Comment: pregnancy after bariatric surgery - achievements and open questions.
Bariatric surgery confers potential advantages for obese patients, but also risks for pregnancy. Perinatal outcomes may be varying between surgical procedures. This topic was recently addressed by a systematic review in BMC Pregnancy and Childbirth. This commentary will discuss the scientific background and implications for future research.


Adoption of cleaner technologies and reduction in fire events in the hotspots lead to global decline in carbon monoxide.
Carbon Monoxide (CO) is not a greenhouse gas (GHG), but has the capacity to change atmospheric chemistry of other GHGs such as methane and ozone, and therefore indirectly affects Earth's radiative forcing of the GHGs and surface temperature. Here, we use the CO mixing ratio at 850 hPa from the Tropospheric Emission Spectrometer (TES) reanalysis and the Measurement of Pollution in the Troposphere (MOPITT) satellite measurements for the period 2005-2019 to examine the spatio-temporal changes in CO across the latitudes. We find a substantial decrease in global CO, about -0.21 ± 0.09 ppb/yr (-0.23 ± 0.12%/yr) with the TES data and about -0.36 ± 0.07 ppb/yr (-0.45 ± 0.08%/yr) with the MOPITT satellite measurements during the study period. The highest CO decreasing trend is observed in Eastern China (-2.7 ± 0.37 ppb/yr) followed by Myanmar (-2.142 ± 0.59 ppb/yr) and South America (-1.08 ± 0.82 ppb/yr). This negative trend in CO is primarily due to the decrease in biomass burning and stringent environmental regulations in the respective regions and countries. The sources including road transport, which account for about 33.6% of CO emissions, followed by industries (18.3%) and agricultural waste burning (8.8%), might also be responsible for the reduction in CO due to the adaptation of improved emission control technology and regulations in the past decades from 2005 to 2019. Therefore, the study provides new insights on the current trends of global CO distribution and reasons for recent reduction in global CO emissions, which would be useful for future decision-making process to control air pollution.


Length of the luteal phase and frequency of the four permutations between two or three follicular waves and ipsilateral or contralateral locations of the corpus luteum and preovulatory follicle in heifers.
In Survey 1, the records for 196 interovulatory intervals (IOIs) from 24 heifers were used to study the frequency and repeatability for number of follicular waves per IOI and to study the ipsilateral and contralateral relationships between the extant corpus luteum and ovulatory follicle. In Survey 2, 96 IOIs were used from the controls of the previous experiments that included the day of the end of the luteolytic period (progesterone <1.0 ng/mL). In Survey 1, the percentage of two-wave IOIs (63%) was greater (P < 0.0002) than for three-wave IOIs (37%). The percentage of ovulatory periods with a contralateral relationship (59%) was greater (P < 0.003) than with the ipsilateral relationship (41%). There were more repeats (66%) than reverses (34%) between adjacent IOIs in number of waves per IOI (P < 0.004), but there was no difference in number of corpus luteum/follicle relationships between the ovulatory periods at the beginning and end of an IOI. For the four permutations of ipsilateral and two waves, contralateral and two waves, ipsilateral and three waves, and contralateral and three waves in Survey 2, the interval (days) from ovulation to the day the progesterone was <1.0 ng/mL was 17.8 ± 0.2(a), 17.6 ± 0.2(a), 20.0 ± 0.3(b), and 21.4 ± 0.3(c), respectively, and the number of IOIs was 33 (34%)(a), 34 (35%)(a), 8 (8%)(b), and 22 (23%)(a), respectively; means with different superscripts are different (P < 0.05). The luteal phase was longer for the contralateral relationship than for the ipsilateral relationship for three-wave IOIs but not for two-wave IOIs. The hypothesis was supported that the frequency of the ipsilateral and three-wave permutation was less than for each of the other three permutations.


Morphological and molecular identification of Hysterothylacium larvae (Nematoda: Raphidascarididae) in marine fish from Tunisian Mediterranean coasts.
The taxonomy of Hysterothylacium genus in Mediterranean waters remains incomplete and unresolved. The aim of the current study was to investigate the morphological and molecular identification of selected species of Hysterothylacium larvae in marine fish from the Tunisian Mediterranean coasts. A total of 192 marine fish samples were examined. In total, thirty-seven third-stage larvae of Hysterothylacium were morphologically identified as Hysterothylacium type V. In the present study, representatives of this type from the Mediterranean Sea were genetically characterized for the first time by sequencing the rDNA ITS (ITS1-5.8S-ITS2) regions and mtDNA cox2 gene. This study represents the first report of Hysterothylacium type V from the Mediterranean Sea. We also report Mullus barbatus, M. surmuletus, and Pagellus erythrinus as new hosts for this larval type. Based upon molecular and phylogenetic analyses considering the rDNA ITS regions, the Hysterothylacium type V described here was classified as a new genotype, named Genotype B. The valid genetic data of the described Hysterothylacium type V in the present study can be used to establish the phylogenetic relationships among Hysterothylacium species from the Mediterranean Sea and worldwide for future research.


A novel canine model of portal vein stenosis plus thioacetamide administration-induced cirrhotic portal hypertension with hypersplenism.
Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism.


Enterocin LD3 from Enterococcus hirae LD3 Inhibits the Growth of Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311 in Fruit Juice.
In order to prevent the growth of pathogens in food, bacteriocins produced by various probiotic lactic acid bacteria have been recognized as potential substitutes of chemical preservatives. In this study, enterocin LD3 was purified from the cell-free supernatant of a food isolate, Enterococcus hirae LD3 using multistep chromatography. In the fruit juice, lethal concentration (LC50) of enterocin LD3 was found to be 260 µg/mL against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The cells treated with enterocin LD3 were red colour indicating dead cells after propidium iodide staining, while untreated cells were found blue after staining with 4', 6-diamidino-2-phenylindole. The mechanism of cell killing was analyzed using infrared spectrum of cells treated with enterocin LD3 which was found altered in the range of 1,094.30 and 1,451.82 cm-1 corresponding to nucleic acids and phospholipids, respectively. The morphology of target cells were severely ruptured and lysed as observed under electron microscopy. Thus, the present study suggested that enterocin LD3 showed bactericidal activity against Salm. enterica subsp. enterica serovar Typhimurium ATCC 13311 and may be applied as a bio-preservative for the safety of fruit juices.


Can we relate MeCP2 deficiency to the structural and chemical abnormalities in the Rett brain?
The mutated gene for Rett syndrome, MECP2, has now been identified in ninety percent of cases. Molecular biologists are immersed in the study of this gene's biology determining how its mutation could be responsible for such an enigmatic phenotype. In this paper the same question is considered, re-examining the structural phenotype of the Rett brain and asking; is MeCP2 present at the appropriate time and place in brain development to influence the structural and chemical abnormalities which characterize the Rett brain? Data from the literature and previous research suggest that MeCP2 is expressed during critical periods of brain development at several sites and in different neurons. It supports the idea that inadequate functioning of MeCP2 alters trophic factors and raises the possibility that replacement of these factors might improve brain function. The availability of mouse models now makes it possible to test such ideas.


Anterior tibiofibular ligament avulsion fracture in weber type B lateral malleolar fracture.
The purpose of this study was to determine the incidence, relationship with the ankle diastasis, and effect of treatment of the anterior tibiofibular ligament avulsion fracture (Wagstaffe fracture) combined with the Weber type B lateral malleolar fracture. This study reviewed 94 cases of ankle fractures treated with operative methods. There were 52 cases of Weber type B lateral malleolar fractures and 13 cases of Wagstaffe fractures combined with them (25%). Ankle diastases were diagnosed in 20 cases (38.5%) in all Weber type B fractures and 11 (84.6%) of the 13 Wagstaffe fractures. The Wagstaffe fracture can be a good diagnostic clue of ankle diastasis in Weber type B lateral malleolar fracture. The accurate reduction and fixation of the avulsed fragment is important for restoration of the stable distal tibiofibular joint and to prevent the chronic ankle joint pain caused by impingement of the avulsed fragment.


Cholera outbreak caused by drinking unprotected well water contaminated with faeces from an open storm water drainage: Kampala City, Uganda, January 2019.
Kampala city slums, with one million dwellers living in poor sanitary conditions, frequently experience cholera outbreaks. On 6 January 2019, Rubaga Division notified the Uganda Ministry of Health of a suspected cholera outbreak in Sembule village. We investigated to identify the source and mode of transmission, and recommended evidence-based interventions. We defined a suspected case as onset of profuse, painless, acute watery diarrhoea in a Kampala City resident (≥ 2 years) from 28 December 2018 to 11 February 2019. A confirmed case was a suspected case with Vibrio cholerae identified from the patient's stool specimen by culture. We found cases by record review and active community case-finding. We conducted a case-control study in Sembule village, the epi-center of this outbreak, to compare exposures between confirmed case-persons and asymptomatic controls, individually matched by age group. We overlaid rainfall data with the epidemic curve to identify temporal patterns between rain and illnesses. We conducted an environmental assessment, interviewed village local council members, and tested water samples from randomly-selected households and water sources using culture and PCR to identify V. cholerae. We identified 50 suspected case-patients, with three deaths (case-fatality rate: 6.0%). Of 45 case-patients with stool samples tested, 22 were confirmed positive for V. cholerae O1, serotype Ogawa. All age groups were affected; persons aged 5-14 years had the highest attack rate (AR) (8.2/100,000). The epidemic curve showed several point-source outbreaks; cases repeatedly spiked immediately following rainfall. Sembule village had a token-operated water tap, which had broken down 1 month before the outbreak, forcing residents to obtain water from one of three wells (Wells A, B, C) or a public tap. Environmental assessment showed that residents emptied their feces into a drainage channel connected to Well C. Drinking water from Well C was associated with illness (ORM-H = 21, 95% CI 4.6-93). Drinking water from a public tap (ORM-H = 0.07, 95% CI 0.014-0.304) was protective. Water from a container in one of eight households sampled tested positive for V. cholerae; water from Well C had coliform counts ˃ 900/100 ml. Drinking contaminated water from an unprotected well was associated with this cholera outbreak. We recommended emergency chlorination of drinking water, fixing the broken token tap, and closure of Well C.


