Reversible and irreversible changes in nucleosome structure along the c-fos and c-myc oncogenes following inhibition of transcription.
A new affinity chromatographic procedure for the separation of transcriptionally active nucleosomes has been used to study the changes that take place in chromatin structure along the c-fos and c-myc genes when RNA synthesis is inhibited. Mercury-affinity chromatography separates the sulfhydryl-reactive nucleosomes of transcriptionally active genes from the compactly beaded, non-reactive nucleosomes of transcriptionally inert DNA sequences. The new procedure also discriminates between nucleosomes that have "unfolded" to reveal the previously shielded SH groups of histone H3 and nucleosomes that bind to the mercury column because of their association with thiol-containing non-histone proteins located in the transcription unit. Both classes of Hg-bound nucleosomes contain the c-fos and c-myc sequences, but only when they are being transcribed. We compared the effects of alpha-amanitin and actinomycin D on the transcription of c-fos and c-myc with the effects of each inhibitor on the distribution of the corresponding oncogenic DNA sequences in the chromatographically separated nucleosome fractions. It was found that the inhibition of RNA polymerase II by alpha-amanitin (added at the peaks of c-fos or c-myc expression in serum-stimulated BALB/c 3T3 cells) resulted in a rapid loss of affinity of the oncogene-containing nucleosomes for the mercury column. There was no corresponding effect on the mercury-binding properties of nucleosomes containing 28 S ribosomal gene sequences, which continue to be transcribed by amanitin-resistant RNA polymerase I. Therefore, the binding of the c-fos and c-myc nucleosomes to the mercury column seems to depend upon reversible structural changes associated with their transcription. Surprisingly, there was no corresponding loss of affinity of the c-fos and c-myc nucleosomes for the mercury column when actinomycin D was employed to inhibit RNA synthesis, despite the fact that transcription of both genes had been arrested abruptly. Measurements of [3H]actinomycin D binding show its preferential intercalation into the transcriptionally active nucleosomes. We suggest that the intercalation of actinomycin D into the DNA of active nucleosomes can lock the transcription complex into an "unfolded" but potentially active configuration. This was confirmed by run-off transcription assays showing a restoration of c-fos and c-myc RNA synthesis when actinomycin D was displaced by proflavine.


The dopamine transporter and cytochrome P45OIID1 (debrisoquine 4-hydroxylase) in brain: resolution and identification of two distinct [3H]GBR-12935 binding proteins.
Two [3H]GBR-12935 binding proteins, identified as the dopamine transporter and cytochrome P45OIID1, were solubilized in digitonin from canine striatal membranes, and were resolved following wheat germ agglutinin (WGA)-lectin column chromatography. Protein adsorbed to and specifically eluted from WGA-lectin with N-acetylglucosamine displayed saturable, high affinity (KD approximately 3 nM), and sodium-dependent binding of [3H]GBR-12935, which was inhibited in a concentration-dependent and stereoselective manner by dopamine uptake blockers and substrates with a pharmacological profile indicative of the dopamine uptake site. Protein not adsorbed to WGA-lectin also bound [3H]-GBR-12935 with high affinity (approximately 7 nM), in a sodium-independent manner, and was insensitive to classical dopamine uptake blockers and substrates such as mazindol or dopamine, corresponding to the so-called "piperazine acceptor" site seen in native membranes. [3H]GBR-12935 binding to this latter protein was, however, inhibited by various compounds with a pharmacological profile indicative of a form of cytochrome P450 designated P45OIID1 (debrisoquine/sparteine monooxygenase) with the following rank order of inhibitory potency: GBR-12909 greater than budipine greater than alpha-lobeline greater than quinidine greater than alpha flupenthixol greater than SKF-525A greater than sparteine greater than quinine. Ki values obtained for inhibition of [3H]-GBR-12935 binding to neuronal WGA passthrough fractions by these drugs correlate well with their respective Ki values for liver P45OIID1 activity. Western blotting and immunoprecipitation analysis with rabbit anti-rat P45OIID1 antibody also supported the identity of the mazindol-insensitive [3H]GBR-12935 binding site (or piperazine acceptor site) as P45OIID1. Furthermore, a [3H]GBR-12935 binding protein with pharmacological and immunological characteristics similar to those of P45OIID1 was solubilized from both bovine and human liver membranes, and GBR-12909 was found to be a potent competitive inhibitor (Ki approximately 100 nM) of sparteine monooxygenase activity in human liver microsomes. These data clearly indicate that [3H]GBR-12935 and its analogs display similar affinities for both the dopamine transporter and neuronal P45OIID1, and that this radioligand may be a useful probe of P45OIID1 activity in brain and liver. The exact molecular and functional association (if any) between these two distinct binding protein populations remains to be established; however, it is tempting to speculate that P45OIID1 is involved in the catabolism and processing of neurotransmitters subsequent to their reuptake into target cells.


Symptom burden trajectories experienced by patients with brain tumors.
Survivors of childhood brain tumors experience persistent health concerns across their lifespan. In the current study, the authors evaluated changes in symptom burden over the course of 12 months using pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Data from 202 survivors aged 8 to 21 years and 262 parents of survivors who were aged 5 to 21 years were analyzed. All completed a PROMIS Cognition short form and computerized adaptive tests of pediatric Anxiety, Depressive Symptoms, Fatigue, Mobility, Upper Extremity Function, and Peer Relationships. Approximately one-half of participants (223 participants: 97 survivors of childhood brain tumors and 126 parents) completed the 12-month follow-up. Linear mixed-effects models evaluated group-level symptoms over time. Cox proportional hazard models explored whether symptoms predicted survival, and latent class growth analysis investigated patterns of individual-level symptom changes over time. Linear mixed-effects models demonstrated that patient-reported Cognition and parent-reported Anxiety worsened over time. Latent class growth analysis results indicated that patient and parent reports diverged, both with regard to the number of classes identified and in the trends of these classes. Parents and patients reported similar patterns of depression over time. For the other areas, parents either were more likely to observe different patterns (Peer Relationships and Mobility) or less likely to observe different patterns (Upper Extremity Function, Cognition, Anxiety, and Fatigue). Baseline patient-reported Mobility and Upper Extremity Function were found to be associated with survival. Survivors of childhood brain tumors demonstrated different trajectory patterns of symptom burden. Along with baseline functioning status and days since treatment, patient-reported Mobility and Upper Extremity Function were associated with survival, suggesting a possible role for patient-reported outcomes in clinical care, especially individualized, tailored assessments such as PROMIS.


Comparative studies on potential of consortium and constituent pure bacterial isolates to decolorize azo dyes.
The decolorization potential of the consortium HM-4 constituted by mixing four laboratory isolates identified as Bacillus cereus (BN-7), Pseudomonas putida (BN-4), Pseudomonas fluorescens (BN-5) and Stenotrophomonas acidaminiphila (BN-3) was compared with that of individual isolates. Six different azo dyes viz., C.I. Acid Red 88 (AR-88), C.I. Acid Red 119 (AR-119), C.I. Acid Red 97 (AR-97), C.I. Reactive Red 120 (RR-120), C.I. Acid Blue 113 (AB-113) and C.I. Acid Brown 100 (AB-100) were used in this study. The individual bacterial isolates were not able to completely decolorize these dyes, except for dyes AR-119 and AB-113. The consortium HM-4 was able to decolorize all the dyes used at an initial dye concentration of 20 mg L(-1) at a significantly higher rate as compared to that achieved by individual isolates.


One step functional assembly of guanosine monophosphate and terbium ion on metal organic frameworks for determination of alkaline phosphatase activity.
Since the abnormal changes of alkaline phosphatase (ALP) content may indicate the occurrence of some diseases, the detection of ALP activity is of great significance in human health monitoring. In this work, the luminescent probe (His@ZIF-8-Tb-GMP) was synthesized by self-assembly of guanosine monophosphate (GMP) and terbium ions with l-Histidine (His) functionalized zeolite imidazole framework ZIF-8 (His@ZIF-8) by one-step method. The abundant amino and carboxyl groups on His@ZIF-8 can be used to capture Tb3+ ions, which increases the load capacity of terbium ions and further enhances its luminescence signals. GMP is the antenna sensitizing ligand of terbium ion and the recognition unit of ALP detection. Dephosphorization of alkaline phosphatase prevents the energy transfer from GMP to terbium ion, which leads to the fluorescence quenching of the probe. Based on the above detection mechanism, a fluorescence sensing platform triggered by cutting off the energy transfer path was developed for the quantitative determination of ALP. Significantly, this sensor possesses ultra-sensitivity and high selectivity in the determination of alkaline phosphatase, whose detection limit is 0.0006 U/L. The successful application of the sensor in serum also shows that the sensor has a good practical application prospect.


Fenestrated Endovascular Repair for Pararenal or Juxtarenal Abdominal Aortic Aneurysms: a Systematic Review.
This review aims to collect all available data on early and late outcomes in patients undergoing fenestrated endovascular aortic aneurysm repair (F-EVAR) for pararenal or juxtarenal abdominal aortic aneurysms (AAAs). The Pubmed, Embase, Scopus and Cochrane Library databases were systematically searched to identify eligible studies. Studies reporting at least early mortality after F-EVAR in patients with pararenal or juxtarenal AAA were included. Thirty-day outcomes were defined as early, and outcomes reported after 30 days postoperatively were defined as late. Basic characteristics of all studies and demographics of patients were reported. Overall, 30 studies (17 retrospective and 13 prospective) including 23,385 patients in total were included. Out of 23,385 patients, a total of 2,271 patients were treated with F-EVAR for pararenal/juxtarenal AAA. Overall, 4,216 target vessels were to be treated (data from 24 studies). Pooled early mortality reached 2.55% (ranging from 0% to 6.74%), with a pooled technical success of 96.8% (ranging from 82.8% to 100%). Regarding late outcomes, pooled all-cause mortality reached 17% (ranging from 0% to 50%), 1-year primary patency was 94.6% (ranging from 91.8% to 97.1%) and reintervention rate was 10.4% (ranging from 0% to 57.4%). Mean/median follow-up ranged from 3 to 60 months. Early outcomes indicate that F-EVAR is a safe and efficient treatment for patients with pararenal/juxtarenal AAAs. Although long-term outcomes are acceptable, late-intervention rate remains high.


