Colgajo dorsal ancho preservador de músculo para la reconstrucción de defectos en la extremidad inferior en niños.
Evaluar los resultados estéticos y funcionales, así como el grado de satisfacción, posteriores a la reconstrucción de defectos de la extremidad inferior en niños con colgajo de dorsal ancho preservador del músculo como una alternativa para estos casos. Se incluyeron pacientes menores de 18 años con defectos en la extremidad inferior tratados en un periodo de 3 años. Se realizó colgajo dorsal ancho preservador de músculo en todos los pacientes. Se valoraron la apariencia estética, la fuerza muscular del área donadora y la función en el área receptora a los 3 meses de realizado el colgajo. Se realizaron 13 colgajos de dorsal ancho preservadores de músculo. La apariencia estética de las áreas donadora y receptora fue satisfactoria en la mayoría de los casos. La mayoría de los pacientes presentaron una fuerza muscular normal (M5) en el sitio donador y pudieron deambular. El colgajo de dorsal ancho preservador de músculo tiene un grado de satisfacción muy elevado, excelente simetría y preservación de la función muscular del sitio donador. Es una técnica ideal en defectos tisulares importantes de la extremidad inferior en la población pediátrica. To evaluate the aesthetic and functional outcomes as well as the degree of postoperative satisfaction of the lower limb's defects reconstruction with a muscle-sparing latissimus dorsi flap in children in order to propose this kind of reconstruction as a secure alternative. In this study were included patients under 18 years with lower limb's defects treated over a period of 3 years. A muscle-sparing latissimus dorsi flaps was performed in all patients. After three months the flap was performed, it was evaluated the donor's area muscular strength, recipient area function and aesthetic appearance. They were made 13 muscle-sparing latissimus dorsi flaps. In most cases, the donor and recipient area has satisfactory aesthetic appearance, most of the patients had a normal muscular strength (M5) in donors area and were able to walk. The reconstruction using a muscle-sparing latissimus dorsi flap has a very high level of satisfaction, excellent symmetry, and preservation of donor area muscle function. It is an ideal technique for major tissue defects of lower limb in children.


Thermodynamics of metal cation binding by a solid soil-derived humic acid: binding of Fe(III), Pb(II), and Cu(II).
Metal binding and release by solid humic acids (HAs) in soils and sediments can affect metal mobility and bioavailability. Isotherms for tight binding of Fe(III), Pb(II) and Cu(II) by a solid humic acid at pH2.0 fit the Langmuir binding model. Low pH was chosen to protonate the HA carboxylate groups and avoid metal cation hydrolysis. Binding of Fe(III), Pb(II) and Cu(II) occurs in one detectable step labeled A. Site capacities nu(A) are temperature-independent from 10.0 to 40.0 degrees C and point to binding by charge-neutralization to form solid complexes M(OOC-R)(n)(s), where n appears to be 2 for Pb(II) and 3 for Fe(III). Thermodynamic data pairs (DeltaH(A), DeltaS(A)) for metal binding are linearly correlated with previous data for Ca(II), Co(II) and Mg(II) binding by solid HAs.


DEL cell line: a "malignant histiocytosis" CD30+ t(5;6)(q35;p21) cell line.
A new cell line DEL, established in vitro, was isolated from a pleural effusion of a boy who died of malignant histiocytosis. Its principal characteristics are: strong positivity with monoclonal antibodies (MAbs) to CD25, CD30, CD45R, KiM7, EMA, HLA Cl I and II; constant presence of acid phosphatase, ANAE, alpha-anti-trypsin, alpha-anti-chymotrypsin and NBT reductase activity; rearrangement of the immunoglobulin heavy-chain gene (JH) and a germ-line configuration of the T-chain gene; and finally a translocation between chromosomes 5-6 with a breakpoint in 5q35. The DEL cell line is appropriate for studying the role of the 5q localized c-fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a 5q35 breakpoint.


