Apolar chemical environments compact unfolded RNAs and can promote folding.
It is well documented that the structure, and thus function, of nucleic acids depends on the chemical environment surrounding them, which often includes potential proteinaceous binding partners. The nonpolar amino acid side chains of these proteins will invariably alter the polarity of the local chemical environment around the nucleic acid. However, we are only beginning to understand how environmental polarity generally influences the structural and energetic properties of RNA folding. Here, we use a series of aqueous-organic cosolvent mixtures to systematically modulate the solvent polarity around two different RNA folding constructs that can form either secondary or tertiary structural elements. Using single-molecule Förster resonance energy transfer spectroscopy to simultaneously monitor the structural and energetic properties of these RNAs, we show that the unfolded conformations of both model RNAs become more compact in apolar environments characterized by dielectric constants less than that of pure water. In the case of tertiary structure formation, this compaction also gives rise to more energetically favorable folding. We propose that these physical changes arise from an enhanced accumulation of counterions in the low dielectric environment surrounding the unfolded RNA.


Phenylarsonics in concentrated animal feeding operations: Fate, associated risk, and treatment approaches.
Phenylarsonics are present as additives in animal feed in some countries. As only a small fraction of these additives is metabolized in animals, they mostly end up in the environment. A comprehensive investigation of the fate of these additives is crucial for evaluating their risks. This review aims to provide a clear understanding of the transformation mechanism of phenylarsonics in vivo and in vitro and to evaluate their fate and associated risks. Degradation of phenylarsonics releases toxic As species (mainly as inorganic arsenic (iAs)). Trivalent phenylarsonics are the metabolites or biotic degradation intermediates of phenylarsonics. The cleavage of As groups from trivalent phenylarsonics catalyzed by C-As lyase or other unknown pathways generates arsenite (As(III)). As(III) can be further oxidized to arsenate (As(V)) and methylated to methyl-arsenic species. The half-lives associated with abiotic degradation of phenylarsonics ranged from a few minutes to tens of hours, while those associated with biotic degradation ranged from several days to hundreds of days. Abiotic degradation resulted in a higher yield of iAs than biotic degradation. The use of phenylarsonics led to elevated total As and iAs levels in animal products and environmental matrices, resulting in As exposure risk to humans. The oxidation of phenylarsonics to As(V) facilitated the sorptive removal of As, which provides a general approach for treating these compounds. This review provides solid evidence that the use of phenylarsonics has adverse effects on both human health and environmental safety, and therefore, supports their withdrawal from the global market.


Variation of MHC class I and II antigen expression in relation to lymphocytic infiltrates and interferon-gamma positive cells.
The occurrence of MHC antigens on epithelial cells in lip salivary glands obtained from patients with various connective tissue diseases and from bone marrow recipients was studied. The amount of infiltrating lymphocytes correlated to an increase in MHC class I and II antigen expression, but not to diagnosis or glandular function. Interferon-gamma + infiltrating cells were scanty. The role of interferon-gamma as the main inducer of MHC antigens and the notion "aberrant" HLA-DR thought to perpetuate chronic autoimmune disease are questioned.


Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer's disease.
Studies on DNA methylation (DNAm) in Alzheimer's disease (AD) have recently highlighted several genomic loci showing association with disease onset and progression. Here, we conducted an epigenome-wide association study (EWAS) using DNAm profiles in entorhinal cortex (EC) from 149 AD patients and control brains and combined these with two previously published EC datasets by meta-analysis (total n = 337). We identified 12 cytosine-phosphate-guanine (CpG) sites showing epigenome-wide significant association with either case-control status or Braak's tau-staging. Four of these CpGs, located in proximity to CNFN/LIPE, TENT5A, PALD1/PRF1, and DIRAS1, represent novel findings. Integrating DNAm levels with RNA sequencing-based mRNA expression data generated in the same individuals showed significant DNAm-mRNA correlations for 6 of the 12 significant CpGs. Lastly, by calculating rates of epigenetic age acceleration using two recently proposed "epigenetic clock" estimators we found a significant association with accelerated epigenetic aging in the brains of AD patients vs. controls. In summary, our study represents the hitherto most comprehensive EWAS in AD using EC and highlights several novel differentially methylated loci with potential effects on gene expression.


Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection.
Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT ("responders") display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas "nonresponders" and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.


Femoral nerve blockade during endovenous laser ablation of great saphenous vein decreases pain but does not affect the use of opioids during the procedure.
Endovenous laser ablation (EVLA) using tumescent anesthesia for treatment of an insufficient great saphenous vein (GSV) can be painful and require intravenous pain management and, sometimes, sedation with propofol. Femoral nerve blockade (FNB) anesthetizes the femoral nerve distribution and is usually used for anterior thigh and knee procedures. It is easy to inject with ultrasound guidance because the nerve is easy to visualize in the groin. The aim of the present double-blind, randomized controlled trial was to determine whether FNB before tumescent anesthesia decreases the pain of GSV EVLA combined with local phlebectomy. Eighty patients who underwent GSV EVLA combined with local phlebectomy under tumescent anesthesia were randomized into two groups. The placebo group (control group; 40 patients) was given placebo FNB with 0.9% saline before tumescent injection. The FNB group (intervention group; 40 patients) received 1% lidocaine with adrenaline for FNB before tumescent injection. Only the study nurse, who performed the randomization, knew which patients were in which group. The patients and operating surgeon were unaware of the randomization group. FNB was performed under ultrasound guidance. The effectiveness of anesthesia was tested 10 minutes after injection using the pin-prick test and a numeric rating scale (NRS). The NRS was completed before and during tumescent anesthesia and during EVLA ablation and local phlebectomy. The motor function of the femoral nerve was tested at the end of the procedure and 1 hour after using the Bromage method. Patients had a follow-up visit 1 month after the procedure, and their need for pain medication and the duration of sick leave were recorded. No differences were found in the gender distribution, age, or GSV dimensions at baseline. The mean length of the treated GSV segment was 28 cm and 30 cm and the mean energy used was 1911 J and 2059 J in the placebo and FNB groups, respectively. The median NRS score for pain during tumescent injection around the GSV was 2 (interquartile range [IQR], 1-4) in the placebo group compared with 1 (IQR, 1-3) in the FNB group. Very little pain was experienced during laser ablation. The median NRS score was 0 (IQR, 0-0) and 0 (IQR, 0-0.75) in the placebo and FNB groups, respectively. The most painful stage was injection of tumescence to the local phlebectomy sites in both groups. The median NRS score was 4 (IQR, 3-7) in the placebo group and 2 (IQR, 1-4) in the FNB group (P = .01). During local phlebectomy, the NRS score was 2 (IQR, 0-4) vs 1 (IQR, 0-3) in the placebo and FNB groups, respectively. Only the difference in pain during injection of tumescence before local phlebectomy was significant. FNB seems to decrease pain during EVLA combined with local phlebectomy. Patients experienced the highest pain when tumescence was injected before local phlebectomy, and those in the FNB group experienced significantly less pain than the placebo group. No indication for routine use of FNB is indicated. However, it could be used to decrease the pain for patients who experience strong pain during varicose vein surgery, especially if extensive local phlebectomies are required.


Inhibitory effects of p38 inhibitor against mitochondrial dysfunction in the early brain injury after subarachnoid hemorrhage in mice.
Brain injury occurred in the early stage after subarachnoid hemorrhage (SAH) can activate p38 mitogen-activated protein kinase (MAPK), which, in turn, not only regulates mitochondrial structure and function, but also triggers cell death though mitochondrial pathway. Although a lot of work has been done, the relationship between p38 and mitochondrial dysfunction has not been delineated in the early brain injury after SAH. The purpose of this study was to do such an exploration. SAH mouse model was established using single-hemorrhage method. We performed immunohistochemical and enzyme activity analysis, respectively, to detect the alteration of p-p38, cytorosome c (cyt c), mitochondrial membrane potential, ATP content, and lactate dehydrogenase (LDH) activation, as well as TUNEL assay to detect cell apoptosis at the different time course of SAH. p-p38 expression after SAH was significantly higher than that of in SB203580 treated counterparts. As for mitochondrial dysfunction events, mitochondrial membrane potential was significantly decreased with the time course of SAH, whereas it was returned to normal level and maintained at a stable level after treatment with SB203580. Meanwhile, after SAH the decreased ATP content, and increased cyt c and LDH level were all returned to normal level in SB203580 treated group. In addition, SB203580 significantly inhibited apoptosis. These results demonstrated that the neuroprotective effects of p38 inhibitor may be rely on the prevention of mitochondrial dysfunction, therefore blocking neuronal cell death, emphasizing on the importance of early therapeutic intervention by targeting p38, and suggesting a potential therapeutic window before greater cortex dysfunction occurs.


Detection of Jupiter's ring at 2.2 microm.
FOLLOWING the announcement of the discovery of a ring around Jupiter by the Voyager spacecraft(1) a successful attempt was made to detect the reflected sunlight from this ring at 2.2microm. We describe here the results of this experiment and the precautions taken to separate the radiation from the ring and the scattered radiation from the planet.


The insulin-sensitizing effect of a single exercise bout is similar in type I and type II human muscle fibres.
Rodent studies suggest muscle fibre type-specific insulin response in the recovery from exercise. The current study investigates muscle fibre type-specific insulin action in the recovery from exercise in healthy subjects. In type I and type II muscle fibres, key proteins in glucose metabolism are similarly regulated by insulin during recovery from exercise. Our findings imply that both type I and type II muscle fibres contribute to the phenomenon of increased insulin sensitivity in the recovery from a single bout of exercise in humans. Human skeletal muscle consists of slow-twitch (type I) and fast-twitch (type II) muscle fibres. Muscle insulin action, regulating glucose uptake and metabolism, is improved following a single exercise bout. Rodent studies suggest that this phenomenon is confined to specific muscle fibre types. Whether this phenomenon is also confined to specific fibre types in humans has not been described. To investigate this, nine healthy men underwent a euglycaemic hyperinsulinaemic clamp (EHC) in the recovery from a single bout of one-legged knee-extensor exercise. Pools of type I and type II fibres were prepared from muscle biopsies taken in the rested and prior exercised leg before and after the EHC. AMPK γ3 and TBC1D4 - two key proteins regulating muscle insulin action following exercise - were higher expressed in type II than type I fibres. However, phosphor-regulation of TBC1D4 was similar between fibre types when related to the total amount of TBC1D4 protein. The activating dephosphorylation of glycogen synthase was also similar in the two fibre types. Thus, insulin-induced regulation of key proteins important for transport and intracellular flux of glucose towards glycogen storage in the recovery from exercise, does not differ between fibre types. In conclusion, the insulin-sensitizing effect of a single bout of exercise includes both type I and type II fibres in human skeletal muscle. This may be an important observation for future pharmacological strategies targeting muscle insulin sensitivity in humans.


