The value of nurse-led anthropometric and oropharyngeal measurements combined with STOP-Bang questionnaire in screening for obstructive sleep apnea in patients with acute coronary syndrome: a prospective cohort study.
Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly important to develop strategies for better screening for OSA in newly admitted ACS patients. From March 2017 to October 2019, consecutive eligible patients with ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. All anthropometric and oropharyngeal parameters are measured by specialist nurses. Finally, 761 ACS patients were recruited in the present study. Prevalence of moderate/severe OSA was 53.2% based on diagnostic criteria of AHI ≥ 15. Correlation analysis illustrated that AHI was positively correlated with anthropometric characteristics. In the multivariate model, only micrognathia (OR 2.02, 95% CI 1.02-4.00, P = 0.044), waist circumference (OR 1.08, 95% CI 1.04-1.11, P < 0.001), and STOP-BANG Questionnaire (SBQ) score (OR 1.45, 95% CI 1.27-1.66, P < 0.001) were independently associated with the prevalence of OSA. Receiver operating characteristic curve (ROC) analysis showed that the area under curve (AUC) of multivariable joint diagnosis (waist circumference, micrognathia combined with SBQ) was significantly better than the AUC of Epworth Sleepiness Scale (ESS) and SBQ (p < 0.0001 and p = 0.0002, respectively), and the results showed that AUC was 0.728. Under the optimal truncation value, the sensitivity was 73%, and the specificity was 61%, which was higher than the single index. Finally, we also constructed a nomogram model based on multiple logistic regression, to easily determine the probability of OSA in ACS patients. The new screening tool has greater power than single questionnaire or measurements in screening of OSA among ACS patients. Clinicaltrials.gov identifier NCT03362385, registered December 5, 2017.


Fetal ovarian cysts: a report of five cases.
Large fetal ovarian cysts are rare; however, widespread use of antenatal ultrasound examination has led to an increased detection rate and surgical removal. A case presenting with bowel obstruction is described along with four other cases that presented in the last 24 years. Previously reported series are reviewed and compared. It is stressed that complications are very rare and hasty surgical management of cases detected by ultrasound scanning is not warranted.


Antiparkinsonian therapy modifications in PD patients after STN DBS: a retrospective observational analysis.
This study reports a retrospective analysis of 67 consecutive parkinsonian patients to assess changes in antiparkinsonian medications after Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN). All antiparkinsonian drugs, including levodopa, dopamine agonists, associated drugs such as COMT and MAO inhibitors, amantadine and anticholinergics, were evaluated pre- and post-operatively at 1 and 3 years follow-up. The levodopa mean daily dose was reduced approximately 60% after 1 year and remained stable after 3 years. Apomorphine, bromocriptine, tolcapone, entacapone and selegiline were withdrawn after STN DBS. Three years post-operatively, 9 patients (13.4%) no longer required levodopa and 6 patients (8.9%) completely stopped all dopaminergic medications. More patients were on monotherapy of either levodopa or dopamine agonist and fewer patients required a combined treatment of dopamine agonist and levodopa, compared to the pre-surgical condition. STN DBS treated PD patients experience a significant long-term reduction and simplification of the pharmacological treatment.


Identification of Molecular and Genetic Resistance Mechanisms in a Candida auris Isolate in a Tertiary Care Center in Türkiye.
Candida auris is a multidrug-resistant pathogen that causes nosocomial outbreaks and high mortality. We conducted this study to investigate the molecular mechanisms of antifungal resistance in our clinical isolate of C. auris with a high level of resistance to three main classes of antifungals. A clinical C. auris isolate was identified by MALDI-TOF MS and antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. After sequencing the whole genome of the microorganism with Oxford Nanopore NGS Technologies, a phylogenetic tree was drawn as a cladogram to detect where the C. auris clade to this study's assembly belongs. The C. auris isolate in this study (MaCa01) was determined to be a part of the clade I (South Asian). The resistance-related genes indicated that MaCa01 would most likely be highly resistant to fluconazole (CDR1, TAC1b, and ERG11), none or little resistant to amphotericin B (AmpB) and echinocandins, and sensitive to flucytosine. The mutations found in the above-mentioned genes in the Türkiye C. auris isolate reveals an antifungal resistance pattern. This molecular resistance pattern was found consistent with the interpretation of MIC values of the antifungals according to CDC tentative breakpoints. We detected the well-known antifungal resistance mutations, responsible for azole resistance in C. auris. Despite no ERG2, ERG6, and FKS mutation identified, the isolate was found to be resistant to AmpB and caspofungin based on the CDC tentative breakpoints which could be related to unidentified mutations.


CPI-203 improves the efficacy of anti-PD-1 therapy by inhibiting the induced PD-L1 overexpression in liver cancer.
Hepatocellular carcinoma (HCC) is one of the commonest lethal malignancies worldwide, and often diagnosed at an advanced stage, without any curative therapy. Immune checkpoint blockers targeting the programmed death receptor 1 (PD-1) have shown impressive antitumor activity in patients with advanced-stage HCC, while the response rate is only 30%. Inducible PD-L1 overexpression may result in a lack of response to cancer immunotherapy, which is attributed to a mechanism of adaptive immune resistance. Our study investigated that the overexpression of PD-L1 promoted the invasion and migration of liver cancer cells in vitro, and the induced overexpression of PD-L1 in the tumor microenvironment could weaken the effects of anti-PD-1 immunotherapy in a BALB/c mouse model of liver cancer. CPI-203, a small-molecule bromodomain-containing protein 4 (BRD4) inhibitor, which can potently inhibit PD-L1 expression in vitro and in vivo, combined with PD-1 antibody improved the response to immunotherapy in a liver cancer model. Cell transfection and chromatin immunoprecipitation assay manifested that BRD4 plays a key role in PD-L1 expression; CPI-203 can inhibit PD-L1 expression by inhibiting the BRD4 occupation of the PD-L1 promoter region. This study indicates a potential clinical immunotherapy method to reduce the incidence of clinical resistance to immunotherapy in patients with HCC.


Disruption of small molecule transporter systems by Transporter-Interfering Chemicals (TICs).
Small molecule transporters (SMTs) in the ABC and SLC families are important players in disposition of diverse endo- and xenobiotics. Interactions of environmental chemicals with these transporters were first postulated in the 1990s, and since validated in numerous in vitro and in vivo scenarios. Recent results on the co-crystal structure of ABCB1 with the flame-retardant BDE-100 demonstrate that a diverse range of man-made and natural toxic molecules, hereafter termed transporter-interfering chemicals (TICs), can directly bind to SMTs and interfere with their function. TIC-binding modes mimic those of substrates, inhibitors, modulators, inducers, and possibly stimulants through direct and allosteric mechanisms. Similarly, the effects could directly or indirectly agonize, antagonize or perhaps even prime the SMT system to alter transport function. Importantly, TICs are distinguished from drugs and pharmaceuticals that interact with transporters in that exposure is unintended and inherently variant. Here, we review the molecular mechanisms of environmental chemical interaction with SMTs, the methodological considerations for their evaluation, and the future directions for TIC discovery.


Non-productive activation of the proteinase binding sites of alpha 2-macroglobulin on reaction of the inhibitor with matrix-linked trypsin.
The reaction of alpha 2-macroglobulin with matrix-linked trypsin is accompanied by apparently identical "bait" region cleavage, thioester cleavage and conformational change as the reaction with the soluble enzyme. However, no binding of proteinase occurs, but instead the inhibitor loses its ability to inactivate soluble trypsin. These findings indicate that the proteinase binding sites of alpha 2-macroglobulin are activated in the normal manner but decay before being able to bind the immobilized enzyme. Such non-productive activation of binding sites may occur also in the reactions of alpha 2-macroglobulin with soluble proteinases, thus explaining apparent enzyme inhibitor stoichiometries of less than 2:1 observed in these reactions.


Evidence for multiple receptors mediating fluid secretion in salivary glands of ticks.
Using isolated salivary glands of the ixodid tick Amblyomma hebraeum Koch, we tested the effectiveness of butaclamol and sulpiride in blocking fluid secretion stimulated by a number of agonists. (+)-Butaclamol was a potent inhibitor of dopamine, N-methyldopamine and noradrenaline (Ki congruent to 30-60 nM), but was less effective on ergometrine (Ki congruent to 310 nM). Tranylcypromine-stimulated fluid secretion in the absence and presence of (+)-butaclamol and (+/-)-sulpiride suggested that tranylcypromine's action is mediated through two receptors. (+/-)-Sulpiride, though a rather weak antagonist of ergometrine (Ki congruent to 6150 nM), was ineffectual as a dopamine blocker, indicating distinct receptor sites on this epithelium for dopamine and ergometrine. Both (+)-butaclamol and sulpiride reversed the autoinhibition associated with supramaximal levels of dopamine. Sulpiride also abolished spiperone's potentiation of dopamine. Butaclamol, on the other hand, had no such effect on spiperone's potentiation of dopamine. Finally, although the CNS of ticks contains both dopamine and noradrenaline in quantity (congruent to 650 and congruent to 370 ng . g-1 res respectively), the salivary glands contain far more dopamine than noradrenaline (congruent to 85 and congruent to 6 ng . g-1 respectively). The data support the hypothesis that dopamine is a natural transmitter substance in the tick salivary gland, and that there are distinct receptor sites in the epithelium mediating the actions of catecholamines, ergot alkaloids and butyrophenones. The physiological significance of the ergot alkaloid and butyrophenone sites is not clear.


Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease.
Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model for MS, myelin-reactive T cells initiate the autoimmune process when entering the nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, the strength of the T-cellular reactivation process within the CNS tissue is crucial for the manifestation and the severity of the clinical disease. Recently, B cells were found to participate in the pathogenesis of CNS autoimmunity, with several diverse underlying mechanisms being under discussion. We here report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. The antibodies accumulated in resident antigen-presenting phagocytes and significantly enhanced the activation of the incoming effector T cells. The ensuing strong blood-brain barrier disruption and immune cell recruitment resulted in rapid manifestation of clinical disease. Therefore, myelin oligodendrocyte glycoprotein (MOG)-specific autoantibodies can initiate disease bouts by cooperating with the autoreactive T cells in helping them to recognize their autoantigen and become efficiently reactivated within the immune-deprived nervous tissue.


