Substrate and electrode potential affect electrotrophic activity of inverted bioanodes.
Electricity-consuming microbial communities can serve as biocathodic catalysts in microbial electrochemical technologies. Initiating their functionality, however, remains a challenge. One promising approach is the polarity inversion of bioanodes. The objective of this study was to examine the impact of bioanode substrate and electrode potentials on inverted electrotrophic activity. Bioanodes derived from domestic wastewater were operated at -0.15V or +0.15V (vs. standard hydrogen electrode) with either acetate or formate as the sole carbon source. After this enrichment phase, cathodic linear sweep voltammetry and polarization revealed that formate-enriched cultures consumed almost 20 times the current (-3.0±0.78mA; -100±26A/m(3)) than those established with acetate (-0.16±0.09mA; -5.2±2.9A/m(3)). The enrichment electrode potential had an appreciable impact for formate, but not acetate, adapted cultures, with the +0.15V enrichment generating twice the cathodic current of the -0.15V enrichment. The total charge consumed during cathodic polarization was comparable to the charge released during subsequent anodic polarization for the formate-adapted cultures, suggesting that these communities accumulated charge or generated reduced products that could be rapidly oxidized. These findings imply that it may be possible to optimize electrotrophic activity through specific bioanodic enrichment procedures.


[Morphologic changes in an artery feeding an arteriovenous aneurysm over a long period following its embolization].
Different materials are used in operations for embolization of arteriovenous aneurysms on which radical operation cannot be performed. A case is described with successful embolization by means of silicon-tantulum balls of vessels supplying a giant arteriovenous aneurysm. The patient died 6 years after operation from recurrent massive hemorrhage with escape of blood into the ventricles. Morphological examination of the artery revealed neither necrotic or inflammatory changes in its walls at the site of the embolism.


Myocardial infarction and cerebrovascular accident following non-cardiac surgery: differences in postoperative temporal distribution and risk factors.
Myocardial infarction and stroke after non-cardiac surgery are two ominous cardiovascular complications believed to share similar pathophysiological processes. However, the differences in the temporal distribution between them have not been adequately investigated in a large cohort of patients. The preoperative clinical features and daily occurrence of myocardial infarction and stroke were routinely recorded in 36 634 consecutive patients following elective non-cardiac, non-carotid surgery. The preoperative characteristics and postoperative daily distribution of postoperative myocardial infarction and stroke were compared using exponential and linear regressions models. Myocardial infarction and stroke occurred in 122 (0.33%) and 126 (0.34%) patients, respectively, during the first 30 days after surgery. More patients with myocardial infarction had diabetes mellitus and cardiac disease (P = 0.041 and <0.0001, respectively) whereas more patients with stroke were older and female (P = 0.003 and 0.038, respectively). The peak incidence of myocardial infarction was on the day of surgery (43%) and declined exponentially thereafter (F = 725.4, P < 0.0001). However, postoperative stroke best fitted a linear regression with almost even daily distribution (F = 15.9, P = 0.0004). The median time to myocardial infarction was one day [95% confidence interval (95% CI) = 0-2 days] compared with nine days (95% CI = 7-11 days) for stroke. The peak incidence of postoperative myocardial infarction is early after non-cardiac surgery and declines exponentially thereafter, as opposed to stroke, which occurs at a constant rate during the postoperative period. Myocardial infarction and cerebrovascular accident following non-cardiac surgery differ in their preoperative risk factors, and in the postoperative time-line of their occurrence.


Short-term distribution, metabolism, and excretion of 2,2',5-tri-, 2, 2',4,4'-tetra-, and 3,3',4,4'-tetrachlorobiphenyls in prepubertal rats.
The excretion and tissue retention of three 14C-labeled lower chlorinated biphenyls were examined in prepubertal male and female Sprague-Dawley rats following IV administration. Urine and feces were collected individually at different time intervals up to 72 h for pharmacokinetic analyses. After 72 h, different organs were removed and extracted in acetone:hexane (1:1, v/v) to determine radioactivity. Within the first 10 h after dosing, 2,2', 5-trichlorobiphenyl (PCB 18) was rapidly excreted in urine (8-18% of the administered dose), whereas only 0.6-0.8% of 2,2',4, 4'-tetrachlorobiphenyl (PCB 47) and 0.3-0.8% 3,3',4, 4'-tetrachlorobiphenyl (PCB 77) were found in urine during this time period. The half-life of elimination was shortest for PCB 18 (37.5 to 49.2 h). The half-lives for PCB 47 and PCB 77 were 351 to 672 h and 152 to 186 h, respectively. The cumulative total excretion (urinary + fecal) of PCB 18 within 72 h was 51-62%, of PCB 77 was 22-25%, and of PCB 47 was 7-10%. No parent PCBs were detected in urine. PCB 47 accumulated preferentially in adipose tissues (subcutaneous fat > mesenteric fat); relatively high levels of PCB 47 were also found in adrenals, ovaries, lungs, liver, and skin. The highest concentration of PCB 77 was found in serum, followed by adipose tissues. Very low concentrations of PCB 18 were found in most tissues; the highest being found in serum, followed by ovaries and adrenal glands. This study suggests that prepubertal rats retain higher short-term serum levels and have lower excretion rates than adult rats.


Relationship between apoptosis and expression of heat shock proteins in peripheral blood lymphocytes of patients with myocardial infarction.
We studied activity and dynamics of apoptosis of peripheral blood lymphocytes in patients with myocardial infarction and analyzed the relationship of these processes with expression of heat shock proteins with a molecular weight of 70 kDa playing an essential role in preventing cell death. Thus, we first demonstrated activation of apoptosis in peripheral blood cells of patients with myocardial infarction compared to the control (healthy individuals) and revealed the expected negative correlation between the expression of heat shock proteins with a molecular weight of 70 kDa by lymphocytes and intensity of their death. The observed dynamics of mononuclear cell apoptosis in the peripheral blood of patients with myocardial infarction can reflect activity of programmed cardiomyocyte death in the focus of ischemic injury.


Unawareness of having hypertension, dyslipidemia, and diabetes among medicated individuals.
The objectives of this study were to assess the level of disease awareness in medicated patients with hypertension, dyslipidemia, or diabetes and to identify potential predictors of unawareness. A total of 17,323 participants who visited an institution for a medical checkup between 2009 and 2017 were investigated retrospectively. Disease unawareness was defined as taking medication for a disease but not being aware of having that disease. Among the medicated participants, 10% (169/1658), 30% (278/919), and 5% (21/389) were unaware of having hypertension, dyslipidemia, and diabetes, respectively. Multivariate analysis identified male sex as an independent predictive factor for unawareness of having hypertension. Participants who had an alcohol consumption habit, higher body mass index (BMI), or higher systolic blood pressure had a lower risk of hypertension unawareness. Male sex and BMI were identified as independent predictive factors for unawareness of having dyslipidemia. Participants with higher hemoglobin A1C levels were at decreased risk of diabetes unawareness. A relatively large number of medicated participants were unaware of the disease they were being treated for. Explanatory factors for disease unawareness included male sex, no alcohol consumption, lower BMI, and disease-related factors, such as lower blood pressure and hemoglobin A1C levels.


A novel Schmallenberg virus subunit vaccine candidate protects IFNAR-/- mice against virulent SBV challenge.
Schmallenberg virus (SBV), an arthropod-transmitted pathogenic bunyavirus, continues to be a threat to the European livestock industry, causing morbidity and mortality among young ruminant livestock. Here, we describe a novel SBV subunit vaccine, based on bacterially expressed SBV nucleoprotein (SBV-N) administered with a veterinary-grade Saponin adjuvant. When assayed in an IFNAR-/- mouse model, SBV-N with Saponin induced strong non-neutralizing broadly virus-reactive antibodies, decreased clinical signs, as well as significantly reduced viremia. Vaccination assays also suggest that this level of immune protection is cell mediated, as evidenced by the lack of neutralizing antibodies, as well as interferon-γ secretion observed in vitro. Therefore, based on these results, bacterially expressed SBV-N, co-administered with veterinary-grade Saponin adjuvant may serve as a promising economical alternative to current SBV vaccines, and warrant further evaluation in large ruminant animal models. Moreover, we propose that this strategy may be applicable to other bunyaviruses.


Pulmonary nontuberculous mycobacterial infections and environmental factors: A review of the literature.
Pulmonary nontuberculous mycobacterial (pNTM) infection is mainly acquired through the inhalation of bioaerosols. Nevertheless, behavioural restrictions are rarely given by clinicians to susceptible populations, in part because the available guidelines for pNTM management emphasize more diagnosis and treatment than prevention. Aim of this review is to clarify if pNTM prevention should routinely include recommendations about risk reducing behaviors. We used PubMed as biomedical database. We limited our search to the publication period 2000 to 2020 with selected keyword combinations including "nontuberculous mycobacteria", "water", "soil", and "exposure". Titles and abstract of selected articles were systematically screened. Articles were included in the analysis if they were published under free access through the digital library of the University of Brescia (Italy), and provided full text either in English, French, German or Italian. Articles were excluded if the topic was beyond the aim of our study. Finally, we selected 20 articles. Studies disagree in identifying the type of aerosol posing the highest risk for the development of pNTM infection. In the retrieved publications the colonization of household niches has been associated with a higher risk of pNTM disease, such as in the exposure to shower aerosols. Considering the non-household settings, the exposure to aerosols in indoor swimming and the higher soil exposure (>2 h/week) seem to correlate with a higher risk to develop pNTM disease. According to our findings, randomized behavioural intervention studies are missing. Stringent scientific evidence is missing to formulate recommendations on behavioural risk reduction for pNTM.


International travel in times of the COVID-19 pandemic: The case of German school breaks.
The COVID-19 pandemic has triggered severe global restrictions on international travel with the intention of limiting the spread of SARS-CoV-2 across countries. This paper studies the causal effect of the partial relaxation of these travel restrictions in Europe on the COVID-19 incidence in Germany during the summer months of 2020. It exploits the staggered start of the summer school breaks across German states as an exogenous shock to the travel opportunities of the population. While the school breaks also increased mobility within Germany, the event-study type regressions precisely control for domestic mobility and local COVID-19-related restrictions. The intention-to-treat effects of the relaxed travel restrictions show a significant and sizable increase of the COVID-19 incidence in German counties during the later weeks of the school breaks. Part of the increase can be attributed to a mandatory testing regime for travel returnees from high-incidence areas.