Modulation of PKR activity in cells infected by bovine viral diarrhea virus.
Bovine viral diarrhea virus is an important animal pathogen. The cytopathic and noncytopathic biotypes of the virus are associated with distinct pathologic entities. A striking difference between the two biotypes is viral RNA accumulation in infected cells. Viral dsRNA is thought to activate protein kinase PKR; an important mediator of innate immunity. In this study, we investigated PKR activation and its consequences in BVDV-infected cells. Infection with cp BVDV was found to induce PKR activation, eIF2alpha phosphorylation, translation inhibition and NF-kappaB activation. In contrast, PKR activity and eIF2alpha phosphorylation were not induced during infection with the ncp BVDV. In addition, cells infected with ncp BVDV showed no PKR phosphorylation in response to infection with the unrelated poliovirus whereas uninfected ncp BVDV cells when infected with poliovirus showed high levels of phosphorylated PKR. Cells infected with ncp BVDV failed to respond to synthetic dsRNA (poly I:C) treatment with NF-kappaB activation. However, the NF-kappaB response to bacterial lipopolysaccarides (LPS) was normal in these cells, suggesting a specific suppression of antiviral response signaling in ncp BVDV infected cells. These results indicate that ncp BVDV has evolved specific mechanisms to prevent activation of PKR and its antiviral effectors, most likely to facilitate the establishment and maintenance of persistent infection.


Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase.
Intravenous enzyme replacement therapy (ERT) with purified glucocerebrosidase (GLA) leads to significant improvement of the clinical manifestations in patients with Type 1 Gaucher disease. However, the high doses required, slow response and inability to recover most of the infused enzyme in the target tissues may be attributed to losses occurring during transit en route to the lysosome. Preincubation of GLA with isofagomine (IFG), a slow-binding inhibitor, significantly increased stability of the enzyme to heat, neutral pH and denaturing agents in vitro. Preincubation of GLA with isofagomine prior to uptake by cultured cells results in increased intracellular enzyme activity accompanied by an increase in enzyme protein suggesting that reduced denaturation of GLA in the presence of isofagomine leads to a decrease in the degradation of the enzyme after internalization. Preincubation of GLA with slow-binding inhibitors before infusion may improve the effectiveness of ERT for Gaucher disease.


Pre-pregnancy planning for female patients seen at a pregnancy and rheumatic diseases clinic: a retrospective analysis of patients with rheumatic diseases seeking pregnancy-related care.
To assess the clinical utility of pre-pregnancy planning among female patients with rheumatic diseases attending a targeted pregnancy and rheumatic diseases clinic. We conducted a retrospective review using data collected via chart review of female patients with rheumatic diseases seen at the Pregnancy and Rheumatic Diseases Clinic at the Mary Pack Arthritis Centre in Vancouver, Canada, between January 2017 and July 2020. Patients were categorized according to an initial presentation at the clinic as (1) pregnant without pre-pregnancy planning; and (2) not pregnant with pre-pregnancy planning. The latter group was further categorized according to whether they had contraindications to pregnancy. Pregnancy outcomes were extracted from electronic medical records and analyzed using descriptive statistics. Our study included 230 female patients with rheumatic diseases. At the initial clinical presentation, 86 were pregnant and 144 were planning to become pregnant and presenting for pre-pregnancy planning. Compared to patients without pre-pregnancy planning, patients who received pregnancy planning experienced fewer prenatal disease flares (61.3% [38/62] vs. 22.6% [7/31]; p < 0.001), fewer medication changes during pregnancy (46.4% [39/84] vs. 18.9% [10/53]; p = 0.002), and improved disease control in the first trimester of pregnancy (p = 0.018). There were no statistically significant differences in the frequency of adverse pregnancy or fetal outcomes between patients with and without pre-pregnancy planning. Evaluation of patient outcomes suggests that pre-pregnancy planning may support early assessment of high-risk pregnancy status; therein, allowing healthcare providers to identify and manage risk factors for adverse pregnancy outcomes among patients living with rheumatic diseases.


Effects of monocolonization with Escherichia coli strains O6K13 and Nissle 1917 on the development of experimentally induced acute and chronic intestinal inflammation in germ-free immunocompetent and immunodeficient mice.
Germ-free immunocompetent (BALB/c) and immunodeficient (SCID) mice were colonized either by E. coli O6K13 or by E. coli strain Nissle 1917 and intestinal inflammation was induced by administering 2.5% dextran sulfate sodium (DSS) in drinking water. Controls were germ-free mice which demonstrated only mild inflammatory changes after induction of an acute intestinal inflammation with DSS as compared with conventional mice in which acute colitis of the colon mucosa similar to human ulcerative colitis is elicited. In mice monocolonized with the nonpathogenic E. coli Nissle 1917 the inflammatory disease did not develop (damage grade 0) while animals monocolonized with uropathogenic E. coli O6K13 exhibited inflammatory changes similar to those elicited in conventionally reared mice (damage grade 3). In the chronic inflammation model, immunocompetent BALB/c mice monocolonized with E. coli Nissle 1917 showed no conspicuous inflammatory changes of the colon mucosa whereas those monocolonized with E. coli O6K13 developed colon inflammation associated with marked infiltration of inflammatory cells. In contrast to germ-free immunodeficient SCID mice that died after application of DSS, the colon mucosa of SCID mice monoassociated with E. coli Nissle 1917 exhibited only moderate inflammatory changes which were less pronounced than changes of colon mucosa of SCID mice monoassociated with E. coli O6K13.


Reversed-phase ion-pair liquid chromatographic procedure with electrochemical detection for the analysis of urinary thiosulphate.
A method using high-performance liquid chromatography with mercury-based electrochemical detection has been developed for the determination of thiosulphate in urine. The chromatographic separation is based upon ion-pair formation between thiosulphate and tetrabutylammonium and reversed-phase chromatography. The method was compared with an earlier reported colorimetric assay and found to be superior with respect to specificity and sensitivity.


Gynecologic complications of cyclic estrogen progestin therapy.
We evaluated the long-term gynecologic risks of postmenopausal estrogen therapy in conjunction with cyclic, monthly progestin (progestin-estrogen replacement therapy, or PERT). Our medical record review showed that incidence of abnormal vaginal bleeding necessitating gynecologic procedures for evaluation was significantly higher (RR, 3.1; 95% CI, 2.1-4.5), as was the rate of endometrial biopsy (RR, 3.4; 95% CI, 2.3-5.1), among women receiving PERT than among women not receiving hormone therapy. We also identified a non-significant trend toward a higher rate of dilation and curettage (RR, 1.5; CI, 0.7-3.3) among women receiving PERT. However, rates of endometrial hyperplasia and hysterectomy were similarly low in both groups. PERT apparently protects women against these serious gynecologic consequences previously seen in women taking unopposed estrogen.


Effects of aging on ATP sensitive K(+) channels and on prostanoid production in the rat mesenteric bed.
The aim of the present work was to evaluate, in the rat isolated mesenteric bed, whether increasing age is associated with alterations in the ATP sensitive K(+) channels functionality. Moreover, studies were performed in order to evaluate the effects of aging on the synthesis of vascular prostanoids as well as on its possible contribution to the pressor responses of this vascular bed. Male Wistar rats of 3 month (adults) and 24 month (aged) were used. Although no differences were found among adult and aged rats in pressor responses to 2-30 nmol noradrenaline and to 40-160 nmol KCl, the relaxant responses to the K(+) channel opener, 10(-6) M cromakalim, were significantly diminished in the aged group compared to the adults. On the other hand, whereas PGF2α and 6-keto PGF1α production was not modified with age, the thromboxane B2 and prostaglandin E2 production in the mesenteric bed from 24 month old rats was significantly increased compared to the adult group. Furthermore, the cyclooxigenase synthesis inhibitor, 10(-5) M indomethacin reduced the pressor responses induced by noradrenaline in the mesenteric beds from adults but not from aged rats. It is concluded that there is an age related reduction in the functionality of the ATP sensitive K(+) channels in the rat mesenteric bed. In addition, aging produces an increase in the release of vasoconstrictor as well as of vasodilator prostanoids, whose contribution to noradrenaline induced pressor responses appears to be less relevant in the older animals.


4-Hydroxy-3-methyl-6-(1-methyl-2-oxoalkyl)pyran-2-one synthesis by a type III polyketide synthase from Rhodospirillum centenum.
The purple photosynthetic bacterium Rhodospirillum centenum has a putative type III polyketide synthase gene (rpsA). Although rpsA was known to be transcribed during the formation of dormant cells, the reaction catalyzed by RpsA was unknown. Thus we examined the RpsA reaction in vitro, using various fatty acyl-CoAs with even numbers of carbons as starter substrates. RpsA produced tetraketide pyranones as major compounds from one C(10-14) fatty acyl-CoA unit, one malonyl-CoA unit and two methylmalonyl-CoA units. We identified these products as 4-hydroxy-3-methyl-6-(1-methyl-2-oxoalkyl)pyran-2-ones by NMR analysis. RpsA is the first bacterial type III PKS that prefers to incorporate two molecules of methylmalonyl-CoA as the extender substrate. In addition, in vitro reactions with (13)C-labeled malonyl-CoA revealed that RpsA produced tetraketide 6-alkyl-4-hydroxy-1,5-dimethyl-2-oxocyclohexa-3,5-diene-1-carboxylic acids from C(14-20) fatty acyl-CoAs. This class of compounds is likely synthesized through aldol condensation induced by methine proton abstraction. No type III polyketide synthase that catalyzes this reaction has been reported so far. These two unusual features of RpsA extend the catalytic functions of the type III polyketide synthase family.


