ability to inhibit CDK2, affect cell cycle progression, and enhance the cytotoxic and apoptotic effects of cisplatin. A panel of guanine derivatives, including O(6)-benzylguanine (O(6)-BG), S(6)-benzyl-6-thioguanine (S(6)-BG), S(6)-[(cyclohexyl)methyl]-6-thioguanine (S(6)-CMG), O(6)-[(cyclohexyl)methyl]guanine (O(6)-CMG), O(6)-benzyl-9-methylguanine (9-CH(3)-BG), O(6)-[(cyclohexyl)methyl]-9-methyl-guanine (9-CH(3)-CMG), and 7-benzylguanine (N7-BG), exhibited varying degrees of CDK2 inhibition with O(6)-CMG being the most potent and 9-CH(3)-BG, 9-CH(3)-CMG, and N7-BG the least potent compounds. Treatment with S(6)-CMG and O(6)-CMG significantly decreased the percentage of cells in S phase. In SQ20b and SCC61 head and neck cancer cell lines, the most potent CDK2 inhibitor, O(6)-CMG, was also the most effective at enhancing cisplatin-induced cytotoxicity and apoptosis. Cisplatin-induced DNA platination increased in SQ20b cells pretreated with S(6)-BG, S(6)-CMG, and O(6)-CMG. Treatment with both O(6)-BG and trichostatin A, an indirect cell cycle inhibitor, demonstrated additive effects on cisplatin-induced cytotoxicity. In summary, we have identified a group of guanine derivatives that were effective modulators of cisplatin-induced cytotoxicity and apoptosis.


Ceramic membrane overview and applications in textile industry: a review.
The importance of water recovery and reuse is increasing day by day. Therefore, the use of advanced technologies is applied for the treatment and recovery of textile wastewater. The fact that ceramic membranes are resistant to the challenging characteristics of textile wastewater makes the use of ceramic membranes useful. Within the scope of this review, general information about the textile industry and treatment techniques are mentioned, as well as the properties of ceramic membranes and textile wastewater treatment. In the literature review made in this study, recent studies on the production of ceramic membranes and laboratory applications have been compiled. However, it has been observed that although the real-scale studies are relatively higher in industries such as the food and petrochemical industry, it is rather limited in the textile industry.


Effects of Inflammatory Disease on Clinical Progression and Treatment of Ischiogluteal Bursitis: A Retrospective Observational Study.
The symptoms of Ischiogluteal Bursitis (IGB) are often nonspecific and atypical, and its diagnosis is more challenging. Moreover, it is difficult to predict cases of chronic progression or poor treatment response. Therefore, the aim of this study was to investigate the clinical course of IGB patients and identify factors that are predictive of failure of conservative treatment. Our study consisted of IGB patients diagnosed between 2010 March and 2016 December who had been followed-up for at least one year. Structured questionnaires and medical records were reviewed to analyse demographic characteristics, lifestyle patterns, blood tests, and imaging studies. We categorized the cases into two groups based on the response to conservative treatment and the need for surgical intervention. The most common initial chief symptoms were buttock pains in 24 patients (37.5%). Physical examinations showed the tenderness of ischial tuberosity area in 59 (92.2%) patients, but no specific findings were confirmed in 5 patients (7.8%). 51 patients (79.7%) responded well to the conservative management, 11 patients (17.2%) needed injection, and 2 patients (3.1%) had surgical treatment performed due to continuous recurrence. There was no difference in demographic and blood lab data between the two groups. However, the incidence of inflammatory diseases (response group: 10.3% vs non-response group: 66.7%, p=0.004) was significantly different between the two groups. The diagnosis of IGB can be missed due to variations in clinical symptoms, and cautions should be exercised in patients with inflammatory diseases as conservative treatment is less effective in them, leading to chronic progression of IGB.


Prevalence & factors associated with depression among schoolgoing adolescents in Chandigarh, north India.
Depression among adolescents is a rising problem globally. There is a need to understand the factors associated with depression among adolescents. This study was conducted to ascertain the prevalence of depressive disorders and associated factors among schoolgoing adolescents in government and private schools in Chandigarh, India. A cross-sectional study was conducted among 542 randomly selected schoolgoing adolescents (13-18 yr), from eight schools by multistage sampling technique. Depression was assessed using Patient Health Questionnaire-9 (PHQ-9) and associated factors by pretested semistructured interview schedule. Multivariate analysis was done to identify significant associated factors. Two-fifth (40%) of adolescents had depressive disorders, 7.6 per cent major depressive disorders and 32.5 per cent other depressive disorders. In terms of severity, 29.7 per cent had mild depression, 15.5 per cent had moderate depression, 3.7 per cent had moderately severe depression and 1.1 per cent had severe depression. Significant associated factors included being in a government school, studying in class Xth and XIIth, rural locality, physical abuse by family members, alcohol use and smoking by father, lack of supportive environment in school, spending less time in studies, lower level of participation in cultural activities and having a boy/girlfriend. Significant predictors on binary logistic regression analysis were being in class Xth [odds ratio (OR)=5.3] and lack of self-satisfaction with own academic performance (OR=5.1). Our study showed that a significant proportion of schoolgoing adolescents suffered from depression. The presence of depression was associated with a large number of modifiable risk factors. There is a need to modify the home as well as school environment to reduce the risk of depression.