Production of knockout mice by gene targeting in multipotent germline stem cells.
Spermatogonial stem cells can convert into embryonic stem (ES) cell-like multipotent germline stem (mGS) cells in vitro and produce germline chimeras by blastocyst microinjection. Although homologous recombination was previously demonstrated in mGS cells, spermatogenesis was not found in chimeras, suggesting that they are not competent for germline modification. Here we conducted detailed analysis of chimeric animals to determine whether mGS cells retain germline potential after genetic manipulation. Spermatozoa that were deficient in the occludin gene could be recovered from animals that were chimeric with mGS cells that underwent homologous recombination. The phenotypes of the occludin knockout (KO) mice were similar to those reported for KO mice produced using ES cells, and the animals showed growth retardation, gastritis and male infertility. Furthermore, we found that heterozygous mGS cells acquire two copies of the G418-resistant genes and become homozygous for the targeted allele by culturing at high concentrations of G418. Cytogenetic analysis showed that the aneuploid mGS cells observed during genetic manipulation were trisomic for chromosome 8 or 11, which is a common chromosomal abnormality in ES cells. Thus, mGS cells can be used to produce KO animals, and this novel method of germline manipulation may prove useful in diverse mammalian species.


The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively bred High-Responder and Low-Responder rats.
Individual differences in exploratory behavior can predictably influence psychostimulant self-administration behavior. Male rats that exhibit a high degree of locomotor activity in a novel environment (High Responders, HR) will self-administer cocaine more readily than males exhibiting low levels of novelty-induced locomotion (Low Responders, LR). The present experiment investigates the combined influences of the sex of an individual and individual phenotypes in novelty-induced locomotion to predispose animals to acquire cocaine self-administration behavior, in male and female rats selectively bred for the HR-LR phenotypes. We first established that HR females, like their male counterparts, exhibit a dramatically greater locomotor response to novelty and less anxiety-like behavior than do LR females. While locomotor behavior was subtly influenced by estrous stage, with both HR and LR females showing increased activity during metestrus and diestrus compared to proestrus and estrus, the effect did not obscure HR-LR differences. When male and female HR-LR animals were trained to self-administer cocaine (2 h/day, 5 days/wk x 3 wk, 0.2 mg cocaine/kg/infusion), HR males and females acquired cocaine self-administration significantly faster than their LR counterparts. Furthermore, HR females self-administered significantly more cocaine than all other groups. In conclusion, female rats, like males, exhibit HR-LR phenotypes that predict rapidity of acquiring cocaine self-administration. Moreover, HR females self-administer more cocaine than HR males and both LR groups.


Ruxolitinib attenuates intimal hyperplasia via inhibiting JAK2/STAT3 signaling pathway activation induced by PDGF-BB in vascular smooth muscle cells.
Cardiovascular diseases are associated with proliferation and phenotypic switch. Platelet-derived growth factor-BB (PDGF-BB) is a major initiating factor for proliferative vascular diseases, such as neointimal lesion formation, restenosis after angioplasty, and atherosclerosis. Ruxolitinib, a potent Janus kinase (JAK) 1 and 2 inhibitor, has been reported to significantly block the proliferation-related signaling pathway of JAK2/signal transducers and activators of transcription 3 (STAT3) and harbor a broad spectrum of anti-cancer activities, including proliferation inhibition, apoptosis induction, and anti-inflammation. However, the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation remains to be elucidated. Thus, this study investigates the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation and its underlying mechanisms. In vivo, the medial thickness of the carotid artery was evaluated using a mouse carotid ligation model, ruxolitinib was administered orally to the mice every other day, and the mice were euthanized on day 28 to evaluate the therapeutic effects of ruxolitinib. Cell proliferation markers were measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. In vitro, VSMCs were treated with ruxolitinib with or without PDGF-BB at an indicated time and concentration. Cell proliferation and apoptosis were measured using Cell Counting Kit-8 assay, MTS assays and flow cytometry. The JAK2/STAT3 signaling pathway involved in the effects of ruxolitinib on VSMCs was detected by western blotting with the specific pathway inhibitor AG490. In vivo, ruxolitinib significantly decreased the ratio-of-intima ratio (I/M ratio) by inhibiting the expression of PCNA and cyclinD1 (p <0.05). In vitro, ruxolitinib inhibited PDGF-BB-induced VSMC proliferation compared with the PDGF-BB treatment group (p <0.05). In addition, ruxolitinib inhibited the PDGF-BB-induced activation of the JAK2/STAT3 signaling pathway and decreased the expression of proliferation related-proteins cyclinD1 and PCNA in VSMCs (p <0.05). Our findings suggest that ruxolitinib inhibits VSMC proliferation in vivo and in vitro by suppressing the activation of the JAK2/STAT3 signaling pathway. Therefore, ruxolitinib has a therapeutic potential for proliferative vascular diseases.


Lessons from Theranos - Restructuring Biomedical Innovation.
After raising more than $700 million, Elizabeth Holmes, the founder and chief executive officer of a healthcare startup once valued at $10 billion, was found guilty on four charges of defrauding investors. Founded in 2003, Theranos Inc. was a privately held corporation that aimed to disrupt the diagnostics industry with rapid, direct-to-consumer laboratory testing using only "a drop of blood" and the company's patented Nanotainer technology. By exploiting gaps in regulatory policy, Theranos brought its panel of laboratory tests to patients without pre-market review or validation from peer-reviewed scientific research. Investigations into Theranos' dubious operations and inaccurate test results exposed the failed venture which had squandered millions of dollars. Theranos affected the lives and health of patients further disrupting an already tenuous relationship between healthcare and the public - the importance of which cannot be understated in the setting of the COVID-19 pandemic. As medical systems address a national public health crisis and pervasive structural inequities, we must align stakeholder incentives between industry and academic biomedical innovation to rebuild trust with our patients.


In vivo incorporation of lauric acid into rat adipose tissue triacylglycerols.
An in vivo approach was taken to examine fatty acid esterification in adipose tissue using a coconut oil-enriched diet. Rats were fed a diet containing coconut oil (50% lauric acid) for six weeks. Triacylglycerols from perirenal adipose tissue were fractionated by silver nitrate-thin layer chromatography and, then, preparative gas chromatography. The distribution of 169 triacylglycerol types accounting for 97% of total triacylglycerols was determined. There was evidence for a very high content of mixed triacylglycerols composed of intermediate (12:0 and 14:0) and long acyl moieties. No significant differences were observed between the experimental distribution of triacylglycerol types and the random distribution, calculated from the total fatty acid composition. This indicated that most long chain triacylglycerols stored before coconut oil feeding would have been rearranged after the six weeks of coconut oil feeding. The experimental proportion of trilauroylglycerol reached 2%, as expected from its random proportion, and the proportions of dilauroylacylglycerols were slightly higher than the random values. Present results were compared with those previously obtained from triacylglycerols of adipose tissue of rats fed a low-fat standard diet. From our results and those of other authors, it is suggested that lauric acid is a good substrate for sn-glycero-3-phosphate acyltransferase and diacylglycerol acyltransferase in rat adipose tissue.


Correlated variations in EEG pattern and visual responsiveness of cat lateral geniculate relay cells.
1. Simultaneous recordings of the EEG and the visual activity of cat dorsal lateral geniculate nucleus (dLGN) relay cells were analysed for covariance. Sliding time-window analyses were performed in parallel for the EEG power spectrum and single unit visual activity. The EEG power ratio (EEG-PR) of low (1-8 Hz) to high (20-40 Hz) frequencies was chosen to achieve a quantitative measure of the EEG which could be compared with the spike rate of a dLGN unit at any time. A high EEG-PR value indicates a synchronized EEG dominated by low frequencies (delta waves and sleep spindles), a low value indicates a less synchronized EEG. 2. In the anaesthetized animal, two different underlying patterns of activity in the EEG-PR were found: slow gradual changes (slow gradations) and oscillatory changes. In many cases both were accompanied by correlated variations in dLGN spike rate, either for overall activity or for burst firing. 3. The slow gradations appear for long time periods of up to 200 s and, in most cases (76.3 %), show a negative correlation between EEG-PR and overall spike rate, but predominantly a positive correlation for burst firing (85.1 %). 4. The oscillatory changes, which have not previously been reported, appear as temporally well-coupled variations in EEG-PR and spike rate with a stable cycle length within the range 4-10 s. In about 77 % of correlated changes the temporal delay between the change in EEG-PR and that of the spike rate was less than +/- 1.0 s. 5. During simultaneous recordings from two dLGN cells the variations in spike rate tend to show the same sign of correlation with respect to the EEG pattern. This relationship is more pronounced with the slow gradations than with the oscillatory changes. 6. Slow gradations in the spectral composition of the EEG may indicate global transitions between different stages within the sleep-wake cycle, reflecting the well-known influences of the brainstem arousal system. The oscillations in the spectral composition of the EEG are accompanied by gradual variations in thalamic transmission mode and are more likely to be due to involvement of a local feedback system via the thalamo-cortico-thalamic loop. The difference between the effects on overall and burst firing activity supports the notion that phasic (burst firing) and tonic visual responses may play distinctive roles in information processing, which are functionally related to the animal's behavioural state.


The null oncogene hypothesis and protection from cancer.
Tumour progression involves the inactivation of tumour suppressor genes and the activation of proto-oncogenes. Inactivation of both copies of a tumour suppressor gene is required for carcinogenesis, while germline deletion or inactivation of one copy results in an increase in the risk of cancer and is responsible for many of the known hereditary cancer syndromes. In contrast, activation of only one copy of a proto-oncogene is required for carcinogenesis. Germline deletion or inactivation of one copy of a proto-oncogene halves the risk of activation at this locus. We propose that studies of high risk cancer patients will show such "null oncogene" mutations.


Contiguous Genome Sequence of Frankia sp. Strain ArI3, Isolated from Root Nodules of Alnus rubra Bong.
We report the genome sequence of Frankia sp. strain ArI3, recovered as a single contig from one run of the Oxford Nanopore Technologies (ONT) MinION instrument. The genome has a G+C content of 72%, is 7,541,222 bp long, and contains 5,427 predicted protein-coding genes.


Treatment of Hereditary Hemorrhagic Telangiectasia-Related Epistaxis.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an incidence of 1:5000. Recurrent, spontaneous epistaxis is the most common presenting symptom. Severity of epistaxis varies widely, from mild, self-limited nosebleeds to severe, life-threatening nasal hemorrhage. Treatment of HHT-related epistaxis presents a challenge to the otolaryngologist due to the recurrent, persistent nature of epistaxis often requiring multiple treatments. Treatment modalities range from conservative topical therapies to more aggressive surgical treatments.