No evidence of ATP1A2 involvement in 12 multiplex Italian families with benign familial infantile seizures.
A missense mutation in the gene encoding the alpha(2) subunit of the Na(+),K(+) ATPase pump (ATP1A2) was found in a family with both familial hemiplegic migraine (FHM) and Benign Familial Infantile Seizures (BFIC). As it is still unclear whether ATP1A2 is responsible for pure BFIC syndromes, we checked mutations of the ATP1A2 gene in probands of 12 Italian multiplex families with pure BFIC, who were negative for mutations in the SCN2A gene. We screened the ATP1A2 gene by denaturing high performance liquid chromatography (D-HPLC) and direct sequencing of DNA fragments showing an aberrant elution pattern. We found one exonic variant and five intronic variants, none leading to significant amino acid changes or causing a modification of the physiological mRNA maturation. The ATP1A2 gene does not appear to be involved in the ethiopathogenesis of pure BFIC syndromes, at least in the explored Italian multiplex families. It could be either responsible of a minority of cases, or of complex syndromes where BFIC and FHM co-occur.


Decrease of activity of antioxidant enzymes, lysozyme content, and protein degradation in milk contaminated with heavy metals (cadmium and lead).
The aim of this study was to evaluate the effect of added Cd and Pb to milk on its stability by determining antioxidant enzymatic activities, lysozyme content, and protein degradation. Antioxidant enzymatic activities were spectrophotometrically determined by superoxide dismutase, catalase, xanthine oxidase, and glutathione peroxidase assays; lysozyme was identified and quantified by HPLC-UV analysis, and protein degradation was investigated by spectrophotometric analysis of advanced oxidation protein products (AOPP) and dityrosine content. In this study, contaminated milk samples showed a significant reduction in activity of all studied enzymes compared with control milk. The contamination of milk also led to a significant reduction in the lysozyme content; lysozyme content was decreased about 22% and 18% in Pb milk and Cd milk, respectively, compared with control milk. The presence of the contaminants in the milk resulted in a significant increase of both dityrosine concentration and AOPP compared with the control milk. Moreover, between types of contaminated milk, dityrosine and AOPP values were significantly higher in the Pb milk than in the Cd milk. Therefore, it is important to monitor the presence of these toxic elements in milk for the damage they cause to consumer health both directly due to their ingestion and indirectly due to loss of milk stability.


Impact of anxiety levels on the perception of pain in patients undergoing office hysteroscopy.
This study aimed at assessing the impact of anxiety on pain perception during hysteroscopy and to highlight the possible contribution of factors related to pain perception. 104 women with indication for office hysteroscopy fullfilled anonymous self-report questionnaires during the waiting time, before the procedure. The first self-report questionnaire included general patient information and an overall assessment of the degree of satisfaction with the information received before the procedure. The level of pre-procedural anxiety was measured through the State-Trait Anxiety Inventory STAI-Y1 (state anxiety). The perceived stress was assessed using the Perceived Stress Scale (PSS). The intensity of pain during the procedure and 20 min later was assessed with VAS score. The average waiting time was of 192.33 ± 91 min. 59 patients (56.7%) performed the examination without analgesia while 45 women (43.3%) required analgesia. 28 women (27%) experienced mild pain, 34 (33%) moderate pain and 42 (40%) severe pain. The patients who performed the procedure without analgosedation had an average STAI-Y1 score of 44.81 ± 1.20, compared to women who required analgosedation (average score of 49.40 ± 1.64). The perceived level of stress was also associated with the use of analgosedation. Patients who did not request any anesthetic intervention obtained a PSS average score of 16.66 ± 0.75, compared to the subgroup with anesthesia (score of 19.76 ± 0.90). Anxiety represents a key element for the success of ambulatory hysteroscopy. The management of anxiety can reduce the request for analgesia with a consequent optimization of time, costs and safety.


1953: when genes became "information".
In 1953, Watson and Crick not only described the double-helix structure of DNA, but also embraced the idea that genes contained a code that expresses information and thereby changed our view of life. This article traces how these ideas entered biological thinking and highlights the connections between different branches of science at the time, exploring the power of metaphor in science.


Quantitative radiology for staging and prognosis of patients with advanced prostatic carcinoma. Correlations with other pretreatment characteristics.
Quantitative radiology of metastases is compared with other pretreatment characteristics in ability to predict survival in 102 patients with advanced Stage IV prostatic carcinoma. Using only two films, the posteroanterior chest and pelvis, radiologic quantitation of metastases is more precise than the other pretreatment characteristics in separating high-risk and low-risk patients. Quantitative radiology is a simple, noninvasive, effective method of stratifying patients in clinical trials or before aggressive therapy. The comparative ability of quantitative radiology and quantitative bone scans to separate high-risk and low-risk patients with advanced prostatic carcinoma can now be assessed.


Cognitive rehabilitation interventions for executive function: moving from bench to bedside in patients with traumatic brain injury.
Executive function mediated by prefrontally driven distributed networks is frequently impaired by traumatic brain injury (TBI) as a result of diffuse axonal injury and focal lesions. In addition to executive cognitive functions such as planning and working memory, the effects of TBI impact social cognition and motivation processes. To encourage application of cognitive neuroscience methods to studying recovery from TBI, associated reorganization of function, and development of interventions, this article reviews the pathophysiology of TBI, critiques currently employed methods of assessing executive function, and evaluates promising interventions that reflect advances in cognitive neuroscience. Brain imaging to identify neural mechanisms mediating executive dysfunction and response to interventions following TBI is also discussed.


Culture of endometrial epithelial cells collected by a cytological brush in vivo.
In cattle, mechanistic studies of endometrial function rely on cell lines or primary culture of cells harvested postmortem. Understanding the endometrial physiology in dairy cows is essential, because approximately 50% of pregnancies are lost in the first 3 wk of gestation for unknown reasons. The objective was to validate an in vivo, minimally invasive, and estrous cycle stage-specific method to obtain endometrial luminal epithelial cells for culture. The uterine body of 26 cows was sampled using a cytology brush (cytobrush) 4 d after estrus. The viability of cells was measured by flow cytometry (80% live cells) and epithelial identity was determined by anti-vimentin and anti-cytokeratin immunofluorescence and quantitative PCR for KRT18 and VIM. A pool of cells from 15 animals was passaged 4 times in culture until confluent and then treated with 0, 0.1, 1, or 10 ng/mL of recombinant bovine interferon-tau (rbIFN-τ). The relative expression of transcripts related to IFN-τ signaling (IFNAR1), early (IRF2) and late (ISG15, OAS1) response to IFN-τ stimulus, and other IFN-τ-stimulated genes (CCL8, CXCL10, and FABP3) was measured by quantitative PCR. The relative expression of KRT18 transcripts was similar across passages; the relative expression of VIM increased at passage 2, and IFNAR1 transcripts decreased in cultured compared with that in fresh cells. The relative expression of ISG15, OAS1, CCL8, and FABP3 increased in response to rbIFN-τ. In conclusion, culture of endometrial luminal cells collected by cytobrush was feasible, generating a monolayer enriched in epithelial cells, and therefore constitutes a novel model by which to study endometrial luminal epithelial cell function, including responses to IFN-τ.


ZNF804A rs1344706 is associated with cortical thickness, surface area, and cortical volume of the unmedicated first episode schizophrenia and healthy controls.
The effects of ZNF804A rs1344706, a prominent susceptibility gene for schizophrenia, on gray matter (GM) structure in unmedicated schizophrenia (SZ) patients are still unknown, although several previous studies investigated the effects in medicated SZ patients and healthy controls (HC). Analyzing cortical thickness, surface area, and GM volume simultaneously may provide a more precise and complete picture of the effects. We genotyped 59 unmedicated first episode SZ patients and 60 healthy controls for the ZNF804A single nucleotide polymorphism (SNP) rs1344706, and examined between-group differences in cortical thickness, surface area, and cortical volume using a full-factorial 2 × 2 analysis of variance (ANOVA). We found the risk allele (T) in ZNF804A rs1344706, compared to the non-risk allele (G), was associated with thinner cortex in the bilateral precuneus, left precentral gyrus, and several other regions, associated with a smaller cortical surface area in the left superior parietal, precuneus cortex and left superior frontal, and associated with a lower cortical volume in the left superior frontal, left precentral, and right precuneus in SZ patients. In contrast, in the controls, the T allele was associated with the increased cortical measurements compared to the G allele in the same regions as those mentioned above. ZNF804A rs1344706 has significant, but different, effects on cortical thickness, surface area, and cortical volume in multiple regions of the brain cortex. Our findings suggest that ZNF804A rs1344706 may aggravate the risk for schizophrenia by exerting its effects on cortical thickness, surface area, and cortical volume in these brain regions.


Emergency medical services in Islamabad, Pakistan: a public-private partnership.
The objective of this study was to evaluate the emergency medical services (EMS) based in Islamabad, Pakistan. Rescue-15 is an innovative EMS collaboration project between the police, the private sector and the community. Data from Rescue-15 were used for systems analysis. The institutional set-up, private-public partnership, client satisfaction and sustainability issues were examined. The access and efficiency of EMS were assessed in terms of ambulance response time. Primarily, systems analysis showed community participation to explain the project's strength. Since its establishment, the project has been meeting its own recurrent expenditures without levying an extra burden on the Government. Sustainability issues such as amendments to legislation have been addressed at departmental and governmental levels. Data analysis showed that rescue time is, on average, 10.4 min (SD=2.6 min). A client survey also demonstrated user satisfaction and increased confidence in the service. This EMS programme exemplifies the potential of public-private partnership involving the police and the private sector in project implementation and management in a developing country with scarce resources. This initiative to involve the public and the private sector may provide a model for implementation of such services in other resource-poor developing countries, which may in turn facilitate realistic solutions for better prehospital care in developing countries.