New light on disordered ensembles: ab initio structure determination of one particle from scattering fluctuations of many copies.
We report on the first experimental ab initio reconstruction of an image of a single particle from fluctuations in the scattering from an ensemble of copies, randomly oriented about an axis. The method is applicable to identical particles frozen in space or time (as by snapshot diffraction from an x-ray free electron laser). These fluctuations enhance information obtainable from an experiment such as conventional small angle x-ray scattering.


Atropine 0.01% Eye Drops for Myopia Control in American Children: A Multiethnic Sample Across Three US Sites.
Topical atropine eye drops at low concentrations have been shown to slow myopia progression in East Asian studies. This study explored the effect of atropine 0.01% eye drops on controlling myopia progression in a multiethnic cohort of children in the USA. A multicenter retrospective case-control study (n = 198) quantified the effect of adding nightly atropine 0.01% eye drops to treatment as usual on the progression of childhood (ages 6-15 years) myopia. Cases included all children treated with atropine for at least 1 year. Controls were matched to cases on both age (± 6 months) and baseline spherical equivalent refraction (SER) (± 0.50 diopters, D) at treatment initiation. The primary endpoint was the average SER myopia progression after 1, 1.5, and 2 years of therapy. A secondary outcome was the percentage of subjects with a clinically significant worsening of myopia, defined as a greater than - 0.75 D SER increase in myopia. The average baseline SERs for the atropine (n = 100) and control (n = 98) groups were similar (- 3.1 ± 1.9 D and - 2.8 ± 1.6 D, respectively) (p = 0.23). The average SER increase from baseline was significantly less for the atropine group than the control group at year 1 (- 0.2 ± 0.8 D compared with - 0.6 ± 0.4 D, p < 0.001) and at year 2 (- 0.3 ± 1.1 D compared with - 1.2 ± 0.7 D, p < 0.001). Secondary analysis at year 2 revealed that 80% of the control group vs. 37% of the atropine group experienced clinically significant worsening myopia of at least - 0.75 D (p < 0.001). There were no major safety issues reported in either group. Similar to results reported in Asia, atropine 0.01% eye drops significantly reduced myopia progression in a cohort of US children over 2 years of treatment. Nevakar, Inc. Plain language summary available for this article.


[Science and development : the action of François Gros at COPED].
This article is a tribute to the action of François Gros within the COPED (Committee of Developing Countries) which he created in 1997 and led until 2017. The COPED aims to reflect on the major scientific problems posed to developing countries and to try to provide them with solutions in partnership with them. Its actions have resulted in the organization of mini-forums, workshops, international symposia and reports for governments and authorities. Without being exhaustive, a number of actions carried out by François Gros or on his initiative are described in fields as diverse as health, chemistry, agronomy, energy, applied mathematics, renewable resources management and biodiversity, or education, training and the role of women in the sustainable development of African societies. The diversity of these concerns is a good illustration of the range of areas in which François Gros saw a possible impact of science in the service of development.


[Optimization of the detection, diagnosis, and prevention of advanced forms of pulmonary tuberculosis].
A rise in the number of patients with disseminated and advanced forms of tuberculosis becomes a great problem in phthisiology. The quality of tuberculosis control depends on the organization of examination of patients with the suspected tuberculosis etiology of the disease. Thus, the authors propose to optimize both general and addressing tuberculosis controlling measures, which include among them to improve general practitioners' qualification as the latter largely determines the efficiency and timeliness of verification of a tuberculous process.


[A low-frequency alternating magnetic field and its combination with radon baths in juvenile rheumatoid arthritis].
Children suffering from juvenile rheumatoid arthritis (JRA) (n-132) were exposed to low-frequency variable magnetic field. Therapeutic response registered consisted of analgetic and anti-inflammatory effects most pronounced in 14-19 mT regimen. The addition of radon baths to the above exposure resulted in higher effectiveness of the treatment due to involvement of pathogenetic JRA mechanisms.


Environment and host species identity shape gut microbiota diversity in sympatric herbivorous mammals.
The previous studies have reported that the mammalian gut microbiota is a physiological consequence; nonetheless, the factors influencing its composition and function remain unclear. In this study, to evaluate the contributions of the host and environment to the gut microbiota, we conducted a sequencing analysis of 16S rDNA and shotgun metagenomic DNA from plateau pikas and yaks, two sympatric herbivorous mammals, and further compared the sequences in summer and winter. The results revealed that both pikas and yaks harboured considerably more distinct communities between summer and winter. We detected the over-representation of Verrucomicrobia and Proteobacteria in pikas, and Archaea and Bacteroidetes in yaks. Firmicutes and Actinobacteria, associated with energy-efficient acquisition, significantly enriched in winter. The diversity of the microbial community was determined by the interactive effects between the host and season. Metagenomic analysis revealed that methane-metabolism-related pathway of yaks was significantly enriched in summer, while some pathogenic pathways were more abundant in pikas. Both pikas and yaks had a higher capacity for lipid degradation in winter. Pika and yak shared more OTUs when food shortage occurred in winter, and this caused a convergence in gut microbial composition and function. From winter to summer, the network module number increased from one to five in pikas, which was different in yaks. Our study demonstrates that the host is a dominant factor in shaping the microbial communities and that seasonality promotes divergence or convergence based on dietary quality across host species identity.


High phosphate content in bioactive glasses promotes osteogenesis in vitro and in vivo.
High phosphate content was found to significantly increase apatite formation of bioactive glasses (BGs) in vitro. However, there is very limited understanding of the effect of phosphate contents on osteogenesis which is important for clinical applications. The aims of this study were to investigate how phosphate content influences apatite formation ability of bioactive glasses in α-MEM culture medium and whether high phosphate content in bioactive glasses promotes osteogenesis in vitro and in vivo. Four phosphate containing bioactive glasses were synthesized via a melt-quench method and characterized using X-ray powder Diffraction (XRD), TGA-DSC and Fourier transform infra-red spectroscopy (FTIR). The apatite formation ability in α-MEM culture medium and the in vitro and in vivo osteogenic potential of these bioactive glass were explored. FTIR spectra confirmed faster apatite formation with an increase in phosphate content. The culture media containing ions released from the BGs showed enhanced cell viability and alkaline phosphatase activity of osteoblasts. Osteoblasts cultured with extracted BGs culture media generally showed increased proliferation, mineralized nodule formation, osteogenic and angiogenic genes expression with an increase in phosphate content in the glass compositions. An in vivo study demonstrated a larger amount of new bone formation in the calvarial defects implanted with high phosphate containing BG granules compared with that of BG without the presence of phosphate at 8 weeks post-surgery. The presence of higher phosphate content accelerates apatite formation and promotes osteogenesis, indicating that both apatite formation and osteogenesis of bioactive glasses can be tailored by varying phosphate content for specific clinical needs and personalized treatments.


Detection of antibiotic residues in calf tissues.
Groups of calves were injected with penicillin, ampicillin or oxytetracycline and a variety of samples were taken from the calves when slaughtered and tested for the presence of antibiotic residues by microbiological assay. Diaphragm and urine samples were found to be suitable for measuring detectable levels of antibiotics in calves given therapeutic injections.


[The presence of antibodies to IBR/IPV virus in cattle in the environs of Leyden (author's transl)].
The appearance of IBR among cattle in the environs of Leyden is reported. Possible explanations of local differences in the incidence of IBR and possible effects on IBR immunisation of cattle in these areas are referred to in the discussion.


Elbow loading promotes longitudinal bone growth of the ulna and the humerus.
Mechanical stimulation plays a critical role in bone development and growth. In view of recently recognized anabolic responses promoted by a joint-loading modality, we examined the effects of elbow loading on longitudinal growth of the ulna and the humerus. Using a custom-made piezoelectric loader, the left elbow of growing C57/BL/6 female mice was given daily 5-min bouts of dynamic loading for 10 days. The right forelimbs of those mice served as contralateral controls, and the limbs of non-treated mice were used as age-matched controls. The effects of elbow loading were evaluated through measurement of bone length, weight, bone mineral density (BMD), and bone mineral content (BMC), as well as mRNA expression levels of load-sensitive transcription factors such as c-fos, egr1, and atf3. The results revealed that the humerus was elongated by 1.2% compared to the contralateral and age-matched controls (both p < 0.001), while the ulna had become longer than the contralateral control (1.7%; p < 0.05) and the age-match control (3.4%; p < 0.001). Bone lengthening was associated with increases in bone weight, BMD and BMC. Furthermore, the mRNA levels of the selected transcription factors were elevated in the loaded ulna and humerus. Interestingly, the increase was observed not only at the elbow but also at the wrist and shoulder in the loaded limb. The present study demonstrates that joint loading is potentially useful for stimulating bone lengthening and treating limb length discrepancy.


Predicting Survival after Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis: Performance of the Myelofibrosis Transplant Scoring System (MTSS) and Development of a New Prognostic Model.
Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5-year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the low- and intermediate-risk groups, as well as the high- and very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P < .001). We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P < .001). In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF.


Ascorbic acid-mediated in situ growth of gold nanostars for photothermal immunoassay of ochratoxin A.
Currently, the development of efficient mycotoxins detection methods, particularly using portable devices as readout devices, remains a great challenge. Herein, a photothermal enzyme-linked immunosorbent assay (ELISA) based on gold nanostars (AuNSs) for the detection of ochratoxin A (OTA) using a "thermometer" was proposed for the first time. AuNSs with photothermal conversion capacity were parepared using an ascorbic acid (AA)-mediated in situ growth methd. Quantification was based on the alkaline phosphatase catalyzing the dephosphorylation of ascorbic acid 2-phosphoate to AA, thereby converting OTA concentration to the amount of in situ synthesized AuNSs, thus achieving straightforward readout by temperature. Benefiting from the classical tyramine signal amplification strategy, a detection limit of 0.39 ng mL-1 was obtained. The recoveries of grape juice and maize samples spiked with 10 ng mL-1 and 30 ng mL-1 OTA ranged from 86.53% to 116.9%. Our method has great potential in on-site OTA detection for food safety.