Discussion: 'Physician gender, specialty, and hysterectomy utilization' by Gretz et al.
In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Gretz H, Bradley WH, Zakashansky K, et al. Effect of physician gender and specialty on utilization of hysterectomy in New York, 2001-2005. Am J Obstet Gynecol 2008;199:347.e1-347.e6.


"Who is first on the scene?".
Forensic specialists are well standardised throughout the world and their opinions are respected by the courts. Doctors involved in the immediate clinical forensic assessment of persons in police custody are not, however, so well standardised. Some countries employ trained police surgeons or police medical officers, other countries rely on hospital interns, others simply accept the first doctor available. Can courts rely on their testimony? Can specialists depend on their skills? A call is made for such generalists to meet on an international basis to establish standards.


Large-scale purification of the proton pumping pyrophosphatase from Thermotoga maritima: a "Hot-Solve" method for isolation of recombinant thermophilic membrane proteins.
Although several proton-pumping pyrophosphatases (H+-PPases) have been overexpressed in heterologous systems, purification of these recombinant integral membrane proteins in large amounts in order to study their structure-function relationships has proven to be a very difficult task. In this study we report a new method for large-scale production of pure and stable thermophilic H+-PPase from Thermotoga maritima. Following overexpression in yeast, a "Hot-Solve" procedure based on high-temperature solubilization and metal-affinity chromatography was used to obtain a highly purified detergent-solubilized TVP fraction with a yield around 1.5 mg of protein per litre of yeast culture. Electron microscopy showed the monodispersity of the purified protein and single particle analysis provided the first direct evidence of a dimeric structure for H+-PPases. We propose that the method developed could be useful for large-scale purification of other recombinant thermophilic membrane proteins.


Bovine Chromaffin Cells: Culture and Fluorescence Assay for Secretion.
Over the last four decades, chromaffin cells originating from the adrenal medulla have been probably one of the most popular cell models to study neurosecretion at the molecular level. Accordingly, numerous seminal discoveries in the field, including the characterization of role of the cytoskeleton, fusogenic lipids, and soluble N-ethylmaleimide-sensitivefactor attachment protein receptor (SNARE) proteins, have been made using this model. In this chapter, we describe a standard method currently used to isolate and culture bovine chromaffin cells, and we illustrate a catecholamine secretion assay based on the successive transformation of adrenaline into adrenochrome and adrenolutine for fluorescence measurements. We also provide some guidelines for efficient cell recovery and for the use of this assay in the laboratory.


Viability of dried vegetative trichomes, formation of akinetes and heterocysts and akinete germination in some blue-green algae under water stress.
Almost all dried vegetative trichomes ofAnabaena iyengarii, Westiellopsis prolifica andNostochopsis lobatus died within 1 h, while those ofOscillatoria acuminata retained viability to some extent for 1 d under similar storage conditions. The viability of dried vegetative trichomes ofO. acuminata decreased about equally on storage at 20 degrees C in the light or in the dark, but dropped rapidly at 12 and 0 degrees C in the dark. Vegetative trichomes ofA. iyengarii, N. lobatus andW. prolifica were more sensitive to frost than those ofO. acuminata, and this correlated with their low resistance to desiccation because both types of exposure involved osmotic stress. Both dried and wet akinetes ofA. iyengarii, W. prolifica andN. lobatus were about equally viable when stored at 20 degrees C in the light or the dark or at 12 and 0 degrees C in the dark, but their germination ability decreased on storage at 0 degrees C. The water stress imposed on growing vegetative trichomes either in high-agar media or in NaCl-supplemented liquid media reduced the survival ofO. acuminata trichomes, decreased or totally suppressed akinete and heterocyst formation and akinete germination inA. iyengarii, W. prolifica andN. lobatus. The sensitivity decreased in the sequenceA. iyengarii <W. prolifica ~N. lobatus. The akinete germination in all three blue-green algae was more sensitive to physiological water stress than their formation. In all of them, akinetes formed under water stress were equally viable as those formed under normal conditions. Trichomes ofO. acuminata became broader when grown in 0.5-0.8 mol/L NaCl-supplemented media, probably due to polyol accumulation, and they also developed a thin sheath-like structure.


Role of bilirubin in the prognosis of coronary artery disease and its relationship with cardiovascular risk factors: a meta-analysis.
Bilirubin is a heme catabolism product with antioxidant, anti-inflammatory, and anti-apoptotic properties and is implicated in the prognosis of several diseases. This study evaluates the prognostic role of bilirubin in coronary artery disease (CAD) patients. After identifying studies from the literature, meta-analyses were performed to achieve a) overall estimates of serum total bilirubin levels in patients with myocardial infarction (MI), non-MI CAD and healthy individuals; b) odds ratios (OR) of adverse outcomes between higher and lower total bilirubin levels; c) standardized mean difference (SMD) in total bilirubin levels in patients with high vs low CAD severity; and d) correlation between disease severity and total bilirubin. Metaregression analyses were performed to examine the relationship between cardiovascular risk factors and increasing quantiles of total bilirubin levels. Forty-three studies were identified. Pooled serum total bilirubin levels were 0.72 mg/dl [95% confidence interval (CI): 0.60, 0.83] in MI patients; 0.65 mg/dl [95% CI: 0.60, 0.69] in non-MI CAD patients; and 0.66 mg/dl [95% CI: 0.56, 0.75] in healthy individuals. Higher total bilirubin levels were associated with greater odds of adverse outcomes in MI patients (OR: 1.08 [95% CI: 0.99, 1.18]) but lower odds in non-MI CAD patients (OR: 0.80 [95%CI: 0.73, 0.88]). Compared to non-severe cases, total bilirubin levels were higher in patients with severe MI (SMD 0.96 [95% CI: - 0.10, 2.01]; p = 0.074) but were lower in severe non-MI CAD patients (SMD - 0.30 [95%CI: - 0.56, - 0.03]; p = 0.02). Total bilirubin levels correlated positively with MI severity (r = 0.41 [95% CI: 0.24, 0.59]; p < 0.01) but correlated negatively with non-MI CAD severity (r = - 0.17 [95% CI: - 0.48, 0.14]; p = 0.28). Female sex was inversely associated with increasing quantiles of bilirubin (meta-regression coefficient: - 8.164 [- 14.531, - 1.769]; p = 0.016) in MI patients. Prognostic role of bilirubin for CAD appears complicated, as different odds are observed for MI and non-MI CAD patients which weakens the case of causal involvement of bilirubin in CAD etiology or prognosis.


SSL2, a suppressor of a stem-loop mutation in the HIS4 leader encodes the yeast homolog of human ERCC-3.
Reversion of haploid, His4- yeast containing a stem-loop mutation in the 5' UTR that blocks HIS4 translation initiation identified four unlinked suppressor genes, SSL1-SSL4, which restore His4+ expression. The SSL2 gene encodes an essential 95 kd protein with ATP-dependent helicase motifs. SSL2 protein is 54% identical to the protein encoded by the human gene, ERCC-3, for which a defective form causes xeroderma pigmentosum and Cockayne's syndrome. An SSL2 allele made to resemble the defective ERCC-3 gene confers UV light hypersensitivity to yeast cells. Hence, SSL2 is the functional homolog of ERCC-3. However, the SSL2 suppressor gene does not restore HIS4 expression by removal of the stem-loop from DNA or the mRNA. We propose that SSL2 and ERCC-3 may have two functions, one defined by a UV repair defect, and a second essential function that is related to gene expression.


[Growth of rat fibroblasts in tissue culture as affected by trypsin immobilized on polyurethane substrates].
The growth of fibroblasts of the rat subcutaneous tissue was studied as affected by different doses of trypsin, free and bound, on polyurethane substrates. The method of tissue culture provides essential criteria for estimating the degree of bioincompatibility of polymeric alloimplants in particular when immobilizing biologically active substances on them. Trypsin adsorbed on the polyurethane substrate diffusing gradually into the culture medium is established to inhibit the cell growth. Chemically bounded trypsin in the composition of the polymeric matrix at the early stages of cultivation stimulates for a long time the division of fibroblastic elements and further accelerates their degeneration. It is shown that on polymeric substrates containing no trypsin, the growth character and dynamics of the fibroblastic elements are similar on the whole to these indices for cultures grown in the plasm clot without the substrate.


Introns in the Naa50 gene act as strong enhancers of tissue-specific expression in Arabidopsis.
Naa50 is the catalytic subunit of N-terminal acetyltransferase complex E, which plays an important role in regulating plant development, endoplasmic reticulum stress and immune responses in Arabidopsis. In this study, the complete genomic sequence (but not the coding sequence) of Naa50 rescued the phenotype of Naa50 deletion mutants. Naa50 expression was noted in whole roots except for central root cap cells. The deletion of intron 1 resulted in a loss of Naa50 expression in the root meristem zone and in the epidermis, cortex and endodermis of the elongation zone and mature zone, while the deletion of intron 2 decreased Naa50 expression in the epidermis, cortex and endodermis of the root elongation zone and mature zone. The native Naa50 promoter together with introns 1 and 2 promotes the expression of Naa50 in sepal vascular bundles, filaments, pollen and stigmas; however, neither intron has positive effect on Naa50 expression in mature rosette leaves. The results of this study show that introns 1 and 2 in the Naa50 gene function as enhancers to promote the tissue-specific expression of Naa50.


Detection of minor subpopulations of colorectal adenocarcinoma cells expressing cancer stem cell markers.
The expression of puitative surface molecular markers of cancer stem cells on human colorectal adenocarcinoma cells was analyzed by flow cytofluorometry. Cell subpopulations expressing markers of epithelial and malignant cells and stem cell markers were identified. Four minor subpopulations with CD24(+)/CD133(+), CD44(+)/CD133(+), CD90(+)/CD71(+), or CD90(+)/CD24(+) phenotypes meeting this requirement were detected; presumably, those were cancer stem cell subpopulations. These results extend our knowledge on heterogeneity of human colorectal adenocarcinoma cell population and outline new trends of research of cancer stem cell phenotype in these tumors.


Repair of burns of the scrotum using a gracilis myocutaneous flap.
An unusual case of isolated burns of the scrotum reconstructed by a unilateral gracilis myocutaneous flap is reported because of its clinical rarity.