Learning to detect the onset of slow activity after a generalized tonic-clonic seizure.
Sudden death in epilepsy (SUDEP) is a rare disease in US, however, they account for 8-17% of deaths in people with epilepsy. This disease involves complicated physiological patterns and it is still not clear what are the physio-/bio-makers that can be used as an indicator to predict SUDEP so that care providers can intervene and treat patients in a timely manner. For this sake, UTHealth School of Biomedical Informatics (SBMI) organized a machine learning Hackathon to call for advanced solutions https://sbmi.uth.edu/hackathon/archive/sept19.htm . In recent years, deep learning has become state of the art for many domains with large amounts data. Although healthcare has accumulated a lot of data, they are often not abundant enough for subpopulation studies where deep learning could be beneficial. Taking these limitations into account, we present a framework to apply deep learning to the detection of the onset of slow activity after a generalized tonic-clonic seizure, as well as other EEG signal detection problems exhibiting data paucity. We conducted ten training runs for our full method and seven model variants, statistically demonstrating the impact of each technique used in our framework with a high degree of confidence. Our findings point toward deep learning being a viable method for detection of the onset of slow activity provided approperiate regularization is performed.


"The suturer": a new suturing instrument.
A new suturing instrument that allows easy placement of sutures in deep inaccessible sites is described. The instrument has been used successfully for pelvic and perineal procedures, and is an invaluable asset to the urologist for urethrovesical anastomoses in radical prostatectomies.


Inhibition of bacterial biofilms by the snake venom proteome.
Snake venoms possess a range of pharmacological and toxicological activities. Here we evaluated the antibacterial and anti-biofilm activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) of venoms from the Samar spitting cobra Naja samarensis and the Puff adder Bitis arietans. Both venoms prevented biofilm production by pathogenic S. aureus in a growth-independent manner, with the B. arietans venom being most potent. Fractionation showed the active molecule to be heat-labile and >10 kDa in size. Proteomic profiles of N. samarensis venom revealed neurotoxins and cytotoxins, as well as an abundance of serine proteases and three-finger toxins, while serine proteases, metalloproteinases and C-lectin types were abundant in B. arietans venom. These enzymes may have evolved to prevent bacteria colonising the snake venom gland. From a biomedical biotechnology perspective, they have valuable potential for anti-virulence therapy to fight antibiotic resistant microbes.


The influence of oral contraceptives on the risk of multiple sclerosis.
To examine the risk of multiple sclerosis in users of combined oral contraceptives. Cohort study conducted between 1968 and 1996 using diagnostic data supplied by general practitioners General practices throughout the United Kingdom. Royal College of General Practitioners' Oral Contraception Study cohort of initially 46,000 women recruited during the late 1960s. Directly standardised incidence rates of multiple sclerosis were calculated for current, former and never-users of oral contraceptives using first ever cases of multiple sclerosis reported by the general practitioners. The standardisation variables were age, parity, social class and smoking history. Five-year survival rates in the different contraceptive groups were calculated using standard life table techniques. One hundred and fourteen first ever cases of multiple sclerosis had been reported by November 1996 during 564,000 woman-years of observation. The incidence rate in both current and former users was not materially different to that in never-users. Although based on limited evidence there was no suggestion that the five-year survival was affected by a woman's use of combined oral contraceptives. These findings do not suggest a greatly elevated risk of multiple sclerosis during, or after, use of combined oral contraceptives.


Fermentation in nutrient salt mixtures affects green Spanish-style Manzanilla table olive characteristics.
This work studies the effects of the substitution of NaCl with KCl and CaCl2 on the physicochemical, mineral and sensory profile of fermented green Spanish-style Manzanilla olives, using an enlarged centroid mixture design. An increasing presence of CaCl2 in the initial brines improved the colour index, L(∗), b(∗) values, and firmness. The Na in the olives decreased (linearly) while the levels of K and Ca increased (quadratic) as a function of the KCl and CaCl2 concentrations in the initial brines. CaCl2 also improved the retention of Zn and P in the flesh. PLS showed a strong relationship between Ca and bitterness, hardness, fibrousness, crunchiness and saltiness (negative) and allowed for the prediction of sensory attributes (except acid) from the mineral contents in the flesh. Most of the treatments could lead to new green Spanish-style Manzanilla olive presentations with reduced Na and healthier characteristics.


Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis.
Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.


Analysis of gas exchange in seedlings of Acer saccharum: integration of field and laboratory studies.
In the field, photosynthesis of Acer saccharum seedlings was rarely light saturated, even though light saturation occurs at about 100 μmol quanta m-2 s-1 photosynthetic photon flux density (PPFD). PPFD during more than 75% of the daylight period was 50 μmol m-2 s-1 or less. At these low PPFD's there is a marked interaction of PPFD with the initial slope (CE) of the CO2 response. At PPFD-saturation CE was 0.018 μmol m-2 s-1/(μl/l). The apparent quantum efficiency (incident PPFD) at saturating CO2 was 0.05-0.08 mol/mol. [Formula: see text] and PPFD-saturated CO2 exchange was 6-8 μmol m-2 s-1. The ratio of internal CO2 concentration to external (C i /C a ) was 0.7 to 0.8 except during sunflecks when it decreased to 0.5. The decrease in C i /C a during sunflecks was the result of the slow response of stomates to increased PPFD compared to the response of net photosynthesis. An empirical model, which included the above parameters was used to simulate the measured CO2 exchange rate for portions of two days. Parameter values for the model were determined in experiments separate from the daily time courses being sumulated. Analysis of the field data, partly through the use of simulations, indicate that the elimination of sunflecks would reduce net carbon gain by 5-10%.


[What do I have to do to start my clinical study?].
"What do I have to do to start my clinical study" is one question often asked by physicians new to the field of medical research. Even many experienced researchers are challenged by this question given the complex and rapidly changing legal and regulatory aspects of clinical studies. In this article we will offer a guide to the planning of your clinical study.


Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats.
Seeds of Apium graveolens L. (Apiaceae) and Hygrophila auriculata (K. Schum.) Heine (Syn. Astercantha auriculata Nees, Acanthaceae) are used in Indian systems of medicine for the treatment of liver ailments. The antihepatotoxic effect of methanolic extracts of the seeds of these two plants was studied on rat liver damage induced by a single dose of paracetamol (3 g/kg p.o.) or thioacetamide (100 mg/kg, s.c.) by monitoring several liver function tests, viz. serum transaminases (SGOT and SGPT), alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase and bilirubin in serum. Furthermore, hepatic tissues were processed for assay of triglycerides and histopathological alterations simultaneously. A significant hepatoprotective activity of the methanolic extract of the seeds of both the plants was reported.


Biological and chemical changes in fluoroquinolone-associated tendinopathies: a systematic review.
The present systematic review investigates the biological and chemical mechanisms that affect the health and structure of tendons following the use of fluoroquinolones (FQs). A total of 12 articles were included, organized, and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five mechanisms were identified: arrest of proliferation through a decreased activity of cyclin B, CDK-1, CHK-1, and increased PK-1; decrease tenocytes migration through decreased phosphorylation of FAK; decrease type I collagen metabolism through increased MMP-2; chelate effect on ions that influence epigenetics and several enzymes; fluoroquinolones-induced ROS (radical oxygen species) production in mitochondria. There is no definite structure-damage relationship. The dose-effect relationship is unclear. Knowing and defining the damage exerted by FQs plays a role in clinical practice, replacing FQs with other antibacterial drugs or using antioxidants to attenuate their pathological effects. Clinical and basic sciences studies for each FQs are necessary.


Prevalence and determinants of Italian physicians' burnout in the "post-COVID-19" era.
Several studies investigated prevalence and determinants of physicians' burnout during the peak of the COVID-19 pandemic, but only a few during the chronic phase of the pandemic. This study thus aimed to examine this topic referring to the "post-COVID-19 era", defined as a chronic and likely-to-be endemic status quo. A cross-sectional, online survey (November 2021-January 2022) was addressed to physicians in Lombardia (Northern Italy). Besides socio-demographic and COVID-19-related data, measures of personal, work- and patient-related burnout (Copenhagen Burnout Inventory; CBI), depression (Patient Health Questionnaire-8), anxiety (General Anxiety Disorder-7), and self-efficacy (General Self-Efficacy Scale) were collected. Linear/generalized linear models were run to test associations/predictions of interest. Among the 958 respondents, burnout symptoms were clinically significant in 18.5% of them. Predictive models showed that female sex (OR = 0.73, 95% CI 0.42-1.27), younger age (OR = 0.94, 95% CI 0.59-1.48), shorter job tenure (OR = 1.01, 95% CI 0.62-1.65), trainee status (OR = 1.41, 95% CI 1.16-7.10), higher PHQ-8 (OR = 1.260, 95% CI 1.16-1.37), and GAD-7 scores (OR = 1.19, 95% CI 1.10-1.30) increased the risk to suffer from clinical burnout. COVID-19-related variables were mostly not related/associated to burnout levels. In Italy, physicians' burnout is moderately prevalent also in the chronic phase of the pandemic, with its determinants being more intrinsic than environmental. The development of effective interventions is needed to help physicians cope with the new challenges of their job.


Sub-basal increases of GABA enhance the synthesis of TNF-α, TGF-β, and IL-1β in the immune system organs of the Nile tilapia.
The cells of the immune and neuronal systems share different receptors for cytokines or neurotransmitters, producing feedback responses between both systems. Cytokines such as IL-1β and TNF-α can induce inflammation; however, the secretion of these molecules can be modulated by anti-inflammatory cytokines, as is the case for TGF-β, as well as by different hormones or neurotransmitters such as the γ-aminobutyric acid (GABA). In this study, we evaluated the secretion of IL-1β, TNF-α, and TGF-β under basal conditions, in the head of the kidney, spleen, thymus, and serum of the Nile tilapia, as well as their release induced by different sub-basal increases of GABA. We found that at the higher dose of GABA these cytokines were synthesised at a higher concentration compared to the control group. These results may suggest that there is feedback between both systems and that GABA plays a role in the modulation of the immune response.