Astrocytes detect and upregulate transmission at inhibitory synapses of somatostatin interneurons onto pyramidal cells.
Astrocytes are important regulators of excitatory synaptic networks. However, astrocytes regulation of inhibitory synaptic systems remains ill defined. This is particularly relevant since GABAergic interneurons regulate the activity of excitatory cells and shape network function. To address this issue, we combined optogenetics and pharmacological approaches, two-photon confocal imaging and whole-cell recordings to specifically activate hippocampal somatostatin or paravalbumin-expressing interneurons (SOM-INs or PV-INs), while monitoring inhibitory synaptic currents in pyramidal cells and Ca2+ responses in astrocytes. We found that astrocytes detect SOM-IN synaptic activity via GABABR and GAT-3-dependent Ca2+ signaling mechanisms, the latter triggering the release of ATP. In turn, ATP is converted into adenosine, activating A1Rs and upregulating SOM-IN synaptic inhibition of pyramidal cells, but not PV-IN inhibition. Our findings uncover functional interactions between a specific subpopulation of interneurons, astrocytes and pyramidal cells, involved in positive feedback autoregulation of dendritic inhibition of pyramidal cells.


Reappraisal of Delorme's procedure for rectal prolapse.
Eighteen patients with second- and third-degree rectal prolapse were treated by simplified Delorme operation during a nine-year period. Operative mortality was nil and significant complications developed in three patients (17 percent). Long-term follow-up (average, 42 months) was established for all 18 patients revealing excellent results in 15 (83 percent). There was only one recurrent prolapse (6 percent) observed during this follow-up period. Technical details of the procedure are described. The simplified Delorme procedure provides acceptable results in the initial surgical management of rectal procidentia.


Neonatal Streptococcus pneumoniae septicemia and meningitis. A case report.
Neonatal septicemia/meningitis from Streptococcus pneumoniae occurred in a 36-hour-old infant. The mother had no overt evidence of infection. This case illustrates the pathogenic potential of this common bacterium in the neonate.


3D landscape of Hepatitis B virus interactions with human chromatins.
Hepatitis B viral (HBV) DNAs, including covalently closed circular DNA (cccDNA) and integrated HBV DNA forms, are considered to be primary contributors to the development and progression of HBV-associated liver diseases. However, it remains largely unclear how HBV DNAs communicate with human chromatin. Here we employed a highly sensitive technology, 3C-high-throughput genome-wide translocation sequencing (3C-HTGTS), to globally identify HBV DNA-host DNA contacts in cellular models of HBV infection. HBV DNA does not randomly position in host genome but instead preferentially establishes contacts with the host DNA at active chromatin regions. HBV DNA-host DNA contacts are significantly enriched at H3K4me1-marked regions modified by KMT2C/D; this histone modification is also observed in the HBV cccDNA mini-chromosome and strongly influences HBV transcription. On the other hand, chromatin loop formed by integrated HBV DNA with host genomic DNA was found in transcriptionally active regions. Furthermore, HBV infection influences host gene expression accompanied with HBV DNA-host DNA contacts. Our study provides a 3D landscape of spatial organization of cccDNA and integrated HBV DNA within the human genome, which lays the foundation for a better understanding of the mechanisms how HBV involves in liver disease development and progression.


A Gastroenterologist's Approach to the Diagnosis and Management of Gastrointestinal Stromal Tumors.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. These tumors have been shown to harbor oncogenic mutations of the c-kit tyrosine kinase receptor or platelet-derived growth factor receptor alpha (PDGFRA). Immunohistochemical analysis of GISTs allows for the differentiation of these tumors from other mesenchymal tumors of the GI tract such as leiomyomas and leiomyosarcomas. All GISTs have the potential to behave in a malignant fashion. Tumor location, size, and mitotic index are factors used to predict the risk of malignant behavior. Endoscopy and endoscopic ultrasound play a critical role in the diagnosis of GISTs and can yield important information to further risk-stratify tumors and determine management. This article provides a gastroenterologist's perspective on the diagnosis and management of GISTs.