Relationship between biochemical and symptomatic hypoglycemia after RYGB. Responses to a mixed meal test: a case-control study.
Postprandial hypoglycemia is a relatively common complication after Roux-en-Y gastric bypass (RYGB). The cause remains incompletely understood, and the association between biochemical hypoglycemia and hypoglycemic symptoms is unclear. To evaluate the association between postprandial hormonal responses and biochemical and symptomatic hypoglycemia after RYGB. University Hospital, Denmark. A case-control study with 3 groups: (1) RYGB group with postprandial hypoglycemic symptoms (HS), n = 13; (2) RYGB-group with no symptoms of hypoglycemia (NHS), n = 13; and (3) nonoperated body mass index-matched controls (CON), n = 7. Plasma glucose (PG) and hormonal responses (insulin, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon) were measured after a mixed meal test (MMT), and hypoglycemic symptoms were determined by a questionnaire. The primary outcomes were differences in subjective and biochemical responses related to hypoglycemia among the 3 groups. Nadir PG was lower (3.1 versus 4.0 mmol/L (56 versus 72 mg/dL); P = .0002) and peak insulin higher in HS than NHS patients (1073 versus 734 pmol/L; P = .0499). Of the 13 patients with a peak insulin >850 pmol/L, 8 patients developed symptoms whereas only 2 out of the 13 patients with peak insulin ≤850 pmol/L developed symptoms, corresponding to an odds ratio of 12 (1.8; 81.7). Post hoc analyses comparing all RYGB patients with biochemical hypoglycemia after the MMT (nadir glucose ≤3.0 mmol/L [54 mg/dL]) with those with glucose >3 mmol/L (54 mg/dL) revealed a difference in both peak insulin (1138 versus 760 pmol/L; P = .042) and peak glucagon-like peptide-1 (182 versus 86 pmol/L; P = .016) concentrations. Patients with HS had lower nadir PG and higher insulin responses than NHS patients after MMT. Regarding PG, PG ≤3.0 mmol/L (54 mg/dL) was the best discriminator of having hypoglycemic symptoms after the MMT. However, high insulin level seems the most important predictor for having both biochemical and symptomatic hypoglycemia.


In-sensor reservoir computing system for latent fingerprint recognition with deep ultraviolet photo-synapses and memristor array.
Detection and recognition of latent fingerprints play crucial roles in identification and security. However, the separation of sensor, memory, and processor in conventional ex-situ fingerprint recognition system seriously deteriorates the latency of decision-making and inevitably increases the overall computing power. In this work, a photoelectronic reservoir computing (RC) system, consisting of DUV photo-synapses and nonvolatile memristor array, is developed to detect and recognize the latent fingerprint with in-sensor and parallel in-memory computing. Through the Ga-rich design, we achieve amorphous GaOx (a-GaOx) photo-synapses with an enhanced persistent photoconductivity (PPC) effect. The PPC effect, which induces nonlinearly tunable conductivity, renders the a-GaOx photo-synapses an ideal deep ultraviolet (DUV) photoelectronic reservoir, thus mapping the complex input vector into a dimensionality-reduced output vector. Connecting the reservoirs and a memristor array, we further construct an in-sensor RC system for latent fingerprint identification. The system maintains over 90% recognition accuracy for latent fingerprint within 15% stochastic noise level via the proposed dual-feature strategy. This work provides a subversive prototype system of DUV in-sensor RC for highly efficient recognition of latent fingerprints.


Aphid adaptation to cucurbits: sugars, cucurbitacin and phloem structure in resistant and susceptible melons.
Aphis gossypii, a strictly phloemophagaous aphid, colonize hundreds of plant families, and a group of clones formed a cucurbit-specialised host-race. Cucurbits are unique in having evolved a specific extra-fascicular phloem (EFP), which carries defence-related metabolites such as cucurbitacin, whereas the fascicular phloem (FP) is common to all higher plants and carries primary metabolites, such as raffinose-family oligosaccharides (RFOs). Both cucurbitacins (in the EFP) and galactinol (in the FP) have been suggested to be toxic to aphids. We investigated these hypotheses in cucurbit-specialized A. gossypii fed on melon plants with or without aphid-resistance conferred by the NLR gene Vat. We selected a plant-aphid system with (i) Vat-mediated resistance not triggered, (ii) Vat-mediated resistance triggered by an aphid clone adapted to the presence of Vat resistant alleles and (iii) Vat-mediated resistance triggered by a non-adapted aphid clone. We quantified cucurbitacin B, its glycosylated derivative, and sugars, in melon plants and aphids that fed on. The level of cucurbitacin in plants was unrelated to both aphid infestation and aphid resistance. Galactinol was present at higher quantities in plants when Vat-mediated resistance was triggered, but its presence did not correlate with aphid performance. Finally, we showed that cucurbit-specialized A. gossypii fed from the FP but could also occasionally access the EFP without sustainably feeding from it. However, the clone not adapted to Vat-mediated resistance were less able to access the FP when the Vat resistance was triggered. We concluded that galactinol accumulation in resistant plants does not affect aphids, but may play a role in aphid adaptation to fasting and that Cucurbitacin in planta is not a real threat to Aphis gossypii. Moreover, the specific phloem of Cucurbits is involved neither in A. gossypii cucurbit specialisation nor in adaptation to Vat-dependent resistance.


Making human eggs in a dish: are we close?
In the space of 50 years, we have seen incredible achievements in human reproductive medicine. With these leaps forward, it is no wonder that there is a major interest in women's reproductive health research, including extension of reproductive lifespan. Substantial effort is currently being made to address this challenge, including from the commercial sector. In vitro gametogenesis (IVG) in mice is a spectacular breakthrough and has the potential to offer hope to women with intractable infertility. However, with such lofty goals, some reflection may be called for: mastering all of the techniques required for complete and safe IVG in women is likely to be extraordinarily difficult.


Effects of chemical sympathectomy by 6-hydroxydopamine on alpha-adrenoceptor-mediated pressor responses in pithed rat.
The effects of 6-hydroxydopamine (6-OHDA) treatment of neonatal and adult rats on vasopressor responses to postsynaptic alpha-adrenoceptor activation were studied in adult pithed rats. The pressor response to electrical stimulation of the thoracosympathetic outflow (T7-T9) was markedly reduced after neonatal or adult 6-OHDA treatment, indicating a functional destruction of the sympathetic input to the vasculature. Pressor response curves to injected noradrenaline (a nonselective alpha-agonist) and phenylephrine (a selective alpha 1-agonist) were shifted to the left in all 6-OHDA-treated animals. However, the pressor response to the selective alpha 2-agonist M-7 (5,6-hydroxy-2-dimethylamino tetralin) was unaltered in all the 6-OHDA-treated animals. It is concluded that functional destruction of peripheral sympathetic nerve endings in vascular smooth muscle by treatment of neonatal or adult rats with 6-OHDA produces an increased pressor response to alpha 1-adrenoceptor agonists, but not to alpha 2-adrenoceptor agonists in the pithed rat.


Abdominal compartment syndrome: an often overlooked cause of acute kidney injury.
Abdominal compartment syndrome (ACS) is defined as any organ dysfunction caused by intra-abdominal hypertension (IAH), referred as intra-abdominal pressure (IAP) ≥ 12 mm Hg according to the World Society of Abdominal Compartment Syndrome. Abdominal compartment syndrome develops in most cases when IAP rises above 20 mmHg. Abdominal compartment syndrome, while being a treatable and even preventable condition if detected early in the stage of intra-abdominal hypertension, is associated with high rates of morbidity and mortality if diagnosis is delayed: therefore, early detection is essential. Acute kidney injury (AKI) is a common comorbidity, affecting approximately one in every five hospitalized patients, with a higher incidence in surgical patients. AKI in response to intra-abdominal hypertension develops as a result of a decline in cardiac output and compression of the renal vasculature and renal parenchyma. In spite of the high incidence of intra-abdominal hypertension, especially in surgical patients, its potential role in the pathophysiology of AKI has been investigated in very few clinical studies and is commonly overlooked in clinical practice despite being potentially treatable and reversible. Aim of the present review is to illustrate the current evidence on the pathophysiology, diagnosis and therapy of intra-abdominal hypertension and abdominal compartment syndrome in the context of AKI.


Developmental changes in frequency mapping of the gerbil cochlea: comparison of two cochlear locations.
The cochlear microphonic measured in scala tympani referenced to that at the round window is used to determine characteristic frequency (CF) at two locations in an age-graded series of Mongolian gerbils. No significant ontogenic shift in CF is seen at a second turn location, while an approximately 1.5 octave shift is seen in the mid-basal turn.


Continuous positive airway pressure alleviates insomnia in workers sleeping near other workers with sleep apnea after the Fukushima Nuclear Power Plant disaster.
To examine the efficacy of continuous positive airway pressure for improving the sleep of all individuals residing in a temporary shelter. Workers at a nuclear power plant using a gymnasium as temporary shelter were divided into two groups: 15 workers with obstructive sleep apnea received continuous positive airway pressure treatment, and 107 workers without obstructive sleep apnea received no treatment. We assessed subjective sleepiness among the workers with obstructive sleep apnea before and after continuous positive airway pressure treatment, and evaluated insomnia in all workers before and after workers with obstructive sleep apnea were given continuous positive airway pressure treatment. Workers who received continuous positive airway pressure treatment reported significantly improved subjective sleepiness, but did not experience a significant change in insomnia symptoms. However, workers without obstructive sleep apnea reported significant improvements in their insomnia symptoms following the treatment of workers with obstructive sleep apnea. Using continuous positive airway pressure to treat workers with obstructive sleep apnea residing in temporary shelters may help prevent adverse health consequences from insomnia among other individuals sleeping nearby.


Design of Instructional Videos for People with Autism Who Want to Learn About Grocery Store Work: A Community, Business, Educational and Health Partnership.
To facilitate the integration of people with autism into the food industry labour market, this cross sectoral project aimed to design, validate and test instructional videos to concretely demonstrate various tasks in the grocery store, and to probe interest and assess knowledge about these tasks. Results are the delivery of 21 instructional videos validated for individuals with autism and 21 for mentors in grocery.


