Neurological complications in critical patients with COVID-19.
We analysed the neurological complications of patients with severe SARS-CoV-2 infection who required intensive care unit (ICU) admission. We conducted a retrospective, observational, descriptive study of consecutive patients admitted to the ICU due to severe respiratory symptoms secondary to SARS-CoV-2 infection between 1 April and 1 June 2020. We included 30 patients with neurological symptoms; 21 were men (72.40%), and mean age (standard deviation [SD]) was 57.41 years (11.61). The mean duration of ICU stay was 18.83 days (14.33). The neurological conditions recorded were acute confusional syndrome in 28 patients (93.33%), neuromuscular disease in 15 (50%), headache in 5 (16.66%), cerebrovascular disease in 4 (13.33%), and encephalopathies/encephalitis in 4 (13.33%). CSF analysis results were normal in 6 patients (20%). Brain MRI or head CT showed alterations in 20 patients (66.6%). EEG was performed in all patients (100%), with 8 (26.66%) showing abnormal findings. In 5 of the 15 patients with clinical myopathy, diagnosis was confirmed with electroneuromyography. We found a correlation between older age and duration of ICU stay (P=.002; 95%CI: 4.032-6.022; OR: 3,594). Severe COVID-19 mainly affects men, as observed in other series. Half of our patients presented acute myopathy, and almost all patients left the ICU with acute confusional syndrome, which fully resolved; no correlation was found with EEG or neuroimaging findings. Older age is associated with longer ICU stay.


Occurrence of psychosis in patients with epilepsy randomized to tiagabine or placebo treatment.
Patients with drug-resistant epilepsy have a higher incidence of psychiatric problems and possibly greater intolerance to antiepileptic drugs (AEDs) than do other patients with epilepsy. Concern has been raised that gamma-aminobutyric acid (GABA)ergic drugs may be associated with treatment-emergent psychosis. Tiagabine (TGB; Gabitril), a new AED that blocks synaptic GABA uptake, was developed in trials of drug-resistant patients with epilepsy. We conducted ad hoc analyses of adverse events, drug intolerance, and treatment response to evaluate the association between TGB treatment and psychosis and whether psychiatric history might be predictive of tolerance or effectiveness of this GABAergic drug. Data were analyzed from two multicenter, randomized, double-blind, placebo-controlled trials of add-on TGB therapy (32 or 56 mg daily) in 554 adolescents and adults with complex partial seizures (CPSs). After an 8- or 12-week baseline phase, double-blind treatment consisted of a 4-week titration period (with TGB dose gradually increased to 32 or 56 mg daily) and an 8- or 12-week fixed-dose period. Adverse events commonly associated with psychosis were evaluated. Treatment intolerance and effectiveness (> or =50% reduction in CPS rate) were compared among patients with and without psychiatric histories. Psychotic symptoms (hallucinations) were observed in three (0.8%) of 356 TGB-treated patients and none of 198 placebo-treated patients (p = 0.556, NS). Statistical analysis showed no interaction between psychiatric history and drug intolerance or treatment outcome. TGB administration appears to carry no significant increased risk of treatment-emergent psychosis. Psychiatric history was not predictive of the tolerance or effectiveness of the drug.


Molecular dynamics of native protein. I. Computer simulation of trajectories.
The motion of the atoms in the small protein bovine pancreatic trypsin inhibitor has been simulated for about 60 picoseconds using two different potential energy functions. In one known as HHL the hydrogen bond is purely electrostatic, in the other, known as L79, the hydrogen bond is a directional O . . . H interaction. The energy parameters and techniques used to obtain an accurate, well-equilibrated trajectory are described in detail. The trajectories calculated here with either potential are superior to those obtained in previous simulations on the same protein in that they treat hydrogen bonding realistically and remain closer to the native X-ray structure. Comparison of the two trajectories shows that the potential energy parameters have a significant effect on the shift from the X-ray structure, the distribution of (phi, psi) torsion angles, the pattern of hydrogen bonds and the accessible surface area of individual residues. The L79 potential with directional hydrogen bonds is used to simulate a longer 132 picosecond trajectory that is analysed in the accompanying paper.


Development of neuromuscular junctions of fast and slow muscles in the chick embryo: a light and electron microscopic study.
The morphogenesis of neuromuscular injections (NMJ) was studied by electron microscopy in fast posterior and slow anterior latissimus dorsi muscles (PLD and ALD) of chick embryos. In 8 day embryos, the NMJ is already established in both types. In PLD at this stage, individual axons completely ensheathed by Schwann cell processes form NMJs with myotubes, whereas in ALD axon terminal lie adjacent to (and not separated by Schwann cell processes from) naked axons which are components of a nerve bundle. At 11-15 days, the number of profiles of axon terminals at each endplate increases in both PLD and ALD. In PLD, individual axon terminals are ensheathed by Schwann cells and often branch. In ALD, several axon terminals become ensheathed as a group by processes of a Schwann cell, along with a small number of adjacent naked axons. The individual axon terminals were confirmed by analysis of serial sections to originate from different preterminal axons. Thus, the increase in number of axon terminals in PLD may be due to extensive terminal branching, whereas in ALD it may be due to the arrival of other nerve fibres. From 16 days, each axon terminal in an endplate of ALD becomes individually ensheathed by Schwann cell processes. However, the property of polyneuronal innervation in each endplate is retained even in the adult muscle. The junctional sarcoplasm protrudes to separate individual axon terminals at certain developmental stages: the protuberances are thinner and more numerous in ALD than in PLD at 15-16 days. It is concluded that NMJ morphogenesis differs between PLD and ALD and that the differences reside mainly on the neuronal side.


Thyroxine and testosterone transcriptionally regulate renin gene expression in the submaxillary gland of normal and transgenic mice carrying extra copies of the Ren2 gene.
Expression of the mouse renin genes (Ren1 and Ren2) in the submaxillary gland of female mice has been analyzed following administration of thyroxine (T4) or dihydrotestosterone (DHT). Both hormones appear to act independently on mRNA accumulation which increases about 5 fold over basal level. In vitro transcription assays in isolated nuclei demonstrate that both hormones act at the transcriptional level. The effects of DHT and T4 were also analyzed in transgenic mice obtained by microinjection of the Ren2 gene. We show that T4 is as efficient as DHT in promoting renin mRNA accumulation in these transgenic animals, in spite of their low basal level of Ren2 mRNA. Structural comparison of the Ren1 and Ren2 promoters with those of other genes regulated by T4 shows the conservation of two discrete regions.


A dose response model for quantifying the infection risk of antibiotic-resistant bacteria.
Quantifying the human health risk of microbial infection helps inform regulatory policies concerning pathogens, and the associated public health measures. Estimating the infection risk requires knowledge of the probability of a person being infected by a given quantity of pathogens, and this relationship is modeled using pathogen specific dose response models (DRMs). However, risk quantification for antibiotic-resistant bacteria (ARB) has been hindered by the absence of suitable DRMs for ARB. A new approach to DRMs is introduced to capture ARB and antibiotic-susceptible bacteria (ASB) dynamics as a stochastic simple death (SD) process. By bridging SD with data from bench experiments, we demonstrate methods to (1) account for the effect of antibiotic concentrations and horizontal gene transfer on risk; (2) compute total risk for samples containing multiple bacterial types (e.g., ASB, ARB); and (3) predict if illness is treatable with antibiotics. We present a case study of exposure to a mixed population of Gentamicin-susceptible and resistant Escherichia coli and predict the health outcomes for varying Gentamicin concentrations. Thus, this research establishes a new framework to quantify the risk posed by ARB and antibiotics.


CX3CL1 represses autophagy via CX3CR1/ CaMKIIδ/HDAC4/Rubicon axis and exacerbates chronic intermittent hypoxia induced Kupffer cell apoptosis.
Nocturnal hypoxemia is an established factor in the pathogenesis and exacerbation of term metabolic (dysfunction) associated fatty liver disease (MAFLD). Kupffer cells (KCs) are resident macrophages in the liver, and their activity is closely related to the progress of MAFLD. KC insufficient autophagy is involved in MAFLD pathogenesis. Herein, the regulatory mechanism of KC autophagy under chronic intermittent hypoxia (CIH) condition was investigated. Primary KCs and hepatic stellate cells (HSCs) were isolated from mouse liver. Immunofluorescence was employed to detect immunofluorescence intensity of LC3 protein and HDAC4 distribution. KC apoptosis was measured by TUNEL staining. Dual-luciferase reporter and ChIP assays were performed to analyze the interactions between HDAC4, MEF2C and RUBCN. Herein, our results revealed that CIH-induced increased CX3CL1 in HSCs inhibited KC autophagy and promoted cell apoptosis by interacting with CX3CR1. Meanwhile, CX3CL1 treatment inhibited KC autophagy (p < 0.001, fold change: 0.059) and promoted cell apoptosis (p < 0.001, fold change: 8.18). Rubicon knockdown promoted KC autophagy (p < 0.001, fold change: 2.90) and inhibited cell apoptosis (p < 0.05, fold change: 0.23), while these effects were reversed by CX3CL1 treatment (p < 0.01, fold change: 6.59; p < 0.001, fold change: 0.35). Our mechanistic experiments demonstrated that HDAC4 overexpression transcriptionally inhibited RUBCN expression by interacting with MEF2C, thereby promoting KC autophagy and inhibiting cell apoptosis. Moreover, CaMKIIδ inhibition promoted the translocation of HDAC4 from the cytosol to the nucleus to promote KC autophagy and inhibit the apoptosis. Taken together, CIH-induced increased CX3CL1 expression in HSCs inhibited KC autophagy and promoted apoptosis by regulating the CX3CR1/ CaMKIIδ/HDAC4/Rubicon axis.