Relationships between disaster nursing competence, anticipatory disaster stress and motivation for disaster engagement.
Nurses are the largest group of healthcare providers and are often the first line responders to a disaster event. Nurses' disaster competence, motivation for disaster engagement, and factors that impact their motivation to respond to disaster events need to be understood. The purposes of the study were to determine the predictive relationships between Taiwanese nurses' disaster competence, anticipatory disaster stress, and motivation for disaster engagement. A cross-sectional design was used to analyze data collected between August 2017 and December 2017 from eight hospitals in southern Taiwan. Ninety participants who met the recruitment criteria completed and returned questionnaires with an 88.24% response rate. Data collection involved administering the Disaster Nursing Competence Questionnaire, Anticipatory Disaster Stress Questionnaire, and the Motivation of Disaster Engagement Questionnaire. The results indicated that anticipatory disaster stress was positively correlated with disaster competence and motivation for disaster engagement. Disaster competence and willingness to join a hospital disaster rescue predicts an individuals' motivation for disaster engagement. The results of the study add to the understanding of factors that correlate with nurses' motivation to participate in disaster events. By understanding these factors, the government and healthcare administrators can design disaster education plans and other strategies to improve Taiwanese nurses' motivation to engage in disaster events.


Effects of cold preservation and rewarming on rat liver cell volume regulation and concentrative amino acid uptake.
Liver graft dysfunction is related to hypothermic preservation and may implicate altered cell volume homeostasis. The aim of this study was to evaluate how cold preservation and rewarming affect hepatocellular volume regulation and concentrative amino acid uptake. Rat hepatocytes suspended for variable times in cold preservation solution were subsequently cultured at 37 degrees C. Cell viability was assessed by trypan blue exclusion. Cell volume was measured by videoplanimetric analysis of microscopic images. Amino acid uptake was assessed by measuring Na+-dependent cell swelling. Cell viability decreased as a function of cold storage time even as early as 4 hours. Upon hypotonic stress, cells swelled similarly irrespective of preservation time. However, the rate of subsequent regulatory volume decrease diminished significantly with increasing preservation time. Upon return to isotonic perfusate, cells shrunk to a similar extent, but the rate of regulatory volume increase was halved by cold storage beyond 24 hours. The rate of proline-induced cell swelling was diminished greatly after cold storage, unlike that induced by aminoisobutyric acid and glutamine. Hepatocellular volume regulatory mechanisms and concentrative proline uptake are significantly impaired after cold preservation and rewarming, unlike alpha-aminoisobutyric acid and glutamine uptake. This may favor chronic cell swelling after transplantation and participate in liver graft dysfunction.


Simple method for preparation of antibody-enzyme conjugates for enzyme-linked immunosorbent assays.
Mixing suspensions of rabbit antibody for staphylococcal enterotoxin A and commercial anti-rabbit immunoglobulin G-alkaline phosphatase conjugate produced a complex conjugate suitable for use as the second antibody in a conventional enzyme-linked immunosorbent assay. The method was useful for detecting 1 ng of staphylococcal enterotoxin A per ml.


Flavonol glycosides from the leaves of Indigofera zollingeriana.
Two new flavonol glycosides were isolated from the 1-butanol (1-BuOH)-soluble fraction of a methanol (MeOH) extract of the leaves of Indigofera zollingeriana, along with four flavonol glycosides and three known megastigmane glucosides. The structures of the new compounds were elucidated by spectroscopic analyses as kaempferol 3-O-β-D-(2"-O-β-D-apiofuranosyl)glucopyranoside 7-O-α-L-rhamnopyranoside and 3-O-β-D-(2"-O-β-D-apiofuranosyl, 6"-O-α-L-rhamnopyranosyl)glucopyranoside 7-O-α-L-rhamnopyranoside.


Mathematical models for assessing vaccination scenarios in several provinces in Indonesia.
To mitigate casualties from the COVID-19 outbreak, this study aims at assessing the optimal vaccination scenarios, considering several existing healthcare conditions and assumptions, by developing SIQRD (Susceptible-Infected-Quarantine-Recovery-Death) models for Jakarta, West Java, and Banten, in Indonesia. The models include an age-structured dynamic transmission model that naturally allows for different treatments among different age groups of the population. The simulation results show that the timing and period of the vaccination should be well planned and prioritizing particular age groups will give a significant impact on the total number of casualties.