CORRIGENDUM to Risk of Cancer in a Community Exposed to Per- and Poly-Fluoroalkyl Substances.
[This corrects the article DOI: 10.1177/11786302221076707.].


Management of male incontinence following artificial urinary sphincter failure.
The artificial urinary sphincter has been used successfully for the treatment of stress urinary incontinence in both male and female patients. Its most common use, however, is in men suffering from postprostatectomy incontinence. The success rates, long-term durability, and patient satisfaction for the artificial urinary sphincter are high. The incidence of complications and adverse events remains low although they are sometimes unavoidable. We believe that continence can be salvaged in the majority of men in whom the device fails or requires explantation and we present the logical analysis for device revision and relocation in this review.


Insecticide resistance of Culex pipiens (L.) populations (Diptera: Culicidae) from Riyadh city, Saudi Arabia: Status and overcome.
Three field populations of Cx. pipiens (L.) mosquitoes were collected from three different localities in Riyadh city. They were tested for developing resistance against commonly used insecticides to control mosquitoes in Riyadh. Two populations from Wadi Namar (WN1 and WN2) were highly resistant to deltamethrin (187.1- and 161.4-folds respectively). The field population from AL-Wadi district (AL-W) showed low resistance to lambda-cyhalothrin (3.8-folds) and moderate resistance to beta-cyfluthrin and bifenthrin (14- and 38.4-folds respectively). No resistance to fenitrothion was observed in WN1 population. Fenitrothion concentrations required to inhibit 50% of Acetylcholinesterase (AChE) activity in both WN1 population and the laboratory susceptible strain (S-LAB) were 0.073 and 0.078 ppm respectively. Piperonyl butoxide suppressed resistance to pyrethroid insecticides (>90%) in field populations indicating that oxidases and/or esterases play an important role in the reduction of pyrethroids toxicity. These results should be considered in the current mosquitoes control programs in Riyadh.


Outcomes of spinal cord injury following cervical fracture in ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis (DISH): A prospective cohort study.
The ankylosed spine is prone to increased fractures risk even after minor trauma. The lower cervical spine is most frequently injured, and fractures of the ankylosed spine tend to precipitate spinal cord injury (SCI). The objective of the current study is to assess the incidence, management, and outcomes of patients with ankylosis of the spine sustaining a cervical fracture with associated SCI over a 7-year period. Prospective cohort study. Patients referred to the institution with a cervical fracture associated with SCI on a background of AS or DISH from 2009 to 2017 were reviewed. Demographics, mechanism of injury, fracture type, neurological level of injury, time to surgery, surgical management, neurological status (AIS), spinal cord independence measure (SCIMIII) scale at admission and discharge, and hospital length of stay. In September 2019 the summative data was analyzed using NDI, VAS, SV-QLI/SCI and length of survival were analyzed for statistical significance. Pathological fractures and dementia were excluded. 1613 patients with traumatic SCI were admitted in this period of whom 37 (12 AS and 25 DISH) met the inclusion criteria (mean age 65 years AS; 67 DISH). Fracture-dislocation was the most frequent fracture type (33% AS patients, 24% DISH patients). C4 was the most common neurological level of injury. SCIMIII score at admission was 1 point and 59 at discharge. AIS at admission was A (50%). At time of discharge no patient had neurologically deteriorated. Post-discharge mortality was 58% in AS patients and 32% in DISH patients (p=0.13). Both AS and DISH patients have high levels of disability and mortality associated with trauma to the cervical spine. Despite their distinct clinical differences, in this cohort there were no statistically significant differences between AS and DISH patients regarding fracture type, SCIMIII, AIS, hospital stay, mortality, VAS, and SV-QLI/SCI after cervical fracture over 7 years follow-up.


Perinatal outcome of spontaneously conceived triplet pregnancies in relation to chorionicity.
The purpose of this study was to determine the perinatal outcome of spontaneously conceived triplet pregnancies in relation to chorionicity. In this retrospective study, maternal, neonatal, and chorionicity data were collected from 88 sets of triplet pregnancies that were delivered at >20 weeks of gestation from 3 tertiary referral centers in the United Kingdom. The data were collected between January 1986 and December 2000. There were 49 sets of trichorionic triamniotic triplet pregnancies and 39 sets of triplet pregnancies with a monochorionic pair (ie, dichorionic triamniotic triplets). The outcome of each pregnancy was assessed in relation to chorionicity. The overall perinatal mortality rate was 151.5 per 1000 total births, with dichorionic triamniotic triplets having a 5.5-fold higher risk than trichorionic triamniotic gestations (odds ratio, 5.5; 95% CI, 2.5-12.2). The dichorionic triamniotic triplets have a higher risk of delivery at < 30 weeks of gestation (odds ratio, 4.6; 95% CI, 1.6-11.8; P < .05) and birth weight of < 1000 g (odds ratio, 53.6; 95% CI, 17.5-164; P < .05) than those of trichorionic triamniotic pregnancies. The neonatal morbidity in terms of respiratory distress syndrome (P < .001), anemia (P < .01), and intraventricular hemorrhage (P < .001) were higher in dichorionic triamniotic compared with trichorionic triamniotic triplets. The premature rupture of membrane (odds ratio, 7.5; 95% CI, 3.5-15.7) and twin-twin transfusion syndrome (odds ratio, 14.9; 95% CI, 6.6-4) were independent risk factors for perinatal death. In spontaneously conceived triplets, the incidence of dichorionicity was 44%. The dichorionic triamniotic triplets have a 5.5-fold higher risk of adverse perinatal outcome predominantly because of twin-twin transfusion syndrome and premature rupture of membranes.


Dicer promotes endothelial recovery and limits lesion formation after vascular injury through miR-126-5p.
The recovery of endothelial cells (ECs) after vascular injury is mainly mediated by the proliferation of resident ECs, thereby reducing neointima formation. The RNase Dicer processes microRNAs (miRNAs) and regulates EC function by controlling miRNA-mediated regulation of gene expression. This study aimed to investigate the impact of miRNA biogenesis in ECs on endothelial repair during lesion formation after vascular injury. To study the effect of Dicer on ECs during neointima formation, conditional deletion of Dicer was induced in Apoe-/- mice (EC-Dicerflox) by tamoxifen injection. Following wire-induced injury to carotid arteries of EC-Dicerflox mice, the EC recovery was impaired and the neointima formation and lesional macrophage accumulation was increased. Moreover, conditional deletion of Dicer in ECs diminished the expression of miR-126-5p in EC-Dicerflox mice. Notably, reconstitution of miR-126-5p in the injured arteries of EC-Dicerflox mice using miR-126-5p mimic, prevented the impaired endothelial recovery and increased lesion formation observed in EC-Dicerflox mice. Deficiency of endothelial Dicer diminished endothelial recovery and promoted neointima formation probably due to impaired miR-126-5p expression. Treatment with miR-126-5p mimics promotes endothelial recovery and thereby limits neointima formation. Thus, miR-126-5p therapy represents a potential approach to improve endothelial recovery and prevent restenosis following vascular injury.


Attitudes towards COVID-19 vaccination among incarcerated persons in the Federal Bureau of Prisons, June-July 2021.
To understand the attitudes towards COVID-19 vaccination and trusted sources of vaccination-related information among persons incarcerated in the Federal Bureau of Prisons. From June-July 2021, persons incarcerated across 122 facilities operated by the Federal Bureau of Prisons were invited to participate in a survey asking their reasons for receiving or declining COVID-19 vaccination and the information sources they relied upon to make these decisions. Descriptive analyses were conducted. A total of 130,789 incarcerated persons with known vaccination status were invited to participate in the survey. At the time of survey, 78,496 (62%) were fully vaccinated; 3,128 (3%) were partially vaccinated and scheduled to complete their second dose, and 44,394 (35%) had declined either a first or second dose. 7,474 (9.5%) of the fully vaccinated group and 2,302 (4.4%) of the group declining either a first or second dose chose to participate in the survey; an overall survey return rate of 7.6% (n = 9,905). Among vaccinated respondents, the most common reason given for accepting vaccination was to protect their health (n = 5,689; 76.1%). Individuals who declined vaccination cited concerns about vaccine side effects (n = 1,304; 56.6%), mistrust of the vaccine (n = 1,256; 54.6%), and vaccine safety concerns (n = 1,252; 54.4%). Among those who declined, 21.2% (n = 489) reported that they would choose to be vaccinated if the vaccine was offered again. Those who declined also reported that additional information from outside organizations (n = 1128; 49.0%), receiving information regarding vaccine safety (n = 841; 36.5%), and/or speaking with a trusted medical advisor (n = 565; 24.5%) may influence their decision to be vaccinated in the future. As the COVID-19 pandemic continues, it is important to increase vaccine confidence in prisons, jails, and detention facilities to reduce transmission and severe health outcomes. These survey findings can inform the design of potential interventions to increase COVID-19 vaccine uptake in these settings.


Validated algorithms for identifying timing of second event of oropharyngeal squamous cell carcinoma using real-world data.
Understanding occurrence and timing of second events (recurrence and second primary cancer) is essential for cancer specific survival analysis. However, this information is not readily available in administrative data. Alberta Cancer Registry, physician claims, and other administrative data were used. Timing of second event was estimated based on our developed algorithm. For validation, the difference, in days between the algorithm estimated and the chart-reviewed timing of second event. Further, the result of Cox-regression modeling cancer-free survival was compared to chart review data. Majority (74.3%) of the patients had a difference between the chart-reviewed and algorithm-estimated timing of second event falling within the 0-60 days window. Kaplan-Meier curves generated from the estimated data and chart review data were comparable with a 5-year second-event-free survival rate of 75.4% versus 72.5%. The algorithm provided an estimated timing of second event similar to that of the chart review.