Acute exposure to air pollution is associated with novel changes in blood levels of endothelin-1 and circulating angiogenic cells in young, healthy adults.
Acute and chronic exposures to particulate matter (PM2.5) air pollution increase the risk for cardiovascular disease (CVD). A hypothesized mechanism linking PM2.5 exposure and CVD is the induction of endothelial dysfunction - a key step to increased CVD risk. Although PM2.5 exposure is associated with endothelial dysfunction and the vasoconstrictor peptide endothelin-1 (ET-1) is upregulated in endothelial dysfunction, the effects of PM2.5 on ET-1 and whether or not ET-1 mediates the downstream effects of PM2.5 are unclear. In addition to examining associations between acute changes in ambient PM2.5 and circulating levels of ET-1, we also looked at whether changes in ET-1 were associated with changes in markers of vascular health and systemic injury. For example, endothelial function is maintained in part by circulating angiogenic cell (CAC)-mediated repair, and our recent studies show that CACs in humans and mice are decreased by ambient PM2.5 exposure. In the current study, we recruited young, healthy adults who were exposed to natural variations in PM2.5, and we analyzed associations between PM2.5 and circulating levels of ET-1, between ET-1 and CACs, and between ET-1 and other biomarkers of injury using linear regression analyses. Surprisingly, ET-1 levels were negatively associated with PM2.5 levels (β = -0.773, P = 0.0005), yet, in contrast, positively associated with two CACs: CAC-2 (CD31+/CD34+/CD45+) and CAC-4 (CD31+/CD34+/CD45+/CD133+). Interestingly, ET-1 levels were negatively associated with some biomarkers (platelet factor 4, β = -0.148, P = 0.0003; triglycerides, β = -0.095, P = 0.041) and positively with other biomarkers: albumin (β = 0.035, P = 0.006) and IL-lβ (β = 0.082, P = 0.012). These findings further reveal the insidious nature of PI2.5's anti-angiogenic effect including a novel relationship between ET-1 and CACs in young adults exposed to acute elevations of air pollution.


COVID-19 and the cardiovascular system: insights into effects and treatments.
Coronavirus disease 2019 (COVID-19), an acute and highly transmissible infectious disease, has reached a pandemic level since 11 March 2020 and continues to challenge the healthcare system worldwide. The pathogenesis of COVID-19 is a complex process involving mechanisms that suppress the host antiviral and innate immune response, while triggering marked activation of coagulation and hyperinflammation leading to cytokine storm in severe COVID-19. This review summarizes current evidence related to COVID-19-associated cardiovascular severe illness and mortality, which encompasses life-threatening clinical manifestations, including myocardial injury, fulminant myocarditis, cardiac arrhythmia, and ischemic stroke. The onset of hypercoagulable state is consistent with increased venous thromboembolism including deep vein thrombosis and pulmonary embolism. Thromboembolic manifestations include arterial thrombotic events such as stroke, myocardial infarction, and limb ischemia. Several treatment strategies have been investigated to mitigate COVID-19-associated cardiovascular clinical manifestations. The prevalence of thrombo-inflammatory syndrome and subsequent cardiovascular dysfunction prompted the implementation of antithrombotic therapy and strategies targeting major pro-inflammatory cytokines involved in COVID-19 cytokine storm. The development of new guidelines for effective treatment strategies requires concerted efforts to refine our understanding of the mechanisms underlying cardiovascular disease and large-scale clinical trials to reduce the burden of COVID-19 hospitalization and mortality.