Predicting long-term prognosis after percutaneous coronary intervention in patients with new onset ST-elevation myocardial infarction: development and external validation of a nomogram model.
The triglyceride glucose (TyG) index is a well-established biomarker for insulin resistance (IR) that shows correlation with poor outcomes in patients with coronary artery disease. We aimed to integrate the TyG index with clinical data in a prediction nomogram for the long-term prognosis of new onset ST-elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI) . This retrospective study included new-onset STEMI patients admitted at two heart centers for emergency PCI from December 2015 to March 2018 in development and independent validation cohorts. Potential risk factors were screened applying least absolute shrinkage and selection operator (LASSO) regression. Multiple Cox regression was employed to identify independent risk factors for prediction nomogram construction. Nomogram performance was assessed based on receiver operating characteristic curve analysis, calibration curves, Harrell's C-index and decision curve analysis (DCA). In total, 404 patients were assigned to the development cohort and 169 to the independent validation cohort. The constructed nomogram included four clinical variables: age, diabetes mellitus, current smoking, and TyG index. The Harrell's C-index values for the nomogram were 0.772 (95% confidence interval [CI]: 0.721-0.823) in the development cohort and 0.736 (95%CI: 0.656-0.816) in the independent validation cohort. Significant correlation was found between the predicted and actual outcomes in both cohorts, indicating that the nomogram is well calibrated. DCA confirmed the clinical value of the development prediction nomogram. Our validated prediction nomogram based on the TyG index and electronic health records data was shown to provide accurate and reliable discrimination of new-onset STEMI patients at high- and low-risk for major adverse cardiac events at 2, 3 and 5 years following emergency PCI.


Awaji criteria for the diagnosis of amyotrophic lateral sclerosis in Hanoi, Vietnam.
The aim of the article was to evaluate the role of electromyography and the value of Awaji criteria for the diagnosis of ALS in the early stage. The study involves 48 patients (27 male and 21 females from 41 to 84 years old) who went to Bach Mai Hospital and Dong Do Clinic in Hanoi and were diagnosed with ALS according to Awaji criteria. All patients underwent clinical examination for ALS. The patients were examined for nerve conduction (motor and sensory conduction) using needle electromyography (EMG). Upper motor neuron (UMN) signs and lower motor neuron (LMN) signs were most common in the cervical region (89.58%), the lumbosacral region (70.83%), and the bulbar region (56.25%). The sensory nerve conduction was normal. The spontaneous activities (fasciculation, fibrillation, positive wave) accounted for more than 50% in all 4 regions: bulbar, cervical, thoracic, and lumbosacral regions. The abnormality of both clinical and electrodiagnosis was seen in the cervical region (87.5%) and lumbosacral one (70.83%) while the bulbar region and thoracic one usually had abnormal electrodiagnosis before clinical. There were 60.42% of patients with "definite ALS" by Awaji criteria. It allowed to make an earlier diagnosis cause the sensitivity of Awaji criteria (93.75%) was higher than the revised El Escorial criteria (85.42%) (p < 0.05). The needle EMG makes it possible to detect the early-stage symptoms of ALS in a situation where there are no clinical manifestations, especially in bulbar and thoracic regions.


The skeletal intermediary organization.
This review offers a synthesis of the intermediary organization (IO) of the skeleton. The multicellular units of its lowest level have a common plan, appropriate variations of which then create simple bony, chondral, dental, and fibrous tissues. The more complex higher IO entities then cause those tissues to grow, organize, and model into organs and then maintain the physiological and mechanical competence of those organs. The varied IO units have indivisible quantum properties which isolated cells lack but which, when summed in bulk at the organ level, effectively mimic continuous functions and create most of the known features of skeletal physiology, anatomy, and disease. Those quantum properties also permit the prediction of previously unperceived and unforeseen states and behavior, both normal and abnormal, many of which have been verified.