Drug-Induced Intracranial Hypertension: A Systematic Review and Critical Assessment of Drug-Induced Causes.
Idiopathic intracranial hypertension (IIH) is a condition with increased intracranial pressure of unknown etiology. Its presenting symptoms include persistent headache, pulsatile tinnitus, and visual obscuration. It tends to occur in obese women of childbearing age, and its greatest risk is irreversible loss of vision. Some of the commonly used medications in dermatology, especially those for acne vulgaris, have been associated with IIH. However, the creation of specific risk categories for drugs as a guide for clinicians has never been performed. The aim of this study was to critically assess all published cases of IIH and identify high-risk drugs associated with drug-induced intracranial hypertension (DIIH), to assist dermatologists and other physicians with patient education and monitoring of symptoms of secondary intracranial hypertension. MEDLINE, EMBASE, and Cochrane Review Databases were searched for all cases of IIH thought to be drug-related between January 1900 and June 2019. A total of 5117 articles were identified, and 235 articles were found to be relevant. All cases were assessed to satisfy the modified Dandy criteria for diagnosis of IIH, and the likelihood of each case being a 'definite' adverse drug reaction (ADR) was determined using the Koh algorithm for ADR. An association category (from weakly associated [Category I] to strongly associated [Category V]) was assigned based on the number of cases meeting these two criteria. There were 259 verifiable cases of DIIH. Vitamin A derivatives, tetracycline-class antibiotics, recombinant growth hormone, and lithium were found to be most strongly associated with DIIH (Categories IV and V). Corticosteroids were moderately associated with DIIH (Category III). Drugs that were weakly associated with DIIH (Categories I and II) include cyclosporine, progestin-only contraceptives, combined oral contraceptives, second- and third-generation fluoroquinolones, sulfenazone, gonadotropin-releasing hormones and luteinizing hormone-releasing hormone agonist, nalidixic acid, amiodarone, stanozolol, danazol, divalproic acid, sulfasalazine, ketoconazole, and ustekinumab. We suggest using the term 'drug-induced intracranial hypertension' (DIIH) and propose a set of diagnostic criteria for DIIH. Our review attempts to identify DIIH-associated drugs based on a strict diagnostic and drug-causality algorithm, then stratify them into appropriate risks categories. This may ultimately assist physicians in counselling patients about the risk of DIIH when prescribing medications and recognizing this uncommon yet sight-threatening condition.


Improving the electro-transformation efficiency of Corynebacterium glutamicum by weakening its cell wall and increasing the cytoplasmic membrane fluidity.
To improve the transformation efficiency of Corynebacterium glutamicum cells with heterogenous plasmid DNA and single-strand DNA (ssDNA) using a methodology based on electro-transformation. A semicomplex hypertonic medium was selected with addition of glycine and DL-threonine to weaken cell walls and addition of Tween 80 and isonicotinic acid hydrazide to increase cytoplasmic membrane fluidity. Their contents were optimized by response surface methodology. Cell growth, electro-transformation buffer, and transformation protocol were also optimized. Temporary heating inactivation of the host restriction enzyme showed a significant effect. Finally, a high transformation efficiency of 3.57 ± 0.13 × 10(7) cfu/μg DNA of plasmid and 1.05 × 10(6) Str (R) cfu per 10(9) viable cells with a ssDNA was achieved. The results shed light on the application in functional genomics and genome editing of C. glutamicum.


Publishing Outside the Box: Unforeseen Dividends of Talking to Strangers.
This article describes publishing outside behavior analysis, letters to editors, and columns, as well as communicating outside the box with editors, authors, and journalists. Publishing can occur in a wide range of journals (e.g., Consciousness and Cognition), in-house publications of professional associations (e.g., Association for Psychological Science's Observer), general science publications (e.g., American Scientist, The Scientist), publications in service to professions (e.g., The Chronicle of Higher Education), general interest and specialized magazines (e.g., Atlantic Monthly, Skeptical Inquirer), and newspapers (e.g., Los Angeles Times). Communicating with editors, authors, and journalists includes, for instance, formal correspondence with editors and personal correspondence with authors and journalists outside the box about misunderstandings, commonalities, and complementarities of their work with respect to ours. The consequences of publishing and communicating are often unforeseen and fortuitous, many of which can never occur by remaining in the box.


Reconstruction of post-orthognathic aseptic necrosis of the maxilla.
We present the reconstruction of near total aseptic necrosis of the maxillary alveolus that occurred after a Le Fort I osteotomy eight years previously.


Enhanced differentiation of the mouse oli-neu oligodendroglial cell line using optimized culture conditions.
Oligodendrocytes (OL) are the glial cell type in the CNS that are responsible for myelin formation. The ability to culture OLs in vitro has provided critical insights into the mechanisms underlying their function. However, primary OL cultures are tedious to obtain, difficult to propagate and are not easily conducive to genetic manipulation. To overcome these obstacles, researchers have generated immortalized OL like cell lines derived from various species. One such cell line is the mouse Oli-neu line which is thought to recapitulate characteristics of OLs in early stages of maturity. They have been extensively utilized in multiple studies as surrogates for OLs, especially in analyzing epigenetic modifications and regulatory pathways in the OL lineage. In this report we present the development of optimized culture media and growth conditions that greatly facilitate the differentiation of Oli-neu cells. Oli-neu cells differentiated using these new protocols exhibit a higher expression of myelin related genes and increased branching, both of which are defining characteristics of mature OLs, when compared to previous culture protocols. We envision that these new culture conditions will greatly facilitate the use of Oli-neu cells and enhance their ability to recapitulate the salient features of primary OLs.


Quantitative analysis of gas losses and gains in the middle ear.
Quantitative analysis of the amount of gas entering and leaving the middle ear (ME) was performed in patients with central perforation or with ventilating tubes. Patients were divided into a 'balanced pressure group' (BP) where pressure remained close to atmospheric throughout the measuring period and an 'unbalanced pressure group' (UBP) where pressure decreased continuously throughout measurements. The rate of gas gain was 41.0 +/- 19.9 microl/h (mean +/- SD, n = 17) in the BP group, significantly higher than in the UBP group (21.4 +/- 9.6 microl/h, n = 8). The rate of gas loss was 34.8 +/- 17.7 and 36.1 +/- 15.9 microl/h in the BP and UBP groups, respectively. Deglutition frequency was 27 +/- 13.4 deglutition/h in the BP group, significantly higher than the deglutition frequency of the UBP group (16 +/- 8.9 deglutition/h). It seems that the amount of gas entering the ME per deglutition is rather stable and does not change significantly with ME pressure level. Negative ME pressure may result from decreased gas gain rate due to increased intervals between deglutitions and loss of interdependence between the rate of gas entering and leaving the ME.


Serotonin-mediated modulation of hypoxia-induced intracellular calcium responses in glomus cells isolated from rat carotid body.
In the present study, we examined serotonin (5-HT)-induced intracellular Ca(2+) ([Ca(2+)]i) responses to hypoxia in glomus cells isolated from carotid body (CB) of the rat. 5-HT did not induce any [Ca(2+)]i responses in clustered glomus cells during normoxia (21% O2), whereas, the perfusion of hypoxic solution (1% O2) induced repetitive increases in [Ca(2+)]i in the same specimens. The frequency and magnitude of hypoxia-induced [Ca(2+)]i changes observed in the glomus cells were enhanced in the presence of 5-HT, and this response was inhibited by the 5-HT2 receptor antagonist, ketanserin. Furthermore, RT-PCR analysis detected the expression of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT3A, and 5-HT3B receptor mRNAs in extracts of the CB. These results suggest that 5-HT increases hypoxia-induced [Ca(2+)]i responses in glomus cells. 5-HT may elevate hypoxic responses in glomus cells in order to increase chemosensory activity of the CB.


Hepatitis E virus serological testing in kidney transplant recipients with elevated liver enzymes in 2007-2011 in southeastern France.
Hepatitis E virus (HEV) is an emerging cause of acute and chronic hepatitis in Europe, particularly in solid organ transplant recipients. Anti-HEV IgG/IgM testing in kidney transplant recipients with liver biological disturbances indicated high HEV exposure in our geographical area and led to diagnose HEV infection in 6% of cases.


Factors influencing somatic cell counts and bacterial contamination in unpasteurized milk obtained from water buffalo in Bangladesh.
Little has been published on the factors influencing the safety and quality of milk derived from water buffalo in Bangladesh. This study aims to describe the milk hygiene parameters and milk chain characteristics of unpasteurized raw milk sold to consumers in order to improve milk hygiene. A quantitative study design evaluated somatic cell counts, total bacterial counts, and specific gram-negative (Enterobacteria) and gram-positive (staphylococci) pathogens in 377 aseptically collected milk samples. Samples were collected at multiple nodes along the buffalo milk value chain: 122 bulk tank milk samples were collected at the farm level, 109 milk samples at the middlemen level, and 111 milk samples at the milk collection centers. In addition, 35 samples were taken from various milk products at the retail level. It was found that progressively increasing somatic cell counts and bacterial counts, including potential pathogens, occurred along the milk chain. A seasonal increase in spring was found, varying based on the farming system (semi-intensive versus intensive). Other factors included water purity and cleanliness of containers, mixing buffalo and cow's milk, and the location of the water buffalo milk producer (coastal or river basin). This study demonstrated how improving udder health and milk hygiene along the water buffalo milk value chain would increase the safety and quality of water buffalo milk in the study area.


Isolation of novel citrus and plum fruit promoters and their functional characterization for fruit biotechnology.
Promoters that confer expression in fruit tissues are important tools for genetic engineering of fruit quality traits, yet few fruit-specific promoters have been identified, particularly for citrus fruit development. In this study, we report five citrus fruit-specific/preferential promoters for genetic engineering. Additionally, we have characterized a novel fruit-preferential promoter from plum. Genes specifically expressed in fruit tissues were selected and their isolated promoter regions were fused with the GUSPlus reporter gene for evaluation in transgenic plants. Stable transformation in Micro-Tom tomato demonstrated that the candidate promoter regions exhibit differing levels of expression and with varying degrees of fruit specificity. Among the five candidate citrus promoters characterized in this study, the CitSEP promoter showed a fruit-specific expression pattern, while the CitWAX and CitJuSac promoters exhibited high fruit-preferential expression with strong activity in the fruit, weak activity in floral tissues and low or undetectable activity in other tissues. The CitVO1, CitUNK and PamMybA promoters, while exhibiting strong fruit-preferential expression, also showed consistent weak but detectable activity in leaves and other vegetative tissues. Use of these fruit specific/preferential promoters for genetic engineering can help with precise expression of beneficial genes and help with accurate prediction of the activity of new genes in host fruit plants.