A biometrical approach for determining the effects of treatment with a chemotherapeutic agent upon heart weight in the mature rabbit.
Changes in heart weight as attributable to treatments involving a chemotherapeutic agent (CTA) were studied using adult rabbits. CTA was administered to each subject three times a week until sacrifice. Dose level per administration was held constant with respect to mg of CTA per kgm of body weight. The level of treatment for a given animals was then determined by the length of time the animal was in the treatment program prior to sacrifice. At sacrifice, variations in heart weight were evaluated relative to sex, initial body weight, relative change in body weight and level of treatment. Regression techniques were used in the analysis of data. This procedures allowed for differentiation between the direct effects and indirect effects of treatment. The direct effect was shown to cause a significant increment in heart weight. The indirect effect as related to loss body weight was shown to lead to a significant decrement in heart weight.


Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney.
Clearance and micropuncture studies have been performed in dogs to examine the effects of acute and chronic metabolic acidosis and acute alkalosis on tubular sodium and calcium transport. Acute metabolic acidosis, induced by the infusion of hydrochloric acid, decreased proximal fluid reabsorption and increased the fractional delivery of sodium and calcium to the distal tubule, but not to the final urine. In comparison with normal dogs, dogs with chronic metabolic acidosis (induced by feeding ammonium chloride) showed an increase in proximal fluid reabsorption and a dissociation of calcium from sodium reabsorption more distally, leading to an increased delivery of calcium relative to sodium at the distal tubule and in the final urine. The infusion of sodium bicarbonate to correct chronic metabolic acidosis, both in intact and thyroparathyroidectomized (TPTX) dogs, reduced proximal fluid reabsorption and caused a selective enhancement of calcium reabsorption relative to sodium in the more distal nephron, resulting in a reversal of the dissociation observed in acidosis, both at the distal tubule and in the final urine. By contrastin fusion of sodium chloride in parathyroid-intact acidotic dogs did not reduce proximal fluid reabsorption or enhance tubular calcium reabsorption. In nonacidotic dogs, both intact and TPTX, infusion of sodium bicarconate to induce acute alkalosis resulted in selhese data demonstrate the presence of a component of tubular calcium reabsorption situated beyond the proximal tubule, which is inhibited by chronic (but not acute) metabolic acidosis and enhanced by metabolic alkalosis (or bicarbonate infusion) independently of parathyroid hormone.


Interleukin-2 production and activity in aged humans.
Peripheral blood mononuclear cells (PBMC) from aged humans were found impaired in their ability to mount T mitogen induced proliferative responses and NK cell activity. The production of IL-2 in response to PHA has also been found decreased in the aged subjects. When the data from IL-2 production and cellular responsiveness of aged and young groups were pooled for regression analysis, a significant correlation was found both for mitogenic responses and NK activity. The reduced proliferative responses and NK cell activity can be enhanced by exposing them to exogenous IL-2. However, they were not fully reconstituted to the levels achieved in PBMC of the young subjects supplemented in vitro with IL-2. This would indicate that the reduced cellular responsiveness in aging may be related both to a defect of IL-2 receptor expression on T cells of aged subjects and to an impairment in the endogenous IL-2 synthesis in the aged individuals.


Improving blunt cerebrovascular injury screening in motor vehicle collision patients: Does airbag deployment matter?
Motor vehicle collisions (MVCs) can cause blunt cerebrovascular injury (BCVI). Exploring MVC characteristics that increase BCVI may reduce missed injuries. This study aims to evaluate the association between airbag deployment and BCVI. We analyzed the 2016-Trauma Quality Improvement Database including adult MVC drivers. Patients were stratified: airbag deployment(A+) and no-airbag deployment(A-). Outcomes were BCVI, and cervical spine injuries (CSI). A total of 122,973 patients were identified: A+: 106,492, and A-: 16,481. The incidence of BCVI was 1907 (1.6%): and CSI was 20,711 (16.8%). A+ patients had a higher rate of BCVI (1.6% vs. 1.1%; p < 0.001), but a lower rate of CSI (16.2% vs. 21.4%; p < 0.001). On regression analysis, A+ was associated with BCVI (1.419[1.184-1.701]; p < 0.001) but was protective for CSI (0.767[0.672-0.878]; p < 0.001). A+ may be an unrecognized risk factor for BCVI even for patients without a CSI. Expanding BCVI screening criteria to include A+ may reduce missed injuries. Level III, prognostic.


Mandatory communication skills training for oncologists: enforcement does not substantially impact satisfaction.
Even though there is evidence that both patients and oncology clinicians are affected by the quality of communication and that communication skills can be effectively trained, so-called Communication Skills Trainings (CSTs) remain heterogeneously implemented. A systematic evaluation of the level of satisfaction of oncologists with the Swiss CST before (2000-2005) and after (2006-2012) it became mandatory. Levels of satisfaction with the CST were high, and satisfaction of physicians participating on a voluntary or mandatory basis did not significantly differ for the majority of the items. The evaluation of physicians' satisfaction over the years and after introduction of mandatory training supports recommendations for generalized implementation of CST and mandatory training for medical oncologists.


Myoelectric signals of levator palpebrae superioris as a trigger for FES to restore the paralyzed eyelid.
Some closed loop FES systems have been designed to restore the blinking function of facial paralysis patients. All of them used myoelectric signal of orbicularis oculi at the normal side as the trigger to stimulate the paralyzed side. They were limited to the one side facial paralysis. Here we proposed that the myoelectric signal of levator palpebrae superioris could be used as the trigger to stimulate the paralyzed orbicularis oculi. Because the levator palpebrae superioris and the innervating nerve are intact, the myoelectric signal of the paralyzed side still could be used as the trigger. It will be more acceptable for the patients and have the potential to resolve the bilateral facial paralysis.


Comparison of the influence of corneo-scleral and scleral lenses on ocular surface and tear film metrics in a presbyopic population.
To assess and compare the effect of the corneo-scleral lenses (C-ScL) and scleral lenses (ScL) on tear film parameters and central corneal thickness (CCT) in healthy presbyopic subjects. Thirty subjects wore two contact lenses (CLs), randomly assigned, of neutral power, but of different diameters, 12.7mm (C-ScL) and 18mm (ScL) and being equal in the others parameters: material (HS100) and centre thickness (0.29mm). At baseline, 20min after insertion and at 8h, the tear meniscus area (TMA) and CCT was measured (with optical coherence tomography) as well as tear osmolarity. TMA revealed statistical differences for both lenses at 20min (p<0.001), and also at 8h (p=0.003), being greater for the C-ScL. CCT showed statistical differences for both lenses at 20min (p=0.002), and also at 8h (p=0.001), being lower for the C-ScL. Osmolarity did not reveal statistical differences at 20min (p=0.29), while it was statistically different at 8h (p=0.03), being lower for the C-ScL. C-ScL lead to a lesser reduction in the TMA and a lower induced hypoxic stress than the ScL. Osmolarity levels remained within normal values across the day with no clinical difference between lenses. Both designs can represent a good optical platform for correcting presbyopia as well as protecting the ocular surface by vaulting the cornea.


Imaging of the Urinary and Reproductive Tract in Small Ruminants.
Ultrasound imaging is the mainstay of urinary and reproductive imaging in small ruminants, assisted by the relatively superficial location of the urinary and reproductive tracts in these species. Radiography can provide an excellent overview of the abdomen, but is often limited by a lack of adequate penetration. Computed tomography scans provide summation-free imaging of the urinary and reproductive tracts in addition to information about the excretion of contrast agent by the kidneys, but can be limited by availability and cost.


Posttraumatic stress disorder: a descriptive study supporting DSM-III-R criteria.
Posttraumatic stress disorder, as defined by DSM-III, remains a controversial diagnostic entity. This descriptive study, which was carried out by the author in a war zone, supports the changes made in the criteria in DSM-III-R.


The anammox coupled partial-denitrification process in an integrated granular sludge and fixed-biofilm reactor developed for mainstream wastewater treatment: Performance and community structure.
This study describes an integrated granular sludge and fixed-biofilm (iGB) reactor innovatively designed to carry out the anammox/partial-denitrification (A/PD) process for nitrogen removal with mainstream municipal wastewater. The iGB-A/PD reactor consists of anammox granules inoculated in the lower region of reactor and an acclimated fixed-biofilm positioned in the upper region. Compared to the other reported A/PD systems for mainstream wastewater treatment, this iGB-A/PD reactor is notable due to its higher quality effluent with a total inorganic nitrogen (TIN) of ∼3 mg•L-1 and operation at a high nitrogen removal rate (NRR) of 0.8 ± 0.1 kg-N•m-3•d-1. Reads-based metatranscriptomic analysis found that the expression values of hzsA and hdh, key genes associated with anammox, were much higher than other functional genes on nitrogen conversion, confirming the major roles of the anammox bacteria in nitrogen bio-removal. In both regions of the reactor, the nitrate reduction genes (napA/narG) had expression values of 56-99 RPM, which were similar to that of the nitrite reduction genes (nirS/nirK). The expression reads from genes for dissimilatory nitrate reduction to ammonium (DNRA), nrfA and nirB, were unexpectedly high, and were over the half of the levels of reads from genes required for nitrate reduction. Kinetic assays confirmed that the granules had an anammox activity of 16.2 g-NH4+-N•kg-1-VSS•d-1 and a nitrate reduction activity of 4.1 g-N•kg-1-VSS•d-1. While these values were changed to be 4.9 g- NH4+-N•kg-1-VSS•d-1and 4.3 g-N•kg-1-VSS•d-1 respectively in the fixed-biofilm. Mass flux determination found that PD and DNRA was responsible for ∼50% and ∼25% of nitrate reduction, respectively, in the whole reactor, consistent with high effluent quality and treatment efficiency via a nitrite loop. Metagenomic binning analysis revealed that new and unidentified anammox species, affiliated with Candidatus Brocadia, were the dominant anammox organisms. Myxococcota and Planctomycetota were the principal organisms associated with the PD and DNRA processes, respectively.


Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression and its association with genes regulating the VEGF signaling pathway in head and neck squamous cell carcinoma.
The PTGS2 gene codes for the cyclooxygenase-2 (COX-2) enzyme that catalyzes the committed step in prostaglandin (PG) synthesis. Various in-vivo and in-vitro data suggest that prostaglandin E2 mediates as a signaling molecule for activating the VEGF signaling pathway (VSP), forming an association between COX-2 and VSP. Several chemotherapy regimens increasingly rely on preventing the synthesis of PGs. The targeted and metronomic chemotherapy agents, which suppress the COX-2 enzymes, have a major role in suppressing the oral cancer cascade. Hence, this study was designed to understand the pattern of PTGS2 expression and genes regulating VSP in head and neck cancers. PTGS2 expression was analyzed in the TCGA database computationally with the help of the UALCAN web-server. The expression of VEGF signaling pathway genes was mined, and their expression pattern was determined. Co-expression analysis was done to elucidate the association between VEGF signaling genes and PTGS2. The ShineyGo web server was used for gene set enrichment. Significantly high PTGS2 expression was observed in tumor samples. Further genes regulating VEGF signaling were significantly overexpressed in tumor samples. Co-expression analysis results showed a significant positive correlation between PTGS2 and angiogenesis-regulating genes. The majority of the genes were enriched for angiogenesis pathways. PTGS2 was significantly expressed in head and neck cancer, and its expression was associated with genes regulating angiogenesis.


Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial.
Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic dermatitis. To demonstrate the superiority of difamilast ointment 1% to vehicle in adult Japanese patients with atopic dermatitis. In this phase 3, randomized, double-blind trial, patients aged 15-70 years with an investigator global assessment score of 2 or 3 received topical difamilast ointment 1% (n = 182) or a vehicle (n = 182) twice daily for 4 weeks. The success rate in investigator global assessment score at week 4 (primary endpoint)-the percentage of patients achieving an investigator global assessment score of 0 or 1 with ≥2-grade improvement-was significantly higher with 1% difamilast than with the vehicle (38.46% vs 12.64%, respectively, P < .0001). The success rates in ≥50%, ≥75%, and ≥90% improvement in overall eczema area and severity index score at week 4 followed the same trend. Difamilast at 1% provided significant mean percent improvement from baseline in overall eczema area and severity index score versus vehicle from week 1 to 4. Treatment-emergent adverse events were mostly mild or moderate and less frequent with difamilast. Study treatment was limited to 4 weeks. Difamilast ointment 1% demonstrated superiority to the vehicle and favorable safety in adult Japanese patients with atopic dermatitis.


Screening of Pharmaceutical Pollutants Along with Emerging Contaminants in the Sediments of the Periyar River, Located in Kerala (India) by Using High-Resolution Mass Spectrometry (UPLC-Q-ToF-MS).
In this study, ultra-performance liquid chromatography coupled with a quadruple time-of-flight mass spectrometry (UPLC-Q-ToF-MS) was employed to screen and identify pharmaceutical pollutants and emerging contaminants (ECs) in the Periyar River near Aster Medicity hospital, the dumping yard of Amrutha hospital, and the Vaduthala bridge regions in Kerala, India. The analysis was conducted in both positive and negative ionization modes using electrospray ionization (ESI). The QuEChERS method was employed for initial sediment sample preparation. Among the twenty-five identified ECs, four compounds were identified as pharmaceutical pollutants. This study have great significance as it represents the first comprehensive investigation of pharmaceutical pollutants in these hospital regions, highlighting the urgent need for further analysis and understanding of the situation. The presence of ECs poses an urgent need for attention due to the irreversible harm caused to the riverine ecosystem by the degradation of water quality resulting from industrial and domestic discharge.


¿ Can COVID-19 exacerbate multiple sclerosis symptoms? A case series analysis.
Peripheral inflammation can exacerbate pre-existing lesions in the Central Nervous System (CNS) in the context of neurodegenerative diseases, including Multiple Sclerosis (MS). To analyze the clinical effect of COVID-19 infection, as a generator of peripheral inflammation, in a MS patients group. A retrospective analysis of 400 medical records of MS patients from a referral center was carried out. MS patients who presented COVID-19 were surveyed about symptoms exacerbation: type, duration and onset of exacerbation, previous vaccination against COVID-19 and MS severity. Clinical and demographic information from the medical records were included. Descriptive and inferential analysis were performed using the GraphPad Prism V6. 41 patients were included, 61% (n = 25) reported neurological worsening, 9.7% (n = 4) as relapses, and 7.3% (n = 3) required corticosteroids. We found significant differences in the EDSS between patients who exacerbated their MS symptoms and those who did not (p = 0.03). When performing a multivariate regression analysis, we found that EDSS was independently associated with the presence of exacerbations of MS in the context of SARS-CoV2 infection (OR = 2.44, p = 0.022). This preliminary study suggests that COVID-19 infection could trigger exacerbations of MS symptoms. New studies are needed to elucidate the relationship between COVID-19 and MS.


Removal of enteric viruses and Escherichia coli from municipal treated effluent by zebra mussels.
Dreissena polymorpha is a widespread filter-feeder species, resistant to a broad range of environmental conditions and different types of pollutants,which has recently colonized Italian freshwaters. Although widely used to monitor pollution in freshwater environments, this species is also an important food source for some fish and water birds. It can also be used to concentrate or remove particulate organic matter to interrupt avian-to-human transmission of pollutants and control health risks for animals and humans. In this study, the accumulation/inactivation in D. polymorpha of human health-related spiked enteric viruses was described. The removal of endogenous Escherichia coli, the classical indicator of fecal contamination,was tested as well.Our preliminary lab-scale results demonstrate that zebra mussels can reduce significantly poliovirus titer after 24 h and rotavirus titer after 8 h. E. coli counts were also reduced in the presence of zebra mussels by about 1.5 log after 4 h and nearly completely after 24 h. The fate of the two enteric viruses after concentration by zebra mussels was also investigated after mechanical disruption of the tissues. To our knowledge, the accumulation from water and inactivation of human health-related enteric viruses by zebra mussels has never been reported.


Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics.
Rare cases of human herpesvirus 8 (HHV8)-negative effusion-based large B-cell lymphoma (EB-LBCL) occur in body cavities without antecedent or concurrent solid mass formation. In contrast to HHV8 + primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. However, the small sample sizes of case reports and series worldwide, especially from non-Japanese regions, have precluded diagnostic uniformity. Therefore, we conducted a retrospective, multi-institutional study of 55 cases of EB-LBCL and performed a comprehensive review of an additional 147 cases from the literature to identify distinct clinicopathologic characteristics. In our study, EB-LBCL primarily affected elderly (median age 80 years), immunocompetent patients and manifested as lymphomatous effusion without a solid component. The lymphomatous effusions mostly occurred in the pleural cavity (40/55, 73%), followed by the pericardial cavity (17/55, 31%). EB-LBCL expressed CD20 (53/54, 98%) and PAX5 (23/23, 100%). Most cases (30/36, 83%) were of non-germinal center B-cell subtype per the Hans algorithm. HHV8 infection was absent (0/55, 0%), while Epstein-Barr virus was detected in 6% (3/47). Clinically, some patients were managed with drainage alone (15/34, 44%), while others received rituximab alone (4/34, 12%) or chemotherapy (15/34, 44%). Eventually, 56% (22/39) died with a median overall survival (OS) of 14.9 months. Our findings were similar to those from the literature; however, compared to the non-Japanese cases, the Japanese cases had a significantly higher incidence of pericardial involvement, a higher rate of chemotherapy administration, and longer median OS. Particularly, we have found that Japanese residence, presence of pericardial effusion, and absence of MYC rearrangement are all favorable prognostic factors. Our data suggest that EB-LBCL portends a worse prognosis than previously reported, although select patients may be managed conservatively. Overall, EB-LBCL has distinct clinicopathologic characteristics, necessitating the establishment of separate diagnostic criteria and consensus nomenclature.


The impact of a high-risk disease management program on perinatal outcomes in a managed care organization.
Improvements in technology have increased the chances of survival for the micropremature infant and the very low birth-weight infant but have significantly increased the financial burden of health care organizations. This economic burden has a significant impact on third-party payers and on society in general. Of the annual US 10.2 billion dollars spent on newborn care alone, 57% is disproportionately consumed by the 10% of infants who are born preterm.


Hyoid expansion with titanium plate and screw: a human cadaveric study using computer-assisted airway measurement.
Hyoid expansion with suspension can potentially increase the upper airway at the hypopharyngeal level, benefitting patients with sleep-related breathing disorder. To document the effect of hyoid expansion using titanium plate and screw on retrolingual hypopharyngeal airway dimension and to compare the airway dimension after isolated hyoid expansion with hyoid expansion + hyomandibular suspension. Anatomical cadaveric dissection study. This study was performed in a laboratory setting using human cadavers. This is an anatomical feasibility study of hyoid expansion using titanium plate and screw on 10 cadaveric human heads and necks. The hyoid bone is trifractured with bony cuts made just medial to the lesser cornu. The freed hyoid body and lateral segments are expanded and stabilized to a titanium adaptation plate. Computer-assisted airway measurement (CAM) was used to measure the airway dimension at the hypopharynx at the level of the tongue base before and after the hyoid expansion. The expanded hyoid bone was then suspended to the mandible, and the airway dimension was measured again with CAM. Airway dimension after isolated hyoid expansion with hyoid expansion with hyomandibular suspension. RESULTS Hyoid expansion with titanium plate and screw resulted in statistical significant increase in the retrolingual hypopharyngeal airway space in all of the 10 human cadavers. The mean (SD) increase in retroglossal area was 33.4 (13.2) mm² (P < .005) (range, 6.0-58.7 mm²). Hyoid expansion with hyomandibular suspension resulted in a greater degree of airway enlargement. The mean (SD) increase in retroglossal area was 99.4 (15.0) mm² (P < .005) (range, 81.9-127.5 mm²). The retrolingual hypopharyngeal airway space increased with hyoid expansion using titanium plate and screw in our human cadaveric study, measured using CAM. The degree of increase is further augmented with hyomandibular suspension.


[Histologic diagnosis of African histoplasmosis (the first case of the disease in the USSR)].
The findings obtained from histological examination of a biopsy specimen enabled a case of African histoplasmosis to be first recorded in the USSR. The disease was detected in an African student who had had a long-term latent period. The diagnosis was culturally and clinically verified. The problems of the histological differential diagnosis of African histoplasmosis are also discussed.


Measurement of serum electrolytes and phosphate after sodium phosphate colonoscopy bowel preparation: an evaluation.
Our purpose was to observe the effects of sodium phosphate (NaP) colonoscopy preparation on serum electrolytes, phosphate, and calcium and to identify factors associated with any adverse effects. In an unselected group of 100 consecutive patients attending for out patient colonoscopy, 45% of patients had raised serum phosphate, which was positively correlated with creatinine and age. There was a negative association of phosphate with calcium; 16% of patients had hypocalcemia and 26% had hypokalemia. Patients taking ACE inhibitors, AT2 antagonists, or diuretics were associated with hyperphosphatemia. Significant electrolyte and metabolic disturbance from colonoscopy preparation has been shown with NaP preparation, without overt clinical effects. We recommend that elderly patients and those with significant comorbidity have their electrolytes and calcium measured, and diuretics and ACE inhibitors stopped, before NaP administration. Endoscopy units should be alert for patients who might be suffering from electrolyte disturbance postpreparation and be prepared to measure their electrolytes.