Diaphyseal medullary stenosis with pleomorphic malignant fibrous histiocytoma of the bone: 99mTc hydroxymethylenediphosphonate and 201Tl chloride scintigraphy findings.
Diaphyseal medullary stenosis (DMS) is an extremely rare hereditary bone dysplasia, which was first described by Arnold in 1973. DMS has a high incidence of pleomorphic malignant fibrous histiocytoma (MFH). In this paper, we report the imaging findings of DMS with pleomorphic MFH of the bone, mainly describing 99mTc hydroxymethylenediphosphonate (HMDP) and thallium-201 (201Tl) chloride scintigraphy findings. On 99mTc HMDP scintigraphy, focal increased uptake area of the right femur corresponded to the area of bone marrow invasion of the tumor and bone infarction. The mechanism of the uptake of 99mTc HMDP to the extraosseous lesion was not clear. On 201Tl chloride scintigraphy, the increased uptake of the periphery of the mass seemed to reflect the aggressiveness of invasion and the cellularity.


Gold(I)-catalyzed formation of furans by a Claisen-type rearrangement of ynenyl allyl ethers.
A series of ynenyl allyl ethers were rearranged into polysubstituted furans in the presence of a gold(I) catalyst. It is proposed that the transformation involves a Claisen-type rearrangement that allows the efficient creation of quaternary centers under mild experimental conditions.


Myeloencephalopathy resembling Alexander's disease in a Scottish terrier dog.
Diffuse degenerative myeloencephalopathy resembling Alexander's disease in a tetraparetic 9-month-old Scottish terrier dog is described. There were widespread deposits of Rosenthal fibers throughout brain and spinal cord in subpial, subependymal, perivascular and white matter regions. A diffuse proliferation of pleomorphic astrocytes in the white matter and subependymal areas was also seen. Demyelination was not a salient feature of the disease.


Short term transcriptional responses of P450s to phytochemicals in insects and mites.
Cytochrome P450 monooxygenases (P450s) play a key role in the detoxification of phytochemicals in arthropod herbivores. We present here an overview of recent progress in understanding the breadth and specificity of gene expression plasticity of P450s in response to phytochemicals. We discuss experimental setups and new findings in mechanisms of P450 regulation. Whole genome transcriptomic analysis of arthropod herbivores, either after direct administration of phytochemicals or after host plant shifts, allowed to integrate various levels of chemical complexity and lead to the unbiased identification of responsive P450 genes. However, despite progress in identification of inducible P450s, the link between induction and metabolism is still largely unexplored, and to what extent the overall response is biologically functional should be further investigated. In the near future, such studies will be more straightforward as forward and reverse genetic tools become more readily available.


Sleep disturbance in children with growth hormone deficiency.
We examined the effects of growth hormone (GH) deficiency on sleep development by performing all-night polysomnography in three female children with GH deficiency (GHD). The percentage of REM sleep seemed to be reduced before the treatment in 2 cases, and human GH (hGH) compensation slightly increased it. Submental twitch movements (mTMs), i.e., body movements during sleep localized in the submental muscle and lasting less than 0.5 seconds, were commonly disturbed in the three patients. Rapid eye movements in REM sleep (REMs) were reduced before the therapy in one case, this decrease being reversed on hGH compensation. REMs also seemed to increase after hGH treatment in the other two cases. Dopamines and cholinergic muscarinic agonists can cause GH release, while mTMs and REMs might be related to dopaminergic and cholinergic systems in the human brain. It is intriguing that GHD, and the disturbance of mTMs and REMs coexisted in children with GHD. Since a relatively poor social outcome in patients with GHD has been reported, even after hGH compensation, it is important to monitor their neurological development by means of evaluation of their sleep disturbance.