Study on the impact of green finance on low carbon development of manufacturing industry from the perspective of multidimensional space: evidence from China.
In order to test the impact of green finance on the low-carbon development level of China's manufacturing industry, this paper takes green finance as an explanatory variable, and chooses the level of fixed asset investment in the manufacturing industry, the intensity of environmental regulations, the proportion of environmental pollution control investment, and the proportion of R&D investment as four control variables. Empirical tests are carried out on the four dependent variables, including manufacturing industry's low-carbon development level, added value growth rate, industrial structure upgrading level, and environmental protection status. The test results show that green finance is positively correlated with the low-carbon development of the manufacturing industry and the growth rate of added value, and inversely correlated with industrial structure upgrading and environmental protection; green finance supports dependent variables in the following order: low-carbon development > environmental protection > economic growth > industrial structure. It can be seen that the main role of green finance is to promote low-carbon development and environmental protection, but it is not the best tool to promote the growth rate of manufacturing industry and upgrade the level of industrial structure. In addition, due to the spillover effect of green finance in the process of promoting the development of the manufacturing industry, it is necessary to increase green financial investment in a long-term and sustained manner to gradually promote the low-carbon and sustainable development of China's manufacturing industry.


A validated cold vapour-AAS method for determining mercury in human red blood cells.
A cold vapour-atomic absorption spectrometry (CV-AAS) method for determining mercury in dental students and clinical teaching staff red blood cells at a dental school using amalgam as a restorative material has been validated. A number of blood samples (n = 122) from dental students in years I to V, clinical teachers in restorative dentistry and controls were collected and analysed. Accuracy, linearity, precision (repeatability and reproducibility) and robustness of the method have been determined, and detection and quantification limits have been calculated. Linearity of response was verified for concentrations ranging from 5 to 40 microgL(-1) of mercury. Correlation coefficient of the calibration straight lines was always >/=0.99. Intra-day precision of the method gave coefficient of variation (CV) of 5.51%. Inter-day precision of the method calculated after analysis of five different concentrations of mercury standard solutions by the same analyst in different days and by two different analysts in different days gave coefficient of variation 4.89 and 5.44%, respectively. The accuracy of the method was calculated a CRM NIST 966 (toxic metals in bovine blood) total amount of mercury was found a concentration of 28.83 +/- 2.2 microgL(-1). Recovery was 89.27%. Robustness of the method evaluated by changing different experimental conditions under which analyses performed, fractional factorial design was done for assessing robustness of the method. Root mean square error was found out as 1.56. Limits of detection and quantification were 1.84 and 4.03 microg of Hg per litre of sample, respectively. Results show the suitability of the method for direct measurement of mercury in red blood cells and the importance of the working conditions for people dealing with amalgam at a dental school.


Potassium homeostasis and hyperkalemic syndromes.
Acute hyperkalemia can be a life-threatening consequence of a variety of pathologic, pharmacologic, and iatrogenic disorders. Recognition and prompt therapy often reverse the electrophysiologic complications within minutes. Therefore, physicians must have a thorough understanding of potassium homeostasis. The causes of hyperkalemia, intracellular-to-extracellular shifts of potassium, excess exogenous potassium loads, and pseudohyperkalemia are discussed.


Endothelial cells co-cultured with renal carcinoma cells significantly reduce RECK expression under chemical hypoxia.
Renal cell carcinoma (RCC) is characterized by excessive angiogenesis, while chronic kidney disease (CKD) suffers from the opposite problem-failure of reparative angiogenesis. It can be due to their different responses to hypoxic environment. But the specific molecular regulators are still unclear. This study is aimed to explore the influence of human renal cell cancer cells (786-0) and human renal tubular epithelial cells (HK-2) on RECK expression, proliferation, and angiogenesis of adjacent microvascular endothelial cells (HMEC-1) under chemical hypoxia. Cobalt chloride (CoCl2 ) treatment was used to simulate the hypoxia environment in RCC and CKD. Co-culture, cell proliferation assay, and tube formation assay were used to evaluate the influence of 786-0 or HK-2 cells on proliferation and angiogenesis of adjacent HMEC-1 cells. Effects of different environments on RECK expressions in 786-0, HK2, or HMEC-1 cells were determined by Western blot. We found that both 786-0 cells and HK2 cells can upregulate RECK expression of adjacent HMEC-1 cells in normoxic conditions. However, under hypoxia, the HMEC-1 cells co-cultured with 786-0 significantly reduced RECK expression and there was no significant change in HMEC-1 cells co-cultured with HK2 cells. We also found that 786-0 significantly enhanced the proliferation and angiogenesis of adjacent HMEC-1 cells. Our results suggested that some paracrine substances produced by 786-0 cells may reduce RECK expression of adjacent HMEC-1 cells and enhance their proliferation and in vitro angiogenic capacity.


Genetic analysis of growth traits in Muzaffarnagari sheep.
Data on 4112 Muzaffarnagari sheep, maintained at the Central Institute for Research on Goats, Makhdoom, Mathura, India, and recorded between 1976 and 1999, were analysed to study the growth-related traits and their genetic control. The average weights at birth, and at 12 months of age were 3.1 +/- 0.2 and 28.0 +/- 0.6 kg, respectively. The pre- and post-weaning average daily weight gains were 127.8 +/- 3.3 g and 49.4 +/- 1.6 g. and the associated growth efficiencies were 3.59 +/- 0.08 and 0.95 +/- 0.03. Significant differences associated with the year of lambing were observed in body weight, weight gain and efficiency in weight gain at different stages of growth. The lambs born in the dam's second parity were generally of heavier weight and higher daily weight gain than those born in other parities. Males were heavier and had a higher weight gain than females at almost all stages of growth and the differences tended to increase with age. Single-born lambs had a distinct advantage over those born in multiple births at all stages of growth. The heritabilities of all body weights, weight gains and efficiency in weight gains at different stages of growth were moderate (0.18-0.26), except for birth weight, which was of low heritability (0.068 +/- 0.01). The phenotypic and genetic correlations among the different body weights were positive and high, except for birth weight. The genetic correlation of the pre- and post-weaning average daily weight gains with body weights were high and positive.


Upper extremity weakness: A novel risk factor for non-cardiovascular mortality among community-dwelling older adults.
Aging-associated upper extremity weakness has been shown to be associated with adverse health outcomes in older adults, but less is known about the association between impaired upper extremity function and cause-specific mortalities. Among the 5512 prospective community-based longitudinal Cardiovascular Health Study participants, 1438 had difficulty with one of the three upper extremity functions of lifting, reaching, or gripping. We assembled a propensity score-matched cohort in which 1126 pairs of participants with and without difficulty with upper extremity function, balanced on 62 baseline characteristics including geriatric and functional variables such as physical and cognitive function. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortalities associated with upper extremity weakness were estimated in the matched cohort. Matched participants had a mean age of 73.1 years, 72.5% were women, and 17.0% African American. During 23 years of follow-up, all-cause mortality occurred in 83.7% (942/1126) and 81.2% (914/1126) of participants with and without upper extremity weakness, respectively (HR, 1.11; 95% CI, 1.01-1.22; p = 0.023). Upper extremity weakness was associated with a higher risk of non-cardiovascular mortality, occurring in 595 (52.8%) and 553 (49.1%) of participants, respectively (HR, 1.17; 95% CI, 1.04-1.31; p = 0.010), but had no association with cardiovascular mortality (30.8% vs 32.1% in those with and without upper extremity weakness, respectively; HR, 1.03; 95% CI, 0.89-1.19; p = 0.70). Among community-dwelling older adults, upper extremity weakness had a weak, albeit independent, significant association with all-cause mortality, which was primarily driven by a higher risk of non-cardiovascular mortality. Future studies need to replicate these findings and understand the underlying reasons for the observed associations.


A theoretical investigation of one-dimensional lithium-bonded chain: enhanced first hyperpolarizability and little red-shift.
We present a theoretical investigation of the electric properties of two kinds of one-dimensional lithium bonded chains: (NC-Li)n and (NC-CC-Li)n (n = 1-8). The resulting (NC-Li)n and (NC-CC-Li)n were found to exhibit enhanced first hyperpolarizabilities (β 0) with increasing n, and a slight change in the absorption maximum wavelength λmax at the crucial transition. Comparing with (NC-Li)n, (NC-CC-Li)n exhibited particularly drastically enhanced β 0 values due to clearly enhanced coupled oscillators and double-degenerated charge transitions. β 0 is known to be the microscopic origin of the second-order non-linear optical (NLO) property, and λmax is an approximate measure of the transparency achievable, thus both are important indices of high-performance NLO molecules. Therefore, our investigations into one-dimensional lithium bond chains will be beneficial to understanding the relationship between β 0 and λmax, thus aiding the design of one-dimensional NLO materials with excellent transparence-efficiency.


A peroperative comparison of Western and Oriental colonic anatomy and mesenteric attachments.
It has been suggested that the Oriental colon is easier to colonoscope than its Western counterpart. The aim of this study was to investigate possible differences in colonic anatomy between Western and Oriental patients that might explain this observation. Measurements of colonic length and mesenteric attachments were taken according to a set protocol from 115 Western (Caucasian) and 114 Oriental patients at laparotomy. Sigmoid adhesions were found more frequently in Western (17%) compared to Oriental (8%) patients, P = 0.047. A descending mesocolon of > or = 10 cm occurred in 10 (8%) Western patients but only 1 (0.9%) Oriental patient, P = 0.01. The splenic flexure was more frequently mobile in Western patients (20%) compared to Oriental (9%) patients, P = 0.016. In 29% - of Western patients the mid-transverse colon reached the symphysis pubis, or lower when pulled downwards in contrast to 10% of Oriental patients, P < 0.001. There was no significant difference in total colonic length comparing Western (median = 114 cm, range 68-159 cm) to Oriental (median = 111 cm, range 78-161 cm) patients. Western patients have a higher incidence of sigmoid colon adhesions and increased colonic mobility when compared to Orientals. These findings support the observation that colonoscopy is a more difficult procedure in Western patients.