Characterization and adsorption properties of a lanthanum-loaded magnetic cationic hydrogel composite for fluoride removal.
In this study, a novel lanthanum-loaded magnetic cationic hydrogel (MCH-La) was synthesized for fluoride adsorption from drinking water. The adsorption kinetics, isotherms, and effects of pH and co-existing anions on fluoride uptake by MCH-La were evaluated. FTIR, Raman and XPS were used to analyze the fluoride adsorption mechanism of MCH-La. Results showed that MCH-La had positive zeta potential values of 23.6-8.0 mV at pH 3.0-11.0, with the magnitude of saturation magnetization up to 10.3 emu/g. The fluoride adsorption kinetics by MCH-La fitted well with the fractal-like-pseudo-second-order model, and the adsorption capacity reached 93% of the ultimate adsorption capacity within the first 10 min. The maximum fluoride adsorption capacity for MCH-La was 136.78 mg F(-)/g at an equilibrium fluoride concentration of 29.3 mg/L and pH 7.0. Equilibrium adsorption data showed that the Sips model was more suitable than the Langmuir and Freundlich models. MCH-La still had more than 100 mg of F(-)/g adsorption capacity at a strongly alkaline solution (pH > 10). The adsorption process was highly pH-dependent, and the optimal adsorption was attained at pH 2.8-4.0, corresponding to ligand exchange, electrostatic interactions, and Lewis acid-base interactions. With the exception of both anions of HCO3(-) and SiO4(4-), Cl(-), NO3(-), and SO4(2-) did not evidently prevent fluoride removal by MCH-La at their real concentrations in natural groundwater. The fluoride adsorption capacity of the regenerated MCH-La approached 70% of the fresh MCH-La from the second to fifth recycles. FTIR and Raman spectra revealed that C-O and CO functional groups on MCH contributed to the fluoride adsorption, this finding was also confirmed by the XPS F 1s spectra. Deconvolution of C 1s spectra before and after fluoride adsorption indicated that the carboxyl, anhydride, and phenol groups of MCH were involved in the fluoride removal.


Functional outcome of unstable pelvic fractures treated in a level III hospital in a developing country: a 10-year prospective observational study.
Unstable pelvic fractures are severe and life-threatening injuries with high morbi-mortality rates. Management of these fractures is a major challenge in orthopaedic practice in limited resource communities. The aim of this study is to evaluate the functional outcome of unstable pelvic fractures managed in a hospital with limited diagnostic and therapeutic facilities. This was a hospital-based prospective observational study carried out from 1st of January 2009 to 31st of December 2018 at the Limbe Regional Hospital, a level III health institution in the South-West region of Cameroon. A total of 68 patients were included in the study. The ages ranged from 18 to 80 years with a mean age of 39 ± 5 years. The average follow-up duration at the latest visit was 36 months (range 3-84 months). There were 59 cases that were evaluated. The overall average Majeed score was fair. Poor outcomes were noted in patients aged 60 years and above, those with co-morbidities, and those managed conservatively. Although the functional outcomes following unstable pelvic fractures have improved with modernised diagnostic and therapeutic modalities, it is not the case in poor resource settings where the lack of these modalities makes the management challenging, consequently affecting the functional outcome.


Primary cutaneous extraskeletal osteosarcoma of the pretibial leg: A case report and summary of the literature.
Primary cutaneous extraskeletal osteosarcoma is a rare tumor, with fewer than 30 known cases worldwide. We report the case of a 60-year-old female who presented with a solitary right pretibial nodule of 3 mm. She had no known comorbidities, trauma to the area, or prior malignancy. The biopsy specimen showed abundant mineralized osteoid, in which pleomorphic and spindled cells with anaplastic features were embedded. The osteoid matrix in this case contained overtly malignant cells, with frequent mitotic figures, as well as multinucleated giant cells. Immunohistochemistry and imaging led to the conclusion that this nodule represented a primary cutaneous extraskeletal osteosarcoma. The previously reported cases are variable in location, size, gross appearance, and clinical course. The prognosis of osteosarcoma is typically poor, with aggressive behavior; this, however, may be less severe in these strictly cutaneous tumors, though additional follow-up would be beneficial to determine long-term outcomes for the known cases. Ultimately, despite the fact that this is an extremely rare entity, primary cutaneous extraskeletal osteosarcomas should be considered when relevant.


Virtual reality exposure therapy for neuro-psychomotor recovery in adults: a systematic review.
To analyse the virtual reality applications in the subjects' neuro-psychomotor functions rehabilitation with motor and/or neuropsychiatric impairment. The search was carried out in nine databases (Scopus, PubMed, Web of Science, ScienceDirect, Cochrane Library, CINAHL, PsycINFO, LILACS, and SciELO), from December 2017 to March 2019. An additional manual search was performed, taking into consideration references of the included papers, through the same eligibility criteria. The methodological quality of the included papers was evaluated using the Physiotherapy Evidence Database (PEDro). One hundred and twenty-two papers were selected by the initial screening, but only 33 studies participated in the final inclusion in the study (11 clinical trials and 14 experimental studies). The data extracted were: the proposed objective, the sample population, the neurological condition treated, the VR modality used in the procedures and the study intervention period. Virtual reality supports the rehabilitation process of neuro-psychomotor functions, allowing potential gains in the patients' recovery. Therefore, its development facilitates its availability and access in the future.Implications for rehabilitationIt has minimal adverse effects during the virtual therapies performance, such as the presence of vertigo related to cybersickness conditions, suggesting virtual reality as a safe rehabilitation tool, compared to other therapies.Virtual reality use is useful and effective in helping the rehabilitation process of motor, cognitive and psychosocial functions.It plays a role as an adjunctive and complementary therapy in the neuro-psychomotor rehabilitation process to obtain a clinically significant result.


Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release.
This 10-day, single-center, open-label, randomized, crossover study compared pharmacokinetic profiles and tolerability of extended release quetiapine fumarate (quetiapine XR) with quetiapine immediate release (quetiapine IR) in patients with schizophrenia, schizoaffective disorder or bipolar disorder. After a 2-day lead-in period during which patients received quetiapine XR 300 mg once daily, patients were randomized to quetiapine IR 150 mg twice daily followed by quetiapine XR 300 mg once daily, or quetiapine XR 300 mg once daily followed by quetiapine IR 150 mg twice daily. Pharmacokinetic parameters were evaluated at the end of each 4-day treatment period at steady state. Vital signs, laboratory values, and adverse events (AEs) were recorded throughout the study. The least squares means (90% confidence interval) of the ratio of the area under the plasma concentration-time curve over a 24 h dosing interval (AUC ([0-24 h])) for quetiapine XR/IR was 1.04 (0.92-1.19) and within the pre-defined range set for equivalence (0.80-1.25). Maximum plasma concentration at steady state (C(max)) was approximately 13% lower for quetiapine XR than for quetiapine IR (495.3 versus 568.1 ng/mL), time to reach C(max) (t(max)) was 5 h versus 2 h and mean concentration at the end of 24 h dosing interval (C(min)) was 95.3 versus 96.5 ng/mL, respectively. No patients withdrew from the study owing to AEs and there were no serious AEs or deaths related to study medication. No unexpected AEs, changes in vital signs or laboratory values were observed. These findings suggest that modifying the formulation does not change the overall absorption or elimination of quetiapine, and support emerging clinical evidence for the use of quetiapine XR as a once daily treatment in patients initiating therapy or those established on quetiapine IR.


Engineering of clarithromycin loaded stimulus responsive dissolving microneedle patches for the treatment of biofilms.
This study aimed to fabricate clarithromycin laden Eudragit S-100-based microfibers (MF), microfibers coated film (MB), clarithromycin loaded polyvinyl pyrollidone, hyaluronic acid and sorbitol-based dissolving microneedle patches (CP) and microfibers coated microneedle patches (MP). Morphological and phase analysis of formulations were carried out by scanning electron microscopy and differential scanning calorimetry, X-ray diffraction, respectively. Substrate liquefaction test, in vitro drug release, antimicrobial assay and in vivo antibiofilm studies were performed. MF exhibited a uniform surface and interconnected network. Morphological analysis of CP revealed sharp-tipped and uniform-surfaced microstructures. Clarithromycin was incorporated within MF and CP as amorphous solid. Liquefaction test indicated hyaluronate lyase enzyme responsiveness of hyaluronic acid. Fibers-based formulations (MF, MB and MP) provided an alkaline pH (7.4) responsive drug release; ∼79 %, ∼78 % and ∼81 %, respectively within 2 h. CP showed a drug release of ∼82 % within 2 h. MP showed ∼13 % larger inhibitory zone against Staphylococcus aureus (S. aureus) as compared to MB and CP. A relatively rapid eradication of S. aureus in infected wounds and subsequent skin regeneration was observed following MP application as compared to MB and CP indicating its usefulness for the management of microbial biofilms.


Quantitative EEG in children with headache.
The object of this work is to determine if Brain Mapping can reveal significant differences between a normal control group and a group whose members suffer from one of three types of headache: tension-type, migraine with aura and migraine without aura. Both groups were formed by children aged between 6 and 14; the latter were undergoing no treatment and were in a headache-free phase. Results demonstrate that there are no significant differences between the control group and the tension-type headache group. Neither were differences found in migraine without aura group but in migraine with aura there was an increase of the theta/alpha ratio in the temporal posterior and occipital zones. This ratio could be used as a neurophysiological indicator in the evolution of the migraine with aura pathology.


Food safety knowledge, attitude and practices of street food vendors and associated factors in Mekelle city, Northern Ethiopia.
The purpose of this study was to evaluate the street food vendors' knowledge, attitudes, and practices regarding food safety as well as the associated factors that may affect those practices in Mekelle City, Northern Ethiopia. A community-based, cross-sectional study was conducted from February 2020 to August 2020 using a quantitative data collection method on a total of 185 street food vendors. The data was collected through face-to-face interviews via administered pre-tested structured questionnaire and an observational checklist. To determine the predictor variables linked to a high level of food safety practice, a multivariable logistic regression analysis with odds ratios and 95% confidence intervals was utilized. In this study, the majority-117(65%), 146(81.1%), and 106(58.9%)-had a good level of knowledge, a positive attitude, and a good level of practice regarding food safety, respectively. A Multivariable analysis result revealed that the street food vendors age (AOR: 0.33, 95% CI: 0.14-0.77), monthly income (AOR: 5.2, 95% CI: 1.42-18.9), educational status (AOR: 0.07, 95% CI: 0.009-0.623), food vending experience (AOR: 0.54, 95% CI: 0.22-1.34), food safety training (AOR: 0.490, 95% CI: 0.317-0.757), food safety knowledge (AOR: 1.04, 95% CI: 0.43-2.48) and food safety attitude (AOR: 1.22, 95% CI: 0.47-3.13) were found to be significantly associated with food safety practice. Conclusion: The results of this study demonstrate that street food vendors had high levels of knowledge, attitudes, and practices regarding food safety and hygiene, and that these practices were significantly associated with sex, monthly income, educational status, food vending experience, and food safety training. Therefore, all street food vendors in the study area should receive efficient and ongoing training on food safety practices, and additional research utilizing mixed methodologies (both quantitative and qualitative approaches) would be needed to reach more thorough results and corroborate our findings.