Field and laboratory studies on Corridor disease (Theileria parva infection) in cattle population at the livestock/game interface of uPhongolo-Mkuze area, South Africa.
Corridor disease (Theileria parva infection in cattle associated with carrier buffaloes) had not been reported to cause serious outbreaks in South Africa prior to 1994. In recent years, there has been an increase in the introduction of T. parva-infected buffaloes onto private game parks in Northern KwaZulu-Natal (KZN). The objectives of this study were to investigate the number of T. parva outbreaks in cattle at the livestock/wildlife interface and to establish the possible T. parva carrier status in cattle which were diagnosed to have recovered from clinical disease. The occurrence of outbreaks was closely monitored from 2004 to 2009 covering a total of 15 localities. The observations included the number of cattle involved in the outbreaks, clinical signs, parasitological and post-mortem examinations, as well as serological and molecular tests specific for T. parva. Sentinel cattle were introduced to monitor tick transmission and some of these recovered from clinical T. parva infection in the field and confirmed to be positive by PCR, were challenged using lethal T. parva stabilates to ascertain their immune status. Thirty-one Corridor disease outbreaks were recorded during the study period. Of the 846 cattle tested for Corridor disease during the study period, 140 (16.5%) were found positive by the real time PCR and IFA tests. Eighty-two (9.7%) cattle were found positive by the IFA test only. The prevalence of T. parva infection was 26.2%. Adult R. appendiculatus fed as nymphs on 5 bovines which recovered from clinical T. parva infection in the field transmitted only T. taurotragi to susceptible bovines. However, 8 of the field-recovered cattle resisted lethal challenge using T. parva tick stabilate. Though the study could not demonstrate cattle-to-cattle transmission by ticks using 5 previously infected cattle in the field, it is suggested that Corridor disease should be considered a potential emerging disease, and more stringent control methods should be implemented.


Effect of the Japanese herbal medicine, Boiogito, on the osteoarthritis of the knee with joint effusion.
Boiogito (Japanese herbal medicine, Tsumura Co. Tokyo, Japan) contains sinomenin which inhibits inflammatory reactions. Since sinomenine is a principle component of the Boiogito, there is a possibility of it being effective on osteoarthritis (OA) of the knee with joint effusion. However, there is no report concerning the effectiveness of Boiogito on knee OA. The objective of the present study is to investigate the therapeutic effect of Boiogito on OA of the knee associated with joint effusion in a comparative study among randomly assigned groups. Study was performed using 50 patients who were diagnosed with primary osteoarthritis of the knee with joint effusion. The patients were randomly assigned to two groups: one group (25 patients) using both loxoprofen (2-{4-[(2-oxocyclopentyl) methyl]} propanoic acid) and Boiogito and the other group (25 patients) using loxoprofen, and were evaluated during a 12 week observation period. The assessment parameters including knee scores in the Knee Society Rating System including Knee score and Functional scores, amount of joint effusion by joint puncture in clinically detected cases, the 36-items short form of the Medical Outcome Study Questionnaire (SF-36) as a measurement of health related quality of life were used. The knee scores based on the Knee Society Rating System were improved in both groups. The staircase climbing up and down ability in the Knee society rating system functional score was significantly improved in the group using Boiogito and loxoprofen compared to the loxoprofen group. In the evaluation using SF-36, significant improvements were found in the scores in both groups in physical functioning after 12 weeks. The amount of joint fluid was significantly decreased at 4, 8 and 12 weeks compared to pre-administration baseline in the group using Boiogito and loxoprofen. A side effect of Boiogito, dry mouth, was found in one case. The symptom was mild and improved immediately after discontinuation of administration. The results indicated that Boiogito have a possibility for a treatment modality for joint effusion with osteoarthritis of the knee.


Kinetics of interaction between normal and proline 12 Ras and the GTPase-activating proteins, p120-GAP and neurofibromin. The significance of the intrinsic GTPase rate in determining the transforming ability of ras.
Single turnover and equilibrium binding measurements on the interaction of Gly-12 and Pro-12 Ras.GTP with the catalytic domains of the GTPase-activating proteins, p120-GAP and neurofibromin, have been made utilizing fluorescent 2'(3')O-(N-methylanthraniloyl)-nucleotides. These have enabled the equilibrium dissociation constants (Kd) for their initial binding and the rate constants of the hydrolysis step to be measured. p120-GAP binds to both Ras proteins with a Kd of 17 microM, whereas neurofibromin binds to both Ras proteins with a Kd of 1 microM. Both p120-GAP and neurofibromin increased the rate constant of the GTP hydrolysis step of Pro-12 Ras, but the maximal activation at 30 degrees C was 120-fold and 560-fold, as compared with 70,000- and 52,000-fold, with Gly-12 Ras. The affinity with which p120-GAP and neurofibromin binds to either Gly-12 or Pro-12 Ras protein was decreased dramatically by increasing ionic strength caused by addition of NaCl. The rate constant of the cleavage step of hydrolysis catalyzed by neurofibromin increases with increasing ionic strength, whereas that catalyzed by p120-GAP appears to be unaffected. The high ionic strength within the cell might result in a much lower overall GTPase-activating protein activity than is measured under conditions of low ionic strength in vitro, with p120-GAP being more severely inhibited. The GTP hydrolysis rate of Pro-12 Ras is 2-fold faster than that of normal Ras. The low oncogenicity of Pro-12 ras is explained by a model in which the intrinsic rates of hydrolysis and exchange, as well as GTPase-activating protein- and exchange factor-stimulated rates, are determinants of the biological activity of Ras proteins in fibroblasts.


Zoledronic Acid Prevents Bone Resorption Caused by the Combination of Radium-223, Abiraterone Acetate, and Prednisone in an Intratibial Prostate Cancer Mouse Model.
An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated with combination treatment with radium-223, abiraterone, and prednisone/prednisolone in the absence of bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking prostate cancer bone metastases. Male NOD.scid mice were inoculated intratibially with LNCaP prostate cancer cells and treated with vehicle, radium-223, abiraterone, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP 5b and PSA levels were measured. Bone structure, quality, and formation rate of non-tumor-bearing and tumor-bearing tibiae were analyzed by microCT, 3-point bending assay, and dynamic histomorphometry, respectively. Radium-223 incorporation into bone was also measured. Radium-223/abiraterone/prednisone combination treatment induced a transient increase in bone resorption indicated by elevated TRACP 5b levels, which was inhibited by concurrent treatment with zoledronic acid. Furthermore, radium-223/abiraterone/prednisone combination reduced periosteal and trabecular new bone formation and the number of osteoblasts, but bone structure or biomechanical quality were not affected. The abiraterone/prednisone treatment decreased radium-223 incorporation into tumor-bearing bone, possibly explaining the lack of additional antitumor efficacy. In conclusion, radium-223/abiraterone/prednisone combination increased bone resorption, which may have been one of the mechanisms leading to an increased fracture risk in patients with mCRPC.


Antitumour activity of endotoxin, concanavalin A and poly I: C and their ability to elicit tumour necrosis factor, cytostatic factors, and interferon in vivo.
Concanavalin A, endotoxin, poly I: C, and tumour necrosis serum (TNS) were compared for antitumour activity against Meth A sarcoma transplanted in syngeneic BALB/c mice and their capacity to induce tumour necrosis factor (TNF), heat-stable cytostatic factors, and heat-labile interferon in the blood of normal and Corynebacterium parvum-pretreated mice. All the agents induced hyperemia and inhibition of mitosis at 4 h, and by 24 h many tumours had a dark necrotic centre. Subsequent tumour growth was inhibited and in some of the treated mice tumours regressed completely. Poly A: U and normal mouse serum did not induce regression and their effects were less marked in all other respects, suggesting that these events may be linked. The necrotizing effects of concanavalin A and poly I: C are unlikely to be mediated by TNF, because neither agent could mimic endotoxin in eliciting RNase-resistant necrotizing and regressing activity in the serum of mice pretreated with C. parvum. Poly I: C did not induce strong cytostatic activity in the sera of C. parvum-treated mice, and for this and other reasons these factors are unlikely to be responsible for the observed effects. Concanavalin A, endotoxin, and poly I: C induced high levels of serum interferon but purified interferon had only weak antitumour activity in the Meth A system, suggesting that interferon may not be the mediator. From these and other data it is concluded that there is no clear relationship between the capacity of the agents to induce tumour necrosis and their capacity to elicit TNF, cytostatic factors, and interferon.


Biochar addition increased soil bacterial diversity and richness: Large-scale evidence of field experiments.
Biochar plays a crucial role in enhancing soil ecological functions and productivity, and mitigating environmental pollution. Despite the available studies conducted through high-throughput sequencing to understand the effects of biochar on soil bacterial diversity and richness, a comprehensive understanding remains elusive. Our global meta-analysis addresses this knowledge gap, incorporating 473 pairs of observations from 84 studies to assess soil bacterial diversity and richness response to biochar addition. We found that biochar application increased bacterial Shannon and Chao1 indices by 0.99 % and 6.45 % respectively. However, these positive effects were context-dependent, especially concerning bacterial diversity. Through aggregated boosted trees analysis, we determined that soil characteristics (including soil organic carbon and nitrogen contents, soil pH, and soil texture) had a more significant influence than biochar properties, experimental conditions, or climatic factors on soil bacterial diversity and richness post biochar addition. In particular, the soil carbon to nitrogen ratio stood out as the leading factor influencing the bacterial Shannon and Chao1 indices following biochar addition. Our findings offer new insights into biochar's influence on soil bacterial activity, taking into account biochar-mediated spatiotemporal variation. This information is pivotal for optimizing biochar characteristics and application to improve soil biological health.


Successful Genetic Transfection of the Colonic Protistan Parasite Blastocystis for Reliable Expression of Ectopic Genes.
The microbial parasite Blastocystis colonizes the large intestines of numerous animal species and increasing evidence has linked Blastocystis infection to enteric diseases with signs and symptoms including abdominal pain, constipation, diarrhea, nausea, vomiting, and flatulence. It has also recently been reported to be an important member of the host intestinal microbiota. Despite significant advances in our understanding of Blastocystis cell biology and host-parasite interactions, a genetic modification tool is absent. In this study, we successfully established a robust gene delivery protocol for Blastocystis subtype 7 (ST7) and ectopic protein expression was further tested using a high sensitivity nano-luciferase (Nluc) reporter system, with promoter regions from several genes. Among them, a strong promoter encompassing a region upstream of the legumain 5' UTR was identified. Using this promoter combined with the legumain 3' UTR, which contains a conserved, precise polyadenylation signal, a robust transient transfection technique was established for the first time in Blastocystis. This system was validated by ectopic expression of proteins harbouring specific localization signals. The establishment of a robust, reproducible gene modification system for Blastocystis is a significant advance for Blastocystis research both in vitro and in vivo. This technique will spearhead further research to understand the parasite's biology, its role in health and disease, along with novel ways to combat the parasite.