Contact depigmentation from free para-tertiary-butylphenol in bindi adhesive.
100 consecutive cases of contact depigmentation due to bindi during a period of 11 months were studied. Bindi adhesive material was found to contain 80% para-tertiary-butylphenol (PTBP), by thin-layer chromatography, infrared spectrophotometry and high-pressure liquid chromatography. The possibility of hypersensitivity to PTBP was ruled out as none of the 15 patients tested with 2% PTBP and 1% para-tertiary-butylphenol-formaldehyde resin gave any positive reactions. Development of depigmentation could have been due either to individual susceptibility or to constant use for a prolonged period. The area of contact being very small, generalised vitiligo as a result of systemic absorption appeared to be a remote possibility.


An in vitro system for studying insulin release: effects of glucose and glucose-6-phosphate.
1. Investigation of the ionic requirements of the in vitro insulin release system, which consists of cod islet plasma membrane and rabbit islet granules incubated at pH 6.5, showed that the presence of Ca(2+) was obligatory for the system to operate.2. Glucose-initiated insulin release was as effective in the presence of beta-gamma-methylene ATP, as it was in the presence of ATP. This analogue of ATP is a substrate neither for adenylate cyclase nor for any known animal membrane proteases. The effect of ATP on glucose mediated release is allosteric.3. Glucose (16 mM)-initiated insulin release was slower than that induced by glucose-6-phosphate (4 mM); 150 and 120 sec, respectively.4. The lag found with glucose-mediated insulin release was dependent upon glucose concentration. The lower the glucose concentration, the longer the lag. With 1 mM glucose the lag extended to 30 min.5. Once insulin release was initiated, the rate and amount of insulin release was independent of the glucose concentration.6. Pre-incubation of membranes with Ca(2+), glucose and ATP prior to the addition of granules, abolished the extended lag that had been obtained with 1 mM glucose. Events in the plasma membrane are the major contributor to the generation of the extended lag.7. The glucose analogue 5'thio-D-glucose, although not able to release insulin, was shown to compete with glucose for the glucoreceptor. By increasing the ratio of analogue to glucose the lag time increased. Thus, the lag time is dependent upon the ;effective' external glucose concentration.8. The max. amount of insulin released by 4 ng of membrane in the presence of glucose (16 mM) was 300 ng. The fact that membranes became refractory to glucose after this max. amount of insulin was released showed that recycling of release sites was not taking place in vitro and that granule: granule interactions were not occurring.9. The 120 sec lag before glucose-6-phosphate-initiated release was independent of glucose-6-phosphate concentration. The rate of insulin release with glucose-6-phosphate was concentration dependent.10. Glucose-6-phosphate did not cause further insulin release from a membrane that had released the max. amount of insulin it was capable of in the presence of glucose. The addition of tolbutamide (10 mM) to such a membrane did cause insulin release. This suggests that glucose and glucose-6-phosphate share a final common pathway.11. Adrenaline and somatostatin did not inhibit glucose-mediated insulin release.


Teriyaki sauce with carvacrol or thymol effectively controls Escherichia coli O157:H7, Listeria monocytogenes, Salmonella Typhimurium, and indigenous flora in marinated beef and marinade.
An effective bactericidal cold-marinating method for beef products is described, exploiting the synergism between soy sauce and natural compounds (carvacrol, CV or thymol, TM) to reduce microbiological risks. Beef slices inoculated with Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella Typhimurium (3.1-3.5logCFU/g) were marinated in a teriyaki sauce with or without CV and TM (0.3 and 0.5%). After 1, 3, and 7days at 4°C, indigenous microflora population, color, lipid oxidation, marinade uptake, and pH of marinated beef and leftover marinade samples were examined. Teriyaki sauce alone did not reduce or inhibit any of the target pathogens or indigenous bacteria, while 0.5% CV- or TM-containing teriyaki sauce inactivated all inocula without recovery within 7days (p<0.05). The pathogens relocated from the beef into the leftover marinade (3.0-3.4logCFU/mL) were also completely inactivated. The treatment inhibited growth of indigenous aerobic bacteria (p<0.05) and inactivated coliform bacteria. Physicochemical parameters were not significantly affected (p>0.05).


Mitigating soil salinity stress with titanium gypsum and biochar composite materials: Improvement effects and mechanism.
Titanium gypsum and biochar are considered effective amendments for mitigating soil salinity stress. However, the knowledge is inadequate regarding their efficiency and application as an improvement. In this study, TG-B composite was prepared by using industrial by-products titanium gypsum and biochar as raw materials and then modified by ball milling method, to characterize its microscopic characteristics and explore the improvement effect on saline-alkali soil and plant growth. Besides, we explored the mechanism of TG-B in improving saline-alkali soil and the dynamic balance of the solution reaction process. Our results showed that the CaSO4·2H2O particles in TG-B were finer, dispersed evenly, and contacted fully with soil gelatinous particles, which was more conducive to the improvement of saline-alkali soil. The results of TG-B with different ball milling ratios and different materials dosages indicated that the application rate of TG-B was 5%, and the optimum ratio of TG-B was TG: B (mass ratio) = 10:1, with the best soil improvement effect. The pot experiment proved that the indicators of indicating soil salinity such as pH, EC, SAR, and soluble Na+ decreased by 20.74%, 77.24%, 68.77%, and 44.70%, respectively, thus playing a good role in improving saline-alkali soil. In addition, pot experiments demonstrated that compared with the control group, the soil porosity and soil moisture content in the TG-B group increased by 15.95% and 38.71%, respectively, and further improve the structure and diversity of soil bacterial community when compared with titanium gypsum and biochar alone. Finally, the application of TG-B promoted the germination and growth of rice significantly through the synergistic effects of composite material components. These results all suggested that the application of TG-B was an effective strategy to improve soil salinity and promote plant growth. Therefore, it might provide new insights into the utilization of solid waste resources to improve saline-alkali lands.


Effect of Prophylactic Intrathecal Pethidine on the Incidence of Shivering on Mothers Undergoing Cesarean Section Under Spinal Anesthesia: A Randomized Controlled Trial.
Shivering is the most common and unpleasant complication of anesthesia with an incidence of 70.7% in cesarean section done under spinal anesthesia which is associated with cardiovascular and respiratory complications. Even though it causes such devastating complications; the prevention of shivering is not well investigated. This study aimed to assess the effect of intrathecal pethidine on the incidence and severity of shivering in patients undergoing cesarean section under Spinal anesthesia. After obtaining ethical clearance double-blinded single centered a randomized controlled trial was conducted in a total of 86 pregnant mothers who were randomly allocated into two groups by computer-generated random number. Approximately 1 ml of 10 mg preservative-free pethidine was added to 12.5 mg of 0.5% bupivacaine for spinal anesthesia in the treatment group and 12.5 mg of 0.5% bupivacaine alone was given in the control group. Incidence and severity of shivering, as well as adverse effect was recorded intraoperatively, in post-anesthesia care unit (PACU) and ward. Independent sample t-test, Mann-Whitney U test and chi-square were used for analysis. A p-value less than 0.05 was considered statistically significant. Shivering was observed in 53.5 and 20.9% in the control and treatment groups, respectively, which was statistically significant with p = 0.002. The risk of developing shivering was reduced by 61% in the treatment group with (RR = 0.39 and CI of 0.205-0.745); the intensity of shivering was also higher in the control group than in the treatment group with p = 0.004. Considering an adverse effect, the incidence of PONV was not significantly different between with p > 0.05 while the incidence of pruritus was higher in the treatment group than the control group with p = 0.003. Adding 10 mg of preservative free pethidine intrathecally during spinal anesthesia is effective in reducing incidence and severity of shivering, without causing significant adverse effects on mother.


Implications for prenatal cadmium exposure and adverse health outcomes in adulthood.
Cadmium is a ubiquitous, non-essential metal that has earned a spot on the World Health Organizations top 10 chemicals of major public health concern. The mechanisms of cadmium-induced adverse health outcomes, such as cardiovascular disease, renal toxicity and cancer, are well studied in adults. However, the implications for early life exposures to low-level cadmium leading to increased risk of developing diseases in adulthood remains elusive. Epidemiological investigation of the long term implications of cadmium-associated adverse birth outcomes are limited and studies do not extend into adulthood. This review will summarize the literature on the non-lethal, adverse health effects associated with prenatal and early life exposure to cadmium and the implications of these exposures in the development of diseases later in life. In addition, this review will highlight possible mechanisms responsible for these outcomes as well as address the inconsistencies in the literature. More recent studies have addressed sex as a biological variable, showing prenatal cadmium exposure elicits sex-specific outcomes that would otherwise be masked by pooling male and female data. Furthermore, researchers have begun to investigate the role of prenatal and early life cadmium exposures in the development of diet-induced diseases with evidence of altered essential metal homeostasis as a likely mechanism for cadmium-enhanced, diet-induced diseases. Although novel experimental models are beginning to be established to study the association between prenatal cadmium exposure and adverse health outcomes in adulthood, the studies are few, highlighting a major need for further investigation.


Unpacking the post-Haiyan disaster resettlement narratives of young Filipino women informal settlers in Tacloban City, Philippines.
Post-disaster resettlement narratives encapsulate the complex mobile-spatial processes that are embedded in a post-disaster context. The existing literature on disaster relocation and resettlement accords primacy to the logistical, practical, structural, and physical dimensions of residential transitioning. Building on this knowledge, this study conducted a spatial narrative inquiry to generate a link to mobile-spatial realities interspersed in diverse temporal trajectories. It did so by tracking the embodied rhythms of people and objects evoked through the retelling of post-disaster resettlement stories by 12 young Filipino women informal settlers. The key findings are organised in three spatial narratives: 'house near the sea'; 'there at the bunkhouse'; and 'here in Ridgeview'. These narratives are anchored in the overarching dimensions that underpin Filipino informal settlers' experiences of (not) moving in and out of disaster resettlement areas. Lastly, the findings are explained in the light of the theoretical, empirical, and practical implications of disaster resettlement specific to informal settlers.