[Methods of comprehensive multifunctional examination of patients with penetrating fragmentation injuries of eye].
The study was aimed at validating the efficacy of all available diagnostic methods for the detection and removal of foreign bodies in the eyes. A total of 563 patients with penetrating fragmentation injuries to the eyes were observed. The advantages and drawbacks of each method for the diagnosis of intraocular foreign bodies are analyzed and causes of differences in the localization of a fragment by different methods discussed. The authors consider that these discrepancies are caused by 1) use of standard schematic size during x-ray localization of a fragment without amendment for the true size of the eyeball; 2) movements of a nonfixed foreign body in the eye; and 3) errors in diagnostic manipulations (dislocation of the indicator prosthesis, wrong position of the eyeball or the probing device). Hence, a complex of diagnostic methods is to be used for localizing intraocular foreign bodies.


The Institute for Biomedical Communication of the South African Medical Research Council.
The need exists in the biomedical community for comprehensive, timely and easily obtainable information. The Institute for Biomedical Communication of the South African Medical Research Council meets this need. An overview of the activities of the institute is presented. Other services, such as the provision of documents, editing of manuscripts, and the evaluation of new information technologies, are also described.


CAR T cell therapy: A new era for cancer treatment (Review).
Cancer has recently been identified as the leading cause of mortality worldwide. Several conventional treatments and cytotoxic immunotherapies have been developed and made available to the market. Considering the complex behavior of tumors and the involvement of numerous genetic and cellular factors involved in tumorigenesis and metastasis, there is a need to develop a promising immunotherapy that targets tumors at both the cellular and genetic levels. Chimeric antigen receptor (CAR) T cell therapy has emerged as a novel therapeutic T cell engineering practice, in which T cells derived from patient blood are engineered in vitro to express artificial receptors targeted to a specific tumor antigen. These directly identify the tumor antigen without the involvement of the major histocompatibility complex. The use of this therapy in the last few years has been successful, with a reduction in remission rates of up to 80% for hematologic cancer, particularly for acute lymphoblastic leukemia (ALL) and non‑Hodgkin lymphomas, such as large B cell lymphoma. Recently, anti‑CD19 CAR therapy, or UCART19, has been shown to be efficacious in treating relapsed/refractory hematologic cancer. Several other cell surface tumor antigens, such as CD20 and CD22, found in the majority of leukemias and lymphomas are considered potential targets by pharmaceutical companies and research organizations, and trials have been ongoing in this direction. Although this therapeutic regimen is currently confined to treating hematologic cancer, the increasing involvement of several auxiliary techniques, such as bispecific CAR, Tan‑CAR, inhibitory‑CAR, combined antigens, the clustered regularly interspaced short palindromic repeats gene‑editing tool and nanoparticle delivery, may substantially improve its overall anticancer effects. CAR therapy has the potential to offer a rapid and safer treatment regime to treat non‑solid and solid tumors. The present review presents an insight into the advantages and the advances of CAR immunotherapy and presents the emerging discrepancy of CAR therapy over usual forms of therapy, such as chemotherapy and radiotherapy.


Effect of lysine, tryptophan and(or) carbadox additions to low protein corn-soybean meal diets for young pigs.
Addition of L-lysine (Lys), L-tryptophan (Trp) and(or 55 ppm carbadox (C) to low protein corn-soybean meal diets was evaluated in two experiments using 444 crossbred pigs. In Exp. 1, initial and final weights of pigs were 17.7 and 33.3 kg, respectively, for the 28 d experiment. Pigs fed the 13% protein diet containing added Lys (.17%) or Lys + C had average daily gains (ADG) similar to those fed the 16% protein diet (positive control group) and greater (P less than .05) than those of pigs fed the 13% protein diet (negative controls). Pigs fed the 13% protein diets containing C had average daily feed intakes (ADFI) and ADG similar to those of pigs fed the 13% protein diet / Lys. Main effect comparisons among the 13% protein groups indicated that C increased (P less than .05) ADFI and ADG and that Lys increased (P less than .01) ADG and G:F ratio. In Exp. 2, the initial pig weight for the 28 d starter period averaged 7.4 kg. A 28 d grower period followed, in which the protein level was lowered 2% across treatments. The high and low dietary protein level sequences consisted of 18 and 15%, respectively, during the starter period followed by 16 and 13%, respectively, during the grower period. Lys and(or) Trp additions were also lowered from .18 and .05% to .15 and .04%, respectively. The overall 56 d performance indicated that pigs fed the low protein dietary sequence supplemented with either Lys or C had ADFI and ADG similar to those of the high protein dietary sequence positive control group and greater (P less than .05) than those of the low protein negative control group. The combination of Lys + C further increased (P less than .05) the ADG over that of the high protein sequence group. Overall main effect comparisons among the low protein dietary sequence groups indicated that either added Lys or C increased (P less than .01) ADFI and ADG, with added Lys also increasing G:F ratio. However, added Trp did not improve any performance characteristics. These results indicate that C had a Lys sparing effect in low protein corn-soybean meal diets fed to young pigs.