A calcium peroxide incorporated oxygen releasing chitosan-PVA patch for Diabetic wound healing.
Impaired wound healing is a major healthcare problem in patients with diabetes often resulting in gangrene, microbial infection and amputation of affected limb. The delay or absence in healing process arises from several abnormalities, among them chronic hypoxia is a major concern due to its associated issues such as lack of collagen deposition, epithelization, fibroplasia, angiogenesis, and resistance to infections at the wound site. To address hypoxia, delivery of oxygen at the wound site through oxygen releasing agents have been proven to be effective therapeutics. Several oxygen releasing nanoparticles such as Sodium Percarbonate (SPC), Calcium Peroxide (CPO), Hydrogen Peroxide, Magnesium Peroxide (MPO) have been investigated in wound healing application. However, the uncontrolled/burst release of these nanotherapeutic agents and its accompanied cytotoxicity pose a barrier in expediting the healing process. In this study, a Chitosan-Polyvinyl alcohol (CS-PVA) based hydrogel containing oxygen releasing nanoparticle, calcium peroxide (CPO) was constructed to provide a slow and sustained delivery of oxygen for at least 5 days. In-vitro cell culture studies with this material using fibroblast and endothelial cell line exhibited improved biocompatibility, cell viability and enhanced proliferation in comparison with the control group. Additionally, cell migration study using scratch assay method showed superior cell migration ability of our proposed materials. Furthermore, In vivo study using diabetic rat model showed accelerated wound closure rate compared to untreated control wounds.


An objective determination of +Gz acceleration tolerance.
Until recently, human +Gz acceleration tolerance has relied solely on subjective criteria relating to loss of vision. By use of newly developed noninvasive instrumentation using a transcutaneous Doppler flow system, objective end point criteria have been developed based on measured blood flow to the head. The system consists of miniature 8 MHz Doppler sensors (2 x 1 x 0.5 cm) placed on the forehead over both frontal branches of the temporal arteries to detect blood flow velocity from back scattered ultrasound. Its use has allowed for correlation of altered, decreased and actual reversal of eye level blood flow with subsequent central light loss. Over 100 subjects have now been studied during more than 2,000 centrifuge runs. Objective changes in temporal artery flow velocity consistently preceded visual degradation for each subject during all acceleration profiles. No subject has gone unconscious without first exhibiting a minimum 6 sec of total flow cessation. Retrograde flow followed by complete flow cessation always preceded central light loss. Results indicate that this method can be successfully used with a wide variety of tasks during exposure to +Gz acceleration. It is recommended for use during evaluation of protective maneuvers or devices on the centrifuge or during actual flight in high performance aircraft. It may also serve as a potential safety monitor during space Shuttle re-entry if there is doubt about a passenger's cardiovascular status.


Exposure risk and emergency evacuation modeling of toxic gas leakage in urban areas under the influence of multiple meteorological factors.
Frequent toxic gas leakage accidents in urban environments cannot be timely controlled and often cause great harm due to the many factors affecting gas diffusion. In this study, based on the coupling method of the Weather Research and Forecasting Model (WRF) and the open source OpenFOAM software platform, the chlorine gas diffusion process at different temperatures, wind speeds, and wind directions in a chemical laboratory and nearby urban areas in Beijing was studied numerically. A dose-response model was used to calculate chlorine lethality and assess exposure risk at the pedestrian level. To predict the evacuation path, an improved ant colony algorithm, a greedy heuristic search algorithm based on the dose-response model, was applied. The results demonstrated that the combination of WRF and OpenFOAM could consider the effects of various factors such as temperature, wind speed, and wind direction on the diffusion of toxic gases. The direction of chlorine gas diffusion was affected by wind direction, and the range of chlorine gas diffusion was affected by temperature and wind speed. The area of high exposure risk (fatality rate above 40%) at high temperatures was 21.05% larger than that at low temperatures. When the wind direction was opposite the building, the high exposure risk area was 78.95% smaller than that under the building direction. The present work provides a promising approach for exposure risk assessment and evacuation planning for the emergency response to urban toxic gas leakage.


Identification of a phosphatidylcholine active phospholipase C in human gallbladder bile.
This study describes the identification of a phospholipase C activity against phosphatidylcholine in delipidated human gallbladder bile. All biles were obtained from cholesterol gallstone patients and were negative on bacterial culture. The biliary enzyme was inhibited by EDTA and had a pH optimum of between 7-8. All of the 15 gallbladders examined contained significant phospholipase C activity (32.85 +/- 8.37 nmol/h/mg delipidated protein). The finding of a phospholipase C in gallbladder bile of patients with cholesterol gallstones may be one of the factors responsible for or related to the rapid in vitro nucleation seen in these biles.


Adrenal angiotensin II type 1 and type 2 receptors in Cushing's and Conn's syndromes.
Cushing's and Conn's syndromes are well recognised endocrine diseases, but the pathobiology of the tumors causing these disorders is unclear. In this study we examined AT1 and AT2 gene expression in adrenal adenomas of Cushing's and Conn's syndromes. AT1 and AT2 receptor mRNA, as well as alternatively spliced AT1 transcripts, were detected by RT-PCR using adjacent adrenal cortex tissue as controls. Whereas no consistent differences in AT1 mRNA were seen compared to control adrenal cortex, AT2 mRNA levels were significantly decreased in the adenomas of Cushing's and Conn's syndromes. No changes in alternative splicing of AT1 mRNA were observed in the adrenal tumors. The fact that no consistent changes were seen in AT1 mRNA or its splicing, whereas AT2 mRNA were reduced in both forms of hormone producing adrenal tumor suggests that the AT2 receptor, rather than the AT1 subtype, may be correlated with adrenal tumorigenesis.


Europe tries to save Mars rover after split with Russia.
Team leader says delay to 2028 or 2030 is likely.


Value of the urine strip test in the early diagnosis of bacterial peritonitis.
In an effort to detect the presence of leukocytes in the peritoneal dialysate fluid (PDF) a urine dipstick may be practical for the early detection of peritonitis in peritoneal dialysis patients. The study was performed in 44 samples of four children with peritonitis. The total counts of white blood cell (WBC) and polimorphonuclear neutrophils (PMNs) were found using both a hemocytometer (CELDYN 3700 R) and a microscopic method. The existence of leukocytes was investigated by urine dipstick tests. The dipstick test was correlated with both hemocytometer and microscopic methods (r = 0.537, P = 0.001; r = 0.560, P = 0.0001, respectively). Our results revealed no false negative values in all strip categories. At the proposed cut-off point (> 100/mm3 of WBC count), a 3+ reading on the strip test reached a sensitivity of 100% for the detection of peritonitis with a specificity of 100%. A 2+ reading reached a sensitivity of 100% with lower specificity (71.4%) at the same cut-off point. The dipstick test correlated significantly with the total counts of PMNs (r = 0.80, P = 0.0001). All positive strip categories had more than 50% of PMNs with a low PMN percentage of negative strip category in PDF samples. It is proposed that the strip test might be a valuable test to diagnose bacterial peritonitis through the detection of both WBC and PMN in peritoneal dialysis patients.


Family and personal factors associated with the participation of children with special needs in leisure activities: A Turkish perspective.
The primary aims of the current study were to describe the participation patterns in leisure activities of children between the ages of 6 and 15 years with special needs and to analyze family behavior and personal factors that affect participation. Overall, 112 children with special needs aged 6-15 years and their families participated in the present study. Children's sociodemographic characteristics, participation patterns in leisure activities, family behavior, and quality of life were evaluated. In this study, it was observed that children participated in recreational activities the most and in physical activities the least. Most of the families reported that they did not have an influence on determining the activity. The findings showed correlations between leisure activities and age, gender, and socioeconomic status (p < 0.05). The findings suggest that (a) children's participation in activities outside the home and (b) family guidance are insufficient. Thus, rehabilitation professionals can inform families about activities appropriate for children, positive family behavior, and social support programs.


'Time-scribe': a universal time writer for any EEG/polygraph chart recorder.
An ubiquitous digital clock 'time-scribe' with a unique pen-galvanometer writer section has been described which should greatly improve the correlation of a long term EEG with any other time related event or medium. The output of the clock generates on any pen-galvanometer based chart recorder numerical and some alpha characters which are easily and immediately readable. Because of its convenience, simplicity and basic practical application it should also stimulate discussion for the unification of time write-out standards and methods.


The Phase Relations of the Co-Ni-In Ternary System at 673 K and 873 K and Magnetic Properties of Their Compounds.
The phase relationships of the ternary Co-Ni-In system at 673 K and 873 K were investigated by means of powder X-ray diffraction, scanning electron microscopy equipped with energy dispersive spectroscopy, and optical microscopy. Though CoIn2 does not exist at 873 K, the ternary solid solution Co1-xNixIn2 exists at both 673 K and 873 K with different composition ranges. The Rietveld refinements were carried out to investigate the crystal structure of Co1-xNixIn2 (x = 0.540, and 0.580) and Ni2-xCoxIn3 (x = 0.200). The magnetization dependence of temperature (MT) curves of Ni2-xCoxIn3 (x = 0.200) and Co1-xNixIn2 (x = 0.540) are similar to those of the ferromagnetic shape memory alloys Ni-Mn-A (A = Ga, Sn, and In), but do not undergo martensitic transformation. The maximum magnetic entropy changes in Ni2-xCoxIn3 (x = 0.200) and Co1-xNixIn2 (x = 0.540) under 3T are 1.25 and 1.475 J kg-1K-1, respectively.