Second pregnancy with spontaneous ovulation following clomiphene- or gonadotropin-induced pregnancy.
For investigation of the rates of spontaneous pregnancy following termination of pregnancy induced by treatment with clomiphene or human menopausal gonadotropin-human chorionic gonadotropin (hMG-hCG) and of spontaneous abortion in the second pregnancy, 119 women (58 with an anovulatory cycle and 141 with amenorrhea) who desired another pregnancy were studied. The rate of spontaneous pregnancy following pregnancy induced by clomiphene was 46.6%, which was significantly (p less than 0.001) higher than that following pregnancy induced by hMG (14.9%). The mean (+/- SEM) period between the termination of the first induced-ovulation pregnancy and the second spontaneous pregnancy was 16.6 +/- 1.4 months. The spontaneous abortion rates in the second pregnancies after pregnancies induced by clomiphene and hMG were 7.5% and 9.8%, respectively, which were significantly (p less than 0.001, p less than 0.05) lower than those in the first pregnancy (25.7%, 33.0%). There was no difference between the spontaneous abortion rates following a first pregnancy which terminated in abortion and those following a pregnancy which ended in birth. These data suggest that a first pregnancy in anovulatory women may restore the ovulatory cycle and have a beneficial effect on the rates of spontaneous abortion in the second pregnancy.


Poor Understanding of Radiation Profiles in Deep Space Causes Inaccurate Findings and Misleading Conclusions.
The radiation environment in deep space, where astronauts are behind the shelter provided by the Earth's magnetosphere, is a major health concern. Galactic cosmic rays (GCR) and solar particle events (SPE) are two basic sources of space radiation in the solar system. The health risks of exposure to high levels of space radiation can be observed either as acute and delayed effects. Zhang et al. in their recently published paper entitled "γ-H2AX responds to DNA damage induced by long-term exposure to combined low-dose-rate neutron and γ-ray radiation" have addressed the effects of different cumulative radiation doses on peripheral blood cell, subsets of T cells of peripheral blood lymphocytes and DNA damage repair. These researchers exposed animals to low dose rate 60Co-rays at 0.0167 Gy h-1for 2 h/d and 252Cf neutrons at 0.028 mGy h-1for 20 h/d for 15, 30, or 60 consecutive days. They reported that the mRNA of H2AX increased significantly, and showed a positive correlation with dose. Despite strengths, this paper has several shortcomings such as poor definition of low dose radiation as well as space and reactor radiation environments. Another shortcoming of this paper comes from this point that blood cell studies do not represent the biological effects of ionizing radiation on the total body. Moreover, the effects of the human immune system and DNA repair mechanisms are not included in the study. The role of pre-exposures and induction of adaptive response phenomena in decreasing the risk of radiation in deep space missions are also ignored.


Role of nucleotide binding oligomerization domain-like receptor protein 3 inflammasome in stress-induced gastric injury.
The inflammasomes promote pro-caspase-1 cleavage, leading to processing of pro-interleukin (IL)-1β into its mature form. We investigated the role of the IL-1β and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in gastric injury in mice receiving water-immersion restraint stress (WIRS), focusing on the cyclooxygenase (COX)-2/prostaglandin (PG) E2 axis. To induce gastric injury, the mice were placed in a restraint cage and immersed in the water bath to the level of the xiphoid process. Protein levels of mature caspase-1 and IL-1β were assessed by western blotting. Water-immersion restraint stress induced gastric injury with increase in IL-1β expression by activation of NLRP3 inflammasome. Exogenous IL-1β attenuated the injury, whereas anti-IL-1β neutralizing antibody and IL-1β receptor antibody aggravated it. NLRP3-/- and caspase-1-/- mice enhanced the injury with reducing of mature IL-1β, and this aggravation was reduced by exogenous IL-1β supplementation. Toll-like receptor 4-/- mice were hyporesponsive to WIRS in terms of mature IL-1β production. Rabeprazole attenuated the injury with preventing inflammasome activation. WIRS injured the stomach with promotion of COX-2 mRNA and PGE2 production, and exogenous IL-1β enhanced these molecules, while IL-1β immunoneutralization exerted opposite effect. PGE2 supplementation abolished the hypersensitivity in NLRP3-/- and caspase-1-/- mice through negative regulation of inflammatory cytokines. These results suggest that NLRP3 inflammasome-derived IL-1β plays a protective role in stress-induced gastric injury via activation of the COX-2/PGE2 axis. Toll-like receptor 4 signaling and gastric acid may be involved in NLRP3 inflammasome activation.


Lipidomic landscape in cancer: Actionable insights for membrane-based therapy and diagnoses.
Cancer cells display altered cellular lipid metabolism, including disruption in endogenous lipid synthesis, storage, and exogenous uptake for membrane biogenesis and functions. Altered lipid metabolism and, consequently, lipid composition impacts cellular function by affecting membrane structure and properties, such as fluidity, rigidity, membrane dynamics, and lateral organization. Herein, we provide an overview of lipid membranes and how their properties affect cellular functions. We also detail how the rewiring of lipid metabolism impacts the lipidomic landscape of cancer cell membranes and influences the characteristics of cancer cells. Furthermore, we discuss how the altered cancer lipidome provides cues for developing lipid-inspired innovative therapeutic and diagnostic strategies while improving our limited understanding of the role of lipids in cancer initiation and progression. We also present the arcade of membrane characterization techniques to cement their relevance in cancer diagnosis and monitoring of treatment response.


Dynamics of Locomotor Fatigue during Supra-critical Power Exercise.
We aimed to measure 1) the dynamics of locomotor fatigue during constant supra-critical power cycling and 2) the magnitude of any reserve in locomotor power at intolerance to constant and ramp-incremental cycling in recreationally active volunteers. Fifteen participants (7 women and 8 men, 22 ± 3 yr, 3.34 ± 0.67 L·min V˙O2peak) completed ramp-incremental and very-heavy constant power (205 ± 46 W) exercise to the limit of tolerance. Immediately after intolerance, the ergometer was switched into the isokinetic mode, and participants completed a short (~5 s) maximal isokinetic effort at 70 rpm. The time course of locomotor fatigue during constant supra-critical power exercise was characterized with these short maximal isokinetic sprints at 30, 60, 120, and 180 s and at the limit of tolerance. Each bout was terminated after the isokinetic sprint. Constant power exercise duration was 312 ± 37 s. Isokinetic power production values at 30, 60, 120, and 180 s and at the limit of tolerance (at 312 ± 37 s) was 609 ± 165, 503 ± 195, 443 ± 157, 449 ± 133, and 337 ± 94 W, respectively. Of the total decline in isokinetic power, ~36% occurred within the first minute of exercise, and significant (P < 0.05) reductions in isokinetic power occurred at all time points versus the baseline maximal isokinetic power (666 ± 158 W). In addition, a significant power reserve of 132 ± 74 W (64% of the task requirement) and 119 ± 80 W (47%) was present at the limit of constant power and ramp-incremental exercise, respectively. Locomotor fatigue occurred rapidly during supracritical power exercise with pseudo-exponential kinetics. Instantaneous isokinetic power production at the limit of tolerance exceeded that of the task requirement, regardless of the constant or ramp work rate profile. Thus, the perceptual and physiologic limits were dissociated at the limit of tolerance in recreationally active volunteers.


Human neuroethology of emotion.
1. Based on ethological theory, the question of what is the difference between human and nonhuman primate emotionality is investigated. 2. The anatomical basis for this difference is the greater number of neurons in the anterior thalamic nuclei in humans than in monkeys and apes. This may represent an increased differentiation of the limbic message being sent to the cortex. 3. Only humans can report about experiences and subjective feelings in certain motivational states. The two most general states are wakefulness and sleep. The subjective aspect of (desynchronized) sleep is dreaming. The causal relationship between dreaming and certain lower brain stem mechanisms is analysed. 4. Whereas the motor system is usually blocked during desynchronized sleep, there are individuals who voice their emotions and speak while sleeping. As there are essential differences in the substrates for the voluntary control of the voice in the human and nonhuman primates there are essential differences in the voluntary control of emotions. 5. Similar to the motor matching theory of speech perception a motor matching process of affect perception is suggested. 6. The evolutionary change in the human motivational system is thought to be one of several prerequisites for the evolution of language.


Thermomucor (Mucorales).
Thermomucor indicae-seudaticae is described in the order Mucorales. Descriptions and illustrations of both the zygosporic and sporangial states are presented.


Impact of simulation training on Jordanian nurses' performance of basic life support skills: A pilot study.
Providing efficient basic life support (BLS) training is crucial for practicing nurses who provide direct patient care. Nevertheless, data addressing the impact of BLS courses on the skills and performance of Jordanian nurses are scarce. This study aimed to assess the effectiveness of a BLS simulation training on Jordanian nurses' skill improvement in cardiopulmonary resuscitation. A prospective quasi-experimental, single group pretest-posttest design was used to study the effect of BLS simulation; using a 9-item checklist; on the spot training; American Heart Association, on a group of Jordanian nurses. A pre-test was conducted following a CPR scenario to test the skills using 9-item checklist extrapolated from the American Heart Association guidelines. After debriefing, an interactive on spot training was provided. Later, participants undertook an unscheduled post-test after four weeks that included the same nine items. Thirty registered nurses with a mean clinical experience of 6.1years participated in the study. Comparing pre-test (M=4.6, SD=2.9, range=0 to 9) with post-test results (M=7.5, SD=1.7, range=4 to 9) showed an overall improvement in skills and BLS scores after the simulation training program (t=7.4, df=29, p<0.0001). BLS simulation training sessions are associated with significant improvement in skills and performance among Jordanian nurses. A refreshment BLS training session for nurses is highly recommended to guarantee nurses' preparedness in actual CPR scenarios.