Nut consumption and risk of cancer and type 2 diabetes: a systematic review and meta-analysis.
The identification of foods that can decrease the risk of cancer and type 2 diabetes may be helpful in reducing the burden of these diseases. Although nut consumption has been suggested to have a disease-preventive role, current evidence remains inconsistent. The aim of this systematic review and meta-analysis was to clarify the association between nut consumption and risk of cancer or type 2 diabetes. Six databases were searched for relevant studies from the time of database inception to August 2014. Reference lists of relevant review articles were hand searched, and authors were contacted when data were insufficient. Eligible studies included epidemiological studies (case-control and cohort) or clinical trials that reported an association between nut consumption and the outcome of type 2 diabetes or specific cancers. Two investigators independently extracted descriptive, quality, and risk data from included studies. Random-effects meta-analysis was used to pool relative risks from the included studies. The I(2) statistic was used to assess heterogeneity. A total of 36 eligible observational studies, which included 30,708 patients, were identified. The studies had fair methodological quality, and length of follow-up ranged between 4.6 years and 30 years. Comparison of the highest category of nut consumption with the lowest category revealed significant associations between nut consumption and decreased risk of colorectal cancer (3 studies each with separate estimates for males and females, RR 0.76, 95% confidence interval [95%CI] 0.61-0.96), endometrial cancer (2 studies, RR 0.58, 95%CI 0.43-0.79), and pancreatic cancer (1 study, RR 0.68, 95%CI 0.48-0.96). No significant association was found with other cancers or type 2 diabetes. Overall, nut consumption was significantly associated with a reduced risk of cancer incidence (RR 0.85, 95%CI 0.76-0.95). Nut consumption may play a role in reducing cancer risk. Additional studies are needed to more accurately assess the relationship between nut consumption and the prevention of individual types of cancer, given the scarcity of available data.


Conventional and Novel Treatment Modalities in Rosacea.
Rosacea is a common skin disease that is troublesome for both the patients and the dermatologists. Erythema, telengiectasia, papulopustular changes and phymatous changes are the main problems faced by the patients and dermatologists in everyday practice. Due to the chronic and relapsing nature of the disease, patients are usually unsatisfied with conventional treatment methods. This article aims at redefining rosacea according to the 2017 consensus and reviewing the different treatment modalities for different manifestations of the disease in depth.


Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer.
The key to a more effective diagnosis, prognosis, and therapeutic management of prostate cancer (PCa) could lie in the direct analysis of cancer tissue. In this study, by comparative proteomics analysis of PCa and benign prostate hyperplasia (BPH) tissues we attempted to elucidate the proteins and regulatory pathways involved in this disease. The samples used in this study were fresh surgical tissues with clinically and histologically confirmed PCa (n = 19) and BPH (n = 33). We used two dimensional difference in gel electrophoresis (2D DIGE) coupled with mass spectrometry (MS) and bioinformatics analysis. Thirty-nine spots with statistically significant 1.8-fold variation or more in abundance, corresponding to 28 proteins were identified. The IPA analysis pointed out to 3 possible networks regulated within MAPK, ERK, TGFB1, and ubiquitin pathways. Thirteen of the identified proteins, namely, constituents of the intermediate filaments (KRT8, KRT18, DES), potential tumor suppressors (ARHGAP1, AZGP1, GSTM2, and MFAP4), transport and membrane organization proteins (FABP5, GC, and EHD2), chaperons (FKBP4 and HSPD1) and known cancer marker (NME1) have been associated with prostate and other cancers by numerous proteomics, genomics or functional studies. We evidenced for the first time the dysregulation of 9 proteins (CSNK1A1, ARID5B, LYPLA1, PSMB6, RABEP1, TALDO1, UBE2N, PPP1CB, and SERPINB1) that may have role in PCa. The UBE2N, PSMB6, and PPP1CB, involved in cell cycle regulation and progression were evaluated by Western blot analysis which confirmed significantly higher abundances of UBE2N and PSMB6 and significantly lower abundance of PPP1CB in PCa. In addition to the identification of substantial number of proteins with known association with PCa, the proteomic approach in this study revealed proteins not previously clearly related to PCa, providing a starting point for further elucidation of their function in disease initiation and progression.