Understanding and dealing with anger, aggression and violence.
Following the launch in 1999 of the government's Zero Tolerance campaign against violence and aggression towards healthcare staff, Phil Garnham looks at how healthcare staff can help to prevent violence and aggression by understanding patient issues, and find a safe, productive solution together.


Directionality of Macrophages Movement in Tumour Invasion: A Multiscale Moving-Boundary Approach.
Invasion of the surrounding tissue is one of the recognised hallmarks of cancer (Hanahan and Weinberg in Cell 100: 57-70, 2000. https://doi.org/10.1016/S0092-8674(00)81683-9 ), which is accomplished through a complex heterotypic multiscale dynamics involving tissue-scale random and directed movement of the population of both cancer cells and other accompanying cells (including here, the family of tumour-associated macrophages) as well as the emerging cell-scale activity of both the matrix-degrading enzymes and the rearrangement of the cell-scale constituents of the extracellular matrix (ECM) fibres. The involved processes include not only the presence of cell proliferation and cell adhesion (to other cells and to the extracellular matrix), but also the secretion of matrix-degrading enzymes. This is as a result of cancer cells as well as macrophages, which are one of the most abundant types of immune cells in the tumour micro-environment. In large tumours, these tumour-associated macrophages (TAMs) have a tumour-promoting phenotype, contributing to tumour proliferation and spread. In this paper, we extend a previous multiscale moving-boundary mathematical model for cancer invasion, by considering also the multiscale effects of TAMs, with special focus on the influence that their directional movement exerts on the overall tumour progression. Numerical investigation of this new model shows the importance of the interactions between pro-tumour TAMs and the fibrous ECM, highlighting the impact of the fibres on the spatial structure of solid tumour.


Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial.
The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF. Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used. All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test. The study group (n = 150) withdrew vaginal progesterone from the day of positive HCG. The control group (n = 153) continued administration of vaginal progesterone during the next 3 weeks of pregnancy. The number of miscarriages prior to and after week 7 of gestation was seven (4.6%) and 15 (10.0%) in the study group and five (3.3%) and 13 (8.5%) in the control group respectively. The number of deliveries was 118 (78.7 %) in the study group and 126 (82.4 %) in the control group. The differences were not significant. Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate, and thus no effect on the delivery rate. Progesterone supplementation can safely be withdrawn at the time of a positive HCG test.


Effects of UV light on DNA chain growth and replicon initiation in human cells.
Exposure of mammalian cells to 254 nm UV light produces lesions that block DNA polymerases at least on the leading strand. For rodent cells the extent and duration of this blockage is both cell line- and fluence-dependent. Using DNA fiber autoradiography we report here similar findings for human cells. Wild-type human cells did not exhibit significant blockage following exposure to 2.5 J/m2. After exposure to 5.0 J/m2, there was significant blockage immediately after exposure, but by 5 h segment lengths returned to control values. Excision-deficient human cells, on the other hand, exhibited significant blockage both immediately and 5.0 h after exposure to 2.5 J/m2. Exposure of rodent cells to UV light is also known to activate alternative sites of replication. Such activation would enable cells to replicate areas of DNA which do not contain a 'normal' site of initiation, yet contain blocking lesions both upstream and downstream. We have previously shown (Griffiths and Ling, 1987) that this activation is more pronounced and long-lived in excision-deficient Chinese hamster ovary (CHO) cells than it is in wild-type CHO cells. We report here that excision-deficient human cells also exhibited a marked and prolonged activation of alternative sites of replicon initiation. Wild-type human cells, on the other hand, exhibited little if any activation.


Understanding the feasibility and implications of implementing early peanut introduction for prevention of peanut allergy.
A recent randomized trial (the Learning Early About Peanut Allergy [LEAP] study) provided evidence that earlier dietary peanut introduction reduces peanut allergy prevalence in high-risk infants. However, questions remain as to how to identify and target the "at-risk" population to facilitate timely introduction of peanut. We sought to use population-based infant peanut allergy data to understand feasibility and implications of implementing the LEAP trial intervention. Using the HealthNuts study cohort (n = 5276) of 1-year-old infants, we explored the impact of using various criteria to identify infants at high risk of developing peanut allergy, and the implications of skin prick test (SPT) screening before peanut introduction. Screening all infants with early onset eczema and/or egg allergy could require testing 16% of the population and would still miss 23% of peanut allergy cases; 29% of screened infants would require clinical follow-up because of being SPT-positive. Around 11% of high-risk infants were excluded from the LEAP study because of an SPT wheal size of more than 4 mm to peanut at baseline; data from the HealthNuts study suggest that 80% of these would be peanut allergic on food challenge. There were no life-threatening events among either low- or high-risk infants whose parents chose to introduce peanut at home in the first year of life, or in 150 peanut-allergic infants during hospital-based challenges. Based on this large epidemiological study, a population program aiming to identify and screen all infants at risk of peanut allergy would pose major cost and logistic challenges that need to be carefully considered. Further research might be required to provide data for low-risk infants.


A colorimetric sensing strategy based on enzyme@metal-organic framework and oxidase-like IrO2/MnO2 nanocomposite for α-glucosidase inhibitor screening.
A highly sensitive colorimetric sensing strategy based on enzyme@metal-organic framework (GAA@Cu-MOF) and IrO2/MnO2 nanocomposite was exploited innovatively for screening of α-glucosidase (GAA) inhibitors. IrO2/MnO2 nanocomposite exhibits excellent oxidase-mimicking activity which can directly catalyze the oxidation of 3,3,5,5,-tetramethylbenzidine (TMB) into a blue product with an absorption maximum at 652 nm. And GAA@Cu-MOF can decompose L-ascorbic acid-2-O-α-D-glucopyranosyl (AAG) to ascorbic acid (AA). The produced AA can destroy the IrO2/MnO2 nanocomposite and reduce its oxidase-like activity. However, the generation of AA is restricted when GAA inhibitors are added to the system, which allows the oxidase-like activity of the IrO2/MnO2 nanocomposite to be maintained. In view of this, a method for screening of GAA inhibitors was developed. In addition to enhancing the stability of GAA, the method can also effectively avoid the potential interference of H2O2 in the screening process of GAA inhibitors, which helps to improve the sensitivity of the method. Therefore, highly sensitive determination for acarbose and ascorbic acid are achieved with detection limits of 6.27 nM and 1.23 μM, respectively. The proposed method was successfully applied to screen potential GAA inhibitors from oleanolic acid derivatives. Graphical abstract.


An overview of current drugs and prophylactic vaccines for coronavirus disease 2019 (COVID-19).
Designing and producing an effective vaccine is the best possible way to reduce the burden and spread of a disease. During the coronavirus disease 2019 (COVID-19) pandemic, many large pharmaceutical and biotechnology companies invested a great deal of time and money in trying to control and combat the disease. In this regard, due to the urgent need, many vaccines are now available earlier than scheduled. Based on their manufacturing technology, the vaccines available for COVID-19 (severe acute respiratory syndrome coronavirus 2 (SAR-CoV2)) infection can be classified into four platforms: RNA vaccines, adenovirus vector vaccines, subunit (protein-based) vaccines, and inactivated virus vaccines. Moreover, various drugs have been deemed to negatively affect the progression of the infection via various actions. However, adaptive variants of the SARS-CoV-2 genome can alter the pathogenic potential of the virus and increase the difficulty of both drug and vaccine development. In this review, along with drugs used in COVID-19 treatment, currently authorized COVID-19 vaccines as well as variants of the virus are described and evaluated, considering all platforms.


Lack of polyamines leads to cotranslational degradation of the general stress factor RpoS in Escherichia coli.
The specialized sigma factor RpoS mediates a general stress response in Escherichia coli and related bacteria, activating promoters that allow cells to survive stationary phase and many stresses. RpoS synthesis and stability are regulated at multiple levels. Translation of RpoS is positively regulated by multiple small RNAs in response to stress. Degradation of RpoS, dependent upon the adaptor protein RssB, is rapid during exponential growth and ceases upon starvation or other stresses, increasing accumulation of RpoS. E. coli carrying mutations that block the synthesis of polyamines were previously found to have low levels of RpoS, while levels increased rapidly when polyamines were added. We have used a series of reporters to examine the basis for the lack of RpoS in polyamine-deficient cells. The polyamine requirement was independent of small RNA-mediated positive regulation of RpoS translation. Mutations in rssB stabilize RpoS and significantly bypassed the polyamine deficit, suggesting that lack of polyamines might lead to rapid RpoS degradation. However, rates of degradation of mature RpoS were unaffected by polyamine availability. Codon optimization in rpoS partially relieved the polyamine dependence, suggesting a defect in RpoS translation in the absence of polyamines. Consistent with this, a hyperproofreading allele of ribosomal protein S12, encoded by rpsL, showed a decrease in RpoS levels, and this decrease was also suppressed by either codon optimization or blocking RpoS degradation. We suggest that rpoS codon usage leads it to be particularly sensitive to slowed translation, due to either lack of polyamines or hyperproofreading, leading to cotranslational degradation. We dedicate this study to Herb Tabor and his foundational work on polyamines, including the basis for this study.


Directed enzyme evolution.
Laboratory evolutionists continue to generate better enzymes for industrial and research applications. Exciting developments include new biocatalysts for enantioselective carbon-carbon bond formation and fatty acid production in plants. Creative contributions to the repertoire of evolutionary methods will ensure further growth in applications and expand the scope and complexity of biological design problems that can be addressed. Researchers are also starting to elucidate mechanisms of enzyme adaptation and natural evolution by testing evolutionary scenarios in the laboratory.


IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype.
Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.