The role of the upper extremity surgeon in the management of tetraplegia.
Despite its demonstrated benefits, the majority of patients with tetraplegia do not have upper extremity surgery. Many upper extremity surgeons are unfamiliar with the techniques, long-term care providers are often unaware of the options or are biased against surgery, and patients might resist surgery based on lack of awareness, misinformation, or hope of a cure. Although it is not without its challenges, some consensus as to a general algorithm for the care of the tetraplegic patient does exist. At the recent 10th International Meeting on Surgical Rehabilitation of the Tetraplegic Upper Limb, there was little disagreement about when and what surgery to perform. The physical examination tools, clinical decision making, and surgical skills required to treat this population should, therefore, be accessible to the vast majority of hand surgeons who wish to take on these rewarding cases. Patients with specific, realistic, functional goals will realize the best self-perceived outcomes.


Treatment and management of cognitive dysfunction in patients with multiple sclerosis.
Cognitive impairment is a common and devastating manifestation of multiple sclerosis (MS). Although disease-modifying therapies have been efficacious for reducing relapse rates in MS, such treatments are ineffective for treating cognitive dysfunction. Alternative treatment approaches for mitigating cognitive problems are greatly needed in this population. To date, cognitive rehabilitation and exercise training have been identified as possible candidates for treating MS-related cognitive impairment; however, cognitive dysfunction is still often considered to be poorly managed in patients with MS. This Review provides a comprehensive overview of recent developments in the treatment and management of cognitive impairment in people with MS. We describe the theoretical rationales, current states of the science, field-wide challenges and recent advances in cognitive rehabilitation and exercise training for treating MS-related cognitive impairment. We also discuss future directions for research into the treatment of cognitive impairment in MS that should set the stage for the inclusion of cognitive rehabilitation and exercise training into clinical practice within the next decade.


The course of pain and the restriction of mobility in patients with shoulder complaints in general practice.
The objective of this research was to study the course of the pain and the restriction of mobility of the scapulohumeral joint (ROM) over time, and the factors influencing it, in patients with shoulder complaints in general practice. A total of 101 patients participated in this 25-week follow-up study. For the first 2 weeks, a non-steroidal anti-inflammatory drug (NSAID) was prescribed, after that period the physician could follow his usual therapeutic approach. The NSAIDs prescribed during the first 2 weeks resulted in a rapid decrease in the pain and the ROM. The group with the most severe pain consumed the most tablets, which resulted in a significant decrease in the pain and the ROM. It appeared that the course of the pain from week 2 to week 8 was significantly influenced by pain at inclusion, diagnosis and therapy. The most rapid decrease in the ROM appeared in the first 2 weeks. At week 0 and week 2, differences, in the ROM were seen in the subgroups for diagnosis pain score and age. The pain and the ROM showed most decrease in the first weeks. After 6 weeks hardly any changes were seen in the pain score and the ROM score. The margin of the pain score and the ROM score between the "cured" and the "not cured" patients was a very narrow one.