Isolated hexadactylia: A rare case of central polydactyly of the foot.
Central polydactyly of foot is uncommon form of polydactyly but it usually causes intermetatarsal widening because of metatarsal bifurcation. Central polydactyly associated with T shaped bifurcation of metatarsal in vertical plane has not been reported yet. We present a 4 year male child with extra toe on the dorsal aspect of right foot with complains of difficulty in wearing footwear and poor cosmesis. The extra digit was fully developed with bifurcation of 2nd metatarsal bone proximal to the head without any intermetatarsal widening. The angular deviation was 45° to the longitudinal axis of foot and in a plane vertical to the transverse arch of foot. The child was operated with excision of extra toe without any residual bony deformity. The central polydactyly is rare type of polydactyly of foot. Central polydactyly with metatarsal extension causing intermetatarsal widening has been well described entity. But the previous classifications need to be modified to include central polydactyly with vertical oriented T bifurcation of metatarsal bone without intermetatarsal widening.


Mechanical power during maximal treadmill walking and running in young and elderly men.
This study determined mechanical power during movements specific to maximal walking and running using a non-motorized treadmill in 38 elderly [69.4 (5.0) years] and 50 young [24.3 (3.4) years] men. The mean mechanical power over a period of time covering six steps, during which the belt velocity peaked and then kept almost plateau, was determined as a performance score in each of maximal walking (WP) and running (RP). In terms of the value relative to body mass, the relative difference between the two age groups was greater for RP (61.7%) than for WP (21.4%) or isometric knee extension (34.1%) and flexion torque (43.8%). In the two groups, WP was significantly ( P<0.05) correlated to knee extension (r=0.582 for the elderly and r=0.392 for the young) and flexion torque (r=0.524 for the elderly and r=0.574 for the young). Similarly, RP was also significantly (P<0.05) correlated to knee extension (r=0.627 for the elderly and r=0.478 for the young) and flexion torque (r=0.500 for the elderly and r=0.281 for the young). In these relationships, the WP adjusted statistically by thigh muscle torque was similar in the two age groups. However, the corresponding value for RP was significantly higher in the young than in the elderly. The findings here indicate that: (1) the difference between the young and elderly men in mechanical power is greater during maximal running than maximal walking, and (2) although the thigh muscle torque contributes to the power production during the two maximal exercise modes in the two age groups, the RP is greater in the young than in the elderly regardless of the difference in the thigh muscle torque.


Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation.
Severely injured patients with hemorrhagic shock can develop endothelial dysfunction, systemic inflammation, and coagulation disturbances collectively known as the endotheliopathy of trauma (EOT). Shedding of the endothelial glycocalyx occurs early after injury, contributes to breakdown of the vascular barrier, and plays a critical role in the pathogenesis of multiple organ dysfunction, leading to poor outcomes in trauma patients. In this review we discuss (i) the pathophysiology of endothelial glycocalyx and vascular barrier breakdown following hemorrhagic shock and trauma, and (ii) the role of plasma and platelet transfusion in maintaining the glycocalyx and vascular endothelial integrity.


Adult coats' disease successfully managed with the dexamethasone intravitreal implant (ozurdex®) combined with retinal photocoagulation.
To report a case of Coats' disease managed with the dexamethasone intravitreal implant Ozurdex(®) (Allergan, Inc., Irvine, Calif., USA) combined with retinal photocoagulation. A 46-year-old female with 20/200 visual acuity was diagnosed with Coats' disease with secondary retinal vasoproliferative tumor. An initial approach was performed with an intravitreal injection of the sustained-release dexamethasone implant Ozurdex. After reattachment of the retina, the telangiectatic vessels were treated with laser photocoagulation. The patient's visual acuity improved to 20/25 after the intravitreal Ozurdex. No further recurrences of exudation were evident through the 12-month follow-up. Ozurdex may be an effective initial therapeutic approach for Coats' disease with immediate anatomical response and visual improvement.


Neutralization escape of Omicron XBB, BR.2, and BA.2.3.20 subvariants.
New Omicron subvariants continue to emerge throughout the world. In particular, the XBB subvariant, which is a recombinant virus between BA.18.104.22.168 and BA.18.104.22.168.1.1, as well as the BA.2.3.20 and BR.2 subvariants that contain mutations distinct from BA.2 and BA.2.75, are currently increasing in proportion of variants sequenced. Here we show that antibodies induced by 3-dose mRNA booster vaccination as well as BA.1- and BA.4/5-wave infection effectively neutralize BA.2, BR.2, and BA.2.3.20 but have significantly reduced efficiency against XBB. In addition, the BA.2.3.20 subvariant exhibits enhanced infectivity in the lung-derived CaLu-3 cells and in 293T-ACE2 cells. Overall, our results demonstrate that the XBB subvariant is highly neutralization resistant, which highlights the need for continued monitoring of the immune escape and tissue tropism of emerging Omicron subvariants.


Internists' attitudes toward prevention of firearm injury.
Professional organizations have called for the medical community's attention to the prevention of firearm injury. However, little is known about physicians' attitudes and practices in preventing firearm injury. To determine internists' attitudes and practices about firearms and to assess whether opinions differ according to whether there are gun owners in a physician's home. Cross-sectional survey. Internal medicine practices. 573 internists representative of American College of Physicians' members. Respondents' experiences and reported practice behaviors related to firearms and their opinions about contributors and public policies related to firearm violence, as well as physician education and training in firearm safety. The survey response rate was 56.5%. Eighty-five percent of respondents believed that firearm injury is a public health issue, and 71% believed that it is a bigger problem today than a decade ago. Seventy-six percent of respondents believed that stricter gun control legislation would help reduce the risks for gun-related injuries or deaths. Although 66% of respondents believed that physicians should have the right to counsel patients on preventing deaths and injuries from firearms, 58% reported never asking whether patients have guns in their homes. The generalizability of these findings to non-American College of Physicians' member internists and other physicians is unknown. Responses may not reflect actual behavior. Most respondents believed that firearm-related violence is a public health issue and favored policy initiatives aimed at reducing it. Although most internists supported a physician's right to counsel patients about gun safety, few reported currently doing it. None.


The pattern of collagen production may contribute to the gluteal muscle contracture pathogenic process.
Arthroscopic release is now the gold standard globally for gluteal muscle contracture (GMC) treatment. However, some patients fail to improve after the first operation and are forced to undergo a second operation. This study explores the essential role collagen fibers may play in muscle contracture in GMC. From February 2010 to May 2018, 1041 hips of 543 GMC patients underwent arthroscopic release. Among them, 498 (91.7%) patients had bilateral GMC and were admitted to the retrospective cohort study. Pathological testing and type III collagen testing were used in contracture tissue studies. Single-cell RNA-sequencing analysis was applied to explore the role of fibroblasts in muscle repair. Compared with GMC II patients, GMC III patients displayed higher clinical symptoms (P < 0.05). Six weeks after the surgery, the patients in GMC II had a lower prominent hip snap rate, higher JOA score, and better hip range of motion (P < 0.05). Compared with normal muscle tissue, contracture-affected tissue tended to have more type III collagen and form shorter fibers. Recurrent GMC patients seemed to have a higher type III collagen ratio (P < 0.05). In contrast to normally repairable muscle defects, fibroblasts in non-repairable defects were shown to downregulate collagen-related pathways at the early and late stages of tissue repair. This study describes the arthroscopic release of GMC. Study findings include the suggestion that the collagen secretion function of fibroblasts and collagen pattern might influence the muscle repair ability and be further involved in the GMC pathogenic process.


Randomized, controlled trial comparing the efficacy of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis.
To compare the efficacy of heart-shaped intrauterine balloon and intrauterine contraceptive device (IUD) in the prevention of adhesion reformation after hysteroscopic adhesiolysis. Prospective, randomized, controlled trial. University hospital. A total of 201 women with Asherman syndrome. Women were randomized to having either a heart-shaped intrauterine balloon or an IUD fitted after hysteroscopic adhesiolysis. The devices were removed after 7 days. A second-look hysteroscopy was carried out 1 to 2 months after the surgery. Incidence of adhesion reformation and reduction of adhesion score before and after surgery. Initially 201 cases were recruited; 39 cases dropped out, resulting in 82 cases in the balloon group and 80 cases in IUD group. The age, menstrual characteristics, pregnancy history, and American Fertility Society score before surgery were comparable between the two groups. The median adhesion score reduction (balloon group, 7; IUD group, 7) and the adhesion reformation rate (balloon group, 30%; IUD group, 35%) were not significantly different between the two groups. The heart-shaped intrauterine balloon and IUD are of similar efficacy in the prevention of adhesion reformation after hysteroscopic adhesiolysis for Asherman syndrome. ISRCTN 69690272.


Patellar Denervation Reduces Postoperative Anterior Knee Pain After Patellar Resurfacing Total Knee Arthroplasty: A Randomized Controlled Trial.
The benefit of patellar denervation (PD) in patellar resurfacing total knee arthroplasty (TKA) is still debatable. This prospective, randomized controlled trial investigated whether circumferential PD should be performed in patellar resurfacing TKA. A total of 241 patients who underwent unilateral TKA were randomized into PD or non-PD groups. Incidence, intensity, and presentation time of anterior knee pain (AKP) and clinical outcomes were evaluated at 3, 6, 9, 12, 18, and 24 months postoperatively. The incidence of AKP was significantly lower in the PD group (6.4% vs 16.2%, P = .032). The intensity of AKP and patient satisfaction scores were significantly better in the PD group at 3 months but not after 3 months. The presentation time of AKP mostly occurs at 3 months after surgery. The Knee Society score, range of motion, Oxford score, patellar score, activity of daily living score, and visual analog scale of overall knee pain were not significantly different between the two groups during the follow-up period. Given that PD can improve AKP and patient satisfaction at an early period postoperatively without jeopardizing clinical outcomes at no additional cost, this inexpensive procedure readily available in nearly every operation room is strongly recommended during primary TKA with patellar resurfacing.