Effect of matrix stiffness and adhesion ligand density on chondrogenic differentiation of mesenchymal stem cells.
Adhesion ligands and mechanical properties of extracellular matrix (ECM) play significant roles in directing mesenchymal stem cells' (MSCs) behaviors, but how they affect chondrogenic differentiation of MSCs has rarely been studied. In this study, we investigated the effects of matrix stiffness and adhesion ligand density on proliferation and chondrogenic differentiation of MSCs by using UV crosslinked hydrogels comprised of methacrylated gelatin (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) of different weight ratios. The PEGDA/GelMA hydrogels were fabricated by adjusting the weight ratio of PEGDA and GelMA with low or high adhesion ligand density (0.05 and 0.5% GelMA, respectively) and independent tunable stiffness (1.6, 6, and 25 kPa separately for hydrogels with 5, 10, and 15% PEGDA). MSCs presented differential behaviors to ECM by adjusting its adhesion ligand density and stiffness. Cell proliferation and chondrogenic differentiation could be enhanced with the improvement of adhesive properties and stiffness, evidenced by cell viability assay, hematoxylin-eosin staining, Safranin O staining, immunohistochemistry (Collagen types II, Col2a1), as well as the chondrogenic genes expression of Col2a1, Acan, and Sox9. This study may provide new strategies to design the scaffolds for cartilage tissue engineering.


EvoAug: improving generalization and interpretability of genomic deep neural networks with evolution-inspired data augmentations.
Deep neural networks (DNNs) hold promise for functional genomics prediction, but their generalization capability may be limited by the amount of available data. To address this, we propose EvoAug, a suite of evolution-inspired augmentations that enhance the training of genomic DNNs by increasing genetic variation. Random transformation of DNA sequences can potentially alter their function in unknown ways, so we employ a fine-tuning procedure using the original non-transformed data to preserve functional integrity. Our results demonstrate that EvoAug substantially improves the generalization and interpretability of established DNNs across prominent regulatory genomics prediction tasks, offering a robust solution for genomic DNNs.


Appetite suppressing pregnane glycosides from the roots of Cynanchum auriculatum.
In the search for plant alternatives to Hoodia gordonii containing P57, a pregnane glycoside with potential appetite suppressant effect, the roots of Cynanchum auriculatum were investigated. As a result, 15 pregnane glycosides including nine never previously reported were isolated. Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical methods. Appetite suppressant effect and body weight loss were observed when tested with the most abundant pregnane glycoside, wilfoside K1N, in an in vivo test with rats.


Myeloperoxidase G463A polymorphism and risk of lung cancer.
Myeloperoxidase (MPO) is a phase I enzyme playing a crucial role in metabolically activating a wide range of procarcinogens, such as polycyclic aromatic hydrocarbons and aromatic amines. The G463A polymorphism in the promoter region of the MPO gene has been indicated in lung cancer risk. To investigate the precise association of MPO G463A polymorphism with the lung cancer risk, we performed this comprehensive meta-analysis with large available data published to date. The included 24 individual studies involving a total of 8,313 cases and 8,728 controls were identified by searching the PubMed, Embase, and Wanfang databases. The crude odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the association. Stratified analyses by ethnicity, source of controls, smoking status, and histological types were also conducted. Overall, the MPO G463A polymorphism was negatively related to the development of lung cancer in the following genetic models (A vs. G, OR = 0.90, 95% CI = 0.82-0.99, P OR = 0.029; GA vs. GG, OR = 0.89, 95% CI = 0.80-0.98, P OR = 0.022; AA + GA vs. GG, OR = 0.89, 95% CI = 0.81-0.98, P OR = 0.023). Stratified analyses by ethnicity indicated that the variant genotype of MPO G463A was associated with a decreased risk of lung cancer in Asians and Caucasians. Similar findings were observed among the smokers and population-based case-control studies. The MPO G463A polymorphism seemed to exert no effect on lung adenocarcinoma and squamous cell carcinoma. The comprehensive meta-analysis shows that the polymorphism of MPO G463A is a protective factor for lung cancer, particularly among the populations of Asians, Caucasians, and smokers.


Deformed wing virus associated with Tropilaelaps mercedesae infesting European honey bees (Apis mellifera).
Mites in the genus Tropilaelaps (Acari: Laelapidae) are ectoparasites of the brood of honey bees (Apis spp.). Different Tropilaelaps subspecies were originally described from Apis dorsata, but a host switch occurred to the Western honey bee, Apis mellifera, for which infestations can rapidly lead to colony death. Tropilaelaps is hence considered more dangerous to A. mellifera than the parasitic mite Varroa destructor. Honey bees are also infected by many different viruses, some of them associated with and vectored by V. destructor. In recent years, deformed wing virus (DWV) has become the most prevalent virus infection in honey bees associated with V. destructor. DWV is distributed world-wide, and found wherever the Varroa mite is found, although low levels of the virus can also be found in Varroa free colonies. The Varroa mite transmits viral particles when feeding on the haemolymph of pupae or adult bees. Both the Tropilaelaps mite and the Varroa mite feed on honey bee brood, but no observations of DWV in Tropilaelaps have so far been reported. In this study, quantitative real-time RT-PCR was used to show the presence of DWV in infested brood and Tropilaelaps mercedesae mites collected in China, and to demonstrate a close quantitative association between mite-infested pupae of A. mellifera and DWV infections. Phylogenetic analysis of the DWV sequences recovered from matching pupae and mites revealed considerable DWV sequence heterogeneity and polymorphism. These polymorphisms appeared to be associated with the individual brood cell, rather than with a particular host.


Walking in pregnancy and prevention of insomnia in third trimester using pedometers: study protocol of Walking_Preg project (WPP). A randomized controlled trial.
Previous studies in pregnancy have not focused in evaluating the effect of walking during pregnancy and prevention of insomnia. Our general objective is to determine the effect of a walking program in preventing the appearance of insomnia in the third trimester of pregnancy, increasing sleep quality and improving quality of life throughout pregnancy. Randomized Controlled trial in parallel in healthy sedentary pregnant women (n = 265), Walking_Preg Project (WPP), from university hospital in Granada, Spain. At 12th gestational week (GW), they will be invited to participate and randomly assigned to one of the three arms of study: the intervention group I1 (pedometer, goal of 11,000 steps/day), intervention group I2 (pedometer, no goal) and control (no pedometer). Duration of intervention: 13-32 GW. At 12th, 19th and 31st GW the average steps/day will be measured in groups I1 and I2. At 13th, 20th and 32nd GW, Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Adherence to Mediterranean Diet (AMD), physical activity (short IPAQ), quality of life (PSI), and consumption of toxic substances (caffeine, illegal drugs, alcohol and tobacco) will be collected. Student t test or Mann-Whitney U will be used to compare 19th and 31st GW mean of daily steps between I1 and I2 groups. To compare differences between groups in terms of frequency of insomnia/quality of life for each trimester of pregnancy, Pearson's Chi-square test or Fisher's exact test will be used. To determine differences in hours of sleep and quality of sleep throughout each trimester of pregnancy, analysis of variance or Friedman test will be used. McNemar-Bowker test will be used to assess differences in life quality in pre-post analyses in the 3 arms. We will use Stata 15 statistical software. promoting walking in second half of pregnancy through use of pedometer and health pre-registration of a goal to be achieved -'10,000-11,000 steps a day'- should prevent appearance of insomnia in third trimester, will increase sleep quality and quality of life in pregnant women. ClinicalTrials.gov Identifier: NCT03735381 . Registered 8th November, 2018.


[Progresses in the orthopedic-reconstructive surgery by microsurgery (author's transl)].
After a short description of the microsurgical technique for operations of periphere nerves and small vessels, the possibilities for reconstructive operations in orthopedic surgery are demonstrated. The actual experiences allow a critical but also cautious prospective statement.


Establishment and characterization of a canine xenograft model of inflammatory mammary carcinoma.
Canine inflammatory mammary cancer (IMC) and human inflammatory breast cancer (IBC) are the most aggressive form of mammary/breast cancer. Both species naturally develop it, sharing epidemiological, clinical and histological characteristics. Thus, IMC has been suggested as a model to study the human disease. We have developed the first IMC xenograft model in SCID mice. Xenografts reproduced the histological features from the primary tumor, were highly aggressive and showed dermal tumor emboli, distinctive hallmarks of IMC/IBC. This model was hormone receptors positive and HER2 negative. Our findings showed that estrogens and androgens are locally produced in tissues. Factors related to tumor vascularization showed positive expression and xenografts with the highest expression of all analyzed vascular factors had the highest rate of tumor proliferation. The role of steroid hormones and the angio/lymphangiogenic properties found in this model, provide additional knowledge for future interventions in the diagnosis, treatment and prevention of the disease.


Postural mechanisms in asthma: importance for nocturnal symptoms.
The supine position impairs ventilatory function in patients with ongoing asthma. The response is dual: an immediate decrease on lying down, present in healthy persons as well, and a progressive decrease specific for asthmatics. The changes are counteracted by bronchodilators, but are not linked to a decreased plasma adrenaline level when supine. The progressive decrease is tentatively explained by an increased vagal tone induced by the resting body position, and is likely to be a key factor in nocturnal asthma.