Comparative inactivation of yeast fatty acid synthetase component enzymes by 100 atmospheres of oxygen.
Yeast fatty acid synthetase at 4 degrees C was stable during 1- and 2-h exposures to oxygen at 100 atm, but was 48% and 90% inactivated after 20 h and 40 h, respectively, with fatty acid synthesis measured by both radioactive and optical assays. Incubation with dithiothreitol did not restore activity. Component enzyme activities were compared before and after 40 h in 100 atm of oxygen. Ketoacyl reductase activity was most reduced followed by ketoacyl synthetase and then acetyl transferase while malonyl transferase, enoyl reductase and palmitoyl transferase were not significantly inactivated.


Collapse following gastrointestinal bleeding secondary to a congenital duodenal diverticulum in two littermate boxer pups.
Two littermates, a young male and female boxer, were admitted to the Utrecht University's Department of Clinical Sciences of Companion Animals within a three month period. Both dogs suffered from anaemia caused by chronic intestinal blood loss, vomiting and weight loss. In both cases, there was no response to conservative medical management. Eventually, the dogs suffered significant gastrointestinal haemorrhage that resulted in collapse. Gastroduodenoscopy and exploratory surgery showed a duodenal diverticulum in both dogs. This is the first report that describes this congenital anomaly in two siblings.


Negative regulation by proBDNF signaling of peripheral neurogenesis in the sensory ganglia of adult rats.
Neurogenesis in the adult brain is well recognized and plays a critical role in the maintenance of brain function and homeostasis. However, whether neurogenesis also occurs in the adult peripheral nervous system remains unknown. Here, using sensory ganglia (dorsal root ganglia, DRGs) as a model, we show that neurogenesis also occurs in the peripheral nervous system, but in a manner different from that in the central nervous system. Satellite glial cells (SGCs) express the neuronal precursor markers Nestin, POU domain, class 4, transcription factor 1, and p75 pan-neurotrophin receptor. Following sciatic nerve injury, the suppression of endogenous proBDNF by proBDNF antibodies resulted in the transformation of proliferating SGCs into doublecortin-positive cells in the DRGs. Using purified SGCs migrating out from the DRGs, the inhibition of endogenous proBDNF promoted the conversion of SGCs into neuronal phenotypes in vitro. Our findings suggest that SGCs are neuronal precursors, and that proBDNF maintains the SGC phenotype. Furthermore, the suppression of proBDNF signaling is necessary for neuronal phenotype acquisition by SGCs. Thus, we propose that peripheral neurogenesis may occur via the direct conversion of SGCs into neurons, and that this process is negatively regulated by proBDNF.


Reconstruction of the electrocardiogram during heart surgery.
Electrocardiograms (ECG) recorded during arrhythmia surgery are used for identification of arrhythmias of different morphology. However, the interpretation of an intraoperative ECG is difficult because some leads cannot be recorded and the signals of the remaining leads often differ from those of a preoperative recording because of the sternotomy. Therefore, a method for reconstruction of a complete intraoperative ECG, which resembles a preoperatively recorded ECG, was studied in 24 patients undergoing heart surgery. The reconstruction method involves calculating coefficients for a transformation matrix, using a preoperative ECG recording and a first intraoperative ECG recording. Once this matrix has been established, further intraoperative recordings can be transformed into an ECG which strongly resembles a preoperative ECG. The correlation between reconstructed intraoperative leads and the corresponding preoperative leads was high in the leads Vx and Vy (median correlation coefficient 0.98 and 0.97) and slightly smaller in lead Vz (0.94). Further studies will prove if the method can be useful in arrhythmia surgery.


Does human toxoplasmosis involve an imbalance in T1/T2 cytokines?
The T1 (interferon-gamma, interleukin-12, interleukin-2) and T2 (interleukin-4, interleukin-10, interleukin-6) cytokine groups constitute two polar responses of the immune system. The T1 group is a predominantly cellular response, while the T2 group response is mainly humoral. The hypothesis forwarded here links these subgroups of induced cytokines to the various clinical forms of human toxoplasmosis. Ocular toxoplasmosis in immunocompetent patients could be attributed to a T1 hyper-response, whereas congenital toxoplasmosis, toxoplasmic encephalitis (in immunodeficient patients) and active chronic toxoplasmosis (with persistent lymphadenophathy) would be characterized by a predominantly T2 response. Confirmation that this kind of immunological imbalance effectively underlies the various clinical forms of toxoplasmosis would open the way for a new range of treatments based on immunomodulation.


Long-term association between urban air ventilation and mortality in Hong Kong.
While associations between population health outcomes and some urban design characteristics, such as green space, urban heat islands (UHI), and walkability, have been well studied, no prior studies have examined the association of urban air ventilation and health outcomes. This study used data from Hong Kong, a densely populated city, to explore the association between urban air ventilation and mortality during 2008-2014. Frontal area density (FAD), was used to measure urban ventilation, with higher FAD indicating poorer ventilation, due to structures blocking wind penetration. Negative binomial regression models were constructed to regress mortality counts for each 5-year age group, gender, and small area group, on small area level variables including green space density, population density and socioeconomic indicators. An interquartile range increase in FAD was significantly associated with a 10% (95% confidence interval (CI) 2%-19%, p = 0.019) increase in all-cause mortality and a 21% (95% CI: 2%-45%, p = 0.030) increase in asthma mortality, and non-significantly associated with a 9% (95% CI: 1%-19%, p = 0.073) in cardio-respiratory mortality. Better urban ventilation can help disperse vehicle-related pollutants and allow moderation of UHIs, and for a coastal city may allow moderation of cold temperatures. Urban planning should take ventilation into account. Further studies on urban ventilation and health outcomes from different settings are needed.


A general framework for predicting delayed responses of ecological communities to habitat loss.
Although biodiversity crisis at different spatial scales has been well recognised, the phenomena of extinction debt and immigration credit at a crossing-scale context are, at best, unclear. Based on two community patterns, regional species abundance distribution (SAD) and spatial abundance distribution (SAAD), Kitzes and Harte (2015) presented a macroecological framework for predicting post-disturbance delayed extinction patterns in the entire ecological community. In this study, we further expand this basic framework to predict diverse time-lagged effects of habitat destruction on local communities. Specifically, our generalisation of KH's model could address the questions that could not be answered previously: (1) How many species are subjected to delayed extinction in a local community when habitat is destructed in other areas? (2) How do rare or endemic species contribute to extinction debt or immigration credit of the local community? (3) How will species differ between two local areas? From the demonstrations using two SAD models (single-parameter lognormal and logseries), the predicted patterns of the debt, credit, and change in the fraction of unique species can vary, but with consistencies and depending on several factors. The general framework deepens the understanding of the theoretical effects of habitat loss on community dynamic patterns in local samples.


The global economic burden of health anxiety/hypochondriasis- a systematic review.
Recent studies have shown a lifetime prevalence of 5.7% for health anxiety/hypochondriasis resulting in increased healthcare service utilisation and disability as consequences. To the best of our knowledge, there has been no systematic review examining the global costs of hypochondriasis, encompassing both direct and indirect costs. Our objective was to synthesize the available evidence on the economic burden of health anxiety and hypochondriasis to identify research gaps and provide guidance and insights for policymakers and future research. A systematic literature search was conducted using PubMed, Web of Science, PsycInfo, EconLit, IBSS and Google Scholar without any time limit, up until April 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this search and the following article selection process. The included studies were systematically analysed and summarized using a predefined data extraction sheet. Of the 3044 articles identified; 10 publications met our inclusion criteria. The results displayed significant variance in the overall costs listed among the studies. The reported economic burden of hypochondriasis ranged from 857.19 to 21137.55 US$ per capita per year. Most of the investigated costs were direct costs, whereas the assessment of indirect costs was strongly underrepresented. This systematic review suggests that existing studies underestimate the costs of hypochondriasis due to missing information on indirect costs. Furthermore, there is no uniform data collection of the costs and definition of the disease, so that the few existing data are not comparable and difficult to evaluate. There is a need for standardised data collection and definition of hypochondriasis in future studies to identify major cost drivers as potential target point for interventions.


Dysregulation of exosomal miR-192 and miR-194 expression in lung adenocarcinoma patients.
Non-small cell lung cancer (NSCLC) is the main reason of cancer linked mortality and around 80% of cases diagnosed in advanced stage. Therefore current study designed to evaluate the deregulation of miRNA-194 and miRNA-192 in different body fluid of Non small cell lung cancer participants. Present study recruited newly diagnosed histopathologically confirmed. It was observed that the 40% NSCLC participants showed elevated miR-194 expression and 60% NSCLC participants showed reduced miR-194 expression in serum sample while in Bronchial wash, only 20% NSCLC participants showed elevated miR-194 expression while 80% showed reduced miR-194 expression (p = 0.003). It was found that the 54% NSCLC participants showed elevated miR-192 expression and 55% NSCLC participants showed reduced miR-192 expression in serum sample while In Bronchial wash sample, only 25% NSCLC participants showed high miR-192 expression while 75% showed low miR-192 expression (P = 0.0004). Expression of miR-194 was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.0009, p = 0.0005) among serum sample and bronchial wash sample. Same observation was found with expression of miR-192 and it was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.006, p = 0.001) among serum sample and bronchial wash sample. It was observed that the NSCLC participants who had high serum based miR-194 expression showed 22 months of overall median survival while low expression of serum based miR-194 expression showed 18 months of overall median survival. Present study suggests that decreased expression of miR-194 and miR-192 was significantly associated with different clinical features of NSCLC cases. However, significantly higher number of NSCLC cases showed low expression of miR-194 and miR-192 in bronchial lavage sample. Decreased poor overall survival was found to be associated with bronchial wash sample with respect to low miR-194 and miR-192 expression while NSCLC participants showed better overall survival with high miR-194 and miR-192 expression. This suggested decreased expression of miR-192 and miR-194 expression could be the potential prognostic marker among NSCLC participants.