Regulation of cGAS activity by RNA-modulated phase separation.
Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA (dsDNA) sensor that functions in the innate immune system. Upon binding dsDNA, cGAS and dsDNA form phase-separated condensates in which cGAS catalyzes the synthesis of 2'3'-cyclic GMP-AMP that subsequently triggers a STING-dependent, type I interferon (IFN-I) response. Here, we show that cytoplasmic RNAs regulate cGAS activity. We discover that RNAs do not activate cGAS but rather promote phase separation of cGAS in vitro. In cells, cGAS colocalizes with RNA and forms complexes with RNA. In the presence of cytoplasmic dsDNA, RNAs colocalize with phase-separated condensates of cGAS and dsDNA. Further in vitro assays showed that RNAs promote the formation of cGAS-containing phase separations and enhance cGAS activity when the dsDNA concentration is low. Cotransfection of RNA with a small amount of dsDNA into THP1 cells significantly enhances the production of the downstream signaling molecule interferon beta (IFNB). This enhancement can be blocked by a cGAS-specific inhibitor. Thus, cytoplasmic RNAs could regulate cGAS activity by modulating the formation of cGAS-containing condensates.


Cohort studies: marching towards outcomes.
A cohort study tracks two or more groups forward from exposure to outcome. This type of study can be done by going ahead in time from the present (prospective cohort study) or, alternatively, by going back in time to comprise the cohorts and following them up to the present (retrospective cohort study). A cohort study is the best way to identify incidence and natural history of a disease, and can be used to examine multiple outcomes after a single exposure. However, this type of study is less useful for examination of rare events or those that take a long time to develop. A cohort study should provide specific definitions of exposures and outcomes: determination of both should be as objective as possible. The control group (unexposed) should be similar in all important respects to the exposed, with the exception of not having the exposure. Observational studies, however, rarely achieve such a degree of similarity, so investigators need to measure and control for confounding factors. Reduction of loss to follow-up over time is a challenge, since differential losses to follow-up introduce bias. Variations on the cohort theme include the before-after study and nested case-control study (within a cohort study). Strengths of a cohort study include the ability to calculate incidence rates, relative risks, and 95% CIs. This format is the preferred way of presenting study results, rather that with p values.


Supercritical CO2 treatment reduces the antigenicity of buttermilk β-lactoglobulin and its inflammatory response in Caco-2 cells.
β-Lactoglobulin (β-LG) is believed to be a common allergen in bovine milk. Buttermilk (BM) powder has abundant contents of milk fat globule membrane and phospholipid, both of which have been demonstrated to have positive effects on brain and cognitive development during early infancy. This study focused on modifying β-LG in BM via supercritical CO2 (ScCO2) treatment to modify its reactivity to antibodies and thus reduce its antigenicity. Buttermilk powder was treated in a supercritical fluid extraction system with food-grade CO2 at 100, 150, 200, 250, 350, and 400 bar at 2 temperatures, 50 and 75°C. All analyses were completed in a 10% BM suspension (wt/vol). The BM proteins were examined using sodium dodecyl sulfate (SDS)-PAGE, Western blot, ELISA, and periodic acid staining methods. Semi-purified β-LG was used to evaluate the cytotoxicity, viability, and inflammatory response in the Caco-2 cell line by means of the lactate dehydrogenase assay, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] assay, and IL-8 production, respectively. The SDS-PAGE showed that the signal intensity of β-LG bands was reduced by up to 50% after being processed at 250 bar and 75°C for 30 min. Lighter and more diffuse signals were found by Western blot, indicating modification of the protein structure. The ELISA demonstrated that ScCO2 treatment could significantly change β-LG antigenicity in BM. Sugar moieties in bands corresponding to β-LG were revealed by periodic acid staining, indicating glycosylation only in samples treated with ScCO2. Caco-2 cells treated with whey proteins had high viability, 24.9% lower inflammation, and no evidence of cytotoxicity compared with untreated cultures. These results showed that reduced antigenicity of β-LG was caused by lactosylation, which has been reported as a possible pathway to reduce the allergenicity in foods. The denaturation of β-LG by supercritical fluid processing is a promising way to address milk allergy, which remains a problem requiring more attention and further research.


A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.
Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy. Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5-15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician's Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.


The application of atomic layer deposition in the production of sorbents for 99Mo/99mTc generator.
New production routes for 99Mo are steadily gaining importance. However, the obtained specific activity is much lower than currently produced by the fission of U-235. To be able to supply hospitals with 99Mo/99mTc generators with the desired activity, the adsorption capacity of the column material should be increased. In this paper we have investigated whether the gas phase coating technique Atomic Layer Deposition (ALD), which can deposit ultra-thin layers on high surface area materials, can be used to attain materials with high adsorption capacity for 99Mo. For this purpose, ALD was applied on a silica-core sorbent material to coat it with a thin layer of alumina. This sorbent material shows to have a maximum adsorption capacity of 120 mg/g and has a99mTc elution efficiency of 55 ± 2% based on 3 executive elutions.


Adrenoleukodystrophy and adrenomyeloneuropathy associated with partial adrenal insufficiency in three generations of a kindred.
Four cases of adrenoleukodystrophy (ALD) and one case of adrenomyeloneuropathy (AMN) have developed in a kindred over three generations demonstrating that AMN is a clinical variant of ALD. Pituitary-adrenal function studies were performed in 10 family members, including two affected males and four females identified as carriers of ALD/AMN. No pituitary-adrenal abnormality was found in the carriers. However, basal morning plasma adrenocorticotropic hormone (ACTH) levels were markedly elevated in the two males with ALD and AMN, despite the fact that they had no clinical signs of adrenal insufficiency and that morning plasma cortisol levels and their response to maximal exogenous ACTH stimulation appeared to be normal. In addition, the integrated 24-hour response to the administration were also subnormal in these two cases. Thus, people with ALD and AMN may have subclinical partial adrenocrotical insufficiency. No other endocrinologic dysfunction was identified.


Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). I. Iron chelation and metabolic studies.
A long-term clinical trial of 1-15 months has been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in 13 transfusion-dependent iron-loaded patients. Urinary iron excretion was greatest in patients with thalassaemia major and was related to the number of previous transfusions but not to the serum ferritin level. Substantial increases of urinary iron were observed in all the patients when the frequency of the daily dose was doubled and in response to 2 x 3 g L1 daily 11 of 12 patients tested excreted greater than 25 mg iron daily, the mean daily intake of iron from transfusion. Serum ferritin levels have fluctuated but overall have remained unchanged. Pharmacological studies in five patients have indicated rapid absorption probably from the stomach and variable plasma half life of 77 +/- 35 min (X +/- SD). Glucuronation was identified as a major route of L1 metabolism. Short-term intensive chelation studies using repeated administration of L1 resulted in further increases of urinary iron excretion by comparison to a single dose. In one case 325 mg of iron were excreted in the urine following the administration of 16 g (5 x 2 g + 2 x 3 g) within 24 h. Iron excretion studies were carried out in six transfusional iron-loaded patients who were maintained on a low iron diet before and during chelation. No significant increases of faecal iron excretion were observed with L1 using daily doses of up to 3 x 3 g and 4 x 2 g. The high level of compliance during treatment with L1 and the levels of urine iron excretion that can be achieved increase the prospects for oral chelation in transfusional iron-loaded patients.


Cholinergic stimulants and excess potassium ion increase the fluidity of plasma membranes isolated from adrenal chromaffin cells.
Chromaffin cell membranes from the bovine adrenal medulla were labelled with the hydrophobic fluorescent probe 1,6-diphenyl-1,3,5-hexatriene, and the fluorescence polarization (P) of the membrane suspensions was measured as a function of temperature. The P versus t profiles, between 20 and 37 degrees C, showed two linear regions separated by a break in the vicinity of 30 degrees C, reflecting a change in the phase behaviour of the constitutent lipids. Decreases in P values at higher temperature indicated progressive fluidization of the lipid bilayer. Previous incubation with either acetylcholine (0.5 mM) or nicotine (50 microM) produced further fluidization, the extent of which depended on the presence of added Ca2+ (2.2 mM). Thus, the flow activation energy, delta E, between approx. 30 and 37 degrees C was 9.1 kcal/mol for acetylcholine and 8.8 kcal/mol for acetylcholine plus Ca2+, as compared to 7.9 kcal/mol in the absence of acetylcholine and Ca2+. In the presence of nicotine, delta E was 11.4 kcal/mol when Ca2+ was absent and 9.5 kcal/mol when it was present. The cholinergic blocker, hexamethonium (0.5 mM), abolished the acetylcholine- or nicotine-induced changes. 65 mM K+ produced a similar fluidization, which was reversed by addition of Ca2+. An additive effect was observed when the membranes were incubated with both nicotine and K+, with delta E = 16.6 kcal/mol in the presence of Cas2+. These results indicate a receptor-mediated modulation of the lipid distribution between rigid and fluid regions in the membrane, which could be of importance for stimulated catecholamine secretion in the intact cell.


The influence of maternal respiratory infections during pregnancy on infant lung function.
We studied whether maternal respiratory infections during pregnancy adversely influence lung growth and development of the offspring, resulting in poor early life lung function. Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements (single occlusion technique) were performed during natural sleep. Questionnaire data were used to obtain information on maternal respiratory infections during pregnancy. Multivariate analysis was conducted to assess the relationship between maternal respiratory infections during pregnancy and resistance and compliance of the respiratory system, adjusting for potential confounding variables. Lower values of compliance (Crs) were found in infants of mothers with respiratory infections during pregnancy; Crs fell by 5.5% (P = 0.031). The difference in Crs between infants of mothers with and without respiratory infections during pregnancy remained unchanged and statistically significant after adjusting for potential confounding variables. The more respiratory infections the mother experienced during pregnancy, the lower the value of Crs was in her offspring (P for trend = 0.016). Using Crs corrected for body weight the relationship with maternal infections was non-significant, however still showing a trend. The results of this study may indicate that mothers who experience respiratory infections during pregnancy have newborns with lower compliance of the respiratory system.