Prognosis comparison between intraoperative radiotherapy and whole-breast external beam radiotherapy for T1-2 stage breast cancer without lymph node metastasis treated with breast-conserving surgery: A case-control study after propensity score matching.
External beam radiotherapy (EBRT), an adjuvant to breast-conserving surgery (BCS), requires a long treatment period, is costly, and is associated with numerous complications. Large sample studies with long follow-up periods are lacking regarding whether intraoperative radiotherapy (IORT), an emerging radiotherapy modality, can replace EBRT for patients with T1-2 early stage breast cancer without lymph node metastasis treated with BCS. We identified 270,842 patients with T1-2N0M0 breast cancer from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. A total of 10,992 patients were matched by propensity score matching (PSM). According to the radiotherapy method, the patients were divided into the IORT and EBRT groups. Overall survival (OS) and breast cancer-specific survival (BCSS) rates were analyzed and compared between the IORT and EBRT groups by Kaplan-Meier analysis. Bilateral P < 0.05 was considered to indicate significance. After PSM, the survival analysis showed no significant differences in OS or BCSS rates between the IORT and EBRT groups. In the subgroup analysis, the IORT population diagnosed from 2010 to 2013 (HRs = 0.675, 95% CI 0.467-0.976, P = 0.037) or with T2 stage (HRs = 0.449, 95% CI 0.261-0.772, P = 0.004) had better OS rates, but in the overall population, the OS and BCSS rates were better in patients with T1 stage than in patients with T2 stage (P < 0.0001), and the proportion of chemotherapy was significantly higher in T2 stage than in T1 stage. Patients who had EBRT with unknown estrogen receptor had better OS rates (HRs = 3.392, 95% CI 1.368-8.407, P = 0.008). In addition, the IORT group had better BCSS rates for married (HRs = 0.403, 95% CI 0.184-0.881, P = 0.023), grade III (HRs = 0.405, 95% CI 0.173-0.952, P = 0.038), and chemotherapy-receiving (HRs = 0.327, 95% CI 0.116-0.917, P = 0.034) patients with breast cancer compared to the EBRT group. Intraoperative radiotherapy results of non-inferior OS and BCSS rates, compared to those of EBRT, in patients with early stage breast cancer without lymph node metastasis treated with BCS, and IORT may provide substantial benefits to patients as an effective alternative to standard treatment. This finding provides new insights into radiotherapy strategies for early stage breast cancer.


Release of core DNA from nucleosomal core particles following (ADP-ribose)n-modification in vitro.
Isolated nucleosomal core particles from rat liver chromatin were ADP-ribosylated in vitro and the consequences of this modification on intranucleosomal DNA-protein interactions were studied by retention gel analysis. A separating force of 11 fN caused the complete release of 146 bp DNA fragments from ADP-ribosylated core particles, while the DNA of unmodified core particles remained protein-associated. We conclude that posttranslational (ADP-ribose)n-modification of chromatin proteins may reduce DNA-protein interactions at the nucleosomal level of chromatin organization.


Chronic muscle weakness caused by Borrelia burgdorferi meningoradiculitis.
A 19-year-old man developed chronic weakness of the lower limbs as the predominant manifestation of Borrelia burgdorferi infection of the nervous system. Spirochetes were demonstrated in the cerebrospinal fluid. The condition resolved following intravenous penicillin treatment.


Towards the application of Tc toxins as a universal protein translocation system.
Tc toxins are bacterial protein complexes that inject cytotoxic enzymes into target cells using a syringe-like mechanism. Tc toxins are composed of a membrane translocator and a cocoon that encapsulates a toxic enzyme. The toxic enzyme varies between Tc toxins from different species and is not conserved. Here, we investigate whether the toxic enzyme can be replaced by other small proteins of different origin and properties, namely Cdc42, herpes simplex virus ICP47, Arabidopsis thaliana iLOV, Escherichia coli DHFR, Ras-binding domain of CRAF kinase, and TEV protease. Using a combination of electron microscopy, X-ray crystallography and in vitro translocation assays, we demonstrate that it is possible to turn Tc toxins into customizable molecular syringes for delivering proteins of interest across membranes. We also infer the guidelines that protein cargos must obey in terms of size, charge, and fold in order to apply Tc toxins as a universal protein translocation system.


Bilateral re-expansion pulmonary edema in a child: a reminder.
Re-expansion pulmonary edema (RPE) is an uncommon complication of sudden reinflation of a lung collapsed by pneumothorax or pleural effusion. We present a case of bilateral pulmonary edema following unilateral drainage of a pleural effusion in a young child with non-Hodgkin's lymphoma.


Polyaniline nanorods dotted on graphene oxide nanosheets as a novel super adsorbent for Cr(VI).
Hierarchical nanocomposites of polyaniline (PANI) nanorods array on graphene oxide (GO) nanosheets are successfully obtained by dilute polymerization under -20 °C. They exhibit excellent water treatment performance with a superb removal capacity of 1149.4 mg g(-1) for Cr(VI).


Can artificial reefs mimic natural reef communities? The roles of structural features and age.
In light of the deteriorating state of coral reefs worldwide, the need to rehabilitate marine environments has greatly increased. Artificial reefs (ARs) have been suggested as a tool for reef conservation and rehabilitation. Although successions of AR communities have been thoroughly studied, current understanding of the interactions between artificial and natural reefs (NRs) is poor and a fundamental question still to be answered is that of whether AR communities can mimic adjacent NR communities. We suggest three alternative hypotheses: Neighboring ARs and NRs will (1) achieve a similar community structure given sufficient time; (2) be similar only if they possess similar structural features; (3) always differ, regardless of age or structural features. We examined these hypotheses by comparing the community structure on a 119-year old shipwreck to a neighboring NR. Fouling organisms, including stony and soft corals, sponges, tunicates, sea anemones and hydrozoans were recorded and measured along belt transects. The ahermatypic stony coral Tubastrea micrantha dominated vertical AR regions while the soft corals Nephthea sp. and Xenia sp. dominated both artificial and natural horizontal surfaces. Our results support the second hypothesis, indicating that even after a century an AR will mimic its adjacent NR communities only if it possesses structural features similar to those of the natural surroundings. However, if the two differ structurally, their communities will remain distinct.


Toxicology of explosives and fireworks in small animals.
Intoxication with explosives or fireworks in dogs or cats is not common, but serious toxicosis can result from exposure to different types of explosives depending on the chemical class of explosive involved. This article will discuss the different types of materials/chemicals, clinical signs of toxicosis, and their treatment. Despite the complexities of explosives and plethora of different devices currently in use worldwide, the toxic potential is more easily explained by looking at the relatively short list of chemical classes used to produce these materials. This article combines structurally similar explosives into different groups and focuses on the toxicity of the most commonly available explosives.


Aortic valve replacement with concomitant aortoventriculoplasty in children and young adults: long-term follow-up.
Sixteen patients (9 male, 7 female) underwent aortic valve replacement (AVR) with a Konno aortoventriculoplasty at the University of Nebraska Medical Center from August, 1976, to May, 1986. There was 1 early death (6%), but no operative deaths have occurred since 1977. There was 1 late death from unknown cause 51 months postoperatively. One patient has been lost to follow-up. Long-term follow-up of 14 patients was 923 months (mean, 66 months; range, 9 to 120 months). Of the 16 patients, 12 (75%) had had previous cardiovascular procedures. A total of thirty-five operations, including the aortoventriculoplasties, were done in the 16 patients. Of the aortic valves inserted, 11 were tissue valves (Carpentier-Edwards, 10; Ionescu-Shiley, 1) and 5 were mechanical valves (St. Jude, 3; Björk-Shiley, 2). Patient age at the time of aortoventriculoplasty ranged from 2 years 3 months to 24 years (median, 11 years 8 months). Size of the aortic annulus ranged from 10 to less than 21 mm (median, 16 mm). Valves inserted ranged from 21 to 29 mm; 13 (81%) of them were 25 mm or larger. In 2 patients, degenerated tissue valves were replaced with mechanical valves after 110 and 33 months. At present, all patients are in New York Heart Association Functional Class I. One female patient married and delivered a normal child approximately five years after AVR with a Carpentier-Edwards valve plus aortoventriculoplasty; she never received anticoagulant medications. We conclude that AVR with a concomitant Konno aortoventriculoplasty can be safely performed in the pediatric and young-adult age groups with satisfactory results for up to ten years.


Mechanism of action of platinum nanoparticles implying from antioxidant to metabolic programming in light-induced retinal degeneration model.
Photoreceptors (PRs) degeneration is central to visual impairment and loss in most blind retinal diseases, including age-related macular disease (AMD) and diabetic retinopathy (DR). PRs are susceptible to oxidative stress owing to their unique metabolic features. Accumulating evidence has demonstrated that the targeting oxidative stress is a promising treatment strategy for PR degeneration. Herein, we introduced potent antioxidative platinum nanoparticles (Pt NPs) to treat PRs degeneration in this study. The Pt NPs exhibited multi-enzymatic antioxidant activity and protected PRs from H2O2-induced oxidative damage in vitro assays. Based on the same mechanism, the intravitreal injection of Pt NPs significantly reduced cell apoptosis, maintained retinal structure and preserved retinal function in a mouse model of light-induced retinal degeneration (LIRD). Most importantly, the results of RNA sequencing showed that the transcription of antioxidative genes was upregulated, and metabolic reprogramming occurred in the LIRD-retina after treatment with Pt NPs, both of which benefited retinal survival from oxidative damage. The results indicated that Pt NPs were indeed potent therapeutic candidates for PRs degeneration in blind retinal diseases.