Cell-penetrating compounds preferentially bind glycosaminoglycans over plasma membrane lipids in a charge density- and stereochemistry-dependent manner.
Cell-penetrating compounds (CPCs) are often conjugated to drugs and genes to facilitate cellular uptake. We hypothesize that the electrostatic interaction between the positively charged amines of the cell-penetrating compounds and the negatively charged glycosaminoglycans (GAGs) extending from cell surfaces is the initiating step in the internalization process. The interactions of generation 5 PAMAM dendrimer, Tat peptide and 25 kDa linear PEI with four different GAGs have been studied using isothermal titration calorimetry to elucidate structure-function relationships that could lead to improved drug and gene delivery methods to a wide variety of cell types. Detailed thermodynamic analysis has determined that CPC-GAG binding constants range from 8.7×10(3) to 2.4×10(6)M(-1) and that affinity is dependent upon GAG charge density and stereochemistry and CPC molecular weight. The effect of GAG composition on affinity is likely due to hydrogen bonding between CPC amines and amides and GAG hydroxyl and amine groups. These results were compared to the association of CPCs with lipid vesicles of varying composition as model plasma membranes to finally clarify the relative importance of each cell surface component in initial cell recognition. CPC-lipid affinity increases with anionic lipid content, but GAG affinity is higher for all cell-penetrating compounds, confirming the role these heterogeneous polysaccharides play in cellular association and clustering.


Production of cellulose nanocrystals extracted from Pennisetum purpureum fibers and its application as a lubricating additive in engine oil.
In the present work, cellulose nanocrystals (CNCs) were successfully produced from the Pennisetum purpureum (PP) fibers through ammonium persulfate (APS) oxidation. The effect of oxidation temperatures (60, 70, and 80 °C) on the properties of CNCs was characterized. In addition, the influence of CNCs addition (0, 0.05, 0.1, and 0.2 wt%) on the lubrication properties of the base oil SAE 40 lubricant was also investigated. The characteristics of the CNCs were determined by using FT-IR, XRD, TEM, and TGA. The lubrication properties were evaluated using kinematic viscosity and viscosity index measurements. The optimal oxidation temperature was found at 60 °C which resulted in the needle-shaped CNCs particles with high crystallinity (66.56%), an average diameter (15 nm), and an average length (79 nm). The resulting CNCs exhibited higher thermal stability than the PP fibers. Both kinematic viscosity and viscosity index did not significantly change by increasing the CNCs contents. However, a slightly higher viscosity index was exhibited for 0.2 wt% CNCs compared to that of neat base oil SAE 40. The CNCs obtained had high potential as a reinforcing agent of nanocomposites and also as a bio-lubricating additive in engine oil.


Sorbent preconcentration procedures coupled to capillary electrophoresis for environmental and biological applications.
Sorbent preconcentration offers good strategies to overcome the poor detection limits of capillary electrophoresis (CE). The present review focuses on the recent trends of the coupling between sorbent preconcentration techniques, namely solid-phase extraction (SPE) and solid-phase microextraction (SPME), to capillary electrophoresis (CE). Special attention is given to their environmental and biological application. We also discuss the most important advantages and disadvantages of the different methodologies and briefly outline the new trends of the coupling between sorbent preconcentration and CE.


Induction of resistance to Staphylococcus aureus in an environmental marine biofilm.
The study of environmental biofilms is complicated by the difficulty of working with them under lab conditions. Nonetheless, knowledge of cellular activity and interactions within environmental biofilms could lead to novel biomedical applications. As a first step in this direction we propose a novel technique for inducing resistance to Staphylococcus aureus (S. aureus) in an intact environmental biofilm. Agar plates were prepared with or without the addition of 20% S. aureus spent culture media and immersed in coastal seawater (Boston Harbor, Massachusetts, USA) for four days to grow up an environmental biofilm. Nucleopore filters inoculated with an overnight culture of S. aureus were then applied to the surface of the agar plates with the environmental biofilms, incubated 4h at 37°C, removed and subsequently stained and analyzed. Marine environmental biofilms grown on agar containing S. aureus spent culture media were significantly more inhibitory of S. aureus growth than were marine environmental biofilms grown on plain agar.


Adjustment of acquisition arc in cardiac malposition during myocardial perfusion SPECT imaging: computer simulation based on deterministic modeling.
To simulate cardiac malpositions, leftward and rightward shift and dextrocardia, and also to compare distribution of activity of septal and lateral walls of left ventricle acquired in standard acquisition arc and after relevant adjustment. In this study, digital phantoms with cardiac malpositions are designed and procedure of acquisition of scan in standard arc (from right anterior oblique to left posterior oblique) and adjusted acquisition arc is simulated. The three situations of malposition including leftward and rightward shift and dextrocardia are considered. For all types, acquisition is conducted in standard and then adjusted arcs (from anterior to posterior and also from right to left for leftward and rightward shifts, respectively, and for dextrocardia, from left anterior oblique to right posterior oblique). All obtained projections are reconstructed using the algorithm of filtered back projection. During forward projection to obtain sinograms, radiation attenuation is also modeled by incorporation of a simplified transmission map to emission map. The resulting tomographic slices of the LV (septum, apex, and lateral wall) are presented visually and are compared by plotting intensity profiles of the walls. Finally, normalized error images are also computed. All the computations are performed in MATLAB software package. In transverse slice, septum and lateral wall are attenuated progressively from apex, which is closer to the camera, to the base in similar fashion. In tomographic slices of standard acquisition arc, the septum shows remarkably higher activity compared to lateral wall. However, after adjustment, both seems equally intense and progressively being attenuated from apex to base, similar to that found in phantom with normally positioned heart. Likewise, for the phantom with rightward shift, when the scanning was done in standard arc, the septum is more intense than the lateral wall. And similarly, adjustment of the arc renders both walls equally intense. In dextrocardia, level of attenuation of basal parts of septum and lateral wall is higher in 360° arc compared to adjusted 180° arc. Adjustment of acquisition arc exerts perceptible changes in distribution of activity over LV walls which are more compatible with normally positioned heart.


Ethnic differences in carotid artery diameter and stiffness: the Northern Manhattan Study.
Race/ethnic differences in carotid arterial function and structure exist among those with cerebrovascular disease, but whether differences persist among healthy populations is unknown. Our objective was to investigate differences in carotid artery diameter and stiffness between race/ethnic groups, and examine whether these race/ethnic differences were age-dependent. Carotid diameters were assessed by B-mode ultrasound among 1536 participants from the Northern Manhattan Study (NOMAS), and carotid stiffness metrics were calculated. We used multivariable linear regression models to determine the relationship between race/ethnicity and both carotid arterial stiffness and carotid diastolic diameter. Mean participant age was 70 ± 9 years (Hispanics = 68 ± 8, blacks = 72 ± 9, and whites = 74 ± 9, p < 0.0001). Mean DDIAM was 6.2 ± 1.0mm (Hispanics = 6.2 ± 0.9 mm, blacks = 6.3 ± 1.0 mm, and whites = 6.3 ± 1.0 mm, p < 0.005) and mean STIFF was 8.7 ± 6.3 (Hispanics = 8.5 ± 5.7, blacks = 9.2 ± 6.2 and whites = 8.9 ± 6.9, p < 0.02). In a model that adjusted for sociodemographics and vascular risk factors including hypertension, diabetes, dislipidemia, renal function, physical acticity and a history of known coronary artery diseases; age was positively associated with greater DDIAM in Hispanics (p < 0.0001) but not among blacks or whites. Older age was associated with greater stiffness among Hispanics (p < 0.0001) and blacks (p < 0.003), but not among whites. We found race/ethnic differences in the association between age and arterial stiffness and diameter, including age-dependent arterial dilation observed in Hispanics that was not observed among blacks or whites.


Home measurement of blood pressure and cardiovascular disease: systematic review and meta-analysis of prospective studies.
Examine the relationship between home blood pressure (BP) and risk for all-cause mortality, cardiovascular mortality and cardiovascular events. We conducted a systematic review and meta-analysis of prospective studies of home BP. Primary outcomes were all-cause mortality, cardiovascular mortality and cardiovascular events. We extracted hazard ratios and 95% confidence intervals (CIs) which were pooled with a random-effects model. Heterogeneity was assessed using the I statistic. We identified eight studies with 17 698 participants. Follow-up was 3.2-10.9 years. For all-cause mortality (n = 747) the hazard ratio for home BP was 1.14 (95% CI 1.01-1.29) per 10 mmHg increase in systolic BP compared to 1.07 (0.91-1.26) for office BP. For cardiovascular mortality (n = 193) the hazard ratio for home BP was 1.29 (1.02-1.64) per 10 mmHg increase in systolic BP compared to 1.15 (0.91-1.46) for office BP. For cardiovascular events (n = 699) the hazard ratio for home BP was 1.14 (1.09-1.20) per 10 mmHg increase in systolic BP compared to 1.10 (1.06-1.15) for office BP. In three studies which adjusted for office and home BP the hazard ratio was 1.20 (1.11-1.30) per 10 mmHg increase in systolic BP for home BP adjusted for office BP compared to 0.99 (0.93-1.07) per 10 mmHg increase in systolic BP for office BP adjusted for home BP. Diastolic results were similar. Home BP remained a significant predictor of cardiovascular mortality and cardiovascular events after adjusting for office BP suggesting it is an important prognostic variable over and above that of office BP.


Use of iminodiacetic acid for the synthesis of piperazinyl peptides related to leu-enkephalin. II.
Piperazinyl peptides related to Leu-enkephalin were obtained using as intermediates condensation products with iminodiacetic acid. The products are devoid of analgesic activity.


[Craniopharyngioma with intraventricular development. Apropos of 2 cases. X-ray computed tomographic aspect].
We report two cases of craniopharyngioma developed within the third ventricle. In this occasion we present the different C. T. findings of these tumors.


Tuberculous epididymitis occurring 35 years after renal tuberculosis.
An unusual case of tuberculous epididymitis occurring 35 years after renal tuberculosis is reported. The possible mechanisms of this delayed presentation of the epididymal lesion are discussed. This case emphasizes the importance of adequate treatment as well as long-term followup of patients with genitourinary tuberculosis.