Transforming growth factor-beta 1 increases lysyl oxidase enzyme activity and mRNA in rat aortic smooth muscle cells.
This investigation was designed to test the hypothesis that transforming growth factor-beta 1 (TGF-beta 1) regulates lysyl oxidase secretion from vascular smooth muscle cells. Lysyl oxidase is an enzyme that catalyzes an essential step in collagen and elastin cross-linking in the extracellular matrix, and TGF-beta 1 has been implicated in the pathogenesis of restenosis after vascular injury. The effect of TGF-beta 1 on lysyl oxidase in vascular smooth muscle cells has not been previously defined. Rat aortic smooth muscle cells were grown in culture to confluence. Cells in passage 2 to 6 were incubated for 24 hours in media containing 0.1, 0.5, 1.0, or 10.0 ng/ml of TGF-beta 1. Lysyl oxidase activity in the media was quantitated with a tritium-release bioassay against an insoluble 3H-labeled aortic clastin substrate. Northern blot analyses were performed to determine steady-state levels of lysyl oxidase mRNA in the smooth muscle cells. Lysyl oxidase activity in the media increased 1.5-fold above control levels after exposure to 10 ng/ml of TGF-beta 1 (p < 0.01). This increase in lysyl oxidase activity was associated with a concentration-dependent increase in steady-state levels of lysyl oxidase mRNA, being 4.3- and 6.2-fold above control levels after exposure to 1 and 10 ng/ml TGF-beta 1, respectively (p < 0.01). The observed increase in steady-state lysyl oxidase mRNA after exposure to TGF-beta 1 was also time-dependent over the 24-hour experimental period. TGF-beta 1 appears to regulate lysyl oxidase in cultured rat aortic smooth muscle cells. Increases in lysyl oxidase activity may be one of the mechanisms by which TGF-beta 1 contributes to arterial restenosis after vascular injury.


Exposure of game birds to ochratoxin A through supplemental feeds.
Thirty randomly selected game bird feeders were sampled at 25-33-day intervals from November 1996 to March 1997 to quantitate ochratoxin A concentrations in supplemental feed. Monthly mean ochratoxin A concentration of grain in feeders was 8.3 +/- 0.8 ppb (n = 167). Ochratoxin A concentrations from individual feeders ranged from <5 to 109.9 ppb, levels that have not been demonstrated to negatively affect game birds in a laboratory environment. Stress may increase the chance of ochratoxin-induced mortality or morbidity for wild game birds. Only mean relative humidity was significantly correlated with monthly mean ochratoxin A concentration.


Objective sleep duration and response to combined pharmacotherapy and cognitive behavioral insomnia therapy among patients with comorbid depression and insomnia: a report from the TRIAD study.
Several studies have shown that patients with short sleep duration show a poor response to cognitive behavioral therapy for insomnia (CBT-I), but such studies have not included patients with comorbid conditions. The current study was conducted to determine whether pretreatment sleep duration moderates the response of patients with major depression and insomnia disorders to a combined CBT-I and antidepressant medication treatment. This study comprised a secondary analysis of a larger randomized trial that tested combined CBT-I/antidepressant medication treatment of patients with major depression and insomnia. Participants (n = 99; 70 women; Mage = 47.712.4 years) completed pretreatment polysomnography and then were randomly assigned to a 12-week treatment with antidepressant medication combined with CBT-I or a sham therapy. Short and longer sleepers were defined using total sleep time cutoffs of < 5, < 6, and < 7 hours for short sleep. Insomnia and depression remission ascertained respectively from the Insomnia Severity Index and Hamilton Rating Scale for Depression were used to compare treatment responses of short and longer sleepers defined by the cutoffs mentioned. Logistic regression analyses showed that statistically significant results were obtained only when the cutoff of < 5 hours of sleep was used to define "short sleep." Both the CBT-I recipients with < 5 hours of sleep (odds ratio = 0.053; 95% confidence interval = 0.006-0.499) and the sham-therapy group with ≥ 5 hours of sleep (odds ratio = 0.149; 95% confidence interval = 0.045-0.493) were significantly less likely to achieve insomnia remission than were CBT-I recipients with ≥ 5 hours of sleep. The shorter sleeping CBT-I group (odds ratio = 0.118; 95% confidence interval = 0.020-0.714) and longer sleeping sham-therapy group (odds ratio = 0.321; 95% confidence interval = 0.105-0.983) were also less likely to achieve insomnia and/or depression remission than was the longer sleeping CBT-I group with ≥ 5 hours of sleep. Sleeping < 5 hours may dispose comorbid major depression/insomnia patients to a poor response to combined CBT-I/medication treatments for their insomnia and depression. Future studies to replicate these findings and explore mechanisms of treatment response seem warranted. Registry: ClinicalTrials.gov; Name: Treatment of Insomnia and Depression (TRIAD); URL: https://clinicaltrials.gov/ct2/show/results/NCT00767624; Identifier: NCT00767624. Edinger JD, Smith ED, Buysse DJ, et al. Objective sleep duration and response to combined pharmacotherapy and cognitive behavioral insomnia therapy among patients with comorbid depression and insomnia: a report from the TRIAD study. J Clin Sleep Med. 2023;19(6):1111-1120.


Spotlights on advances in mycotoxin research.
A remarkable feature of filamentous fungi is their ability to produce small yet structurally complex and often bioactive natural products. In this mini-review, we cover advances in the research on fungal secondary metabolites, particularly mycotoxins, and focus on biosynthetic aspects as well as on the complex regulatory mechanisms which control the expression of biosynthetic genes. We also highlight the increasing impact of genomics and transcriptomics, which help explore the realm of secondary metabolism of fungi.


Human medial olivocochlear reflex: effects as functions of contralateral, ipsilateral, and bilateral elicitor bandwidths.
Animal studies have led to the view that the acoustic medial olivocochlear (MOC) efferent reflex provides sharply tuned frequency-specific feedback that inhibits cochlear amplification. To determine if MOC activation is indeed narrow band, we measured the MOC effects in humans elicited by 60-dB sound pressure level (SPL) contralateral, ipsilateral, and bilateral noise bands as a function of noise bandwidth from 1/2 to 6.7 octaves. MOC effects were quantified by the change in stimulus frequency otoacoustic emissions from 40 dB SPL probe tones near 0.5, 1, and 4 kHz. In a second experiment, the noise bands were centered 2 octaves below probe frequencies near 1 and 4 kHz. In all cases, the MOC effects increased as elicitor bandwidth increased, with the effect saturating at about 4 octaves. Generally, the MOC effects increased as the probe frequency decreased, opposite expectations based on MOC innervation density in the cochlea. Bilateral-elicitor effects were always the largest. The ratio of ipsilateral/contralateral effects depended on elicitor bandwidth; the ratio was large for narrow-band probe-centered elicitors and approximately unity for wide-band elicitors. In another experiment, the MOC effects from increasing elicitor bandwidths were calculated from measurements of the MOC effects from adjacent half-octave noise bands. The predicted bandwidth function agreed well with the measured bandwidth function for contralateral elicitors, but overestimated it for ipsilateral and bilateral elicitors. Overall, the results indicate that (1) the MOC reflexes integrate excitation from almost the entire cochlear length, (2) as elicitor bandwidth is increased, the excitation from newly stimulated cochlear regions more than overcomes the reduced excitation at frequencies in the center of the elicitor band, and (3) contralateral, ipsilateral, and bilateral elicitors show MOC reflex spatial summation over most of the cochlea, but ipsilateral spatial summation is less additive than contralateral.


[Electronic patient records and teleophthalmology. Part 2: concrete projects in ophthalmology].
Electronic storage of patient-related data will replace paper-based patient records in the near future. Because of the high visualization needed in ophthalmology integrated electronic data storage and usage will be very useful. Chronic diseases like glaucoma, macular degeneration and diabetic retinopathy would benefit from long-term data storage and analysis. Unfortunately there are nearly no widely accepted systems available providing these options. Another important point is the simplification of existing diagnostic procedures and nomenclature on an international level. Increasing mobility of patients requires a better portability of existing medical examination data between different physicians. This is the only way to provide continuously high levels of quality in patient care and to simultaneously reduce costs and prevent unnecessary secondary examinations.


Selenomethionyl analog of recombinant human choriogonadotropin.
Selenomethionyl and high mannose type analog of recombinant human choriogonadotropin (hCG) to solve the crystallization and phase problems has been obtained by gene transfer methodology. SF9 insect cells were infected with the recombinant viruses containing hCG alpha and hCG beta cDNAs in selenomethionine containing methionine-free Grace's medium. The selenomethionyl hCG (SehCG) was purified from the culture medium by one step immunoaffinity chromatography using an immobilized monoclonal antibody against hCG beta. The presence of selenomethionine was demonstrated by amino acid analysis of SehCG. The amino acid composition indicated that more than 84% of methionine residues were substituted by selenomethionine. Its sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis yielded a single 38-kDa protein band under nonreducing conditions. The carbohydrate analysis of SehCG was consistent with the presence of four N-linked high mannose type carbohydrates and four O-linked simple disaccharide chains. The in vitro immunological and biological studies of SehCG indicated that selenomethionine substitution had no effect on the immunopotency, receptor binding, and steroidogenic activities of the hormone.