Use of the sentinel node procedure to stage endometrial cancer.
Lymph node status is a major prognostic factor and a criterion for adjuvant therapy in endometrial cancer. The sentinel lymph node (SN) procedure has emerged as a possible alternative to systematic lymphadenectomy. The aims of this study were to determine the detection rate and the false-negative rate of the SN procedure, and its contribution to the staging of women with endometrial cancer. Forty-six patients with endometrial cancer underwent the sentinel node procedure followed by pelvic lymphadenectomy. SNs were detected with a dual or single labelling method in 39 and 7 cases, respectively. All SNs were analysed by both hematoxylin and eosin (H&E) staining and immunochemistry. SNs were identified in 40 patients (87%), whose mean number of SN was 2.6 (range 1-5). The SN detection rate was significantly lower with the single label than with the dual label (p = 0.01). Ten women (25%) had a positive SN on final histology (i.e. there were no false negatives). A correlation was observed between lymph node involvement and both histological grade (p = 0.01) and lymphovascular space involvement (p = 0.001). The stage predicted by magnetic resonance (MR) imaging correlated poorly with the Federation International of Gynaecology and Obstetrics (FIGO) stage. Among the ten women with a positive SN, three of the four women with a grade 1 tumour at biopsy had grade 2-3 disease on final histology. Seven of the ten women with a positive SN underwent external pelvic radiotherapy, based solely on their SN involvement. The SN procedure can reliably determine lymph node status in women with endometrial cancer. Given the limited capacity of MR imaging to detect myometrial invasion, and of biopsy to determine histological grade, our results support the systematic use of the SN procedure in women with endometrial cancer, including those with presumed early-stage disease and/or well-differentiated tumours.


[Wolff-Parkinson-White syndrome in a case of acute rejection of cardiac transplantation].
A Wolff-Parkinson-White syndrome was observed during acute rejection in a patient who had undergone orthotopic cardiac transplantation. The sometimes intermittent nature of this syndrome could explain its postoperative appearance in this patient; the relationship with the episode of rejection is discussed.


Multilayered Stigma and Vulnerabilities for HIV Infection and Transmission: A Qualitative Study on Male Sex Workers in Zimbabwe.
Male sex workers are marginalized in most societies due to intersectional stigma between prostitution and homosexuality. In Zimbabwe, a proliferation of male sex workers in major cities such as Harare and Bulawayo has been reported. However, there is a shortage of studies that explore their lives. The current qualitative study aims to describe the practices of sex work, life contexts, and HIV risks and vulnerabilities based on in-depth interviews among 15 male sex workers in Bulawayo. Our studies suggest that the stigma against male sex workers comes from diverse sectors including culture ("homosexuality is un-African, introduced by the Whites"), religion ("same sex is a sin before the God"), law and police ("homosexuality is illegal in Zimbabwe. Engaging in it can send one to prison"), media ("the media is hostile to sex workers particularly men as we are regarded as abnormal and unclean"), and their family ("should they get to know about it, they will disown me"). In this context, male sex workers were excluded from national HIV prevention and treatment programs. They had limited knowledge and many misconceptions about HIV. The stigma and discrimination from health-care providers also discouraged them from health seeking or HIV testing. The non-disclosure to female partners of convenience and sexual relations further increased their vulnerabilities to HIV infection and transmission. Current efforts to address the HIV epidemic should pay attention to male sex workers and tackle the intersecting stigma issues. male sex workers need support and tailored HIV prevention and treatment services to improve their HIV prevention practices, health, and well-being.


Resveratrol inhibition of human keratinocyte proliferation via SIRT1/ARNT/ERK dependent downregulation of aquaporin 3.
Aquaporin 3 (AQP3) is the predominant aquaporin in the skin and is overexpressed in hyperplastic epidermal disorders. Upregulation of AQP3 contributes to keratinocyte proliferation and epidermal hyperplasia. Resveratrol, a natural polyphenol, has an anti-proliferative effect on normal human epidermal keratinocytes (NHEKs), but its exact mechanism remains largely unknown. To investigate the ability and mechanism of resveratrol to affect the proliferation and the AQP3 expression in NHEKs. NHEKs treated with resveratrol were analyzed. BrdU incorporation assay, real-time PCR, Western blotting and RNA interference using small interfering RNA were employed. At non-toxic concentrations (less than 40μM), resveratrol inhibited the proliferation of NHEKs. Resveratrol inhibited the ERK phosphorylation and the AQP3 expression with reciprocal upregulation of ARNT expression in a concentration-dependent manner. The inhibitory effects of resveratrol on the ERK phosphorylation and the AQP3 expression were canceled by transfection of siRNA for ARNT, but not by that for AhR. Furthermore, the induction effect of resveratrol on ARNT expression was canceled after SIRT1 was knocked down in NHEKs. Resveratrol inhibited NHEK proliferation by downregulating the expression of AQP3 in an SIRT1/ARNT/ERK dependent fashion. This novel mechanism may facilitate drug innovation for hyperplastic skin disorders.


Long-term structural and functional effects of autologous muscle precursor cell therapy in a nonhuman primate model of urinary sphincter deficiency.
We measured the long-term efficacy of autologous muscle precursor cell therapy in premenopausal female nonhuman primates with sustained urinary sphincter deficiency. Urinary sphincter deficiency was created in adult premenopausal female cynomolgus monkeys by selectively cauterizing and then transecting the pudendal innervation to the sphincter complex. The monkeys were then treated (18) or not treated (18) with intra-urinary sphincter injections of 5 million autologous green fluorescent protein labeled skeletal muscle precursor cells. Four untreated, uninjured monkeys served as controls. Maximal urethral pressure measurement and corresponding histological analysis of the structural and cellular components of the sphincter complex were performed up to 12 months after injection. Cell treatment produced sustained (12 months) increases in resting, somatic nerve stimulated and adrenergic nerve stimulated maximal urethral pressure, and a greater percent of sphincter area occupied by muscle as well as a decrease in the sphincter area occupied by collagen compared to the untreated group (each p>0.05). These results were within control values (each p>0.05). By 3 months after injection green fluorescent protein positive cells were found in the skeletal muscle layer, expressing desmin and connexin-43, and in the smooth muscle layer, expressing α-smooth muscle actin and connexin-43, and they were incorporated into the subendothelial vasculature, expressing Von Willebrand factor. Cell injected sphincter tissue contained a mixture of green fluorescent protein positive cells and predominantly green fluorescent protein negative cells. Injected skeletal muscle progenitor cells incorporated into the injured sphincter complex resulted in long-term structural and functional restoration of the injured sphincter complex in this nonhuman primate model.


SARS-CoV-2 vaccine-induced antibody and T cell response in SARS-CoV-1 survivors.
Preexisting immunity cross-reactive to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in SARS-CoV-1 survivors suggests that a coronavirus disease 2019 vaccine may boost such preexisting cross-reactive memory T cells. We measure SARS-CoV-2 and SARS-CoV-1 spike-specific neutralizing antibody and T cell responses in a single dose of Ad5-nCoV-immunized SARS-CoV-1 survivors 6 months after vaccination. Compared with Ad5-nCoV-immunized naive healthy individuals (NHIs), vaccination of Ad5-nCoV in SARS-CoV-1 survivors boosts the antibody response against SARS-CoV-1 but induces a limited neutralizing antibody that is capable of neutralizing SARS-CoV-2 variants of concern, and nearly all serum samples lose neutralization to Omicron subvariants. Immunized SARS-CoV-1 survivors produce a T cell response to SARS-CoV-2 comparable with that of Ad5-nCoV-immunized NHIs. However, a robust cross-reactive T cell response to SARS-CoV-1 is identified in immunized SARS-CoV-1 survivors compared with Ad5-nCoV-immunized NHIs. These findings suggest that vaccination with Ad5-nCoV elicits a stronger neutralizing antibody and cross-reactive T cell responses against SARS-CoV-1 in SARS-CoV-1 survivors.


Improving FLAIR SAR efficiency at 7T by adaptive tailoring of adiabatic pulse power through deep learning B1+ estimation.
The purpose of this study is to demonstrate a method for specific absorption rate (SAR) reduction for 2D T2 -FLAIR MRI sequences at 7 T by predicting the required adiabatic radiofrequency (RF) pulse power and scaling the RF amplitude in a slice-wise fashion. We used a time-resampled frequency-offset corrected inversion (TR-FOCI) adiabatic pulse for spin inversion in a T2 -FLAIR sequence to improve B1+ homogeneity and calculated the pulse power required for adiabaticity slice-by-slice to minimize the SAR. Drawing on the implicit B1+ inhomogeneity in a standard localizer scan, we acquired 3D AutoAlign localizers and SA2RAGE B1+ maps in 28 volunteers. Then, we trained a convolutional neural network (CNN) to estimate the B1+ profile from the localizers and calculated pulse scale factors for each slice. We assessed the predicted B1+ profiles and the effect of scaled pulse amplitudes on the FLAIR inversion efficiency in oblique transverse, sagittal, and coronal orientations. The predicted B1+ amplitude maps matched the measured ones with a mean difference of 9.5% across all slices and participants. The slice-by-slice scaling of the TR-FOCI inversion pulse was most effective in oblique transverse orientation and resulted in a 1 min and 30 s reduction in SAR induced delay time while delivering identical image quality. We propose a SAR reduction technique based on the estimation of B1+ profiles from standard localizer scans using a CNN and show that scaling the inversion pulse power slice-by-slice for FLAIR sequences at 7T reduces SAR and scan time without compromising image quality.


The process of gas exchange in the pulmonary circulation incorporating the contribution of axial diffusion.
A mathematical model is made to describe the process of gas exchange in the pulmonary circulation incorporating the contribution of axial diffusion. The model takes into account the transport mechanisms of molecular diffusion, convection and facilitated diffusion due to the presence of haemoglobin as a carrier of the gases. The mathematical formulation leads to a coupled system of non-linear elliptic partial differential equations. A numerical scheme is described to solve such a system. It is found that the axial diffusion does not have an appreciable effect on the transport of the species in the blood.


Conformational nonequivalence of chains 1 and 2 of dipalmitoyl phosphatidylcholine as observed by Raman spectroscopy.
Raman spectroscopic data indicate that the conformations of the two hydrocarbon chains of dipalmitoyl phosphatidylcholine in aqueous dispersions of the lipid differ signficantly. The compounds 1-palmitoyl, 2-palmitoyl-d31-3-sn-phosphatidylcholine and 1-palmitoyl-d31, 2-palmitoyl-3-sn-phosphatidylcholine were synthesized. Aqueous dispersions of these phospholipids display very similar phase behavior, with both premelting and melting transitions at nearly identical temperatures, midway between the comparable transition temperatures of undeuterated and completely deuterated dipalmitoyl phosphatidylcholine. We have monitored the state of chains 1 and 2 of these molecules simultaneously and independently by Raman spectroscopy. Raman difference spectra taken between samples of the two compounds under identical conditions show significant features. We attribute these spectral differences to nonequivalent conformations of the fatty acyl chains attached at positions 1 and 2 on the glycerol backbone. Below the pretransition the conformation of chain 2 is, on average, slightly less all-trans than is the chain at position 1. There is some evidence that the conformations of the terminal methyl group of the two chains are significantly different at low temperatures.