Association Between Ambient Heat and Risk of Emergency Department Visits for Mental Health Among US Adults, 2010 to 2019.
The implications of extreme heat for physical health outcomes have been well documented. However, the association between elevated ambient temperature and specific mental health conditions remains poorly understood. To investigate the association between ambient heat and mental health-related emergency department (ED) visits in the contiguous US among adults overall and among potentially sensitive subgroups. This case-crossover study used medical claims data obtained from OptumLabs Data Warehouse (OLDW) to identify claims for ED visits with a primary or secondary discharge psychiatric diagnosis during warm-season months (May to September) from 2010 through 2019. Claims for adults aged 18 years or older with commercial or Medicare Advantage health insurance who were living in 2775 US counties were included in the analysis. Emergency department visits were excluded if the Clinical Classifications Software code indicated that the visits were for screening for mental health outcomes and impulse control disorders. County-specific daily maximum ambient temperature on a continuous scale was estimated using the Parameter-Elevation Relationships on Independent Slopes model. Extreme heat was defined as the 95th percentile of the county-specific warm-season temperature distribution. The daily incidence rate of cause-specific mental health diagnoses and a composite end point of any mental health diagnosis were assessed by identifying ED visit claims using primary and secondary discharge diagnosis International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Conditional logistic regression models were used to estimate the incidence rate ratio (IRR) and 95% CIs for the association between daily temperature and incidence rates of ED visits. Data from 3 496 762 ED visits among 2 243 395 unique individuals were identified (56.8% [1 274 456] women; mean [SD] age, 51.0 [18.8] years); of these individuals, 14.3% were aged 18 to 26 years, 25.6% were aged 27 to 44 years, 33.3% were aged 45 to 64 years, and 26.8% were aged 65 years or older. Days of extreme heat were associated with an IRR of 1.08 (95% CI, 1.07-1.09) for ED visits for any mental health condition. Associations between extreme heat and ED visits were found for specific mental health conditions, including substance use disorders (IRR, 1.08; 95% CI, 1.07-1.10); anxiety, stress-related, and somatoform disorders (IRR, 1.07; 95% CI, 1.05-1.09); mood disorders (IRR, 1.07; 95% CI, 1.05-1.09); schizophrenia, schizotypal, and delusional disorders (IRR, 1.05; 95% CI, 1.03-1.07); self-harm (IRR, 1.06; 95% CI, 1.01-1.12); and childhood-onset behavioral disorders (IRR, 1.11; 95% CI, 1.05-1.18). In addition, associations were higher among men (IRR, 1.10; 95% CI, 1.08-1.12) and in the US Northeast (IRR, 1.10; 95% CI, 1.07-1.13), Midwest (IRR, 1.11; 95% CI, 1.09-1.13), and Northwest (IRR, 1.12; 95% CI, 1.03-1.21) regions. In this case-crossover study of a large population of US adults with health insurance, days of extreme heat were associated with higher rates of mental health-related ED visits. This finding may be informative for clinicians providing mental health services during periods of extreme heat to prepare for increases in health service needs when times of extreme heat are anticipated.


The use of lingual mucosal graft in adult anterior urethroplasty: surgical steps and short-term outcome.
Investigate the tolerability, safety, and efficacy of using the lingual mucosal graft (LMG) for anterior urethroplasty. Ten patients (average age, 41 yr) underwent substitution urethroplasty LMG. Harvesting the graft from the tongue was performed by either the oral surgeon or the urologist. In five patients with penile urethral strictures, the grafts were placed on the dorsal urethral surface as a "dorsal inlay." In five patients with bulbar urethral strictures, the grafts were used as a "dorsal inlay" (3 cases) or "ventral onlay" (2 cases). The average follow-up was 5 mo (range: 3-12 mo). Nine cases (90%) were successful and one (10%) was a failure. Three patients who underwent bulbar urethroplasty showed prior failed repair using buccal mucosal grafts harvested from a single cheek (1 case), from both cheeks (1 case), or from the lip (1 case). The length of the lingual grafts was 4-6cm (mean: 4.5cm) with a width of 2.5cm. No patient developed early or late postoperative complications on the harvest site related to the tongue surgery. No difference was observed in patients in whom the graft harvesting was performed by the oral surgeon compared to the patients in whom the procedure was performed by the urologist. The surgical technique for harvesting a graft from the tongue is simple and safe. The tongue may be the best alternative donor site to the lip when a thin graft is required for urethroplasty or when the cheek harvesting is not possible.


Depot fluphenazine and plasma prolactin.
In 14 schizophrenic patients, prolactin levels are studied in relation to dosage of depot fluphenazine and gender of patient. Prolactin levels in individual patients are similar across injection cycles. For males, the association between fluphenazine dosage and prolactin level was found to be significant (Spearman rho = .925, p less than .05).


Hemispheric antagonism in visuo-spatial neglect: a case study.
We report a case of severe visuo-spatial neglect consequent upon right-hemisphere stroke. At the time of testing, the patient had no visual field cut and no significant hemiparesis. Conventional testing on cancellation tasks with the right hand revealed reliable left neglect, but performance was significantly improved when the left hand was used. Investigations of (manual) line bisection showed normal performance with the right hand but right neglect when the left hand was used. Right neglect was also observed on a purely perceptual version of the line bisection task. We argue that the attentional vectors of the cerebral hemispheres can be modulated by (perceptual) task-demands and by (motoric) response-demands.