Intraintestinal capsaicin transiently reduces CGRP-like immunoreactivity in rat submucosal plexus.
Intraintestinal infusion of the sensory neurotoxin, capsaicin, transiently abolishes behavioral responses to chemical stimulation of the intestine. This desensitizing action of capsaicin may be due to an action on CGRP-containing nerve terminals, which are postulated to serve a sensory function in the enteric plexuses. To determine whether intraintestinal capsaicin treatment alters CGRP-like immunoreactivity (CGRP-li) in the enteric plexuses, we performed immunohistochemical analyses of the small intestinal submucosal and myenteric plexuses of rats at various times after intestinal infusion of capsaicin (5 mg) or its vehicle. Intestinal capsaicin treatment, but not vehicle treatment, reduced CGRP-li, but not substance-P-like immunoreactivity (SP-li), in nerve fibers of the submucosal plexus. CGRP-li was reduced in submucosal interganglionic connectives and in nerve fibers associated with submucosal blood vessels. CGRP-li of submucosal connectives was reduced by 1 h post-infusion. Reduction of CGRP-li in the submucosal fibers also was pronounced 24 h after intraintestinal capsaicin treatment. By 48 h after intestinal capsaicin infusion, CGRP-li was not distinguishable from vehicle-treated animals. There were no consistent immunohistochemical changes in CGRP-li or SP-li in the myenteric plexus at any time. These results indicate that intestinal capsaicin selectively induces transient reduction of CGRP-li in nerve fibers of the submucosal plexus. The chronology of depletion and reappearance of CGRP-li is congruent with previously reported, transient impairment of sensory function observed following intestinal capsaicin infusion.


Oral coenzyme Q10 supplementation in patients with nonalcoholic fatty liver disease: effects on serum vaspin, chemerin, pentraxin 3, insulin resistance and oxidative stress.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Chronic exposure to oxidative stress leads to depletion of liver antioxidants and abnormal cytokine production; antioxidant therapy is one of the main therapeutic lines in NAFLD. In the current study we aimed to investigate the effect of coenzyme Q10 (coQ10) therapy on several adipocytokines and insulin resistance in patients with NAFLD. In the current randomized double-blind placebo controlled trial 44 NAFLD patients were enrolled. After randomization into two groups, 22 patients received 100 mg/day coQ10 capsules and 22 patients received placebo daily for 4 weeks. BMI and WHR were calculated for patients at the beginning and end of the study and blood samples were obtained from the patients to measure serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting serum glucose (FSG), insulin resistance (IR), vaspin, chemerin, pentraxin 3 (PTX3) and markers of oxidative stress including total antioxidant capacity (TAC) and malondialdehyde (MDA). After 4 weeks of coQ10 supplementation, waist circumference (WC) and serum AST and TAC concentrations significantly decreased in intervention group (p <0.05) but no significant changes occurred in placebo-treated group. In stepwise multivariate linear regression model, change in serum FSG was a significant predictor of changes in serum vaspin, chemerin and pentraxin 3 (p <0.001). The present study showed a potential for coQ10 therapy in improving several anthropometric and biochemical variables in NAFLD. Longer studies with higher doses of coQ10 are required to further evaluate this potential benefit.


Endocrine organs and laser scanning confocal microscopy (LSCM) imaging: vascular bed in human spleen.
This work was aimed to utilize the precise method of laser confocal microscopy (LSCM) to depict the image of spatial relationships of the vessel network in the tissue structures of the human spleen. With the use of serial paraffin or vibratome sections of more than 20 μm thickness infiltrated with eosin fluorescence dye the images of arterial and venous walls of different calibres, capillaries, and venous sinuses were morphologically revealed. Venous sinuses were frequently found to create mutually communicating branches and their lining projected into the lumen protruding cells with distinct spherically or ovally shaped nuclei, positioned on the brightly fluorescent and fragmented lamina basalis. The presence of lymphocytes was distinct in periarteriolar lymphoid sheath (PALS) and lymphatic follicles. Lining cells of the red pulp veins sporadically contained marked eosinophilic granules. The method of LSCM allowed: 1. to reveal two-dimensional and sharp image of the human spleen structures, 2. to investigate the vertical course of venous structures in the tissue, 3. to obtain serial optic sections in z axis to their maximum spatial projections. These data will also serve for the creation of three-dimensional images of vessel network in the human spleen in the future studies.


Etomidate induced retinal changes.
The author examined the effect of etomidate-anaesthesia of one hour duration on the ultrastructure of the retina in animal experiments. Immediately after the exposure only the Müller's cells were moderately damaged. One day following the narcosis more serious pathological changes developed in the external nuclear layer which were partly irreversible. The changes found in the internal nuclear layer were less serious. The structure of the glial cells also altered. In the specimens taken 48 h following the anaesthesia the pathological changes of the neurons regressed to some degree, the Müller's cells reorganised and masses of glycogen accumulated in them. Further studies are needed to explain the eventual retinal toxic effect of this agent.


Co-administration of pazopanib and enteral nutrition with omega-3 fatty acids as a safety issue in a patient treated for metastatic clear cell renal cancer: A case report.
Pazopanib is an oral multitargeting tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs), approved as the first-line treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma (STS) at a fixed dose of 800 mg daily taken fasted. Potential drug-meal interactions and adverse events (AEs) may lack recognition and the related data in literature. We report one case of stomatitis/oral mucositis associated with pazopanib administrated with an oral nutritional supplement enriched with omega-3 fatty acids. The 50-year-old patient with mRCC started pazopanib treatment at standard doses of 800 mg daily as first-line therapy for mRCC, and after a few days, he developed stomatitis. Co-administration of pazopanib with high-fat meals could increase the solubility of highly lipophilic pazopanib, increasing its plasma pazopanib area under the curve (AUC), and maximum concentration (Cmax) above optimal therapeutic level can consequently lead to increased frequency/grade of AEs.


Focus on the role of synthetic phytohormone for mixotrophic growth and lipid accumulation by Chlorella pyrenoidosa.
Synthetic phytohormone (SP) is regarded as an attractive candidate for microalgae cultivation due to its potential for high-value microalgae biomass production. Herein, α-naphthylacetic acid (NAA), indomethacin (IN) and 2,4-dichlorophenoxyacetic acid (2,4-D) were used for the mixotrophic cultivation of Chlorella pyrenoidosa with mariculture wastewater (MW) acidogenic fermentation effluent. The growth and lipid accumulation of Chlorella pyrenoidosa added with SP were enhanced, given their high bioavailability of the nutrients. Among these three SPs, IN was optimal for Chlorella pyrenoidosa growth, with the maximum optical density of 1.81. NAA exhibited the best performance for lipid production and the proportion of lipid reached 50.24%. Furthermore, the energy of Chlorella pyrenoidosa cultured with SP preferentially allocated to lipogenesis. To understand the mechanism of lipid accumulation in Chlorella pyrenoidosa in response to SP, the enzyme activities involved in carbon metabolism were determined. The malic enzyme (ME) and acetyl-CoA carboxylase (ACCase) were positively correlated with lipid accumulation. Phosphoenolpyruvate carboxylase (PEPC) was the negative feedback enzyme for lipid synthesis. The findings could provide valuable information for regulation mechanism of lipid accumulation and value-added products recovery by microalgae.


Small Animal IMRT Using 3D-Printed Compensators.
Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.


Fish oil fat emulsion alleviates traumatic brain injury in mice by regulation of microglia polarization.
Microglia activation, a hallmark of brain neuroinflammation, contributes to the secondary damage following traumatic brain injury (TBI). To explore the potential roles of different fat emulsions-long chain triglyceride (LCT) / medium chain triglyceride (MCT) and fish oil (FO) fat emulsion in neuroprotection and neuroinflammation in TBI, in this study, we first generated the controlled cortical impact (CCI) model of TBI mice. Then either LCT/MCT or FO fat emulsion treated mice were studied by Nissl staining to assess the lesion volume. Sham and TBI mice treated with 0.9% saline were used as controls. The fatty acid composition in different TBI mouse brains was further evaluated by gas chromatography. Immunofluorescent staining and quantitative RT-PCR both demonstrated the suppression of pro-inflammatory microglia and upregulated anti-inflammatory microglia in FO fat emulsion treated TBI brain or primary microglia induced by lipopolysaccharide (LPS) in vitro. Furthermore, motor and cognitive behavioral tests showed FO fat emulsion could partially improve the motor function in TBI mice. Together, our results indicate that FO fat emulsion significantly alleviates the TBI injury and neuroinflammation probably by regulating microglia polarization.


Generation and application of a monoclonal antibody against the 18-kDa oncosphere antigen of Taenia pisiformis.
Taenia pisiformis is a parasite that causes cysticercosis pisiformis, which has acquired economic relevance because of its effects on animal welfare and production. A useful assay for the detection of T. pisiformis is needed for the prevention of cysticercosis pisiformis and control of the parasite. The 18-kDa oncosphere antigen is expressed in the oncosphere of several cysticerci in species of the genus Taenia, including T. pisiformis. This protein plays an important role in tissue invasion and has extensive applications in diagnosis. In this study, the T. pisiformis 18-kDa oncosphere antigen (TPO18) was expressed in soluble form and successfully purified for use in the production of monoclonal antibodies (MAbs) against TPO18. Twenty hybridomas were obtained using ELISA, and the subcloning process identified three positive hybridoma cell lines, which were designated as 4E8, 5G5, and 7E8. MAb 7E8 exhibited the highest titer and had an IgG2b heavy chain and a kappa light chain. Western blot analysis demonstrated that MAb 7E8 reacted with GST-TPO18. Immunohistochemistry showed that TPO18 was widely distributed in the drape and wall of uteri in adults of T. pisiformis adults and in the fibrous layer of the sucker and cyst cavity of T. pisiformis cysticerci. This research will provide a foundation for the development of diagnostic tools and will contribute to a better understanding of the functions of TPO18.