A new combined approach of neural-metaheuristic algorithms for predicting and appraisal of landslide susceptibility mapping.
In this research, to predict landslide susceptibility mapping (LSM), we have studied and optimized an artificial neural network (ANN) by utilizing the backtracking search algorithm (BSA) as well as the Cuckoo optimization algorithm (COA). Multiple research studies have shown that ANN-based techniques can be used to figure out the LSM. Still, ANN computing models have big problems, like slow system learning and getting stuck in their local minimums. Optimization strategies may improve ANN performance results. Existing uses of the BSA and COA models in ANN training have not been used to map landslides, nor have the best ways to set up networks or other factors that affect this problem been examined. Consequently, the present research focuses on predicting landslide susceptibility for hazardous mapping using hybrid BSA and COA-based ANN algorithms (BSA-MLP and COA). A large data set was provided from an area in the province of Kurdistan, west of Iran, to provide training and testing datasets for the algorithms. All of the BSA and COA algorithms' parameters and weights, for instance, were fine-tuned to make the utmost accurate maps of landslide risk. The input dataset consists of elevation, slope angle, slope orientation, NDVI, fault tolerance, profile curvature, plan curvature, distance to the river, rainfall, far from the road, SPI, STI, TRI, TWI, land use, and geology; the output is landslide susceptibility value. In the testing phase, the AUC rose significantly from 0.701 to 0.864 for BSA-MLP and 0.738 to 0.822 for COA-MLP after using the abovementioned techniques. We have used the area under the curve (AUC) to evaluate how well the probabilistic models worked. In addition, the computed AUCs for the BSA-MLP available databases and the actual AUCs were 0.864, 0.857, 0.833, 0.778, 0.777, 0.769, 0.763, 0.758, 0.727, and 0.701 and 0.822, 0.808, 0.807, 0.805, 0.804, 0.777, and 0.769 for the COA-MLP combination. The integrated models can produce beneficial results for this area of research. The results suggest that the BSA-ANN model is better than the COA-ANN in optimizing an artificial neural network model's structure and computational parameters. The collected landslide susceptibility maps are significant for figuring out how dangerous landslides are in the studied area.


Solubility of enamel powder following treatment with a sodium-n-lauroyl sarcosinate containing toothpaste in the presence and absence of fluoride.
Toothpaste solution exerts an inhibitory effect on dissolution of enamel in acidic solution. The presence of a detergent will not predispose enamel to acid dissolution or affect the inhibitory effect of fluoride on dissolution.


LECT2: A pleiotropic and promising hepatokine, from bench to bedside.
LECT2 (leucocyte cell-derived chemotaxin 2) is a 16-kDa protein mainly produced by hepatocytes. It was first isolated in PHA-activated human T-cell leukaemia SKW-3 cells and originally identified as a novel neutrophil chemotactic factor. However, many lines of studies suggested that LECT2 was a pleiotropic protein, it not only functioned as a cytokine to exhibit chemotactic property, but also played multifunctional roles in some physiological conditions and pathological abnormalities, involving liver regeneration, neuronal development, HSC(haematopoietic stem cells) homeostasis, liver injury, liver fibrosis, hepatocellular carcinoma, metabolic disorders, inflammatory arthritides, systemic sepsis and systemic amyloidosis. Among the above studies, it was discovered that LECT2 could be a promising molecular biomarker and therapeutic target. This review summarizes LECT2-related receptors and pathways, basic and clinical researches, primarily in mice and human, for a better comprehension and management of these diseases in the future.


Unpacking atitudes towards genetically modified food.
The present study investigates the structure of attitudes towards genetically modified (GM) food. A total of 431 respondents completed a questionnaire measuring their overall attitude, cognition and affect towards GM food. A model with distinct positive and negative, affective and cognitive components and a separate factor for perceived risk and worry best accounted for the data. Negative--but not positive--components directly affected behavioural intentions. Implications of these findings for our understanding of attitudes towards GM food and their impact on behaviour are discussed.


Detection of SARS-CoV-2 in pets living with COVID-19 owners diagnosed during the COVID-19 lockdown in Spain: A case of an asymptomatic cat with SARS-CoV-2 in Europe.
Pets from COVID-19 owners were screened for SARS-CoV-2 (April-May 2020). From 23 pets, an asymptomatic cat showed positive RT-qPCRs results from oropharyngeal swab (negative rectal swab). Remaining pets were negative. This suggests that cats can contract the virus from their infected owners and may act as potential hosts for SARS-CoV-2. Their role in carrying live or infectious viruses and disseminating them needs more investigation.


Neurocutaneous syndrome with excessive macrohydrocephalus. (Sturge-Weber/Klippel-Trenaunay syndrome).
2.5 years of follow-up of a boy with progressive macrohydrocephalus possibly as a consequence of an intracranial vascular malformation. There are prominent features of a Sturge-Weber as well as a Klippel-Trenaunary-syndrome.


Affinity chromatography using competitive elution separates polyclonal glucocorticoid antisera into fractions of varying cross-reactivity.
Affinity chromatography of glucocorticoid antisera using cross-reacting steroid-Sepharose columns and competitive elution with the immunising steroid has allowed the separation of polyclonal antibodies into fractions of varying cross-reactivity. Elution was at neutral pH in the presence of 20% acetonitrile followed by dissociation of the eluted immunoglobulin-steroid complex, by dialysis. A polyclonal cortisol antibody with an initial 70% cross-reactivity to 11-deoxycortisol yielded a fraction with 10% cross reactivity and improved affinity. This fraction was suitable for determining plasma cortisol on patients undergoing the metyrapone test whereas another fraction of similar affinity but higher cross reactivity to 11-deoxycortisol, as well as the intact antiserum, grossly over-estimated plasma cortisol on these patients. This technique should permit the use of antibody fractions for immunoassay when the intact antiserum may be unsatisfactory due to lack of specificity.


[Posttraumatic or inflammatory acute respiratory distress syndrome on high altitude area: a retrospective analysis of 94 deaths due to ARDS/MOF].
To determine the characteristic predictors of acute respiratory distress syndrome (ARDS) in the high altitude area of China. According to the diagnostic criteria of ARDS, 2 325 cases were screened in the recent 10 years. Except malignant tumors, cardio-cerebrovascular diseases, chronic obstructive pulmonary disease, and chronic multiple organ failure, the causes of death were analysed retrospectively. 94 cases (4.04%) were diagnosed as ARDS, but in the primary case record, only 27 cases (1.16%) had been diagnosed as ARDS/MOF. Of the 94 ARDS patients, 79 complicated by extrapulmonary organ damage involving the kidney, heart, liver, gastro-intestinal tract, and brain. A total of 305 organs were involved (average 3.24 organs each case). Lung failure only accounted for 15 cases. The combination of the diagnostic criteria of ARDS for high altitude area and flate area, injury severity scale, blood gas monitoring, and integrated traditional Chinese medicine and western medicine may improve the prognosis of ARDS.


Hybridization of DNA to RNA in methylmercuric hydroxide agarose gels.
We describe a method for hybridization of cDNA probes to RNA directly in agarose gels which provides a practical alternative to methods involving transfer of the RNA out of the gel. Total cellular RNA is subjected to electrophoresis in agarose gels containing methylmercuric hydroxide as the denaturing agent. After removal of the methylmercuric hydroxide, the gel is dried and 32P-labeled DNA probes are hybridized to the immobilized RNA. This method is more economical in time and expense than methods involving transfer of the RNA out of the gel, while maintaining a level of sensitivity comparable to other procedures.


Intracortical horizontal connections of neurons in cat and monkey motor cortex.
The present paper deals with the study of the structure of horizontal neuron chains, one of the aspects of intracortical intraneuronal relationships. The motor cortex (field 4) of cats and lower monkeys (Papio hamadryas and Macacus rhesus s. M. mullata) was treated by the impregnating method of Golgi--Kopsh. The drawings of neurons from 90-micrometer sections were made by means of a camera lucida. Three possible pathways of impulse transmission along neuron chains in a horizontal direction were revealed. These were: a pyramido-pyramidal system of connections which may possibly spread excitatory influence among several columns; a basket-pyramidal connection system; and connections which arise from successive switchings between neighboring neurons of one layer.


The Presence of a Zygomatic Nerve Plexus in a Cadaveric Specimen Without a Zygomatic Branch of the Facial Nerve.
The extratemporal course of the facial nerve distributes in facial mimic muscles in a complex pattern. The traditional depictions of five main branches without anastomoses are not common. Davis classification remains the gold standard in the classification of facial nerve branching patterns. During a routine dissection of an 74-year-old male cadaveric specimen, we detected a very rare anatomical variation. The zygomatic branch of the facial nerve was totally absent. The temporofacial division of the main trunk was bifurcated to a temporal and a buccal branch. The anterior temporal and posterior buccal branches formed a plexus to supply the orbicularis oculi muscle. This unique variability highlights the complexity of the extratemporal facial nerve course. Retrograde facial nerve dissection requires deep knowledge of every anatomical variation of the facial nerve course to avoid an iatrogenic injury. The online version contains supplementary material available at 10.1007/s12070-023-03601-y.


Deciphering the absorption profile and interaction of multi-components of Zhi-Zi-Da-Huang decoction based on in vitro-in silico-in vivo integrated strategy.
Zhi-Zi-Da-Huang decoction (ZZDHD) has been acknowledged with striking therapeutic effects for hepatobiliary disorders in the history of China. As decoctions are usually administrated orally, intestinal absorption, the prerequisite task of exerting therapeutic effects, is of utmost significance for screening potential active compounds and understanding the mechanism of drug action. In this work, an in vitro-in silico-in vivo strategy based on HPLC-DAD-ESI-TOF/MS was adopted for precisely profiling the intestinal absorption of ZZDHD, which integrated information obtained from rat everted gut sac model, octanol-water partition model, in silico prediction and in vivo experimental data. Besides, 34 main absorbed ingredients were selected as chemical markers to investigate the compatible interaction of the decoction on absorption level using rat everted gut sac experiment. In total, 106 compounds of ZZDHD were speculated as potential absorptive. Among them, 90 constituents predicted absorbable in at least two experimental models were finally recognized as intestinal absorbable ingredients. In addition, the absorption level of iridoids, terpenoids and flavonoid glycosides were found improved and the absorption of catechins and anthraquinones were inhibited after prescription compatibility. Taken together, this study presents a reliable strategy for evaluating intestinal absorption of herbal medicines and offers a reference for the rationality of herbal compatibility and the modernization of traditional Chinese medicine (TCM).