In vivo release of cisplatin from a needle-type copolymer formulation implanted in rat kidney.
Cisplatin, cis-dichlorodiamine platinum (II), was incorporated in a needle-type copolymer formulation (0.8 mm diameter, 6 mm long) by radiation-induced polymerization. The copolymer used was copoly(diethylene glycol dimethacrylate/polyethylene glycol #600 dimethacrylate, 80/20 vol%). This copolymer, containing 6 mg of cisplatin, was implanted into the kidney of adult male Wistar rats (420 +/- 20 g). A total of 70 d was required for 100% release of cisplatin in vivo. The kidney tissue surrounding the formulation was strongly necrotized by the action of cisplatin. Two layers of necrosis could be distinguished: necrotic tissue surrounding the formulation and necrobiotic tissue surrounding the necrotic tissue. The amount of necrotic tissue changed markedly over time, but no change was apparent in the amount of necrobiotic tissue. The maximal amounts of necrotized tissue were observed 14 d after implantation: 3100 microns and 600 microns thick for the necrotic and necrobiotic tissues, respectively.


Twitter-Derived Social Neighborhood Characteristics and Individual-Level Cardiometabolic Outcomes: Cross-Sectional Study in a Nationally Representative Sample.
Social media platforms such as Twitter can serve as a potential data source for public health research to characterize the social neighborhood environment. Few studies have linked Twitter-derived characteristics to individual-level health outcomes. This study aims to assess the association between Twitter-derived social neighborhood characteristics, including happiness, food, and physical activity mentions, with individual cardiometabolic outcomes using a nationally representative sample. We collected a random 1% of the geotagged tweets from April 2015 to March 2016 using Twitter's Streaming Application Interface (API). Twitter-derived zip code characteristics on happiness, food, and physical activity were merged to individual outcomes from restricted-use National Health and Nutrition Examination Survey (NHANES) with residential zip codes. Separate regression analyses were performed for each of the neighborhood characteristics using NHANES 2011-2016 and 2007-2016. Individuals living in the zip codes with the two highest tertiles of happy tweets reported BMI of 0.65 (95% CI -1.10 to -0.20) and 0.85 kg/m2 (95% CI -1.48 to -0.21) lower than those living in zip codes with the lowest frequency of happy tweets. Happy tweets were also associated with a 6%-8% lower prevalence of hypertension. A higher prevalence of healthy food tweets was linked with an 11% (95% CI 2% to 21%) lower prevalence of obesity. Those living in areas with the highest and medium tertiles of physical activity tweets were associated with a lower prevalence of hypertension by 10% (95% CI 4% to 15%) and 8% (95% CI 2% to 14%), respectively. Twitter-derived social neighborhood characteristics were associated with individual-level obesity and hypertension in a nationally representative sample of US adults. Twitter data could be used for capturing neighborhood sociocultural influences on chronic conditions and may be used as a platform for chronic outcomes prevention.


A Lattice-Matching Strategy for Highly Reversible Copper-Metal Anodes in Aqueous Batteries.
Copper metal is an attractive anode material for aqueous rechargeable batteries due to its high theoretical specific capacity (844 mAh g-1 ), good environmental compatibility and high earth abundance. However, the Cu anodes often suffer from poor deposition/stripping reversibility and nonuniform deposition during the charge/discharge process, degrading the lifetime of aqueous Cu-metal batteries. Herein, a lattice-matching strategy was developed to design high-performance Cu-metal anodes. In such a strategy, Ni substrates that exhibit high lattice matching with Cu were selected to support the Cu anodes. The high lattice matching endows Cu anodes with high deposition/stripping reversibility, low nucleation overpotential as well as a uniform and dense electrodeposition on Ni substrates. Based on the Ni substrate-supported Cu anodes, the full cells paired with lead dioxide cathodes show a stable cycling behavior. This work provides a route for the design of high-performance Cu electrodes in aqueous rechargeable batteries.


Enhanced optical microlithography with a Fabry-Perot-based spatial filtering technique.
A coherent multiple imaging technique for use in optical microlithography was studied. The technique involves placing a thin Fabry-Perot etalon between the mask and the projection lens of an optical stepper. An optical lithographic computer simulation tool, Prolith/2, was used to evaluate the aerial image profile obtained for extended mask structures such as typical contact hole arrays and line-space patterns used in integrated circuit fabrication. Additionally, a set of experimental studies were performed to validate the simulation results. Enhancement of both resolution and depth of focus can be obtained simultaneously with appropriate etalon parameters.


Effect of a traditional herbal medicine (shakuyaku-kanzo-to) on testosterone secretion in patients with polycystic ovary syndrome detected by ultrasound.
In 20 infertile Japanese with polycystic ovary syndrome Shakuyaku-Kanzo-To was used to lower plasma testosterone levels and hence to induce pregnancy. The polycystic ovary was classified into two types; general cystic and peripheral cystic patterns. Plasma testosterone was decreased in 18/20 (90%) and 5/20 (25%) became pregnant. The plasma testosterone concentration in the case of the general cystic pattern was significantly higher than that of peripheral cystic pattern, and the pregnancy rate in those with the general cystic pattern was lower. The efficacy of Shakuyaku-Kanzo-To therefore seems to vary according to the type of polycystic ovary syndrome treated.


Bath-PUVA therapy decreases infiltrating CCR4-expressing tumor cells and regulatory T cells in patients with mycosis Fungoides.
Mycosis fungoides (MF) is a malignant lymphoma characterized by expansion of CD4(+) memory T-cell clones. Infiltrating cells express CCR4, which is attracted to CC chemokine ligands 17 and 22 (thymus and activation-regulated chemokine [TARC]/CCL17 and TARC/CCL22). Bath-psoralen plus ultraviolet A (PUVA) is effective against MF. In patients with psoriasis, bath-PUVA induces circulating regulatory T cells (Tregs), which suppress effector T cells. To understand the mechanisms in MF, we analyzed lesion-infiltrating cells before and after bath-PUVA therapy. Thirteen patients with MF (12 stage IB, 1 stage III; mean age 69.2 years, range 35-87 years; 6 men, 7 women) were recruited. Immunohistochemical analysis revealed that lesion CCR4-positive (CCR4(+)) cells and Tregs significantly decreased from 105.1 ± 164.8 cells/10(-2) mm(2) to 31.4 ± 39.0 cells/10(-2) mm(2) and from 78.1 ± 67.8 cells/10(-2) mm(2) to 24.7 ± 25.0 cells/10(-2) mm(2), respectively. Serum TARC levels significantly correlated with infiltrating CD3(+) (r = 0.997), CCR4(+) (r = 0.991), and forkhead box P3-positive (Foxp3(+)) cells (r = 0.843). Circulating Tregs before bath-PUVA therapy were not significantly different from those in healthy volunteers. Bath-PUVA did not significantly change the percentage of circulating Tregs. Bath-PUVA decreased CCR4(+) cells and Tregs in MF lesions but did not induce circulating Tregs, which might suppress effector T cells. Direct effects through skin lesions might eliminate both pathogenetically relevant cells and Tregs. Systemic immunosuppression was not induced.


Complete nucleotide sequence of plasmid pND6-2 from Pseudomonas putida ND6 and characterization of conjugative genes.
Pseudomonas putida ND6 was shown to be capable of growth using naphthalene as sole carbon and energy sources. One plasmid from this strain, pND6-1, which was associated with the metabolism of naphthalene, was characterized; and the complete nucleotide sequence (101,858bp) and annotation of the plasmid were reported previously. In this paper, another plasmid (117,003bp) from P. putida ND6, pND6-2, was sequenced and 136 putative coding sequences (CDSs) were annotated. Among them, 9 CDSs were predicted to be involved in replication and partition of the plasmid, 32 CDSs encoded proteins associated with plasmid conjugative transfer, 2 CDSs encoded transcriptional regulators, 9 CDSs were necessary for DNA-associated function (including metabolism, recombination and repair), and 5 CDSs encoded proteins associated with other functions. The filter matting experiment indicated that pND6-2 is a helper plasmid, which could assist the naphthalene catabolic plasmid pND6-1 without any conjugative genes being transferred from P. putida ND6 to Escherichia coli AD256.


Tandem UIMs confer Lys48 ubiquitin chain substrate preference to deubiquitinase USP25.
Ubiquitin-specific protease (USP) 25, belonging to the USP family of deubiquitinases, harbors two tandem ubiquitin-interacting motifs (UIMs), a ~20-amino-acid α-helical stretch that binds to ubiquitin. However, the role of the UIMs in USP25 remains unclear. Here we show that the tandem UIM region binds to Lys48-, but not Lys63-, linked ubiquitin chains, where the two UIMs played a critical and cooperative role. Purified USP25 exhibited higher ubiquitin isopeptidase activity to Lys48-, than to Lys63-, linked ubiquitin chains. Mutations that disrupted the ubiquitin-binding ability of the tandem UIMs resulted in a reduced ubiquitin isopeptidase activity of USP25, suggesting a role for the UIMs in exerting the full catalytic activity of USP25. Moreover, when mutations that convert the binding preference from Lys48- to Lys63-linked ubiquitin chains were introduced into the tandem UIM region, the USP25 mutants acquired elevated and reduced isopeptidase activity toward Lys63- and Lys48-linked ubiquitin chains, respectively. These results suggested that the binding preference of the tandem UIMs toward Lys48-linked ubiquitin chains contributes not only to the full catalytic activity but also to the ubiquitin chain substrate preference of USP25, possibly by selectively holding the Lys48-linked ubiquitin chain substrates in the proximity of the catalytic core.


Does Green's Word Memory Test really measure memory?
This study investigated whether the Multiple Choice, Paired Associates, Free Recall, and Long Delayed Free Recall subtests of Green's Word Memory Test (WMT) were sensitive to memory impairment after traumatic brain injury (TBI) in 107 persons who passed performance validity criteria on the same instrument. Whereas several of the California Verbal Learning Test-Second Edition indices demonstrated a statistically significant correlation with coma duration, and also showed statistically significant mean differences between TBI severity groups, none of the four WMT memory subtests did so. It is concluded that, although the WMT is an excellent performance validity test, it is not sensitive to memory impairment after TBI.