A dynamic programming algorithm for binning microbial community profiles.
A number of community profiling approaches have been widely used to study the microbial community composition and its variations in environmental ecology. Automated Ribosomal Intergenic Spacer Analysis (ARISA) is one such technique. ARISA has been used to study microbial communities using 16S-23S rRNA intergenic spacer length heterogeneity at different times and places. Owing to errors in sampling, random mutations in PCR amplification, and probably mostly variations in readings from the equipment used to analyze fragment sizes, the data read directly from the fragment analyzer should not be used for down stream statistical analysis. No optimal data preprocessing methods are available. A commonly used approach is to bin the reading lengths of the 16S-23S intergenic spacer. We have developed a dynamic programming algorithm based binning method for ARISA data analysis which minimizes the overall differences between replicates from the same sampling location and time. In a test example from an ocean time series sampling program, data preprocessing identified several outliers which upon re-examination were found to be because of systematic errors. Clustering analysis of the ARISA from different times based on the dynamic programming algorithm binned data revealed important features of the biodiversity of the microbial communities.


Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group.
A randomized, double-blind trial comparing oral fluconazole (400 mg daily) with placebo as prophylaxis for adult patients receiving intensive cytotoxic therapy for acute leukemia or autologous bone marrow transplantation was conducted in 14 Canadian university-affiliated hospitals. Although fluconazole prophylaxis did not obviate the need for parenteral antifungal therapy compared with placebo (81 [57%] of 141 vs. 67 [50%] of 133, respectively), its use resulted in fewer superficial fungal infections (10 [7%] of 141 vs. 23 [18%] of 131, respectively; P = .02) and fewer definite and probable invasive fungal infections (9 vs. 32, respectively; P = .0001). Fluconazole recipients had fewer deaths attributable to definite invasive fungal infection (1 of 15 vs. 6 of 15, respectively; P = .04) and achieved more frequent success without fungal colonization (52 [37%] of 141 vs. 27 [20%] of 133, respectively; P = .004; relative risk reduction, 85%) than did placebo recipients. Patients benefiting the most from fluconazole prophylaxis included those with acute myeloid leukemia who were undergoing induction therapy with cytarabine plus anthracycline-based regimens and those receiving marrow autografts not supported with hematopoietic growth factors. Fluconazole prophylaxis reduces the incidence of superficial fungal infection and invasive fungal infection and fungal infection-related mortality among patients who are receiving intensive cytotoxic chemotherapy for remission induction.


Further studies on the anti-immunoglobulin G hemagglutination-inhibition test for influenza.
Incorporating species-specific anti-immunoglobulin G (IgG) serum into the hemagglutination-inhibition (HI) test for influenza markedly increased sensitivity without loss of specificity. The effectiveness of anti-IgG serum for augmenting antibody titers may be influenced by the variable potency of commercial anti-IgG preparations. Maximal enhancement of HI titers was achieved when anti-IgG serum and virus-antiserum mixtures were incubated at 23 C for 10 min. Precision and reproducibility of the test were within acceptable limits. Other conditions likely to affect the test were investigated.


Multiple Timescales Account for Adaptive Responses across Sensory Cortices.
Sensory systems encounter remarkably diverse stimuli in the external environment. Natural stimuli exhibit timescales and amplitudes of variation that span a wide range. Mechanisms of adaptation, a ubiquitous feature of sensory systems, allow for the accommodation of this range of scales. Are there common rules of adaptation across different sensory modalities? We measured the membrane potential responses of individual neurons in the visual, somatosensory, and auditory cortices of male and female mice to discrete, punctate stimuli delivered at a wide range of fixed and nonfixed frequencies. We find that the adaptive profile of the response is largely preserved across these three areas, exhibiting attenuation and responses to the cessation of stimulation, which are signatures of response to changes in stimulus statistics. We demonstrate that these adaptive responses can emerge from a simple model based on the integration of fixed filters operating over multiple time scales.SIGNIFICANCE STATEMENT Our recent sensations affect our current expectations and perceptions of the environment. Neural correlates of this process exist throughout the brain and are loosely termed adaptation. Adaptive processes have been described across sensory cortices, but direct comparisons of these processes have not been possible because paradigms have been tailored specifically for each modality. We developed a common stimulus set that was used to characterize adaptation in somatosensory, visual, and auditory cortex. We describe here the similarities and differences in adaptation across these cortical areas and demonstrate that adaptive responses may emerge from a set of static filters that operate over a broad range of timescales.