Acylation of proteins by myristic acid in isolated mitochondria.
Isolated and highly purified mitochondria from rat liver were incubated with [1-14C]myristate, solubilized in boiling sodium dodecyl sulfate, and analyzed by polyacrylamide gel electrophoresis and autoradiography. Six to eight protein bands were found to be radioactively labeled. If the mitochondria were heated for 5 min at 95 degrees C prior to incubation with this fatty acid, no labeling was observed. By preexposing the mitochondria to unlabeled fatty acids of varying chain lengths, the extent of labeling by [1-14C]myristate was reduced in a chain length-dependent manner, exhibiting maximal inhibition at lauric acid. Reversibility of the labeling was demonstrated by chasing the incorporated radioactivity with unlabeled fatty acids of varying chain length, resulting in a maximal displacement of the tracer again by lauric acid. Fractionation of the labeled mitochondria into mitochondrial matrix and inner mitochondrial membrane components before or after labeling showed that the modified proteins are located inside the inner mitochondrial membrane. In both cases, the pattern of labeling was different from the one observed with intact mitochondria. The labeled bands in the gel were sensitive to alkaline methanol or hydroxylamine treatment. The radioactivity recovered after this treatment co-migrated with myristic acid on thin layer chromatography plates. The chain length specificity and the rapid reversibility of the observed acylation argue for a new type of reaction, different from the acylation observed in whole cells. The possible involvement of the acylated proteins in the regulation of oxidative phosphorylation is discussed.


Reduced Prescription of Baloxavir After Suspected Prevalence of a Baloxavir-Resistant Influenza Virus Strain and the Emergence of SARS-CoV-2 in a Tertiary Hospital in Japan.
The use of baloxavir, a new anti-influenza agent, began in Japan from the 2018 to 2019 season and became the focus of attention due to its efficient viral reduction ability; therefore, we should know the prescription changes of anti-influenza agents. We analyzed the changes in the prescription of anti-influenza agents between the 2018-19 season and the 2019-20 season in our hospital. The share of baloxavir was 15%, while the shares of oseltamivir and laninamivir were 42% and 31%, respectively in the 2018-2019 season. However, in the 2019-20 season, the share of baloxavir and laninamivir was reduced to 3% and 17%, respectively, in contrast to an increase in the share of oseltamivir (66%). The total prescription of anti-influenza agents for patients decreased in the 2019-20 season (205 patients), compared with the 2018-19 season (509 patients). These results suggest significant changes such as a reduction in the prescription of anti-influenza agents, especially baloxavir, likely due to the suspected prevalence of a baloxavir-resistant strain of influenza virus and the emergence of SARS-CoV-2 in Japan.


Neighborhood social environments, healthy resources, and adult diabetes: Accounting for activity space exposures.
This study broadens contextual environments to include adults' activity spaces-inside and outside the residential neighborhood-to examine how contextual exposures shape type 2 diabetes risk. We use novel longitudinal data from the Los Angeles Family and Neighborhood Survey, construct time-weighted exposure measures of adults' social-structural and healthy resource environments, and execute random effects logistic models predicting the probability of being diabetic. Results indicate that residential and activity space exposures are independently associated with adult diabetes, and that residential and activity space healthy resources combine to influence diabetes risk in synergistic ways. Living in more socioeconomically advantaged neighborhoods reduces diabetes risk, particularly when spending time in activity spaces with greater access to recreational facilities. Moreover, healthier activity space environments may compensate for living in neighborhoods devoid of healthy food options to lessen diabetes risk. Adopting an activity space framework can inform multilevel interventions aimed at alleviating type 2 diabetes and other chronic ailments.


Immunization with Fasciola hepatica thioredoxin glutathione reductase failed to confer protection against fasciolosis in cattle.
The liver fluke Fasciola hepatica remains an important agent of food-borne trematode disease producing great economic losses due to its negative effect on productivity of livestock grazing in temperate areas. The prevailing control strategy based on anthelmintic drugs is unsustainable due to widespread resistance hence vaccination appears as an attractive option to pursue. In this study we evaluate the effect of vaccination in calves with a functional recombinant thioredoxin glutathione reductase (rFhTGR) from liver fluke, a critical antioxidant enzyme at the crossroads of the thioredoxin and glutathione metabolism in flatworms. The recombinant enzyme produced in Escherichia coli was tested in two vaccination experiments; in the first trial rFhTGR was administered in combination with Freund́s Incomplete Adjuvant (FIA) in a three-inoculation scheme on weeks 0, 4 and 8; in the second trial rFhTGR was given mixed with Adyuvac 50 or Alum as adjuvants on weeks 0 and 4. In both cases calves were challenged with metacercariae (400 in the first and 500 in the second trial) 2 weeks after the last inoculation. Our results demonstrate that two or three doses of the vaccine induced a non-significant reduction in worm counts of 8.2% (FIA), 3.8% (Adyuvac 50) and 23.0% (Alum) compared to adjuvant controls indicating that rFhTGR failed to induce a protective immunity in challenged calves. All vaccine formulations induced a mixed IgG1/IgG2 response but no booster was observed after challenge. No correlations between antibody titres and worm burdens were found.


The stability of axis I diagnoses in youth across multiple psychiatric hospitalizations.
The literature has yet to reach a consensus as to the stability of severe psychiatric diagnoses in youth. Previous studies among youngsters tracked over set follow-up periods have reported diagnostic stability estimates that are similar to or slightly lower than those of adults. Less is known, however, about the stability of youth psychiatric diagnoses across multiple episodes of psychopathology, such as recurrent inpatient hospitalizations. The present study investigated diagnostic stability among inpatient youth with multiple hospitalizations through longitudinal and cross-sequential designs. Results indicate that diagnostic stability, as measured by positive concordance rates and the kappa coefficient, is highest for mood disorders, especially bipolar disorder. Externalizing disorders and schizophrenia displayed moderate to low stability, with oppositional-defiant disorder displaying the lowest stability. Substance use disorders were found to have moderate stability. Overall, across-episode diagnostic stability among hospitalized youngsters appears to be lower than that of adults. This finding appears to be due to lower stability among certain externalizing disorders and substance use disorders, whereas mood disorders display stability rates resembling those of adults. Potential explanations for and implications of these findings are discussed.


Radio-anatomical analysis of the pericranial flap "money box approach" for ventral skull base reconstruction.
To evaluate the versatility of the pericranial flap (PCF) to reconstruct the ventral skull base, using the frontal sinus as a gate for its passage into the sinonasal corridor "money box approach." Anatomic-radiological study and case series. Various approaches and their respective defects (cribriform, transtuberculum, clival, and craniovertebral junction) were completed in 10 injected specimens. The PCF was introduced into the nose through the uppermost portion of the frontal sinus (money box approach). Computed tomography (CT) scans (n = 50) were used to measure the dimensions of the PCF and the skull base defects. The vertical projection of the external ear canal was used as the reference point to standardize the incisions for the PCF. The surface area and maximum length of the PCF were 121.5 ± 19.4 cm2 and 18.3 ± 1.3 cm, respectively. Using CT scans, we determined that to reconstruct defects secondary to transcribriform, transtuberculum, clival, and craniovertebral approaches, the PCF distal incision must be placed respectively at -3.7 ± 2.0 cm (angle -17.4 ± 8.5°), -0.2 ± 2.0 cm (angle -1.0 ± 9.3°), +5.5 ± 2.3 cm (angle +24.4 ± 9.7°), +8.4 ± 2.4 cm (angle +36.6 ± 11.5°), as related to the reference point. Skull base defects in our clinical cohort (n = 6) were completely reconstructed uneventfully with the PCF. The PCF renders enough surface area to reconstruct all possible defects in the ventral and median skull base. Using the uppermost frontal sinus as a gateway into the nose (money box approach) is feasible and simple. NA. Laryngoscope, 127:2482-2489, 2017.


A child-holding thought experiment: students prefer to imaging holding an infant on the left side of the body.
The tendency of women to prefer to hold infants on the left side of the body has been confirmed by several methods: surveys of works of art and of photographs, field observations, and experimental methods. The present study developed a new method to examine the patterns of child-holding, that is, the child-holding thought experiment. 2287 female and 1268 male undergraduates were instructed to imaging nursing or feeding a baby. Then, they were asked on which side of the body they imagined holding the baby. Seventy-two percent of the women and 65% of the men reported imaging holding a baby on the left side of the body. This preference for the left side was noted, irrespective of handedness. These results indicate that both women and men who have never fed their own babies prefer to imaging holding a baby on the left side of the body. Moreover, that the magnitude of this preference was significantly stronger for the women adds to the evidence of a gender-dependent expression for lateral preferences in holding a baby.


Ascorbic acid reduces the dopamine depletion induced by MPTP.
The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice was found to cause a long-lasting depletion of striatal dopamine concentrations, but did not alter striatal serotonin concentrations. The concomitant administration of ascorbic acid attenuated this MPTP-induced dopamine depletion. These observations are discussed in reference to the possible mechanisms through which MPTP exerts its neurotoxic actions on dopaminergic neurons.


Factors associated with stress and coping at 5 and 10 years after heart transplantation.
Heart transplant-related stressors and coping are related to poor outcomes early after transplant. The purposes of our study were to (1) identify the most frequent and bothersome stressors and most used and effective coping strategies and (2) compare the most frequent and bothersome stresses and most used and effective coping styles between patients at 5 and 10 years after heart transplantation. We also examined differences in coping styles by patient characteristics and factors associated with frequency and intensity of stress at 5 and 10 years after heart transplantation. This report is a secondary analysis of data from a prospective, multisite study of quality of life outcomes. Data are from separate cohorts of 199 patients at 5 years after transplant and 98 patients at 10 years. Patients completed the Heart Transplant Stressor Scale and Jalowiec Coping Scale. Statistical analyses included frequencies, measures of central tendency, t-tests, chi-square, and generalized linear models. At 5 and 10 years after heart transplantation, the most bothersome stressors were regarding work, school, and financial issues. Patients who were 10 years after transplant reported less stress, similar stress intensity, and less use and perceived effectiveness of negative coping than patients who were 5 years after transplant. Long-term after transplant, demographic characteristics, psychologic problems, negative coping, and clinical factors were related to stress frequency and/or intensity. Heart transplant-related stress occurs long-term after surgery. Types of transplant-related stress and factors related to stress confirm the importance of ongoing psychologic and clinical support after heart transplantation.