Gut microbiota dysbiosis is associated with sepsis-induced cardiomyopathy in patients: A case-control study.
Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.


On-road bicycle facilities and bicycle crashes in Iowa, 2007-2010.
An average of 611 deaths and over 47,000 bicyclists are injured in traffic-related crashes in the United States each year. Efforts to increase bicycle safety are needed to reduce and prevent injuries and fatalities, especially as trends indicate that ridership is increasing rapidly. The objective of this study was to evaluate the effect of bicycle-specific roadway facilities (e.g., signage and bicycle lanes) in reducing bicycle crashes. We conducted a case site-control site study of 147 bicycle crash-sites identified from the Iowa Department of Transportation crash database from 2007 to 2010 and 147 matched non-crash sites. Control sites were randomly selected from intersections matched to case sites on neighborhood (census block group) and road classification (arterial, feeder, collector, etc.). We examined crash risk by any on-road bicycle facility present and by facility type (pavement markings--bicycle lanes and shared lane arrows, bicycle-specific signage, and the combination of markings and signage), controlling for bicycle volume, motor vehicle volume, street width, sidewalks, and traffic controls. A total of 11.6% of case sites and 15.0% of controls had an on-road bicycle facility. Case intersections had higher bicycle volume (3.52 vs. 3.34 per 30 min) and motor vehicle volume (248.77 vs. 205.76 per 30 min) than controls. Our results are suggestive that the presence of an on-road bicycle facility decreases crash risk by as much as 60% with a bicycle lane or shared lane arrow (OR=0.40, 95% CI=0.09-1.82) and 38% with bicycle-specific signage (OR=0.62, 95% CI=0.15-2.58). Investments in bicycle-specific pavement markings and signage have been shown to be beneficial to traffic flow, and our results suggest that they may also reduce the number of bicycle-motor vehicle crashes and subsequent injuries and fatalities. As a relatively low-cost traffic feature, community considerations for further implementation of these facilities are justified.


Living in the Community With Dementia: Who Receives Paid Care?
Paid caregivers (eg, home health aides and personal care attendants) provide hands-on care that helps individuals with dementia live in the community. This study (a) characterizes paid caregiving among community-dwelling individuals with dementia and (b) identifies factors associated with receipt of paid care. Cross-sectional analysis. The 2015 National Health and Aging Trends Study (NHATS), a nationally representative study of Medicare recipients aged 65 years and older. Community-dwelling individuals with dementia (n = 899). Paid and family caregiving support was determined by participant or proxy report of help received with functional tasks. Multivariable logistic regression was used to examine factors associated with receipt of paid care. NHATS population sampling weights were used to produce national paid caregiving prevalence estimates. Only 25.5% of community-dwelling individuals with dementia received paid care, and 10.8% received 20 hours or more of paid care per week. For those who received it, paid care accounted for approximately half of the 83 total caregiving hours (paid and family) that they received each week. Among the subgroup of individuals with advanced dementia (those with impairment in dressing, bathing, toileting, and managing medications and finances), nearly half (48.3%) received paid care. Multivariable analysis, adjusting for sociodemographic, family caregiving support, functional, and clinical characteristics, found that the odds of receiving paid care were higher among men (odds ratio [OR] = 1.91; 95% confidence interval [CI] = 1.24-2.95), the unmarried (OR = 2.20; 95% CI = 1.31-3.70), those with Medicaid (OR = 2.16; 95% CI = 1.27-3.66), and those requiring more help with activities of daily living (ADLs) (OR = 1.32; 95% CI = 1.18-1.48) and instrumental ADLs (OR = 1.29; 95% CI = 1.14-1.46). New ways of making paid caregiving more accessible throughout the income spectrum are required to support family caregivers and respect the preferences of individuals with dementia to remain living in the community. J Am Geriatr Soc 68:186-191, 2019.


Integrated model for methane emission and dispersion assessment from landfills: A case study of Ho Chi Minh City, Vietnam.
Methane is considered to be one of the main causes of global warming. Quantifying methane emissions from landfills is the subject of many studies, especially emphasizing the role of two parameters: methane generation potential capacity (L0), methane generation rate (k). In this study, we propose a system of integrated environmental information and mathematical model named EnLandFill (ENvironmental information - model integrated system for air emission and dispersion estimation from LandFill) that allows calculation L0 from database and experimentally to determine optimal k. To perform experimental calculations, meteorological data were extracted from the WRF model and verified with real measurements. The novelty of this study lies in the inferred database system, the math model bank, especially the dispersion model, taking note account the complex topography, meteorological factors that change by the hour. EnLandFill was applied to Phuoc Hiep Landfill (PHLF) in Ho Chi Minh City as a case study, the results have identified the amount of methane released that is equal to 44,094,697.88 m3/year in 2019, but EnLandFill is designed to be general, applicable to other landfill entities.


Foreign body in the ureter: a particle of glue after transarterial embolization of a renal pseudoaneurysm during percutaneous nephrostomy.
Reports on foreign bodies within the ureter are extremely rare in the literature. Herein, we present a case of a foreign body in a ureter, specifically a particle of glue resulting from transarterial embolization of a renal pseudoaneurysm secondary to percutaneous nephrostomy. Emergent transarterial embolization was required due to life-threatening active bleeding of the pseudoaneurysm. However, the glue material subsequently fell into the ureter where it became a foreign body, resulting in obstructive uropathy. Several surgical interventions, including endoscopic and laparoscopic methods, were performed to retrieve the foreign body, but these attempts were unsuccessful. Finally, the glue material was spontaneously passed out by chance. To the best of our knowledge, this type of complication (a glue particle left over from an embolization procedure migrating into the urinary collecting system) has never been reported. We recommend close follow-up examinations after transarterial embolization for renal pseudoaneurysm in order to avoid possible obstructive uropathy caused by glue materials or coils.


Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer.
In locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and the anti-PD-1 antibody camrelizumab in patients with LARC. This was a prospective, single-arm, phase II trial. Treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma received 5×5 Gy SCRT with two subsequent 21-day cycles of CAPOX plus camrelizumab after 1 week, followed by radical surgery after 1 week. The primary endpoint was pathological complete response (pCR) rate. Biomarker analysis was performed to identify a potential predictor of pCR to treatment. From November 7, 2019 to September 14, 2020, 30 patients were enrolled, and 27 patients received at least one dose of CAPOX plus camrelizumab. Surgery was performed in 27 (100%) patients. The pCR (ypT0N0) rate was 48.1% (13/27), including 46.2% (12/26) for proficient mismatch repair (MMR) tumors and 100% (1/1) for deficient MMR tumors. Immune-related adverse events were all grade 1-2, with the most common being reactive cutaneous capillary endothelial proliferation (81.5%). No grade 4/5 adverse events occurred. Biomarker analysis showed patients without FGFR1-3 deletions had a better tendency for pCR. SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. A randomized controlled trial is ongoing to confirm these results. ClinicalTrials.gov identifier: NCT04231552.


Arachidonic acid release from PC12 pheochromocytoma cells is regulated by I1-imidazoline receptors.
Rat PC 12 pheochromocytoma cells lack alpha2-adrenergic receptors but express plasma membrane I1-imidazoline receptors. In response to the I1-agonist moxonidine, diglycerides are generated via phosphatidylcholine-selective phospholipase C, and prostaglandin E2 is released. This report characterizes I-receptor-mediated release of arachidonic acid, the precursor to the prostaglandins. PC12 cells were incubated with [3H]arachidonic acid for 24 h and superfused with 0.01% bovine serum albumin in Krebs' physiological buffer at 1 ml/min. Calcium ionophore increased arachidonic acid release only marginally, implying that in PC12 cells arachidonic acid release is not driven by calcium. The I1-agonist moxonidine at concentrations between 10 nM and 1.0 microM rapidly elicited up to two-fold increases in [3H]arachidonic acid release. Guanabenz, a potent alpha2-agonist and I2-ligand, had no effect. The selective I1-antagonist efaroxan blocked the action of moxonidine. The phospholipase A2 inhibitor aristolochic acid had no effect, suggesting that arachidonic acid release may be through an indirect pathway, possibly involving diglycerides. Thus, I1-imidazoline receptors in PC12 cells are coupled to arachidonic acid release through an as yet unknown pathway.


Optical diagnosis of gastric cancer using near-infrared multichannel Raman spectroscopy with a 1064-nm excitation wavelength.
Gastric cancer is one of the most common cancers in Japan. The use of endoscopy is increasing, along with the number of histological examinations of specimens obtained by endoscopy. However, it takes several days to reach a diagnosis, which increases the medical expense. Raman spectroscopy is one of the available optical techniques, and the Raman spectrum for each molecule and tissue is characteristic and specific. The present study investigated whether Raman spectroscopy can be used to diagnose gastric cancer. A total of 251 fresh biopsy specimens of gastric carcinoma and non-neoplastic mucosa were obtained from 49 gastric cancer patients at endoscopy. Without any pretreatment, the fresh specimens were measured with a near-infrared multichannel Raman spectroscopic system with an excitation wavelength of 1064 nm, and Raman spectra specific for the specimens were obtained. A principal component analysis (PCA) was performed to distinguish gastric cancer and non-neoplastic tissue, and a discriminant analysis was used to evaluate the accuracy of the gastric cancer diagnosis. The Raman spectra for cancer specimens differed from those for non-neoplastic specimens, especially at around 1644 cm(-1). Sensitivity was 66%, specificity was 73%, and accuracy was 70%. The accuracy of diagnosis using the single Raman scattering intensity at 1644 cm(-1) was 70%, consistent with the PCA result. The present results indicate that near-infrared multichannel Raman spectroscopy with a 1064-nm excitation wavelength is useful for gastric cancer diagnosis. Establishment of a Raman diagnostic system for gastric cancer may improve the clinical diagnosis of gastric cancer and be beneficial for patients.