Characterization of epidermal growth factor-like domain 7 (EGFL7) expression in normal endometrium and in the endometrium of women with poor reproductive outcomes.
Could epidermal growth factor-like domain 7 (EGFL7) be a factor involved in the preparation of the endometrium for implantation and could its dysregulation be implicated in poor reproductive outcomes? EGFL7 is highly expressed in the endothelium and glandular epithelium throughout the menstrual cycle; it is upregulated by stromal cells in secretory phase and appears strongly reduced in endometrial biopsies and isolated stromal cells of women with unexplained recurrent pregnancy loss (uRPL) and recurrent implantation failure (RIF). The secreted factor EGFL7, originally identified as a gene primarily expressed in endothelial cells, is also expressed by the mouse blastocyst and by mouse and human trophoblast cells. It regulates trophoblast migration and invasion by activating NOTCH1 signaling. NOTCH1 has been demonstrated to play a fundamental role in endometrial receptivity and its dysregulation may be involved in selected pregnancy complications characterized by altered endometrial receptivity, such as uRPL. This is an exploratory study for which 84 endometrial biopsies were collected from normally fertile women, as well as from women with uRPL and RIF. Samples were collected from women in both the proliferative and secretory phases of the menstrual cycle and stratified into three sub-groups according to the patient clinical history: 20 fertile women (8 in proliferative and 12 in secretory phase), 41 women with uRPL (6 in proliferative and 35 in secretory phase), and 27 women with RIF (8 in proliferative and 19 in secretory phase). Immunohistochemistry, real-time PCR, and western blot analyses were performed to study the expression of EGFL7 and NOTCH1, as well as the NOTCH target genes. Analysis of spatial and temporal distribution of EGFL7 in endometrial biopsies from fertile women revealed higher levels of EGFL7 in samples from the secretory phase compared to proliferative phase. The expected expression of EGFL7 in endothelial cells was shown as well as the novel, not previously reported, expression in endometrial glands and stromal cells. EGFL7 was significantly reduced in the endometrium of women with uRPL and RIF in the secretory phases and this was associated with a downregulation of the NOTCH1 signaling pathway. Human recombinant EGFL7 was able to activate the NOTCH1 signaling pathway in endometrial stromal cells (EndSCs) obtained from fertile women but not in cells from uRPL or RIF patients. EndSCs from fertile women and decidualized in vitro for three days showed an upregulation of EGFL7 expression, whereas cells obtained from women with uRPL and RIF and decidualized in vitro did not. This study was conducted with a relatively small number of patient samples. Although results are highly reproducible and consistent, additional observations from multicentric cohorts would strengthen the relevance of the data. Moreover, this is an in vitro study, which might only partially represent the in vivo conditions. Our results demonstrate for the first time that EGFL7 is new player involved in decidualization and provide new insights into the pathophysiology of selected implantation defects and early pregnancy complications. Our studies have revealed that alterations in EGFL7 expression and the consequent dysregulation of NOTCH signaling are potential underlying causes of RIF and uRPL. Our results might have therapeutic relevance, as the EGFL7/NOTCH pathway may represent a potential target for medical intervention. This study has been supported by the Grant for Fertility Innovation 2017 (Merck KGaA). There are no competing interests to disclose. Not applicable.


The role of triglycerides in atherosclerosis.
Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD) and increasingly important in the setting of current obesity and insulin resistance epidemics. High triglyceride (TG) levels are markers for several types of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at significant risk for CVD even if low-density lipoprotein cholesterol levels are at goal, and therefore warrant treatment that optimizes diet, reduces overweight, and promotes regular exercise. High-risk patients with hypertriglyceridemia, such as those with diabetes, CVD, or metabolic syndrome, may benefit from additional drug treatment aside from a statin to address other lipid abnormalities. In this discussion, we review the role of hypertriglyceridemia and its associated atherogenic lipoproteins in the pathogenesis of atherosclerosis, the relevance of a high TG level as a predictor of CVD, the cardiovascular outcomes from TG-lowering intervention trials, and the current guidelines for treating hypertriglyceridemia.


Changing the Discourse in Ambitions Towards Universal Health Coverage: Lessons From Australian Primary Healthcare Comment on "Universal Health Coverage for Non-communicable Diseases and Health Equity: Lessons From Australian Primary Healthcare".
While Australia's health system has reached universal health coverage (UHC), recent scholarship points to its strengths and identifies ways it could be more effective and equitable, especially for tackling non-communicable diseases (NCDs). Building on the Australian experience, we add to these perspectives and present pertinent lessons for the quest towards UHC, and for policy-makers globally with regard to NCDs. Potential lessons include: the need for (i) vigilance - UHC requires ongoing monitoring and evaluation of not only financial risk protection but non-financial barriers and impacts such as forgone care; (ii) investment and action now on structural determinants of NCDs and related inequalities to avoid potentially higher (fiscal, social and health) costs in the longer term; and (iii) the opportunity for policy-makers globally and nationally to revisit their ambitions for UHC to include population health policies/ programs beyond essential health services that are required for healthier, more equitable and thriving societies.


Eradication of urinary tract infection following spinal cord injury.
A prospective study to evaluate the microbiological efficacy of antimicrobial treatment for urinary tract infection (UTI) was performed in 64 catheter-free spinal cord injured (SCI) patients who were visited monthly by a public health nurse who collected urine for culture and urinalysis. Patients also mailed urine dip slides for weekly bacterial counts. UTI was defined as a culture yielding > or = 100,000 colonies/ml. Treatment was given to asymptomatic patients only if pyuria (> or = 10 urinary leukocytes/high powered microscopic field) was present. Initial treatment was for 7-14 days (group 1). When it became apparent during the study that eradication was difficult and relapse or reinfection frequently occurred within a short time after cessation of antibiotic, a second treatment course of > or = 28 days (group 2) was given. By the end of the study, in which all patients were followed for a minimum of 30 days post treatment, 39/42 (93%) cases in group 1 and 11/13 (85%) in group 2 who had initial eradication, had relapsed or become reinfected. The median number of days and standard error for group 1 to relapse or become reinfected was 16 +/- 2.5, and for group 2 it was 27 +/- 6. Development of drug resistance was documented when bacteria isolated prior to any treatment were compared with strains isolated after > or = 28 days of antibiotics. In this study, urine sterility was achieved in a minority of treated UTIs and was relatively short lived.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic manipulations in aquaculture: a review of stock improvement by classical and modern technologies.
The aim of this review was to highlight the extent to which the genetic technologies are implemented by the aquaculture industry. The review shows that some of the modern genetic technologies are already extensively applied by the diverse aquaculture industries, though not to the same extent for all important aquacultured species (according to FAO 1998 figures). Some species (common carp, Atlantic salmon, rainbow trout, channel catfish, Nile tilapia, and the Pacific oyster) received concentrated breeding efforts, while other major cultured species (Chinese and Indian carps and the giant tiger shrimp) received, so far, relatively limited attention, and a few species (Yesso scallop, blue mussel, white Amur bream, and milkfish) have, apparently, not been genetically improved at all. Most of the genetically improved strains reaching the aquaculture industry were developed through traditional selective breeding (selection, crossbreeding, and hybridization). Emerging, more modern technologies for genetic manipulation seem to take 10-20 years from being established experimentally until applications affect the industry. Thus, chromosome-set and sex manipulations started to affect the industry during the 1980's and 1990's. DNA marker technology and gene manipulations have yet hardly affected the industry. The former have not matured yet, but hold much promise. The latter could have affected the industry already had it not been restricted by public concern.


Antibacterial activity of ticarcillin in the presence of clavulanate potassium.
The antibacterial effects produced by ticarcillin disodium plus clavulanate potassium, a combination of the broad-spectrum penicillin ticarcillin, and the beta-lactamase inhibitor clavulanic acid as the potassium salt, have been measured in vitro and in experimental infection studies. The presence of clavulanic acid resulted in a significant enhancement of the activity of ticarcillin against a wide range of beta-lactamase-producing bacteria. These included ticarcillin-resistant strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris, Yersinia enterocolitica, and the anaerobe Bacteroides fragilis. In addition, beta-lactamase-producing isolates of Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, and Staphylococcus aureus were susceptible to ticarcillin and clavulanate. Clavulanic acid did not influence the activity of ticarcillin against ticarcillin-susceptible bacteria. The bactericidal effects of the antibiotic combination were measured in an in vitro kinetic model in which the drug concentrations were varied to simulate those measured in humans after intravenous dosing with ticarcillin (3.0 g) and clavulanate potassium (100 mg clavulanic acid). In these tests, ticarcillin plus clavulanic acid had pronounced bactericidal activity against ticarcillin-resistant bacteria. The protection of ticarcillin by clavulanic acid from inactivation by bacterial beta-lactamases in vivo was demonstrated in experimental infection models in which the efficacy of the ticarcillin plus clavulanic acid combination against infections caused by beta-lactamase-producing bacteria was correlated with the presence of effective concentrations of both antibiotic and inhibitor at the site of infection.


Synthesis, crystal structure, DNA and protein binding studies of novel binuclear Pd(II) complex of 6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-4(N,N)-dimethylthiosemicarbazone.
A novel binuclear palladium(II) complex [(AsPh3)2ClPd(L)PdCl] (LPd2) has been synthesized by reacting 2-oxo-1,2-dihydroquinoline-3-carbaldehyde-4(N,N)-dimethylthiosemicarbazone (HL) with [PdCl2(AsPh3)2], and the molecular structure was confirmed by single crystal X-ray diffraction studies. The DNA interactions of the free ligand and of the complex have been evaluated by absorption and ethidium bromide (EB) competitive studies which revealed that the complex could interact with calf thymus DNA (CT-DNA) through intercalation. In addition, the interactions with bovine serum albumin (BSA) were also studied showing that the new binuclear palladium complex had a strong binding affinity with BSA.


Vasoactive mediators (VEGF and TNF-alpha) in patients with malignant and tuberculous pleural effusions.
Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen that promotes angiogenesis, vascular hyperpermeability, and vasodilatation by autocrine mechanisms involving nitric oxide (NO). This study was undertaken to determine the potential role of VEGF in the pathogenesis of pleural effusions, and its relationship with tumour necrosis factor (TNF)-alpha and NO in the pleural fluid and serum of patients with tuberculous and malignant pleural effusions. Pleural fluid and serum (SE) VEGF, TNF-alpha and NO levels were measured in 30 patients with exudative pleural effusion (15 with malignancies and 15 with tuberculosis). Control pleural fluid was obtained from 10 patients with transudative pleural effusion due to congestive heart failure and control serum samples were obtained from 10 healthy individuals. VEGF and TNF-alpha were measured by enzyme-linked immunosorbent assay and NO by a colorimetric method. Pleural biopsy, cytology or microbiological methods were used to make the final diagnosis. In patients with exudative pleural effusions, the mean pleural fluid and serum VEGF levels and their ratios (P < 0.0001 for all) and TNF-alpha levels (P < 0.01, P < 0.0001 and P < 0.05) were significantly elevated compared to those with transudative pleural effusion. In malignant effusions, pleural fluid and serum VEGF levels were significantly elevated (P < 0.001 and P < 0.0001) while pleural fluid, and serum levels and their ratios of TNF-alpha (P < 0.001, P < 0.01 and P < 0.05) were significantly lower than those in tuberculosis. NO levels did not distinguish between tuberculous and malignant effusions. In patients with malignant pleural effusions, levels of VEGF were significantly higher, while levels of TNF-alpha were significantly lower, than in patients with tuberculous effusions. In malignant pleural effusions, the elevated pleural fluid levels of VEGF and TNF-alpha are noteworthy. Our data support the hypothesis that blockade of VEGF, might benefit cancer patients with recurrent ascites or pleural fluid accumulation.


Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation.
To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF4), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGI2) (2 to 8 ng/kg/min) on PF4, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF4, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGI2 infusion resulted in a significant decrease of PF4 at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF4 levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF4 levels. The value of PF4 coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 +/- 28.9 vs 4.2 +/- 3.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of novel skeletogenesis target genes by comprehensive analysis of a Runx2(-/-) mouse model.
Runx2 is an essential factor for skeletogenesis and heterozygous loss causes cleidocranial dysplasia in humans and a corresponding phenotype in the mouse. Homozygous Runx2-deficient mice lack hypertrophic cartilage and bone. We compared the expression profiles of E14.5 wildtype and Runx2(-/-) murine embryonal humeri to identify new transcripts potentially involved in cartilage and bone development. Seventy-one differentially expressed genes were identified by two independent oligonucleotide-microarray hybridizations and quantitative RT-PCR experiments. Gene Ontology analysis demonstrated an enrichment of the differentially regulated genes in annotations to terms such as extracellular, skeletal development, and ossification. In situ hybridization on E15.5 limb sections was performed for all 71 differentially regulated genes. For 54 genes conclusive in situ hybridization results were obtained and all of them showed skeletal expression. Co-expression with Runx2 was demonstrated for 44 genes. While 41 of the 71 differentially expressed genes have a known role in bone and cartilage, we identified 21 known genes that have not yet been implicated in skeletal development and 9 entirely new transcripts. Expression in the developing skeleton was demonstrated for 21 of these genes.


Measuring actual reduction of risk to child abuse: a new approach.
Previous efforts to measure the effectiveness of child abuse prevention programs have relied on proximate measures presumed to be predictive of actual skills. This paper presents documentation that brings those assumptions into question, describes actual observation and measurement of behavioral change in children before and after prevention education, and correlates that behavioral response with more traditional measures of effectiveness. Unique to the evaluation was the staging of an actual situation in which each of the children had an opportunity to leave the school building with a stranger. Each simulation was videotaped and conducted in such a way that the children remained unaware of the fact that they had been tested. In addition, tests of language development, self-esteem and knowledge of prevention and safety concepts were administered before and after participating in the Children Need to Know Personal Safety Training Program [1]. Several findings have significant value for future examinations and programming. The effectiveness of a primary prevention program based on age-appropriate, experiential and interactive instruction was empirically documented. Traditional instrumentation which elicits written or verbal responses to cognitive questions about safety may be misleading in assessing children's vulnerability. Higher self-esteem before instruction and higher knowledge/attitude scores after instruction were found to be predictive of a reduction in vulnerability. While this is a significant series of findings, some children did not achieve the objectives of the prevention program. These results suggest further possibilities for evaluation and some direction for improving prevention education.


Circulating MicroRNAs and Extracellular Vesicle-Containing MicroRNAs as Response Biomarkers of Anti-programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Therapy in NSCLC.
Anti-programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) antibody therapy is a standard treatment for advanced NSCLC, and PD-L1 immunohistochemistry is used as a predictive biomarker for therapeutic response. However, because not all patients with NSCLC with high PD-L1 respond, and some patients with low PD-L1 expression exhibit durable benefit, more accurate predictive biomarkers are needed. Circulating microRNA (miRNA) and miRNA packaged in extracellular vesicles (EVs) are believed to play a role in intercellular communication among immune cells and between immune cells and tumor cells and may represent a good source of mechanism-related biomarkers. Pretreatment plasma of patients with advanced NSCLC treated with single-agent anti-PD-1 or anti-PD-L1 antibody was used in this study. Plasma EVs were isolated using size-exclusion chromatography. Whole plasma and EV-containing RNAs were extracted. The miRNA profile was analyzed with a next-generation sequencing platform. Samples from 14 responders (patients who exhibited partial response or stable disease ≥6 mo) and 15 nonresponders (patients who exhibited progressive disease as per Response Evaluation Criteria in Solid Tumors) were analyzed. In total, 32 miRNAs (p = 0.0030-0.0495) from whole plasma and seven EV-associated miRNAs (p = 0.041-0.0457) exhibited significant concentration differences between responders and nonresponders. The results of some of these circulating miRNAs were validated in a separate cohort with eight responders and 13 nonresponders. The tumor PD-L1 level was also assessed using immunohistochemistry for patients involved in both cohorts. Specific circulating miRNAs in whole plasma and plasma EVs are differentially expressed between responders and nonresponders and have potential as predictive biomarkers for anti-PD-1/PD-L1 treatment response.


Low blood lead levels impair intellectual and hematological function in children from Cartagena, Caribbean coast of Colombia.
Lead produces numerous biochemical and physiological changes in humans, including hematological disorders, toxic effects on the central nervous system and in the function of several organs. The aim of this study was to determine blood lead levels (BLL) in children from Cartagena, Colombia, associating those with hematological and liver damage markers, the intelligence quotient (IQ), as well as with gene expression of the aminolevulinate dehydratase (ALAD), superoxide dismutase 1 (SOD1), gamma interferon (INF-γ), tumor necrosis factor (TNF) and tumor protein (p53). To achieve this purpose, 118 blood samples were collected from children 5-16 years old, with their respective informed consent from their parents. BLL was measured by atomic absorption; hematological parameters were obtained with automated systems; plasma was utilized to analyze hepatic toxicity markers, alanine aminotransferase (ALT), gamma-glutamyltransferase (γ-GT) and alkaline phosphatase (ALP); the Kaufman Brief Intelligence Test (K-BIT) was administered to measure the IQ; and gene expression was quantified from blood RNA. The mean BLL was 1.7±0.3μg/dL. A low proportion of the children (3.4%) had BLL above the CDC recommended limit (5μg/dL). BLL were correlated weakly, but negatively with child age, weight, height, body mass index, platelets wide distribution, mean platelet volume, γ-GT and IQ. There were not significant changes in the expression of evaluated genes. These results support the hypothesis that BLL below 5μg/dL may still be a detrimental factor on children's cognitive abilities, development and hematology, in line with recent concerns that there is no safe level of pediatric lead exposure.


Efficient low-cost chromatin profiling with CUT&Tag.
We recently introduced Cleavage Under Targets & Tagmentation (CUT&Tag), an epigenomic profiling strategy in which antibodies are bound to chromatin proteins in situ in permeabilized nuclei. These antibodies are then used to tether the cut-and-paste transposase Tn5. Activation of the transposase simultaneously cleaves DNA and adds adapters ('tagmentation') for paired-end DNA sequencing. Here, we introduce a streamlined CUT&Tag protocol that suppresses DNA accessibility artefacts to ensure high-fidelity mapping of the antibody-targeted protein and improves the signal-to-noise ratio over current chromatin profiling methods. Streamlined CUT&Tag can be performed in a single PCR tube, from cells to amplified libraries, providing low-cost genome-wide chromatin maps. By simplifying library preparation CUT&Tag requires less than a day at the bench, from live cells to sequencing-ready barcoded libraries. As a result of low background levels, barcoded and pooled CUT&Tag libraries can be sequenced for as little as $25 per sample. This enables routine genome-wide profiling of chromatin proteins and modifications and requires no special skills or equipment.


Cytogenetic activity of some common antioxidants and their interaction with x-rays.
Experiments were designed to investigate the cytogenetic activity of some commonly used phenolic antioxidants, namely BHA, BHT, BMP and PG, all used widely to preserve and stablize food products rich in fats and oils. Barley and onion were used as test systems. The treatments reduced seed germination and induced a significant amount of seedling injury. Only PMP treatments produced a moderate amount of chromosomal aberrations while others failed to do so. Being strong antioxidants it was expected that these compounds would reduce the cytogenetic damage caused by the radiations. Contrary to expectations, however, a significant increase was observed in the radiation damage measured as seed and seedling lethality and chromosomal aberrations. Chemical post-treatments also increased the radiation damage. The damage was, however, reduced with ATP post-irradiation treatment.


ENT and general practice: a study of paediatric ENT problems seen in general practice and recommendations for general practitioner training in ENT in Ireland.
A questionnaire survey of 225 general practitioners was carried out to establish the proportion of their workload formed by paediatric ENT problems. Approximately 50% of children seeking medical care from their general practitioners had problems in this area. Infections of the upper respiratory tract and associated organs were the most commonly dealt with complaints. The monthly referral rate by GPs of paediatric patients in their practice to an ENT outpatient clinic was 4.3%. As ENT problems are seen so commonly in general practice it is important that teaching of otolaryngology at undergraduate and postgraduate levels is emphasised. We examined the present teaching structure of ENT in Irish universities and established that the appointment of a professorial unit dramatically improved the extent of the undergraduate curriculum. Non-specialist postgraduate ENT exposure was found to be inadequate and a number of mechanisms to improve postgraduate ENT training for GPs are suggested.