Ambulatory blood pressure monitoring and blood pressure control in patients with coronary artery disease-A randomized controlled trial.
Office blood pressure (OBP) is used for diagnosing and treating hypertension but ambulatory blood pressure measurement (ABPM) associates more accurately with patient outcome. BP control is important in secondary prevention but it is unknown whether the use of APBM improves BP-control in this setting. Our objective was to investigate whether physician awareness of ABP after percutaneous coronary intervention (PCI) improved BP-control. Methods: A total of 200 patients performed ABPM before and after their PCI follow-up visit. Patients were randomized to open (O) or concealed (C) ABPM results for the physician at the follow-up visit. The change in ABP and antihypertensive medication in relation to baseline ABP was compared between the two groups. Results: The average OBP (O and C: 128/76 mmHg) and ABP (O: 123/73 mmHg, C: 127/74 mmHg) was well controlled and did not change between the first and second measurement. A slight increase in systolic ABP during night time was observed in the open arm compared to the concealed arm. Among patients with high ABP (>130/80 mm Hg) at baseline more patients in the C compared to O group remained with a high ABP at the end of study 34/44 (77%) vs 19/34 (56%), p = 0.045. There was a positive correlation between baseline systolic ABP and ABP change in both the O (r = 0.41, p < 0.001) and the C (r = 0.24, p = 0.014) groups but the association was steeper in the open group (p = 0.035). In patients with low ABP an increase and in patients with high ABP a decrease in ABP was observed in the O group where more changes in medication were done. Conclusions: ABPM did not lower blood pressure in patients with CAD apart from in those with elevated ABP but led to more relevant changes in antihypertensive treatments. Further studies are needed to answer whether patient outcome is affected.


Multi-drug resistant (MDR), extended spectrum beta-lactamase (ESBL) producing and carbapenem resistant Escherichia coli in rescued Sloth bears (Melursus ursinus), India.
The study reports the multi-drug resistant (MDR), extended spectrum beta-lactamase (ESBL) producing and carbapenem resistant Escherichia coli (CRE) isolated from rescued sloth bear (Melursus ursinus), India. Non-duplicate faecal samples from 21 adult rescued sloth bears were collected at once during 2015-2016 and processed for isolation of E. coli and antibacterial susceptibility pattern. From 21 samples, 45 E. coli were isolated and on phenotypic screening, 23 were MDR, 17 were ESBL producers, and five were carbapenem-resistant (CR). Three E. coli isolates (6.67%, 3/45) showed no resistance, however 42 isolates (93.33%, 42/45) exhibited resistant to at least one antibiotics. The MDR isolates carried beta-lactamase, chloramphenicol, aminoglycosides, tetracycline, fluroquinolone, and sulphadimidine resistance genes. All the phenotypic ESBL producing isolates harbored blaCTX-M genes. On genotypic screening, three CRE (60.0%, 3/5) were positive for blaNDM carbapenemase gene and efflux pump-mediated carbapenem resistance was detected in two CRE isolates (40.0%, 2/5) which were negative for carbapenemase genes. The CRE isolates (n = 5) also co-harbored AMR genes like blaTEM-1, blaAmpC, qnrA, qnrB, qnrS, tetA, tetB and sulI. Virulence screening of the resistant isolates detected the presence of Stx1(n = 1), Stx2 (n = 3), eaeA (n = 4) and hlyA (n = 3) genes. Plasmid incompatibility (Inc) typing revealed that two isolates harboured blaNDM-5 gene on Incl1 and one isolate on IncF plasmid. Apart from the NDM gene, the plasmids also carried tetracycline, beta-lactamase and quinolone resistance genes. The plasmid multilocus sequence typing (pMLST) of the E. coli Incl1 plasmid showed the Sequence Type (ST) 297. This appears to be the first report of MDR, ESBL producing and blaNDM-5 genes on Incl1 and IncF plasmids from rescued sloth bear.


Socioeconomic Status and Waiting Times for Health Services: Current Evidences and Next Area of Research.
Waiting times are an issue in many countries, excessive waiting for treatments may deteriorate patient's health status and reduce treatment effectiveness potentially, becoming a barrier in the access to health care services. Waiting time to be equitable should be related only to the health need, people with the same health need have to wait the same time, without any difference due to socioeconomic status. In the commentary, the results of the extensive literature review and policy implications are discussed.


Extraction and utilization of active substances from edible fungi substrate and residue: A review.
The expansion of the edible fungi industry has resulted in the production of large amounts of edible fungus residues, causing great pressure on environmental protection.Therefore, research on edible fungus residue utilization has become a controversial issue. Thus far, numerous efforts have been devoted to separate active substances from edible fungus substrates and residues for high application value utilization. Building upon this, the main methods for extracting active substances from edible mushroom residues are reviewed, and the mechanisms, influencing factors, and trade-offs of the various methods are analysed. Furthermore, the existing and possible directions of utilization of the extracted active substances are reviewed and discussed. Finally, challenges and prospects for the extraction and utilization of different substances in edible fungus residues are proposed. This review provides an effective strategy for protecting the ecological environment and promoting the sustainable development of human society.


Alternated biodegradation of naphthalene (NAP), acenaphthylene (ACY) and acenaphthene (ACE) in an aerobic granular sludge reactor (GSBR).
The paper presents quantitative changes of selected 2- and 3-ring PAHs after process phases of GSBR reactor. The studies have been carried out for 264 cycles of GSBR reactor, during which concentration of naphthalene was increased in the range of 3.00-710.00 μg/L, acenaphthylene 1.00-160.00 μg/L, acenaphthene 3.00-440.00 μg/L. GSBR operating cycle consisted of filling (30 min), mixing (90 min), aeration (540 min), sedimentation (10 min), decanting (30 min) and downtime (20 min) phases. Activated sludge dry mass concentration was 4.00 kg/m3. Conducted studies showed that in GSBR reactor naphthalene was degraded with the highest intensity. Results of the statistical analysis confirmed that naphthalene concentrations were statistically significantly different (α = 0.05) after each individual GSBR process phase, while in case of acenaphthene and acenaphthylene, the differences were observed only between mixing and aeration phases. Additionally, equations estimating concentrations of PAHs in treated wastewater were developed. Selected activated sludge technological parameters (sludge volume index, sludge and hydraulic retention time) and concentration of PAHs were used for equations. The R2 coefficients of equations were above 0.99, which indicates a good adjustment of estimation to observed values.


Anticipating Greater Impact of the COVID-19 Pandemic on Social Life Is Associated With Reduced Adherence to Disease-Mitigating Guidelines.
People regularly make decisions about how often and with whom to interact. During an epidemic of communicable disease, these decisions gain new weight, as individual choices exert more direct influence on collective health and wellbeing. While much attention has been paid to how people's concerns about the health impact of the COVID-19 pandemic affect their engagement in behaviors that could curb (or accelerate) the spread of the disease, less is understood about how people's concerns about the pandemic's impact on their social lives affect these outcomes. Across three studies (total N = 654), we find that individuals' estimates of the pandemic's social (vs. health) impact are associated with an unwillingness to curtail social interaction and follow other Centers for Disease Control guidelines as the pandemic spreads. First, these associations are present in self-report data of participants' own behaviors and behavior across hypothetical scenarios; second, participants' estimates of the pandemic's impact on social life in their location of residence are associated with movement data collected unobtrusively from mobile phones in those locations. We suggest that perceptions of social impact could be a potential mechanism underlying, and therefore potential intervention target for addressing, disease-preventing behavior during a pandemic.


Syringomyelia secondary to congenital intraspinal lipoma.
Preoperative evaluation using serial magnetic resonance imaging was performed on an infant with lumbosacral lipoma. Syrinx formation arising just above the lipoma was observed in conjunction with rapid growth of the lipoma. Definite shrinkage of syringomyelia was obtained after radical excision of the lipoma. The syrinx formation was possibly caused by compression from the extramedullary lipoma.


Small Cajal body-associated RNA 2 (scaRNA2) regulates DNA repair pathway choice by inhibiting DNA-PK.
Evidence that long non-coding RNAs (lncRNAs) participate in DNA repair is accumulating, however, whether they can control DNA repair pathway choice is unknown. Here we show that the small Cajal body-specific RNA 2 (scaRNA2) can promote HR by inhibiting DNA-dependent protein kinase (DNA-PK) and, thereby, NHEJ. By binding to the catalytic subunit of DNA-PK (DNA-PKcs), scaRNA2 weakens its interaction with the Ku70/80 subunits, as well as with the LINP1 lncRNA, thereby preventing catalytic activation of the enzyme. Inhibition of DNA-PK by scaRNA2 stimulates DNA end resection by the MRN/CtIP complex, activation of ATM at DNA lesions and subsequent repair by HR. ScaRNA2 is regulated in turn by WRAP53β, which binds this RNA, sequestering it away from DNA-PKcs and allowing NHEJ to proceed. These findings reveal that RNA-dependent control of DNA-PK catalytic activity is involved in regulating whether the cell utilizes NHEJ or HR.


Exercise routine change is associated with prenatal depression scores during the COVID-19 pandemic among pregnant women across the United States.
The COVID-19 pandemic has negatively affected physical and mental health worldwide. Pregnant women already exhibit an elevated risk for depression compared to the general public, a pattern expected to be exacerbated by the pandemic. Certain lifestyle factors, including moderate exercise, may help support mental health during pregnancy, but it is unclear how the pandemic may impact these associations across different locations. Here, we test whether: (i) reported exercise routine alterations during the pandemic are associated with depression scores; and, (ii) the likelihood of reporting pandemic-related exercise changes varies between women living in metro areas and those in non-metro areas. This cross-sectional study used data from the COVID-19 And Reproductive Effects (CARE) study, an online survey of pregnant women in the United States. Participants were recruited April-June 2020 (n = 1,856). Linear regression analyses assessed whether reported COVID-19-related exercise change was associated with depression score as measured by the Edinburgh Postnatal Depression Survey. Logistic regression analyses tested whether a participant's Rural-Urban Continuum Code classification of "metro" was linked with higher odds of reporting exercise changes compared to a "non-metro" classification. Women who reported exercise changes during the pandemic exhibited significantly higher depression scores compared to those reporting no changes. Moreover, individuals living in metro areas of all sizes were significantly more likely to report exercise changes compared to women living in non-metro areas. These results suggest that the ability to maintain an exercise routine during the pandemic may help support maternal mental health. It may therefore be prudent for providers to explicitly ask patients how the pandemic has impacted their exercise routines and consider altered exercise routines a potential risk factor for depression. An effort should also be made to recommend exercises that are tailored to individual space restrictions and physical health.