Optimal therapy in genotype 1 patients.
Most infections with hepatitis C virus (HCV) fail to resolve spontaneously and progress to chronic hepatitis C. Genotype 1 HCV accounts for most hepatitis C infections in North America, Western Europe, and Japan. Patients infected with HCV genotype 1 are the most resistant to treatment, which results in poor treatment outcomes. Although sustained virologic response (SVR) rates have significantly improved with introduction of combination therapy with pegylated interferon alfa and ribavirin, the rates are still lower than those in genotype 2 or 3 infections. This review discusses how treatment outcomes in patients with HCV genotype 1 infection can be optimized by using the drugs currently licensed for treatment of hepatitis C: pegylated interferon alfa-2a/b and ribavirin. Dose modifications and variations of treatment duration are the two strategies that have been investigated best, so far. Treatment--naïve patients and non-responders and relapsers to prior antiviral therapy are discussed separately.


Urinary tract calculi in man and laboratory animals: incidence, composition, and etiology.
Calculi in the urinary tract is a disease which afflicts not only man, but also experimental animals. The incidence of human stone disease varies widely according to the geographical area. With the advent of sophisticated physicochemical techniques, the elucidation of structure and the quantification of mineral components of urinary calculi have been greatly facilitated. In addition to calcium oxalate and calcium phosphate, more than ten other minerals and a large number of trace elements have been identified to date. Matrix material consists of such macro-molecules as proteins and mucopolysaccharides. The etiology of urinary calculi is varied; diet, drugs, chemicals, bladder implants, infections, metabolic derangements, and environmental influences are some of the factors that can contribute to the pathogenesis of stones. The literature findings reflect the complexity of urolithiasis as a clinicopathological problem.


A low RENAL Nephrometry Score can avoid the need for the intraoperative insertion of a ureteral catheter in robot-assisted partial nephrectomy.
Intraoperative urinary collecting system entry (CSE) in robot-assisted partial nephrectomy (RAPN) may cause postoperative urinary leakage and extend the hospitalization. Therefore, identifying and firmly closing the entry sites are important for preventing postoperative urine leakage. In RAPN cases expected to require CSE, we insert a ureteral catheter and inject dye into the renal pelvis to identify the entry sites. We retrospectively analyzed the factors associated with intraoperative CSE in RAPN and explored the indications of intraoperative ureteral catheter indwelling in RAPN. Of 104 Japanese patients who underwent RAPN at our institution from August 2016 to March 2020, 101 were analyzed. The patients were classified into CSE and non-CSE groups. The patients' background characteristics, RENAL Nephrometry Score (RNS), and surgical outcomes were analyzed. Intraoperative CSE was observed in 41 patients (41%). The CSE group had a significantly longer operative time, console time, ischemic time, and hospital stay than the non-CSE group. In a multivariable analysis, the N-score (odds ratio [OR] = 3.9, P < 0.05) and RNS total score excluding the L-score (OR = 3.1, P < 0.05) were associated with CSE. In a logistic regression analysis, CSE showed a moderate correlation with the RNS total score excluding the L-score (AUC 0.848, cut-off 5, sensitivity 0.83, specificity 0.73). A ureteral catheter should not be placed in patients with an RNS total score (excluding the L-score) of ≤ 4.


Dispersal and migration have contrasting effects on butterfly flight morphology and reproduction.
Movement may fundamentally alter morphology and reproductive states in insects. In long-distance migrants, reproductive diapause is associated with trade-offs between diverse life-history traits such as flight morphology and lifespan. However, many non-diapausing insects engage in shorter resource-driven dispersals. How diapause and other reproductive states alter flight morphology in migrating versus dispersing insects is poorly understood. To find out, we compared flight morphology in different reproductive states of multiple butterfly species. We found that dispersers consisted of ovulating females with higher egg loads compared with non-dispersing females. This trend was in stark contrast with that of migrating female butterflies in reproductive diapause, which made substantially higher investment in flight tissue compared with reproductively active, non-migrating females. Thus, long-distance migration and shorter resource-driven dispersals had contrasting effects on flight morphology and egg loads. By contrast, male flight morphology was not affected by dispersal, migration or associated reproductive states. Thus, dispersal and migration affected resource allocation in flight and reproductive tissue in a sex-specific manner across relatively mobile versus non-dispersing individuals of different species. These findings suggest that dispersals between fragmented habitats may put extra stress on egg-carrying females by increasing their flight burdens.