Humoral and cellular immune responses to a hepatitis B vaccine booster 15-18 years after neonatal immunization.
Whether hepatitis B (HB) vaccine-conferred immunity persists into adulthood is unknown. We aimed to investigate long-term HB immunity in adolescents. In 2004-2005, 6156 high school students (15-21 years old) who had been vaccinated with plasma-derived HB vaccine as infants were recruited for HB seromarker screening. The immune response to an HB vaccine booster was evaluated in 872 subjects who were seronegative. HB surface antibody (anti-HBs) titers and levels of HB surface antigen (HBsAg)-specific interferon (IFN)-gamma- or interleukin (IL)-5-secreting peripheral blood mononuclear cells (PBMCs; measured by enzyme-linked immunospot assay) were determined 4 weeks later. Although the vaccine remained highly efficacious in reducing the HBsAg positivity rate, 63.0% of the vaccinees had no protective anti-HBs. After the booster, anti-HBs remained undetectable in 28.7% (158/551) of the subjects who had received complete HB vaccination (4 doses) during infancy. We estimated that 10.1% of the total population had lost their HB vaccine-conferred booster response. HBsAg-specific IFN-gamma- or IL-5-secreting PBMCs remained negative in 27.2% (25/92) of subjects after the booster. A notable proportion of fully vaccinated adolescents had lost immune memory conferred by a plasma-derived HB vaccine 15-18 years later. This decay of immune memory may raise concerns about the need for a booster vaccine for high-risk groups in the long run.


Maintenance of IL-12-responsive CD4+ T cells during a Th2 response in Leishmania major-infected mice.
BALB/c and anti-IL-12-treated C3H mice infected with Leishmania major develop a Th2 cell response. However, in contrast to BALB/c mice, C3H mice treated transiently with an anti-IL-12 monoclonal antibody switch from a Th2 to a Th1 response and resolve their lesions once treatment is terminated. We report here that the critical difference in the Th2 response between BALB/c and C3H mice is in their ability to respond to IL-12. Thus, C3H mice with a Th2 response maintain a CD4+ T cell population that expresses IL-12 receptor beta1 and beta2 mRNA and produces IFN-gamma after exposure to IL-12. These results indicate that Th2 cell populations from different genetic backgrounds differ in their stability, and that this difference can be related to differential regulation of the IL-12 receptor.


The effects of intravenous and oral cimetidine in primary hyperparathyroidism.
In vitro studies suggest that cimetidine affects parathyroid hormone secretion. It has been reported that cimetidine (Ci) reduces serum immunoreactive parathyroid hormone (iPTH) in hyperparathyroid subjects (HPTH) and chronic renal failure patients. Studies were performed to determine the effects of intravenous and 8 days of oral Ci on serum iPTH, total calcium (TCAL), ionized calcium (ICAL), phosphorus (PHO), and magnesium (MAG), as well as on the urinary excretion of calcium, PHO, and cAMP. Ci, 300 mg, was injected intravenously into 11 HPTH and 9 of these received normal saline as a control. Eight normal subjects (N) were similarly studied. Results analyzed by analysis of variance indicated that although IV Ci and placebo both caused a significant change with time in iPTH, in HPTH and N, the fall was greater with Ci (P less than 0.005). Intravenous Ci decreased iPTH in HPTH approximately 36% (P less than 0.001) and N approximately 25% (P less than 0.025). In HPTH and N, ICAL was affected by neither IV cimetidine nor placebo. IV Ci decreased TCAL and MAG in a similar fashion when compared to placebo, though change in each variable was statistically insignificant. In 6 HPTH an 8 day period of oral Ci, 300 mg every 8 hours, produced no consistent changes in the measured serum variables. In summary, though the acute effect of IV Ci was to reduce iPTH, it appears to have no independent effect on ICAL or TCAL. Oral Ci during an 8 day period of administration had no consistent effect on mineral metabolism. We conclude that the therapeutic efficacy of oral Ci in HPTH has yet to be demonstrated.


Prognostic role of myocardial performance index on long-term survival after heart transplantation: a prospective study.
The survival rate of heart transplant patients is increasing, underlying the need for accurate predictors of adverse events during clinical follow-up. Myocardial performance index (MPI) is a Doppler-derived index of combined systolic and diastolic function: we assessed the prognostic role of MPI in survival of patients >1 year after heart transplantation (HT). A total of 152 consecutive HT patients referred to our institution were enrolled in this prospective study. Primary endpoints were cardiac death and a composite of major adverse cardiac events (MACE). During follow-up (69 ± 22 months), 68 (44.7%) patients had an adverse event and 20 (13.15%) patients died. Patients with MACE during follow-up showed lower EF (57.3 ± 9.3 vs. 63 ± 6.1; P < 0.001) and higher MPI (0.45 ± 0.19 vs. 0.31 ± 0.13; P < 0.001) at enrolment. MPI and EF were independently related to MACE (OR = 2.2; 95% confidence interval [CI] = 1.01-5.1; and OR = 6.6; 95% CI = 3.5-11.2, respectively) and showed strong diagnostic power (MPI: receiver operating characteristic [ROC] area = 79%, with 79% sensitivity and 81% specificity; EF: ROC area = 77%, with 54% sensitivity and 91% specificity) in the subsequent year. Patients with EF > 50% and MPI < 0.45 at enrolment showed 75% event-free survival 5 years after HT. In HT patients, MPI combined with EF was an accurate means of predicting long-term adverse events.


Molecular characterization of a suspected IMP-type carbapenemase-producing Pseudomonas aeruginosa outbreak reveals two simultaneous outbreaks in a tertiary-care hospital.
To describe IMP-type carbapenemase-producing Pseudomonas aeruginosa outbreaks at Galdakao University Hospital between March 2021 to December 2021. Outbreak report. Galdakao University Hospital is a tertiary-care hospital in the Basque Country (northern Spain). All patients with a positive IMP-type carbapenemase producing Pseudomonas aeruginosa (IMP-PA) culture were included in this study, both colonization and infection cases. An outbreak investigation was conducted, in which molecular epidemiology analysis [pulsed-field gel electrophoresis and whole-genome sequencing (WGS)] and environmental screenings were performed. Between March and December 2021, 21 cases of IMP-PA were detected in Galdakao University Hospital: 18 infection cases and 3 colonization cases. In total, 4 different pulsotypes were detected belonging to 4 clones according to WGS: ST175 (n = 14), ST633 (n = 3), ST179 (n = 3), and ST348 (n = 1). IMP-13 was detected in most isolates belonging to the ST175 clone and in all ST179 and ST348 clones, whereas IMP-29 was detected in isolates belonging to the ST633 clone. Clinical isolates belonging to the ST175 clone were isolated mainly from patients admitted to the respiratory ward, and isolates belonging to the ST633 clone from patients admitted to the ICU. Two environmental isolates belonging to the ST175 clone were detected in the respiratory ward. Molecular and genomic epidemiology revealed that there had been 2 independent IMP-PA outbreaks, one of long duration in the respiratory ward and the other more limited in the ICU.


[Epidemiology and etiopathogenesis of oral carcinoma: current aspects].
This work reviews all the data actually known about the epidemiology and the etiopathogenesis of the oral cancer. Based on an exhaustive literature review, this paper analyses the epidemiological and etiopathogenic factors of the oral cancer.


WITHDRAWN: Dealing with COVID-19 in small European island states: Cyprus, Iceland and Malta.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Fast, simple and efficient salting-out assisted liquid-liquid extraction of naringenin from fruit juice samples prior to their enantioselective determination by liquid chromatography.
In this study, an easy, simple and efficient method for the determination of naringenin enantiomers in fruit juices after salting-out-assisted liquid-liquid extraction (SALLE) and high-performance liquid chromatography (HPLC) with diode-array detection (DAD) was developed. The sample treatment is based on the use of water-miscible acetonitrile as the extractant and acetonitrile phase separation under high-salt conditions. After extraction, juice samples were incubated with hydrochloric acid in order to achieve hydrolysis of naringin to naringenin. The hydrolysis parameters were optimized by using a half-fraction factorial central composite design (CCD). After sample preparation, chromatographic separation was obtained on a Chiralcel® OJ-RH column using the mobile phase consisting of 10mM aqueous ammonium acetate:methanol:acetonitrile (50:30:20; v/v/v) with detection at 288nm. The average recovery of the analyzed compounds ranged from 85.6 to 97.1%. The proposed method was satisfactorily used for the determination of naringenin enantiomers in various fruit juices samples.


Estrogen receptors and the metabolic network.
The metabolic syndrome has reached pandemic level worldwide, and evidence is that estradiol plays a key role in its development. The discovery of the second estrogen receptor, ERβ, in tissues previously not considered targets of estradiol was a breakthrough in endocrinology. In the present review, we discuss how the presence of ERβ and the previously described ERα in tissues involved in glucose and lipid homeostasis (brain, skeletal muscle, adipose tissue, pancreas, liver, and heart) may have important implications to risk factors associated with the metabolic syndrome. Imbalance of ERα/ERβ ratio in this "metabolic network" may lead to the metabolic syndrome.


Mesosternal bristle number in a cosmopolitan drosophilid: an X-linked variable trait independent of sternopleural bristles.
Mesosternal (MS) bristles in Drosophila are a pair of machrochaetae found at the sternal end of the sternopleural (STP) microchaetae, and are thought to be invariable. In a closely related drosophilid genus, Zaprionus, their number is four and, in contrast to Drosophila, they show interspecific and intraspecific variability. The genetic basis of MS bristle number variability was studied in Z. indianus, the only cosmopolitan species of the genus. The trait responded rapidly to selection and two lines were obtained, one lacking any bristles (0-0) and the other bearing the normal phenotype (2-2). Other symmetrical phenotypes, (1-1) and (3-3), could also be selected for, but with lesser success. By contrast, STP bristle number did not vary significantly between the two lines (0-0) and (2-2), revealing its genetic independence from MS bristle number. Reciprocal crosses between these two lines showed that MS bristle number is mainly influenced by a major gene on the X chromosome (i.e. F(1) males always resembled their mothers) with codominant expression (i.e. heterozygous F(1) females harboured an average phenotype of 2 bristles). However, trait penetrance was incomplete and backcrosses revealed that this variability was partly due to genetic modifiers, most likely autosomal. The canalization of MS bristle number was investigated under different temperatures, and the increased appearance of abnormal phenotypes mainly occurred at extreme temperatures. There was a bias, however, towards bristle loss, as shown by a liability (developmental map) analysis. Finally, when ancestral and introduced populations were compared, the latter were far less stable, suggesting that genetic bottlenecks may perturb the MS bristle number canalization system. MS bristle number, thus, appears to be an excellent model for investigating developmental canalization at both the quantitative and the molecular level.