Protective effects of the thiol compounds GSH and NAC against sulfur mustard toxicity in a human keratinocyte cell line.
Sulfur mustard (SM) is a chemical warfare agent causing blistering, inflammation and ulceration of the skin. Thiol compounds such as glutathione (GSH) and N-acetylcysteine (NAC) have been suggested as potential antidotes. We investigated SM toxicity in a human keratinocyte cell line (HaCaT) and used GSH and NAC to counteract its cytotoxic effects. Cells were treated with 1, 5 or 10mM GSH or NAC and exposed to 30, 100 or 300μM SM. Different treatment regimens were applied to model extra- and intra-cellular GSH/NAC effects on SM toxicity. Necrosis, apoptosis and interleukin-6 and -8 levels were determined 24h post-exposure. Necrosis and apoptosis increased with SM dose. Interleukin-6 and -8 production peaked at 100μM and decreased at 300μM probably due to reduced ability for interleukin biosynthesis. Intracellular GSH/NAC diminished necrosis induced by 100μM SM. Extracellular GSH/NAC protected against necrosis and apoptosis induced by 100 and 300μM SM. Interleukin-6 and -8 production, induced by 100μM SM was reduced by GSH/NAC. However, low-dose GSH/NAC treatment of cells exposed to 300μM SM led to increased interleukin production. Thus, moderately poisoned cells are mostly responsible for SM-induced secretion of pro-inflammatory cytokines. GSH and NAC treatment can reduce SM-induced toxic effects. Protective effects were more pronounced by extracellular GSH or NAC administration. Rescue of severely poisoned cells may result in a strong secretion of pro- inflammatory cytokines. In summary, thiol compounds such as GSH or NAC constitute a promising approach to improve the therapy for SM injury. Additional intervention to prevent adverse effects of interleukin production might be beneficial.


Cobalt(III)- and Rhodium(III)-Catalyzed C-H Amidation and Synthesis of 4-Quinolones: C-H Activation Assisted by Weakly Coordinating and Functionalizable Enaminone.
Cobalt(III) and rhodium(III) catalysts exhibited complementary scope in C-H amidation of aryl enaminones. The amidation reactions proceeded with broad scope under the assistance of a weakly coordinating and bifunctional enaminone directing group. The electrophilicity of the enaminone group can be further utilized in subsequent hydrolysis-cyclization reactions to afford NH 4-quinolones in telescoping reactions.


CDC7 as a novel biomarker and druggable target in cancer.
Due to the bottlenecks encountered in traditional treatment for tumor, more effective drug targets need to be developed. Cell division cycle 7 kinase plays an important role in DNA replication, DNA repair and recombination signaling pathways. In this review, we first describe recent studies on the role of CDC7 in DNA replication in normal human tissues, and then we integrate new evidence focusing on the important role of CDC7 in replication stress tolerance of tumor cells and its impact on the prognosis of clinical oncology patients. Finally, we comb through the CDC7 inhibitors identified in recent studies as a reference for further research in clinical practice.


Single nucleotide polymorphisms in genes involved in immune responses and outcome of tegumentary leishmaniasis.
Leishmaniases are neglected tropical diseases with a broad clinical spectrum. Tegumentary leishmaniasis (TL) is a disease caused by different Leishmania species, transmitted by phlebotomine sand flies and distributed worldwide. TL can present a cutaneous (CL) or mucocutaneous (MCL) clinical form depending on factors inherent to the parasite, the host and the vector. Polymorphisms in the immune response genes are host genetic factors that influence the pathogenesis or control of leishmaniasis. Single nucleotide polymorphisms (SNPs) in immune genes have been evaluated in several countries where leishmaniasis is endemic. In this review, we report studies on SNPs in several immune genes that might be associated with susceptibility or resistance to TL. We summarize studies from around the world and in Brazil, highlight the difficulties of these studies and future analyses needed to enhance our knowledge regarding host genetic factors in TL. Understanding the genetic characteristics of the host that facilitate resistance or susceptibility to leishmaniasis can contribute to the development of immunotherapy schedules for this disease. The current treatment methods are toxic, and no human vaccine is available.


Nitric oxide-dependent and independent effects on human platelets treated with peroxynitrite.
Peroxynitrite (ONOO-) is an oxidant formed from the rapid reaction of superoxide and nitric oxide (NO) at sites of inflammation. The literature reports conflicting data on the effects of ONOO- in biological systems, with both NO- and oxidant-dependent effects having been demonstrated. The aim of this study was to investigate these distinct mechanisms through examining molecular aspects of the effects of ONOO- on human platelets, a system in which we have previously shown that ONOO- has both pro- and anti-aggregatory effects. Platelet function was assessed by measuring platelet P-selectin expression flow cytometrically, intraplatelet Ca2+ concentrations, and by light aggregometry. A colorimetric method was used to measure extracellular platelet membrane thiols. The contribution of NO and cGMP to the pharmacological effects of ONOO- was investigated using an inhibitor of the soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), and the NO scavenger oxy-haemoglobin. Peroxynitrite (50-400 microM) caused a concentration-dependent increase in the number of platelets expressing P-selectin, an increase in intraplatelet Ca2+ concentrations and a decrease in platelet membrane thiols. Peroxynitrite-induced P-selectin expression was augmented by ODQ. In contrast, when P-selectin expression was elicited by collagen, ONOO- acted as an inhibitor of this process, an effect that was further enhanced by the addition of 1% plasma, ODQ or oxy-haemoglobin abolished this inhibitory effect. Finally, low concentrations (50-100 microM) of ONOO- inhibited collagen-induced platelet aggregation, an effect that was reversed by oxy-haemoglobin. Peroxynitrite exerts dual effects on platelets, which are either activating or inhibitory due to the conversion of ONOO- to NO or NO donors. Peroxynitrite-induced platelet activation seems to be due to thiol oxidation and an increase in intracellular Ca2+. It is important to note that inhibitory, NO-dependent effects occur at lower concentrations than the activating effects. These data are then consistent with the conflicting literature, showing both damaging and cytoprotective effects of ONOO- in biological systems. We hypothesize that the conversion of ONOO- to NO is the critical factor determining the outcome of ONOO- exposure in vivo.


Nurses' patient-education work: conditional factors - an integrative review.
The aim of this review was to identify conditional factors for nurses' patient-education work and to identify foundational aspects of significance when designing studies on this patient-education work. A few reviews of nurses patient education work exist, published up to 30 years ago, spawning interest in performing a review of more recent studies. A search of CINAHL, MEDLINE and ERIC was made for articles dating from 1998 to 2011. Thirty-two articles were selected and an integrative review was performed. Conditional factors were identified and beliefs and knowledge, environment, organization, interdisciplinary cooperation, collegial teamwork and patient education activities. A model was developed to describe foundational aspects of significance when designing studies. The conditional factors are to be seen as either enabling or hindering the accomplishment of evidence-based patient education and the level of person centredness, patient safe care and ethics - something that has to be considered when designing studies. More detailed studies are required to clarify the nature of patient education work and to create realistic conditions that enable the role to be fulfilled in everyday work. Such knowledge is of significance for nursing management in developing supportive activities for nurses.


Monocyte-directed RNAi targeting CCR2 improves infarct healing in atherosclerosis-prone mice.
Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. Here, we used nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6C(high) monocyte subset traffic, to reduce infarct inflammation in apolipoprotein E-deficient (apoE(-/-)) mice after MI. We used dual-target positron emission tomography/magnetic resonance imaging of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset-targeted RNAi altered infarct inflammation and healing. Flow cytometry, gene expression analysis, and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE(-/-) mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix cross-linking noninvasively, we developed a fluorine-18-labeled positron emission tomography agent ((18)F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged with a molecular magnetic resonance imaging sensor of MPO activity (MPO-Gd). Positron emission tomography/magnetic resonance imaging detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal; P<0.05), whereas (18)F-FXIII positron emission tomography reflected unimpeded matrix cross-linking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29% to 35% (P<0.05). CCR2-targeted RNAi reduced recruitment of Ly-6C(high) monocytes, attenuated infarct inflammation, and curbed post-MI left ventricular remodeling.


Readmission Risk after COVID-19 Hospitalization: A Moderation Analysis by Vital Signs.
Readmission to the hospital after hospitalization with coronavirus disease 2019 (COVID-19) is associated with significant morbidity and mortality. Hospital clinicians may identify the presence of a patient's comorbid conditions, overall severity of illness, and clinical status at discharge as risk factors for readmission. Objective data are lacking to support reliance on these factors for discharge decision making. The objective of our study was to examine risk factors for readmission to the hospital after COVID-19 hospitalization and the impact of vital sign abnormalities, within 24 hours of discharge, on readmission rates. In total, 2557 COVID-19-related hospital admissions within the Lifespan Health System, a large multicenter health system (Rhode Island), of 2230 unique patients aged 18 years and older, occurring from April 1, 2020 to December 31, 2020 were analyzed. Risk factors associated with readmission within 30 days were identified and analyzed using Cox regression. A moderation analysis by vital signs at discharge on the risk of readmission was performed. Clinical factors associated with readmissions included existing cardiovascular conditions (risk ratio 2.32, 95% confidence interval [CI] 1.10-4.90) and pulmonary disease (risk ratio 3.25, 95% CI 1.62-6.52). The absence of abnormal vital signs within 24 hours of discharge was associated with decreased 30-day readmission rates (risk ratio 0.70, 95% CI 0.52-0.94). Elevated C-reactive protein and d-dimer values and in-hospital complications including stroke, myocardial infarction, acute renal failure, and gastrointestinal bleeding were not associated with an increased risk of readmission. In moderation analysis, the presence of normal vital signs within 24 hours of discharge was associated with decreased readmission risk in patients who had primary risk factors for readmission including pulmonary disease (risk ratio 0.80, 95% CI 0.65-0.99), psychiatric disorders, and substance use (risk ratio 0.70, 95% CI 0.52-0.94). Comorbid conditions, including pulmonary and cardiovascular disease, are associated with readmission risk after COVID-19 hospitalization. The normalization of vital signs within 24 hours of discharge during COVID-19 hospitalization may be an indicator of readiness for discharge and may mitigate some readmission risk conferred by comorbid conditions.