Aerobic biodegradation of the sulfonamide antibiotic sulfamethoxazole by activated sludge applied as co-substrate and sole carbon and nitrogen source.
Potential aerobic biodegradation mechanisms of the widely used polar, low-adsorptive sulfonamide antibiotic sulfamethoxazole (SMX) were investigated in activated sludge at bench scale. The study focused on (i) SMX co-metabolism with acetate and ammonium nitrate and (ii) SMX utilization when present as the sole carbon and nitrogen source. With SMX adsorption being negligible, elimination was primarily based on biodegradation. Activated sludge was able to utilize SMX both as a carbon and/or nitrogen source. SMX biodegradation was enhanced when a readily degradable energy supply (acetate) was provided which fostered metabolic activity. Moreover, it was raised under nitrogen deficiency conditions. The mass balance for dissolved organic carbon showed an incomplete SMX mineralization with two scenarios: (i) with SMX as a co-substrate, 3-amino-5-methyl-isoxazole represented the main stable metabolite and (ii) SMX as sole carbon and nitrogen source possibly yielded hydroxyl-N-(5-methyl-1,2-oxazole-3-yl)benzene-1-sulfonamide as a further metabolite.


Graphene e-tattoos for unobstructive ambulatory electrodermal activity sensing on the palm enabled by heterogeneous serpentine ribbons.
Electrodermal activity (EDA) is a popular index of mental stress. State-of-the-art EDA sensors suffer from obstructiveness on the palm or low signal fidelity off the palm. Our previous invention of sub-micron-thin imperceptible graphene e-tattoos (GET) is ideal for unobstructive EDA sensing on the palm. However, robust electrical connection between ultrathin devices and rigid circuit boards is a long missing component for ambulatory use. To minimize the well-known strain concentration at their interfaces, we propose heterogeneous serpentine ribbons (HSPR), which refer to a GET serpentine partially overlapping with a gold serpentine without added adhesive. A fifty-fold strain reduction in HSPR vs. heterogeneous straight ribbons (HSTR) has been discovered and understood. The combination of HSPR and a soft interlayer between the GET and an EDA wristband enabled ambulatory EDA monitoring on the palm in free-living conditions. A newly developed EDA event selection policy leveraging unbiased selection of phasic events validated our GET EDA sensor against gold standards.


Debulking Surgery for Clear Cell Carcinoma of the Ovary - A Case Report and Literature Review.
Ovarian clear cell carcinoma represents a distinct histopathological subtype of epithelial ovarian cancer, with poor outcomes, especially in cases diagnosed in advanced stages of disease. However, even in these cases, it seems that the most effective treatment remains debulking surgery to no residual disease. We present the case of a 56-year-old patient diagnosed with a large pelvic mass invading the rectosigmoidal colon, and ileal loop who was successfully submitted to cytoreductive surgery to no residual disease. The histopathological studies demonstrated the presence of a well-differentiated clear cell ovarian carcinoma of the ovary. At 1-year follow-up there is no evidence of residual disease.


Aqua-bis-(1,1,1,5,5,5-hexa-fluoro-acetyl-acetonato)[4'-(4-pyrid-yl)-2,2':6',2''-terpyridine]-ytterbium(III) chloride methanol monosolvate monohydrate.
The title compound, [Yb(C(5)HF(6)O(2))(2)(C(20)H(14)N(4))(H(2)O)]Cl·CH(3)OH·H(2)O, adopts an eight-coordinated geometry around the Yb(III) atom consisting of a 4'-(4-pyrid-yl)-2,2':6',2''-terpyridine (pytpy) ligand, two 1,1,1,5,5,5-hexa-fluoro-acetyl-acetonate (hfac) anions and an aqua ligand. In the solid state, the compound forms supra-molecular chains running along the b-axis via inter-molecular hydrogen bonds between the Yb-OH(2) unit and the N-atom donor of the 4-pyridyl pendant of pytpy, with an O⋯N distance of 2.686 (4) Å. A chloride counter-anion and lattice methanol and water solvent mol-ecules occupy a hydro-philic columnar space along the coordination chains. O-H⋯Cl hydrogen bonds occur. The two water molecules and the four trifluoromethyl groups are disordered over two sets of sites, each with different occupancy ratios.


Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.
Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel "ape-specific" enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.


Multi-channel near-infrared spectroscopy shows reduced activation in the prefrontal cortex during facial expression processing in pervasive developmental disorder.
The purpose of the present study was to investigate whether individuals with pervasive developmental disorders (PDD) show differential activation during an emotional activation task compared with age- and sex-matched controls, by measuring changes in the concentration of oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin, using near-infrared spectroscopy (NIRS). Fourteen patients with PDD and 14 age- and sex-matched healthy controls participated in the study. The relative changes of concentrations of oxyHb and deoxyHb were measured on NIRS during an implicit processing task of fearful expression using Japanese standard faces. PDD patients had significantly reduced oxyHb changes in the prefrontal cortex (PFC) compared to healthy controls. PFC dysfunction may exist in PDD.


tRNA-rRNA sequence homologies: evidence for an ancient modular format shared by tRNAs and rRNAs.
Homologies between tRNAs and rRNAs are identified in searches using various combinations of Escherichia coli, yeast, Halobacterium volcanii and bovine mitochondrial sequences. As in previously reported comparisons, the homologies are too frequent and long to be attributed to coincidence, and similar frequencies from inter- and intraspecies comparisons preclude evolutionary convergence as an explanation. In contrast to the earlier studies, patterns in the positioning of the homologies are now described. Graphing the positions of the homologies along orthogonal axes that represent numbers of bases in tRNA and rRNA shows recurring patterns in the alignments. Preferred spacings of integral multiples of 9 bases are found, suggesting a periodicity in the ancestral structure from which the tRNAs and rRNAs were derived. The periodicity also suggests persistence of a modular format in both classes of molecules that survived changes in sequence that occurred during evolution. A model is proposed for the generation of the ancestral molecule and the early evolution of the coding mechanism. Elongation by self-priming and self-templating gave a hairpin with a 9 base stem. Two additional cycles gave a 70-80 base tRNA-like structure. Additional cycles yielded a tandem repeat of this unit, roughly equivalent in size to the combined rRNAs of prokaryotes. The larger RNA would contain the information and materials for generating the smaller RNAs. It is proposed that multiple recombination among such molecules gave composite structures, presumed progenitors of today's t- and rRNAs. The distribution of the conserved domains among today's species argues for the existence of the ancestral molecule prior to divergence of lines leading to the various kingdoms. Their presence in the different nucleic acids suggests the existence of a nucleic acid with multiple functions prior to partitioning of these functions among the nucleic acids that exist today. The occurrence of overlaps, overlays and consensus alignments among the homologies provides the means for identifying contiguous and neighboring conserved regions and holds promise for the reconstruction of the sequence of an ancestral molecule.


Data for the analysis of PolyHIPE scaffolds with tunable mechanical properties for bone tissue engineering.
This article presents data related to the research article titled, 'Emulsion templated scaffolds with tunable mechanical properties for bone tissue engineering' (Owen et al., in press) [1]. This data article contains excel files with the results obtained during the mechanical characterisation of 20 acrylate-based PolyHIPE compositions, giving the Young's modulus, ultimate tensile stress and strain at failure for each specimen tested. Also included are the measurements taken to determine the degree of openness (DOO) of each composition, and the data for the cell viability and alkaline phosphatase (ALP) activity on the emulsion templated scaffolds.


Digoxin reduces the mutagenic effects of Mitomycin C in human and rodent cell lines.
Digoxin is a drug widely used to treat heart failure and studies have demonstrated its potential as anticancer agent. In addition, digoxin presents the potential to interact with a series of other compounds used in medicine. The aim of the present study was to evaluate in vitro the cytotoxicity, genotoxicity and mutagenicity of digoxin and its potential to interact with the mutagen Mitomycin C (MMC). The cytotoxicity of digoxin was assessed by employing the MTT method and the comet assay was performed to assess the genotoxicity of this medicine in CHO-K1 and HeLa cell lines. Besides, the cytokinesis-block micronucleus assay was performed to assess the mutagenicity and the antimutagenicity of this drug. The Ames assay was also performed with TA98 and TA100 strains of S. typhimurium. Results showed that digoxin was cytotoxic, genotoxic and mutagenic for HeLa and CHO-K1 cell lines at concentrations many times higher than those observed in human therapeutic conditions. Nevertheless, an antimutagenic effect against the mutagen MMC was observed on both cell lines in concentrations near those used therapeutically in humans. This chemoprotective effect observed is an interesting finding that should be better explored regarding its impact in anticancer chemotherapy.


Intelligence and neural efficiency: further evidence of the influence of task content and sex on the brain-IQ relationship.
In the field of physiological study of human intelligence, strong evidence of a more efficient operation (i.e., less activation) of the brain in brighter individuals (the neural efficiency hypothesis) can be found. Most studies in this field have used single, homogeneous tasks and have not examined sex differences. In analyzing the extent of Event-related Desynchronization (ERD) in the EEG during the performance of a verbal and a visuo-spatial task, we recently found that males and females display neural efficiency primarily in the domain where they usually perform better (i.e., verbal in females and spatial in males; cf. A.C. Neubauer, A. Fink, D.G. Schrausser, Intelligence and neural efficiency: the influence of task content and sex on brain-IQ relationship. Intelligence, 30 (2002) 515-536). However, this interpretation was complicated by differences in the complexity of the two tasks. By using a verbal (semantic) and a spatial (rotation) task of comparable complexity in this research, we sought to replicate and extend our earlier findings by additionally considering the individual differences in intelligence structure and the topographical distribution over the cortex. Findings were similar to the previous study: Females (n = 35) display neural efficiency (i.e., less brain activation in brighter individuals) primarily during the verbal task, males (n = 31) in the spatial task. However, the strength of this brain activation-IQ relationship varies with the intelligence factor: In males, the highest correlations were observed for spatial IQ, in females for verbal IQ. Furthermore, the sexes displayed topographical differences of neural efficiency patterns.