Confirmation of regional assignment of nucleoside phosphorylase (NP) on chromosome 14 by gene dosage studies.
Gene dosage studies yielded results consistent with assignment of the locus for nucleoside phosphorylase to band 14q13. The red blood cells from a patient with the karyotype 47,XX,+der(14),t(8;14)(8qter leads to 8q24::14q21 leads to 14pter)pat had enzyme activity 50% higher than red cells from 47 normal controls, two trisomies involving chromosomes other than 14, and five balanced translocations involving chromosome 14. On the other hand, the red cells of a case with a karyotype 45,XX,-14,-22+der(22),t(14;22)(14qter leads to 14q11 or 14q12::22p11 leads to 22qter)mat and a case with a a karyotype 47,XX,+der(14),t(14;16)(14pter leads to 14q11::16q24 leads to 16qter)mat had normal activity


Role of hysteroscopy and ultrasound in early identification of post-molar gestational trophoblastic neoplasia.
To evaluate the role of hysteroscopy and ultrasound in early identification of gestational trophoblastic neoplasia (GTN) after molar evacuation. This was a prospective study involving 52 women with an ultrasound diagnosis of complete hydatidiform mole, attending a tertiary centre in south India between August 2016 and August 2019. Baseline characteristics such as age, serum beta-human chorionic gonadotropin(β-hCG) level, gestational age, and uterine size were noted. After the evacuation of molar pregnancy, weekly follow-up with β-hCG was performed, until three consecutive values were normal and then monthly for six months. Findings of transvaginal ultrasound and diagnostic hysteroscopy, performed on follow up at three weeks, were noted. Primary outcome was the development of GTN. Area under the curve(AUC) was calculated to assess the usefulness of these methods in early identification of GTN. Thirteen women (25 %) developed GTN during follow up, within 6 months. Twenty six(50 %) cases had high-risk molar pregnancy. Positive findings on hysteroscopy and ultrasonography were noted in 44.2 % and 19.2 % respectively. AUC was 0.83(95 % CI, 0.70-0.97) for ultrasound and 0.82(95 % CI, 0.72-.92) for hysteroscopy. Sensitivity and specificity were 69.2 % and 97.4 % for ultrasound and it was 92.3 % and 71.8 % respectively for hysteroscopy in identifying those who developed GTN on follow-up. Transvaginal ultrasound as well as hysteroscopy may help in early identification of women at risk of developing GTN following a molar evacuation. Being a non-invasive method with similar discriminative value, ultrasonographic evaluation may be used for early identification of women with GTN after validation in future studies.


Direct and straightforward access to substituted alkyl selenols as novel carbonic anhydrase inhibitors.
Functionalised aliphatic selenols, straightforwardly obtained through ring-opening reaction of strained heterocycles, represent a new chemotype acting as carbonic anhydrase inhibitors (CAIs). These compounds showed pronounced selectivity towards the cytosolic human (h) isoforms such as the hCA I, II and VII rather than the membrane tumor associate hCA IX. In addition, we reported for the first time the X-ray crystal structure of an aliphatic selenol bound to the hCA I zinc ion, and that afforded the opportunity to decipher in detail the inhibition mechanism underpinning such a new class of CAIs. In this context selenols are interesting leads worth developing for the obtainment of novel and efficient selective CAIs potentially useful for the management of a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy and arthritis.


Climate change, insurance market, renewable energy, and biodiversity: double-materiality concept from BRICS countries.
The threat of biodiversity loss and mass extinction of species with an aftermath will shape all lives now and those to come. In this context, recent empirical studies illustrate various drivers of biodiversity for better environmental quality; however, the impact of the insurance market has not been thoroughly examined. Likewise, the possible non-linearities between biodiversity and its determinants are ignored in the current empirical literature for BRICS economies. Therefore, this work is the first to explore the effect of the insurance market, climate change, and renewable energy on biodiversity in BRICS economies using an advanced method of the non-linear autoregressive distributed lag (NARDL) method. The findings illustrated that a decline in the insurance market alleviates biodiversity loss and stimulates environmental quality. In contrast, an increasing insurance market augments biodiversity loss and negatively affects ecological quality. Furthermore, the findings uncovered that carbon emissions are detrimental to environmental quality. Lastly, the results report that reducing the level of renewable energy worsens biodiversity loss while boosting renewable energy utilization declines biodiversity loss. The policymakers and regulatory authorities in the BRICS should adopt the risk-based approach proposed by the network of greening the financial system (NGFS) to tackle the dilemma of double materiality between financial institutions and biodiversity.


Matching mouse models to specific human liver disease states by comparative functional genomics of mouse and human datasets.
Omics has broadened our view of transcriptional and gene regulatory networks of multifactorial diseases, such as metabolism associated liver disease and its advanced stages including hepatocellular carcinoma. Identifying liver disease biomarkers and potential treatment targets makes use of experimental models, e.g. genetically engineered mice, which show molecular features of human pathologies but are experimentally tractable. We compared gene expression profiling data from human to our studies on transgenic mice with hepatocyte deletion of Cyp51 from cholesterol synthesis with the aim of identifying the human liver disease state best matched by the Cyp51 knockout model. Gene Expression Omnibus was used to identify relevant human datasets. We identified enriched and deregulated genes, pathways and transcription factors of mouse and human disease samples. Analysis showed a closer match of the Cyp51 knockout to the female patient samples. Importantly, CYP51 was depleted in both mouse and female human data. Among the enriched genes were the oxysterol-binding protein-related protein 3 (OSBPL3), which was enriched in all datasets, and the collagen gene COL1A2, which was enriched in both the mouse and one human dataset. KEGG and Reactome analyses revealed the most enriched pathway to be ECM-receptor interaction. Numerous transcription factors were differentially expressed in mice of both sexes and in the human female dataset, while depleted HNF4α and RXRα:PPARα-isoform1 were a hallmark in all cases. Our analysis exposed novel potential biomarkers, which may provide new avenues towards more personalized approaches and different targets in females and males. The analysis was only possible because of availability of open data resources and tools and broadly consistent annotation.


Examining equivalence of concepts and measures in diverse samples.
While there is growing awareness for the need to examine the etiology of problem behaviors across cultural, racial, socioeconomic, and gender groups, much research tends to assume that constructs are equivalent and that the measures developed within one group equally assess constructs across groups. The meaning of constructs, however, may differ across groups or, if similar in meaning, measures developed for a given construct in one particular group may not be assessing the same construct or may not be assessing the construct in the same manner in other groups. The aims of this paper were to demonstrate a process of testing several forms of equivalence including conceptual, functional, item, and scalar using different methods. Data were from the Cross-Cultural Families Project, a study examining factors that promote the healthy development and adjustment of children among immigrant Cambodian and Vietnamese families. The process described in this paper can be implemented in other prevention studies interested in diverse groups. Demonstrating equivalence of constructs and measures prior to group comparisons is necessary in order to lend support of our interpretation of issues such as ethnic group differences and similarities.


Immune consequences of nonoperative treatment of splenic trauma in the rat model.
To investigate the immunologic consequences of non-operative management of splenic injury, three parameters were studied: survival following pneumococcal sepsis, clearance of blood-borne bacteria, following Hemophilus influenzae challenge, and antibody response to type III pneumococcal capsular polysaccharide. Two hundred twenty-five Sprague-Dawley rats were divided into three groups and subjected either to a splenectomy, a sham operation, or standard blunt trauma. A significant increase in mortality was noted in the splenectomized group as compared with both the traumatized and control groups when challenged with Streptococcus pneumoniae. In both the control and trauma groups, H influenzae cleared significantly within 18 hours. Blood-borne bacteria persisted at the same level for 72 hours in the splenectomized animals. Four and 11 days later, the antibody level in both traumatized and control groups was higher than in the splenectomized subjects (P less than .001). There was no difference in the serum antibody level between the control and trauma groups at four days. However, at 11 days the trauma group showed a significant decrease in the antibody level (P less than .05). It can be concluded that following spontaneously-healing splenic trauma in the rat model, survival, bacterial clearance, and antibody response were all superior to that observed in the splenectomized subjects. In addition, the healed splenic disruption did not impair clearance of blood-borne encapsulated bacteria.


Spontaneous and electrically induced ventricular arrhythmias during acute ischemia superimposed on 2 week old canine myocardial infarction.
The arrhythmogenic effect of acute reversible myocardial ischemia before and 2 weeks after experimental myocardial infarction was investigated in 37 dogs that underwent reversible 10 min occlusion of the first major marginal branch of the left circumflex coronary artery. Subsequently, 24 of the dogs underwent experimental myocardial infarction with permanent left anterior descending coronary ligation, and 13 dogs served as sham-operated controls. Two weeks later, an open chest programmed electrical stimulation was performed in the 13 sham-operated and 24 postinfarction dogs to determine its accuracy in predicting the ventricular arrhythmias that develop during a subsequent episode of acute reversible ischemia. After programmed electrical stimulation, the left circumflex marginal branch was reversibly occluded for 10 min at the same site. The incidence of spontaneous ventricular fibrillation during reversible left circumflex marginal coronary occlusion did not differ from the first to the second study in sham-operated dogs, whereas in the postinfarction dogs, it increased from 13% before infarction to 54% after infarction (p = 0.005). The outcome of programmed electrical stimulation predicted spontaneous ventricular arrhythmias during coronary occlusion in only 21% of the postinfarction dogs. The accuracy of programmed electrical stimulation was 42% and its predictive value was 47% in detecting the dogs with spontaneous ventricular fibrillation. Regional myocardial blood flow measurements by microsphere technique identified the severity of reversible ischemia in the infarct border and periinfarction zones as a correlate of spontaneous ventricular fibrillation during coronary occlusion. In contrast, total infarct size correlated with electrically induced but not with spontaneous ventricular arrhythmias.


Impact of sleep deprivation on anaesthesia residents' non-technical skills: a pilot simulation-based prospective randomized trial.
Sleep deprivation is common in anaesthesia residents, but its impact on performance remains uncertain. Non-technical skills (team working, situation awareness, decision making, and task management) are key components of quality of care in anaesthesia, particularly in crisis situations occurring in the operating room. The impact of sleep deprivation on non-technical skills is unknown. We tested the hypothesis that in anaesthesia residents sleep deprivation is associated with impaired non-technical skills. Twenty anaesthesia residents were randomly allocated to undergo a simulation session after a night shift [sleep-deprived (SLD) group, n =10] or after a night of rest [rested (R) group, n =10] from January to March 2015. The simulated scenario was a situation of crisis management in the operating room. The primary end point was a composite score of anaesthetists' non-technical skills (ANTS) assessed by two blinded evaluators. Non-technical skills were significantly impaired in the SLD group [ANTS score 12.2 (interquartile range 10.5-13)] compared with the R group [14.5 (14-15), P <0.02]. This difference was mainly accounted for by a difference in the team working item. On the day of simulation, the SLD group showed increased sleepiness and decreased confidence in anaesthesia skills. In this randomized pilot trial, sleep deprivation was associated with impaired non-technical skills of anaesthesia residents in a simulated anaesthesia intraoperative crisis scenario. NCT02622217.