Identification of key genes and associated pathways in KIT/PDGFRA wild‑type gastrointestinal stromal tumors through bioinformatics analysis.
Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet‑derived growth factor receptor α (PDGFRA) wild‑type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild‑type GIST samples compared with KIT/PDGFRA mutant GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was conducted using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology‑Based Annotation System (KOBAS) online tools, respectively. Protein‑protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub‑networks using the Molecular Complex Detection (MCODE) plug‑in. Furthermore, enrichment analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were identified, including 238 upregulated genes primarily enriched in 'cell adhesion', 'biological adhesion', 'cell‑cell signaling', 'PI3K‑Akt signaling pathway' and 'ECM‑receptor interaction', while the 308 downregulated genes were predominantly involved in 'inflammatory response', 'sterol metabolic process' and 'fatty acid metabolic process', 'small GTPase mediated signal transduction', 'cAMP signaling pathway' and 'proteoglycans in cancer'. A total of 25 hub genes were obtained and four modules were mined from the PPI network, and sub‑networks also revealed these genes were primarily involved in significant pathways, including 'PI3K‑Akt signaling pathway', 'proteoglycans in cancer', 'pathways in cancer', 'Rap1 signaling pathway', 'ECM‑receptor interaction', 'phospholipase D signaling pathway', 'ras signaling pathway' and 'cGMP‑PKG signaling pathway'. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild‑type GISTs, including phosphatidylinositol‑4,5‑bisphosphate 3‑kinase, catalytic subunit γ, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb‑B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results.


Mass production of C50 carotenoids by Haloferax mediterranei in using extruded rice bran and starch under optimal conductivity of brined medium.
Microbial carotenoids have potentially healthcare or medical applications. Haloferax mediterranei was difficult to economically grow into a large quantities as well as producing a valuable pigment of carotenoids. This study reports a novel investigation into the optimal conductivity on the mass production of carotenoids from H. mediterranei. The major component at about 52.4% in the extracted red pigment has been confirmed as bacterioruberin, a C50 carotenoids, by liquid chromatography separation and mass spectrometry analysis. By maintaining higher conductivity of 40 S/m in the brined medium, the cell concentration attained to 7.73 × 10(9) cells/L with low pigments concentration of 125 mg/L. When the conductivity was controlled at about 30 S/m, we obtained the highest cell concentration to 1.29 × 10(10) cells/L with pigments of 361.4 mg/L. When the conductivity was maintained at optimal 25 S/m, the pigments can be increased to maximum value of 555.6 mg/L at lower cell concentration of 9.22 × 10(9) cells/L. But conductivity below 20 S/m will cause the significant decrease in cell concentration as well as pigments due to the osmotic stress around the cells. Red pigment of carotenoids from an extremely halophilic archaebacterium could be efficiently produced to a high concentration by applying optimal conductivity control in the brined medium with extruded low-cost rice bran and corn starch.


In alkaline aqueous solution, the sedimentation coefficients of DeoxyHb, HbO(2) and HbCO of Lampetra fluviatilis L. are 1.9 +/- 0.1 S. This value corresponds to a molecular weight of about 17,000, i.e. the value of a single haem polypeptide chain. In weak acidic conditions, both the non-liganded DeoxyHb and the liganded forms, HbO2 and HbCO, associate to form dimers and oligomers. The monomer-oligomer transitions of these compounds take place at different pH values: DeoxyHb pHO.5 approximately 6.7; HbO(2) and HbCO pH(O.5) approximately 5.9. With respect to the association modus, the equilibrium: 4 Hb &rlhar2; 2 Hb(2)&rlhar2;Hb(4) may be preferred.


Special uses of a gas chromatograph-mass spectrometer in endocrinology.
Based on the isotope dilution principle, and using deuterium-labelled steroids as tracers combined with GC-MS analysis, clinically acceptable procedures for the measurement of daily urinary production rates (UPR's) and metabolic clearance rates (MCR's), of hormonal steroids, have been developed. In clinical tests, using progesterone and androstenedione as models the UPR's and MCR's obtained compared favourably with values obtained using radioisotope-labelled tracers. The heavy isotope procedure proved, however, to be superior to the radioisotope methods in accuracy, speed and patient safety.


Differential Power Analysis as a digital forensic tool.
Electronic payment fraud is considered a serious international crime by Europol. An important part of this fraud comes from payment card data skimming. This type of fraud consists of an illegal acquisition of payment card details when a user is withdrawing cash at an automated teller machine (ATM) or paying at a point of sale (POS). Modern skimming devices, also known as skimmers, use secure crypto-algorithms (e.g. Advanced Encryption Standard (AES)) to protect skimmed data stored within their memory. In order to provide digital evidence in criminal cases involving skimmers, law enforcement agencies (LEAs) must retrieve the plaintext skimmed data, generally without having knowledge of the secret key. This article proposes an alternative to the current solution at the Bundeskriminalamt (BKA) to reveal the secret key. The proposed solution is non-invasive, based on Power Analysis Attack (PAA). This article first describes the structure and the behaviour of an AES skimmer, followed by the proposal of the full operational PAA process, from power measurements to attack computation. Finally, it presents results obtained in several cases, explaining the latest improvements and providing some ideas for further developments.


Contributions from the 2019 Literature on Bioinformatics and Translational Informatics.
Summarize recent research and select the best papers published in 2019 in the field of Bioinformatics and Translational Informatics (BTI) for the corresponding section of the International Medical Informatics Association Yearbook. A literature review was performed for retrieving from PubMed papers indexed with keywords and free terms related to BTI. Independent review allowed the section editors to select a list of 15 candidate best papers which were subsequently peer-reviewed. A final consensus meeting gathering the whole Yearbook editorial committee was organized to finally decide on the selection of the best papers. Among the 931 retrieved papers covering the various subareas of BTI, the review process selected four best papers. The first paper presents a logical modeling of cancer pathways. Using their tools, the authors are able to identify two known behaviours of tumors. The second paper describes a deep-learning approach to predicting resistance to antibiotics in Mycobacterium tuberculosis. The authors of the third paper introduce a Genomic Global Positioning System (GPS) enabling comparison of genomic data with other individuals or genomics databases while preserving privacy. The fourth paper presents a multi-omics and temporal sequence-based approach to provide a better understanding of the sequence of events leading to Alzheimer's Disease. Thanks to the normalization of open data and open science practices, research in BTI continues to develop and mature. Noteworthy achievements are sophisticated applications of leading edge machine-learning methods dedicated to personalized medicine.


Vascular endothelial growth factor C/A 2578 gene polymorphism and umbilical artery Doppler in preeclamptic women.
Preeclampsia is strongly associated with placental hypoperfusion. Genetic factors have an impact on the pathogenesis of preeclampsia. The aim is to assess the association of Vascular Endothelial Growth Factor (C2578A) gene polymorphism with the occurrence and severity of preeclampsia and the umbilical artery Doppler changes among preeclamptic women. This case-control study was conducted in clinical and Chemical pathology and Obstetrics departments in Beni- Suef University, Egypt. Two hundred and ninety pregnant women above 20 weeks gestational age until delivery were divided into 2 main groups. The patient group included 145 preeclamptic women who were further sub grouped according to the severity of preeclampsia into 82 severe and 63 mild cases. Control group included 145 normotensive pregnant women. Our primary outcome was detection of VEGF C 2578 A gene mutations by a polymerase chain reaction. A secondary outcome was Doppler changes in the pulsatility index of the umbilical artery compared with VEGF genotypes. Our study showed that VEGF C 2578 A genotype and alleles frequencies were not related to the occurrence of preeclampsia (p-value 0.513 and 0.549, respectively), odds ratio (95%CI) 1.154 (0.724-1.848). Mild preeclamptic cases showed no significance comparing VEGF genotypes studied and pulsatility index of the umbilical artery. However, severe cases showed p-value < 0.0001. We concluded that VEGF 2578C/A polymorphism had no association with the occurrence of preeclampsia in studied groups, whereas there was a significant relationship among severe cases between CA and CC genotypes and pulsatility index of the umbilical artery.


Catecholaminergic and opioidergic mechanisms involved in the hypotensive response of pindolol.
The present study evaluated the involvement of opioidergic and catecholaminergic mechanisms in the hypotensive action of pindolol. Pindolol (1 mg/kg i.a.) was administered to unanesthetized spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats instrumented for direct arterial pressure monitoring. Peripheral administration of pindolol produced a significant decrease in blood pressure in both SHR and WKY rats with SHR animals having a greater response. Heart rate was reduced in SHR; however, a tachycardia was observed in WKY rats. Pretreatment with naloxone (100 micrograms/kg i.a.) 10 min prior to pindolol administration prevented the hypotensive response. Similar pretreatment with yohimbine, an alpha 2-receptor antagonist, also prevented the pindolol-induced hypotensive response in both SHR and WKY rats. Neither naloxone nor yohimbine alone significantly affected blood pressure or heart rate. These results suggest that opioidergic and catecholaminergic mechanisms are involved in the hypotensive action of pindolol.


Rationale and design of the Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS Cognitive and Affective sub study (KEEPS Cog).
This manuscript describes the study design and rationalle for the Kronos Early Estrogen Prevention Study (KEEPS) and the KEEPS Cognitive and Affective ancillary study (KEEPS Cog). KEEPS is a multicenter, randomized, double-blinded, placebo-controlled trial, designed to test the hypothesis that low-dose hormone therapy (HT) initiated in recently postmenopausal women will reduce the progression of subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC) over four years. The KEEPS Cog ancillary study was designed to assess potential estrogenic treatment effects on cognition and mood. We present the KEEPS trial in the context of issues raised by the Women's Health Initiative (WHI) and the Women's Health Initiative Memory Study (WHIMS). Here we also describe the most recent results and ongoing HT-related research studies designed to address similar issues. This article is part of a Special Issue entitled Hormone Therapy.