CFI 25 Subunit of Cleavage Factor I is Important for Maintaining the Diversity of 3' UTR Lengths in Arabidopsis thaliana (L.) Heynh.
Cleavage and polyadenylation at the 3' end of the pre-mRNA is essential for mRNA function, by regulating its translatability, stability and translocation to the cytoplasm. Cleavage factor I (CFI) is a multi-subunit component of the pre-mRNA 3' end processing machinery in eukaryotes. Here, we report that plant CFI 25 subunit of CFI plays an important role in maintaining the diversity of the 3' ends of mRNA. The genome of Arabidopsis thaliana (L.) Heynh. contained four genes encoding three putative CFI subunits (AtCFI 25, AtCFI 59 and AtCFI 68), orthologous to the mammalian CFI subunits. There were two CFI 25 paralogs (AtCFI 25a and AtCFI 25b) that shared homology with human CFI 25. Two null alleles of AtCFI 25a displayed smaller rosette leaves, longer stigmatic papilla, smaller anther, earlier flowering and lower fertility compared to wild-type plants. Null alleles of AtCFI 25b, as well as, plants ectopically expressing full-length cDNA of AtCFI 25a, displayed no obvious morphological defects. AtCFI 25a was shown to interact with AtCFI 25b, AtCFI 68 and itself, suggesting various forms of CFI in plants. Furthermore, we show that AtCFI 25a function was essential for maintaining proper diversity of the 3' end lengths of transcripts coding for CFI subunits, suggesting a self-regulation of the CFI machinery in plants. AtCFI 25a was also important to maintain 3' ends for other genes to different extent. Collectively, AtCFI 25a, but not AtCFI 25b, seemed to play important roles during Arabidopsis development by maintaining proper diversity of the 3' UTR lengths.


Centimeter-Scale Surface Interactions Using Hydrodynamic Flow Confinements.
We present a device and method for selective chemical interactions with immersed substrates at the centimeter-scale. Our implementations enable both, sequential and simultaneous delivery of multiple reagents to a substrate, as well as the creation of gradients of reagents on surfaces. The method is based on localizing submicroliter volumes of liquids on an immersed surface with a microfluidic probe (MFP) using a principle termed hydrodynamic flow confinement (HFC). We here show spatially defined, multiplexed surface interactions while benefiting from the probe capabilities such as non-contact scanning operation and convection-enhanced reaction kinetics. Three-layer glass-Si-glass probes were developed to implement slit-aperture and aperture-array designs. Analytical and numerical analysis helped to establish probe designs and operating parameters. Using these probes, we performed immunohistochemical analysis on individual cores of a human breast-cancer tissue microarray. We applied α-p53 antibodies on a 2 mm diameter core within 2.5 min using a slit-aperture probe (HFC dimension: 0.3 mm × 1.2 mm). Further, multiplexed treatment of a tissue core with α-p53 and α-β-actin antibodies was performed using four adjacent HFCs created with an aperture-array probe (HFC dimension: 4 × 0.3 mm × 0.25 mm). The ability of these devices and methods to perform multiplexed assays, present sequentially different liquids on surfaces, and interact with surfaces at the centimeter-scale will likely spur new and efficient surface assays.


Fingerprinting Alzheimer's Disease by 1H Nuclear Magnetic Resonance Spectroscopy of Cerebrospinal Fluid.
In this study, we sought for a cerebrospinal fluid (CSF) metabolomic fingerprint in Alzheimer's disease (AD) patients characterized, according to the clinical picture and CSF AD core biomarkers (Aβ42, p-tau, and t-tau), both at pre-dementia (mild cognitive impairment due to AD, MCI-AD) and dementia stages (ADdem) and in a group of patients with a normal CSF biomarker profile (non-AD) using untargeted 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolomics. This is a retrospective study based on two independent cohorts: a Dutch cohort, which comprises 20 ADdem, 20 MCI-AD, and 20 non-AD patients, and an Italian cohort, constituted by 14 ADdem and 12 non-AD patients. 1H NMR CSF spectra were analyzed using OPLS-DA. Metabolomic fingerprinting in the Dutch cohort provides a significant discrimination (86.1% accuracy) between ADdem and non-AD. MCI-AD patients show a good discrimination with respect to ADdem (70.0% accuracy) but only slight differences when compared with non-AD (59.6% accuracy). Acetate, valine, and 3-hydroxyisovalerate result to be altered in ADdem patients. Valine correlates with cognitive decline at follow-up (R = 0.53, P = 0.0011). The discrimination between ADdem and non-AD was confirmed in the Italian cohort. The CSF metabolomic fingerprinting shows a signature characteristic of ADdem patients with respect to MCI-AD and non-AD patients.


Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials.
Current guidelines to treat iron deficiency recommend daily provision of ferrous iron divided through the day to increase absorption. However, daily dosing and split dosing might increase serum hepcidin and decrease iron absorption from subsequent doses. Our study aim was to compare iron absorption from oral iron supplements given on consecutive versus alternate days and given as single morning doses versus twice-daily split dosing. We did two prospective, open-label, randomised controlled trials assessing iron absorption using (54Fe)-labelled, (57Fe)-labelled, or (58Fe)-labelled ferrous sulfate in iron-depleted (serum ferritin ≤25 μg/L) women aged 18-40 years recruited from ETH Zurich and the University of Zurich, Switzerland. In study 1, women were randomly assigned (1:1) to two groups. One group was given 60 mg iron at 0800 h (±1 h) on consecutive days for 14 days, and the other group was given the same doses on alternate days for 28 days. In study 2, women were assigned to two groups, stratified by serum ferritin so that two groups with similar iron statuses could be formed. One group was given 120 mg iron at 0800 h (±1 h) and the other was given the dose split into two divided doses of 60 mg at 0800 h (±1 h) and 1700 h (±1 h) for three consecutive days. 14 days after the final dose, the groups were each crossed over to the other regimen. Within-individual comparisons were done. The co-primary outcomes in both studies were iron bioavailability (total and fractional iron absorption), assessed by measuring the isotopic label abundance in erythrocytes 14 days after administration, and serum hepcidin. Group allocations in both studies were not masked and primary and safety analyses were done on an intention-to-treat basis. The studies were registered at ClinicalTrials.gov, numbers NCT02175888 (study 1) and NCT02177851 (study 2) and are complete. For study 1, 40 women were enrolled on Oct 15-29, 2015. 21 women were assigned to the consecutive-day group and 19 to the alternate-day group. At the end of treatment (14 days for the consecutive-day group and 28 days for the alternate-day group), geometric mean (-SD, +SD) cumulative fractional iron absorptions were 16·3% (9·3, 28·8) in the consecutive-day group versus 21·8% (13·7, 34·6) in the alternate-day group (p=0·0013), and cumulative total iron absorption was 131·0 mg (71·4, 240·5) versus 175·3 mg (110·3, 278·5; p=0·0010). During the first 14 days of supplementation in both groups, serum hepcidin was higher in the consecutive-day group than the alternate-day group (p=0·0031). In study 2, 20 women were enrolled between Aug 13 and 18, 2015. Ten women were assigned to receive once-daily dosing and ten were assigned to receive twice-daily divided dosing. No significant differences were seen in fractional (day 1-3 geometric mean: 11·8% [7·1, 19·4] once daily vs 13·1% [8·2, 20·7] twice daily; p=0·33) or total iron absorption (day 1-3: 44·3 mg [29·4, 66·7] once daily vs 49·4 [35·2, 69·4] twice daily; p=0·33) between the two dosing regimens. Twice-daily divided doses resulted in a higher serum hepcidin concentration than once-daily dosing (p=0·013). No grade 3 or 4 adverse events were reported in either study. In iron-depleted women, providing iron supplements daily as divided doses increases serum hepcidin and reduces iron absorption. Providing iron supplements on alternate days and in single doses optimises iron absorption and might be a preferable dosing regimen. These findings should be confirmed in iron-deficient anaemic patients. Swiss National Science Foundation, Bern, Switzerland.


Stationary velocity and charge distributions of grains in dusty plasmas
Within the kinetic approach the velocity and the charge distributions of grains in stationary dusty plasmas are calculated and the relations between the effective temperatures of such distributions and plasma parameters are established. It is found that the effective temperature which determines the velocity grain distribution could be anomalously large due to the action of accelerating ionic bombarding force. The possibility to apply the results obtained to the explanation of the increasing grain temperature in the course of Coulomb-crystal melting by reduction of the gas pressure is discussed.


Shared vector-borne zoonoses of the Old World and New World: home grown or translocated?
Humans inhabiting the Old World and New World share a wide variety of pathogens. Processes that result in the disjunct biogeographic distribution of pathogens with common vertebrate reservoirs or vectors are more difficult to unravel than those influencing the distribution of infections spread only through human-to-human transmission. The origins of species and complexes of tick-borne bacteria are unclear. The agent of Lyme borreliosis may have speciated in the New World following geographical isolation of ticks harboring ancestral spirochetes; the subsequent spread to Europe of B. burgdorferi sensu stricto may have occurred within historical times. Other tick-borne agents, such as the ehrlichiae causing human granulocytic ehrlichiosis, are genetically very similar in the Old World and New World. As the taxonomic distinctions among these related agents of human and veterinary importance appear increasingly blurred, the processes leading to the current discontinuous geographic distributions will also become the source of continuing speculation. Accumulating data suggest an Old World origin for a group of bacteria that include B. elizabethae, a human pathogen first identified from the New World. The potential public health significance of these newly described organisms is undefined, but of international interest as their vertebrate reservoir has been introduced throughout the world.