Convergence of signals from red-sensitive and green-sensitive cones onto L-type external horizontal cells of the goldfish retina.
The types of photoreceptors converging onto L-type external horizontal cells (LEHCs) were studied intracellularly in live, immobilized goldfish under dark-adapted conditions, and interactions between inputs from these photoreceptors were demonstrated. Our analysis of the color-dependence of response waveform, and the spectral sensitivity of LEHCs during various phases of their responses, suggests that LEHCs receive inputs not only from red-sensitive cones, but also from green-sensitive cones. Furthermore, inputs from red- and green-sensitive cones were found to interact so as to enhance LEHC responses. By presenting two successive flashes of different colors, the response enhancement was demonstrated only when green flashes preceded red flashes, indicating that responses to the input from green-sensitive cones affected the input from red-sensitive cones. A hypothetical model which incorporates reciprocal connections between green-sensitive cones and LEHCs is proposed, and shown to be consistent with most of the phenomena described in this paper, including the response enhancement.


Atrial fibrillation following physostigmine.
The side effects of physostigmine, a tertiary amine anticholinesterase agent commonly used to treat postanaesthetic depression caused by a large number of drugs, are thought to be fairly mild. A case is reported in which atrial fibrillation followed a total dose of 2 mg of this drug to a patient who was slow in recovering from a general anaesthetic. The arrhythmia was self-limiting and required no therapy. Indications and precautions for the use of physostigmine are discussed.


WITHDRAWN: The MCM2p-binding is crucial for the function of CDC7-DBF4 protein kinase during the initiation of chromosomal DNA replication in budding yeast.
This manuscript was withdrawn at the request of the authors.


Determination of platelet factor 3 by thrombin generation using a micro-coagulation assay.
Platelet factor 3 activity is usually determined by the Stypven method in which factor Xa generation is measured indirectly. The determination is dependent on factors I, II, V, X in the test sample. A coagulation assay for platelet factor 3, which measures the thrombin generation promoted by platelet factor 3, is presented. The test depends on platelet factor 3 only, because factors II, Xa, V, fibrinogen and Ca++ are added in excess. The usability of the new method is shown by platelet factor 3 determinations in patients with various platelet diseases, after ingestion of aspirin and in samples of platelet concentrates before and after storage.


Unexpected mitochondrial matrix localization of Parkinson's disease-related DJ-1 mutants but not wild-type DJ-1.
DJ-1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ-1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ-1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ-1 is still controversial. Here, we show the mitochondrial matrix localization of various pathogenic and artificial DJ-1 mutants by multiple independent experimental approaches including cellular fractionation, proteinase K protection assays, and specific immunocytochemistry. Localization of various DJ-1 mutants to the matrix is dependent on the membrane potential and translocase activity in both the outer and the inner membranes. Nevertheless, DJ-1 possesses neither an amino-terminal alpha-helix nor a predictable matrix-targeting signal, and a post-translocation processing-derived molecular weight change is not observed. In fact, wild-type DJ-1 does not show any evidence of mitochondrial localization at all. Such a mode of matrix localization of DJ-1 is difficult to explain by conventional mechanisms and implies a unique matrix import mechanism for DJ-1 mutants.


[Tumor angiogenesis].
Following the work of Folkman, it appears that angiogenesis, which consists in the formation of new blood vessels able to deliver oxygen and nutriments to tumor cells, is a major step in the evolution of tumors, which can only grow after the onset of the angiogenic switch. Numerous factors play a role in angiogenesis stimulation or inhibition : the vascular endothelial growth factor and fibroblastic growth factors as well as angiopoietin are proangiogenic, whereas angiostatin and platelet factor 4 are anti-angiogenic. The discovery of these molecules and of the molecular mechanisms of their activity allowed the identification of new therapeutic targets, which appear relevant for the treatment of cancer.


Portulaca oleracea L. Extract Ameliorates Intestinal Inflammation by Regulating Endoplasmic Reticulum Stress and Autophagy.
To investigate the role of endoplasmic reticulum stress (ERS)-induced autophagy in inflammatory bowel disease (IBD) and the intervention mechanism of Portulaca oleracea L. (POL) extract, a medicinal herb with anti-inflammatory, antioxidant, immune-regulating, and antitumor properties, in vitro and in vivo. An IL-10-deficient mouse model is used for in vivo experiments; a thapsigargin (Tg)-stimulated ERS model of human colonic mucosal epithelial cells (HIECs) is used for in vitro experiments. The levels of ERS-autophagy-related proteins are examined by immunofluorescence and Western blot. Cellular ultrastructure is assessed with transmission electron microscopy. POL extract promotes a healing effect on colitis by regulating ERS-autophagy through the protein kinase R-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (eIF2α)/Beclin1-microtubule-associated protein light chain 3II (LC3II) pathway. Overall, the results of this study further confirm the anti-inflammatory mechanism and protective effect of POL extract and provide a new research avenue for the clinical treatment of IBD.


Aldehyde-functionalized cellulose as reactive sorbents for the capture and retention of polyamine odor molecules associated with chronic wounds.
Aldehyde-functionalized cellulose (AFC) was prepared by oxidizing cellulose with sodium metaperiodate. The reaction was characterized by Schiff's test, FT-IR, and UV-vis study. AFC was evaluated as a reactive sorbent for controlling polyamine-based odor from chronic wounds, and its performance was compared with charcoal, one of the most widely utilized odor-control sorbents through physisorption. Cadaverine was used as the model odor molecule. A liquid chromatography/mass spectrometry (LC/MS) method was established to quantify the compound. AFC was found to rapidly react with cadaverine through the Schiff-base reaction, which was confirmed by FT-IR, visual observation, CHN elemental analysis, and the ninhydrin test. The sorption and desorption behaviors of cadaverine onto AFC were quantified. With clinic-relevant cadaverine concentrations, AFC demonstrated much better sorption performance than charcoal. At even higher cadaverine concentrations charcoal showed higher sorption capacity, probably due to its high surface area. On the other hand, in desorption studies, AFC retained much more of the sorbed cadaverine than charcoal. When AFC and charcoal were combined, the pair demonstrated excellent sorption and desorption behaviors. The XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay confirmed that AFC has very good in vitro biocompatibility. These results suggest that AFC-based reactive sorption can be a new strategy to control odors associated with chronic wounds for improved healthcare.


Designing an effective statewide tobacco control program--Arizona.
In this article, the author examines the creation and development of Arizona's statewide tobacco control program. In particular, he examines the three basic goals of prevention, cessation, and policy and emphasizes the need to focus equally on all to build an effective program. The need for sound theory and research to guide statewide comprehensive programs is highlighted.


A sustainable approach by using microalgae to minimize the eutrophication process of Mar Menor lagoon.
The present study evaluates the removal capacity of microalgae photobioreactors of environmental pollutants present in wastewater from the dry riverbed El Albujón, as a way to minimize the eutrophication process of the Mar Menor. Particularly, the capacity of four autochthonous microalgae consortia collected from different locations of the salty lagoon to remove emerging contaminants (simazine, atrazine, terbuthylazine, adenosine and ibuprofen), nitrates, and phosphates, was evaluated. Among the four microalgae consortia, consortium 1 was the best in terms of biomass productivity (0.11 g L-1 d-1) and specific growth rate (0.14 d-1), providing 100% removal of emerging contaminants (simazine, atrazine, terbuthylazine, adenosine and ibuprofen), and a maximal reduction and consumption of macronutrients, especially nitrates and phosphates, reaching levels below 28 mg L-1, that is, a decrease of 89.90 and 99.70% of nitrates and phosphates, respectively. Therefore, this consortium (Monoraphidium sp., Desmodesmus subspicatus, Nannochloris sp.) could be selected as a green filter for successful large-scale applications. This study is the first one that combines the successful removal of herbicides, ibuprofen and adenosine as emerging contaminants, and nitrate removal.


Effects of soil amendments on Cd and As mobility in the soil-rice system and their distribution in the grain.
The accumulation, mobilization, and distribution of toxic metal(loid)s in rice are key factors that affect food security and determine bio-utilization patterns. In this study, five soil amendments with different components were used in paddy fields to study the key factors: organic amendments: (1) polyaspartic acid (OA1) and (2) organic fertilizer (OA2); inorganic amendments: (3) kaolinite (IA1) and (4) magnesium slag (IA2); and organic-inorganic composite amendments: (5) modified biochar/quicklime (OIA). Although the Cd and As exhibited opposite chemical dissolution behaviors, IA1/OIA, can simultaneously reduce their accumulation and transfer coefficients in rice tissues, while other amendments only work for one of them. The in situ distribution in grains showed that IA1/OIA changed the original Cd distribution in the lemma and palea, whereas all amendments reduced Cd accumulation in the germ. In contrast, OA1/IA2 amendments led to more As accumulation in the rice husks and bran than in the endosperm center, and the germ had higher As signals. Because of their similar transport pathways and interactions, the concentrations of Cd and As in the grains were correlated with a variety of mineral elements (Fe, Mo, Zn, etc.). Changes in the Cd/As concentration and distribution in rice were achieved through the improvement of soil properties and plant growth behavior through amendments. The application of OIA resulted in the highest immobilization indices, at 82.17 % and 35.34 % for Cd and As, respectively. The Cd/As concentrations in the rice grains were highly positively correlated with extractable-Cd/As in the soil (Cd: R2 = 0.95, As: R2 = 0.93). These findings reveal the migration and distribution mechanisms of Cd and As in the soil-rice system, and thus provide fundamental information for minimizing food safety risk.


A mechanism for the entrapment of DNA at an air-water interface.
Addition of the intercalating dye quinacrine to a low ionic strength solution of DNA in quantities sufficient to saturate the high affinity sites in the DNA will result in the accumulation of the DNA at the solution interface. This entrapment of DNA at the air-water interface has been assayed by the adsorption of DNA to untreated carbon-coated electron microscope grids touched to the solution surface. Other intercalating dyes can also bring about this entrapment, if they possess a side arm large enough to occupy one of the DNA grooves when the dye is intercalated into the DNA. The extension and unwinding of the DNA helix brought about by the intercalating chromophore of the dye molecules are not requirements for the entrapment process. Spermidine, a simple polyamine that will bind to the DNA minor groove but that has no intercalating chromophore, was found to bring about this entrapment. Even simple mono- and divalent cations in the absence of the above ligands were found to promote a low level of surface entrapment. A model for the entrapment of DNA at the air-water interface is proposed in which one (or both) of the hydrophobic grooves of the DNA becomes a surface-active agent as a consequence of the association of various ligands and charge neutralization.