Acinus-provoked protein kinase C delta isoform activation is essential for apoptotic chromatin condensation.
Histone H2B phosphorylation tightly correlates with chromatin condensation during apoptosis. The caspase-cleaved acinus (apoptotic chromatin condensation inducer in the nucleus) provokes chromatin condensation in the nucleus, but the molecular mechanism accounting for this effect remains elusive. Here, we report that the active acinus p17 fragment initiates H2B phosphorylation and chromatin condensation by activating protein kinase C delta isoform (PKC-delta). We show that p17 binds to both Mst1 and PKC-delta, which is upregulated by apoptotic stimuli, enhancing their kinase activities. Acinus mutant susceptible to degradation elicits stronger chromatin condensation and higher H2B phosphorylation than wild-type acinus. Dominant-negative PKC-delta but not Mst1 robustly blocks acinus-initiated H2B phosphorylation. Surprisingly, depletion of Mst1 triggers caspase-3 activation, provoking H2B phosphorylation through activating PKC-delta. Further, acinus-elicited H2B phosphorylation and chromatin condensation are abrogated in PKC-delta-deficient mouse embryonic fibroblast cells and siRNA-knocked down PC12 cells. Thus, PKC-delta but not Mst1 acts as a physiological downstream kinase of acinus in promoting H2B phosphorylation and chromatin condensation.


Accountability Studies on Air Pollution and Health: the HEI Experience.
Assessing health effects of air quality interventions is of ever-increasing interest. Given the prominent role Health Effects Institute (HEI) has played in accountability research, this review focuses on HEI's recent experiences, the challenges it has encountered, and provides possible directions for future research. Most accountability studies to date have focused on effects of relatively short-term, local-scale, and sometimes temporary interventions. Only a few recent accountability studies have sought to investigate large-scale, multiyear regulatory programs. Common challenges encountered include lack of statistical power, how to account appropriately for background trends in air quality and health, and difficulties in direct attribution of changes in air pollution and health to a single intervention among many regulatory actions. New methods have been developed for accountability research that has shown promise addressing some of those challenges, including use of causal inference methods. These and other approaches that would enhance the attribution of changes in air quality and health directly to an intervention should continue to be further explored. In addition, integration of social and behavioral sciences in accountability research is warranted, and climate related co-benefits and dis-benefits may be considered.


Behaviors of treated hypertensive patients and patient demographic characteristics.
The relationships between self-reported hypertension-related patient behaviors and patient demographic characteristics were examined in a sample of 2,044 patients being treated for hypertension in 111 primary care medical practices. The patient behaviors of sodium intake, weight, alcohol, exercise, relaxation and adherence to medication regimen could be predicted to some extent by patient demographic characteristics. Whether patients recalled receiving advice from their physicians about these behaviors could also be predicted by patient demographic characteristics. Patients demographically similar to physicians, i.e., male, younger, more educated and White, reported receiving more advice from their physicians. Patients with behavioral problems who received relatively less advice from their physicians included: less educated younger patients whose sodium intake was relatively high; younger and less educated over-weight women; overweight Black patients; and older women who exercised less than average.


Approach to the difficult transseptal: diathermy facilitated left atrial access.
Percutaneous transseptal left atrial (LA) access is increasingly becoming a routine procedure in the electrophysiology and cardiac catheterisation laboratories. Our aim was to review an unselected large series of this procedure performed over a period of five years. We clinically characterised difficult cases and presented a method of safe and expeditious LA access. Overall, 543 transseptal punctures were performed. Of those, 10 were classified as difficult, with failure to access the LA in three or more attempts. In all 10 cases, surgical electrocautery was successfully used to facilitate needle puncture of the septum. All patients subsequently underwent an uncomplicated procedure. In conclusion, we describe a method to trouble-shoot the difficult transseptal access procedure, outlining the clinical characteristics, echocardiographic features and special precautions that need to be considered when utilising this method.


Preoperative risk evaluation in diabetic patients without angina.
The aim of the current study was to clarify whether stress myocardial perfusion single-photon emission computed tomography (SPECT) stratifies perioperative cardiac risk in noncardiac surgery of diabetic patients without chest pain. This study enrolled consecutive 284 patients with diabetes mellitus (DM) without chest pain who underwent noncardiac surgery after dipyridamole stress SPECT. Myocardial perfusion and cardiac function were simultaneously evaluated in the SPECT examination. We sought clinical and imaging variables predictive of perioperative cardiac events, and estimated the prognostic value of SPECT. No clinical risk factors were proved to be significant predictors of perioperative cardiac events except the duration of diabetes. In contrast, myocardial perfusion imaging itself and the combination of information on perfusion and cardiac function provided significant risk stratification. The event rate in patients with normal perfusion was low regardless of surgical procedures, while that in patients with abnormal perfusion increased depending on the operation risk. Normal myocardial SPECT findings ensure the low likelihood of perioperative cardiac events in DM patients without chest pain. Perfusion and/or functional abnormalities are associated with the adverse outcome especially in high-risk operation.


Mortality and pathophysiology of acute kidney injury according to time of occurrence in acute heart failure.
Acute kidney injury (AKI) during acute heart failure (AHF) is common and associated with increased morbidity and mortality. The underlying pathophysiological mechanism appears to have prognostic relevance; however, the differentiation of true, structural AKI from hemodynamic pseudo-AKI remains a clinical challenge. The Basics in Acute Shortness of Breath Evaluation Study (NCT01831115) prospectively enrolled adult patients presenting with AHF to the emergency department. Mortality of patients was prospectively assessed. Haemoconcentration, transglomerular pressure gradient (n = 231) and tubular injury patterns (n = 253) were evaluated to investigate pathophysiological mechanisms underlying AKI timing (existing at presentation vs. developing during in-hospital period). Of 1643 AHF patients, 755 patients (46%) experienced an episode of AKI; 310 patients (19%; 41% of AKI patients) presented with community-acquired AKI (CA-AKI), 445 patients (27%; 59% of AKI patients) developed in-hospital AKI. CA-AKI but not in-hospital AKI was associated with higher mortality compared with no-AKI (adjusted hazard ratio 1.32 [95%-CI 1.01-1.74]; P = 0.04). Independent of AKI timing, haemoconcentration was associated with a lower two-year mortality. Transglomerular pressure gradient at presentation was significantly lower in CA-AKI compared to in-hospital AKI and no-AKI (P < 0.01). Urinary NGAL ratio concentrations were significantly higher in CA-AKI compared to in-hospital AKI (P < 0.01) or no-AKI (P < 0.01). CA-AKI but not in-hospital AKI is associated with increased long-term mortality and marked by decreased transglomerular pressure gradient and tubular injury, probably reflecting prolonged tubular ischemia due to reno-venous congestion. Adequate decongestion, as assessed by haemoconcentration, is associated with lower long-term mortality independent of AKI timing.


Machine Learning and Lean Six Sigma to Assess How COVID-19 Has Changed the Patient Management of the Complex Operative Unit of Neurology and Stroke Unit: A Single Center Study.
Background: In health, it is important to promote the effectiveness, efficiency and adequacy of the services provided; these concepts become even more important in the era of the COVID-19 pandemic, where efforts to manage the disease have absorbed all hospital resources. The COVID-19 emergency led to a profound restructuring-in a very short time-of the Italian hospital system. Some factors that impose higher costs on hospitals are inappropriate hospitalization and length of stay (LOS). The length of stay (LOS) is a very useful parameter for the management of services within the hospital and is an index evaluated for the management of costs. Methods: This study analyzed how COVID-19 changed the activity of the Complex Operative Unit (COU) of the Neurology and Stroke Unit of the San Giovanni di Dio e Ruggi d'Aragona University Hospital of Salerno (Italy). The methodology used in this study was Lean Six Sigma. Problem solving in Lean Six Sigma is the DMAIC roadmap, characterized by five operational phases. To add even more value to the processing, a single clinical case, represented by stroke patients, was investigated to verify the specific impact of the pandemic. Results: The results obtained show a reduction in LOS for stroke patients and an increase in the value of the diagnosis related group relative weight. Conclusions: This work has shown how, thanks to the implementation of protocols for the management of the COU of the Neurology and Stroke Unit, the work of doctors has improved, and this is evident from the values of the parameters taken into consideration.


Comparative study of the effect of auxiliary energies on the extraction of Citrus fruit components.
A comparative study of methods for ultrasound-assisted extraction (USAE), microwave-assisted extraction (MAE) and superheated liquid extraction (SHLE) of compounds from citrus has been performed. The suited conditions for each method were evaluated to maximize the concentration of 10 representative compounds (sugars, carboxylic acids, phenolic acids and flavonoids) by a desirability function approach based on the chromatographic peaks obtained by LC-DAD. Extracts obtained under the suited conditions were analyzed by LC-QTOF MS/MS. The ANOVA on the molecular entities showed 232 significant entities (p<0.01), and pairwise comparison revealed that USAE and MAE methods are the most similar (50 different entities), and USAE and SHLE the most dissimilar (224 different entities). A discrimination test by PCA showed a clear discrimination among the extraction methods, explaining 78.51% of the total variability. Similarities in the abundance of the monitored compounds was tested by ANOVA showing that the extraction of carboxylic acids (malic and citric acids) was equal by all methods; while for each of the other eight compounds, at least one extraction method is different from the others. Under the evaluated conditions the SHLE method is the less favorable to extract metabolites from citrus, being the best the USAE method.


Ribosomal protein P0 from Aedes albopictus mosquito cells: cDNA cloning and analysis of expression.
Ribosomal protein P0 is one of the highly conserved phosphorylated proteins in the large subunit of eukaryotic ribosomes. P0 has been shown in Drosophila to be a multifunctional protein that associates with elongation factor eEF2 to facilitate translation and also plays a role in DNA repair. In this paper we describe the cloning and characterization of the full-length cDNA encoding P0 from the mosquito, Aedes albopictus. In vitro translation showed that the cDNA encoded a 34kDa protein that corresponded in size to a phosphorylated protein from the large ribosomal subunit after in vivo labeling with [32P]orthophosphate. When cells were exposed to various stresses, expression of P0 appeared to differ from that of rpL34. Preliminary RNAi experiments suggested that downregulation of P0 is correlated with apoptosis in C7-10 mosquito cells.