A comparison of periodised and fixed repetition training protocol on strength in older adults.
It has been forwarded that strength training is the primary intervention for improving and maintaining functional independence of the elderly. The purpose of this study was to determine if a periodised strength-training program was superior to a fixed repetition protocol for enhancing strength in older adults. Previously untrained male and female participants (71.6+/-5.3 y) were separated into three groups: fixed repetition (FR: n= 18), periodised (PER: n= 21) and control (C: n= 21). FR and PER protocols trained 2 days/week performing knee extensions, leg press, leg curl, biceps curl, triceps extension, lat pull downs, shoulder press and seated bench press. FR performed three sets of 9RM/exercise throughout the 18-week study. PER performed two sets of 15RM/exercise (weeks 1-6), three sets of 9RM/exercise (weeks 7-12) and four sets of 6RM/exercise (weeks 13-18). Pre-post 1RM were collected for each exercise. The sum of 1RM for the eight exercises was considered indicative of total body strength and served as the dependent variable. An ANOVA with Bonferroni post hoc was utilised to analyse the data. FR (p< 0.01) and PER (p< 0.01) groups experienced significant strength gains compared to C but were not different from each other. The results suggest that previously untrained older adults could expect similar strength gains from FR or PER strength-training protocols of 18 weeks or less.


Randomized study of six umbilical cord care regimens. Comparing length of attachment, microbial control, and satisfaction.
Two hundred and seventy one infants were enrolled in a study to compare six different methods of treating the umbilical cord. Antimicrobial control was equal for all methods. Repeated triple dye application was considered least acceptable by staff and parents and had the longest attachment time. Povidone-iodine was associated with the shortest attachment time and was most liked. If there is no special need to treat a specific nosocomial outbreak, duration of cord attachment and satisfaction of staff and parents can help clinicians decide on a cord care regimen.


Hevein-like protein domains as a possible cause for allergen cross-reactivity between latex and banana.
Patients allergic to natural rubber latex (NRL) frequently exhibit immediate hypersensitivity reactions to banana, but the molecular basis of these putative cross-reactions is unknown. We wanted to examine whether proteins resembling hevein, a major NRL allergen, exist in banana and whether coexisting allergy to NRL and banana can be explained by IgE cross-reactivity to these proteins. Allergens in banana cross-reacting with hevein were identified by IgE immunoblot inhibition. The cross-reacting proteins were purified by reversed-phase chromatography and characterized by amino acid sequencing. Allergen cross-reactivity was further assessed by IgE ELISA, IgE ELISA inhibition, and skin prick testing. In immunoblotting, 9 of 15 sera from patients allergic to NRL with IgE to hevein showed IgE binding to 32- and 33-kd banana proteins. These 2 protein bands were also targets to IgG from a hevein-immunized rabbit. IgE binding to both 32- and 33-kd protein bands was totally inhibited by hevein (10 ng/mL) in all 5 sera from patients allergic to NRL sera studied. N-terminal sequencing of the purified 32- and 33-kd proteins revealed 80% identity to the N-terminus of hevein. An internal peptide (19 amino acids) of the 33-kd protein gave over 90% identity to endochitinases of several plants. In ELISA all 15 sera from patients allergic to NRL had IgE to the purified 32-kd banana protein. In ELISA inhibition hevein (10 ng/mL) inhibited approximately 50% of IgE binding to the solid-phase 32-kd banana protein in a pool of sera from patients allergic to NRL. These results suggest that the commonly occurring hypersensitivity to banana in patients allergic to NRL could be explained by cross-reacting IgE antibodies binding to epitopes in hevein and in a hevein-like domain of a previously undescribed endochitinase in banana.


Cultural differences in preferences for shapes.
It was predicted that since there is less sexual restraint in Jamaica the sex difference in shape preference should be larger for native adult Jamaicans than Caymanian adults. Pairs of drawings of a "female" and a "male" object, depicted according to the theory of sexual symbolism, were shown to 200 subjects, who indicated which of each pair they preferred. The larger sex difference found among Jamaicans was interpreted in terms of primary sexual stimulus generalization.


Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the "Probio-HIV" Clinical Trial.
HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation. In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma. We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls. Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis. ClinicalTrials.gov NCT02164344.


Muscular activity and torque of the foot dorsiflexor muscles during decremental isometric test: A cross-sectional study.
To analyse the torque variation level that could be explained by the muscle activation (EMG) amplitude of the three major foot dorsiflexor muscles (tibialis anterior (TA), extensor digitorum longus (EDL), extensor hallucis longus (EHL)) during isometric foot dorsiflexion at different intensities. In a cross-sectional study, forty-one subjects performed foot dorsiflexion at 100%, 75%, 50% and 25% of maximal voluntary contractions (MVC) with the hip and knee flexed 90° and the ankle in neutral position (90° between leg and foot). Three foot dorsiflexions were performed for each intensity. Outcome variables were: maximum (100% MVC) and relative torque (75%, 50%, 25% MVC), maximum and relative EMG amplitude. A linear regression analysis was calculated for each intensity of the isometric foot dorsiflexion. The degree of torque variation (dependent variable) from the independent variables explain (EMG amplitude of the three major foot dorsiflexor muscles) the increases when the foot dorsiflexion intensity is increased, with values of R2 that range from 0.194 (during 25% MVC) to 0.753 (during 100% MVC). The reliability of the outcome variables was excellent. The EMG amplitude of the three main foot dorsiflexors exhibited more variance in the dependent variable (torque) when foot dorsiflexion intensity increases.


Mildly Elevated Cardiac Troponin below the 99th-Percentile Upper Reference Limit after Noncardiac Surgery.
In patients with perioperative cardiac troponin (cTn) I below the 99th-percentile upper range of limit (URL), mortality according to cTn I level has not been fully evaluated. This study evaluated the association between postoperative cTn I level above the lowest limit of detection but within the 99th-percentile URL and 30-day mortality after noncardiac surgery. Patients with cTn I values below the 99th-percentile URL during the perioperative period were divided into a no-elevation group with cTn I at the lowest limit of detection (6 ng/L) and a minor elevation group with cTn I elevation below the 99th percentile URL (6 ng/L < cTn I < 40 ng/L). The primary outcome was 30-day mortality. Of the 5,312 study participants, 2,582 (48.6%) were included in the no-elevation group and 2,730 (51.4%) were included in the minor elevation group. After propensity score-matching, the minor elevation group showed significantly increased 30-day mortality (0.5% vs. 2.3%; hazard ratio, 4.30; 95% confidence interval, 2.23-8.29; p<0.001). The estimated cutoff value of cTn I to predict 30-day mortality was 6 ng/L with the area under the receiver operating characteristic curve 0.657. A mild elevation of cTn I within the 99th-percentile URL after noncardiac surgery was significantly associated with increased 30-day mortality as compared with the lowest limit of detection. Clinical Research Information Service Identifier: KCT0004244.


Real-world analysis of insurance churn among young adults with schizophrenia using the Colorado All-Payer Claims Database.
BACKGROUND: Most patients with schizophrenia are diagnosed in their early twenties and often have commercial insurance at diagnosis. These young adults can experience changes in insurance coverage, that is, "churn," which can lead to disruptions in care. OBJECTIVE: To examine the frequency, speed, and type of insurance churn events in a young adult schizophrenia population with commercial insurance coverage at diagnosis. METHODS: The Colorado All-Payer Claims Database, containing insurance claims data from commercial and public insurers for Colorado residents, was used for the study. Eligible patients were required to have at least 1 inpatient or 2 outpatient claims for schizophrenia or schizoaffective disorder, be of age 18-34 years at index, have previous insurance coverage for 12 consecutive months, and have commercial insurance at diagnosis. These patients were 1:5 propensity score matched (PSM) with nonschizophrenia members. Percentages of members on different insurance types were calculated monthly to assess churn events. Cohorts were compared using descriptive statistics, Cox proportional hazards, and generalized estimating equation models. RESULTS: The matched schizophrenia and nonschizophrenia cohorts comprised 501 and 2,510 members, respectively. Before PSM, cohorts were imbalanced (schizophrenia cohort had a younger median age and higher proportion of males). After matching, the cohorts were similar in terms of the matched baseline characteristics. Previous mental health disorders were more common in the schizophrenia cohort (75%) than in the nonschizophrenia cohort (26%). The proportion of members with at least 1 churn event for the schizophrenia and nonschizophrenia cohorts, respectively, were 53.8% vs 36.5% after 12 months and 84.6% vs 69.2% after 48 months. Time to first churn event was significantly shorter in the schizophrenia cohort (16 months) than the nonschizophrenia cohort (23 months; P < 0.001). Schizophrenia cohort members had 64.1 and 56.8 churn events per 1,000 members per month vs 43.0 (P ≤ 0.001) and 42.8 (P = 0.011) churn events for nonschizophrenia cohort members in the first and second 6-month periods, respectively. Proportions of members in the schizophrenia and nonschizophrenia cohorts on public insurance, respectively, were 22.9% vs 6.9% after 12 months and 52.4% and 10.7% after 48 months. In the schizophrenia cohort, the most common churn event type was from commercial to public insurance rather than to a different commercial insurance; notably, 41% of members were still on a commercial plan 4 years after diagnosis. CONCLUSIONS: Young adults with schizophrenia experienced churn events more rapidly and more frequently than those without schizophrenia for the first 4 years studied after the index date. These disruptions may be associated with reduced access to care and treatment gaps in this vulnerable patient population. DISCLOSURES: This research was sponsored by Janssen Scientific Affairs, LLC. Pesa, Benson, and Patel are employees of Janssen Scientific Affairs, LLC, and are stockholders of Johnson & Johnson. Potluri, Rotter, and Papademetriou are employees of SmartAnalyst Inc, and their work on this study was funded by Janssen Pharmaceuticals. A version of this study was presented as a poster at the Psych Congress 2020 Virtual Experience, September 10-13, 2020.