Honey dressing: a missed way for orthopaedic wound care.
Orthopaedic-related wounds are critical situations calling for care to avoid deep infections and its consequences. The purpose of this study was to evaluate the efficacy of using honey for care of orthopaedic-related wounds with limited resources. This prospective study included 50 cases with an average age of 38.18 (range 17-63) years with 38 males and 12 females. The most frequent wound location was the leg (41 patients; 82%), then the foot (six patients; 12%), and the ankle in three patients (6%). The aetiologies were open fractures (34 cases; 68%), infected tibial non-unions (nine cases; 18%), and post-operative infections (seven cases; 14%). Exposed tendon was present in three cases. Bone exposure was present in two cases. Deep infection was present in 29 cases (58%). Besides treating the primary cause, a ribbon of gauze soaked with honey was applied to the wounds after thorough saline washing. Wound sizes were variable. All cases showed improvement in all parameters with complete wound healing and full coverage of bone and tendons. Recurrence of deep infection occurred in three cases and treated by debridement. One case needed sequestrectomy of a small exposed tibial cortical fragment. Exposed tendon cases showed superficial necrosis which was treated by simple debridement. Initial mild itching occurred in five patients with spontaneous resolution. With treating the underlying aetiology and optimising the patient's general condition, honey was an effective, simple, and affordable method of wound care in different orthopaedic conditions even with exposed bone or tendons.


Ultrasound scanning of the ovarian cycle.
Ultrasound scanning of the ovarian cycle is a simple noninvasive technique for monitoring ovarian activity. It helps to predict a mature follicle and the time of ovulation more accurately than the basal body temperature and more rapidly and cheaply than a hormone profile, but still only one facet of ovarian activity. With respect to in vitro fertilization, egg collection can be undertaken by means of sonically guided puncture via the bladder, which is reported later in this issue. Replacement of the embryo can be controlled by sonar visualization of catheter. The use of ultrasound has proved to be extremely helpful in the management of the infertile couple.


Fabrication, optimization and characterization of electrospun poly(caprolactone)/gelatin/graphene nanofibrous mats.
Recently graphene-based materials have been exploited widely in graphene-polymer nanocomposites and hold notable potential for various applications. In this study novel graphene-incorporated poly(caprolactone)/gelatin nanofibrous web were produced by electrospinning technique using acetic acid as a cost-effective eco-friendly solvent. Response surface methodology was used for optimizing the diameter of the electrospun nanofibrous web. To tailor electrospun nanofibers with suitable mechanical and electrical properties, the impact of affecting electrospinning parameters was studied. Our results show that, with increasing the PCL/gelatin ratio, the diameter of nanofibers increases, whereas increasing graphene concentration decreased the diameter of nanofibers up to an optimum content. With the incorporation of 1.5% graphene into PCL/gelatin matrix the tensile strength and Young modulus of nanofibrous mat considerably increased by 117 and 128% respectively. The electrical conductivity results demonstrated that nanofibrous mats own nearly 11 times higher conductivity than that of PCL/gelatin nanofibers when the graphene concentration reached the percolation threshold. Contact angle measurements confirmed that graphene-incorporated electrospun nanofibers were more hydrophilic than that of neat nanofibrous mats. Cellular toxicity results of electrospun nanofibers ascertained almost no toxicity to PC12 cells. The morphology of electrospun nanofibers was investigated by means of scanning electron microscopy (SEM). FTIR and DSC analysis revealed that there might be possible interactions between graphene and PCL/gelatin matrix. XRD analysis demonstrated that graphene-incorporated PCL/gelatin nanofibers exhibited higher crystallinity. The uniform dispersion of graphene nanosheets in nanofibrous mat was also verified through Raman spectroscopy.


Activation of functionally protective K(+) channels by methylmercury in rat alveolar macrophages.
Methylmercury (MeHg) is generally known as a neurotoxic heavy metal while its effect on alveolar macrophages is still rarely studied. In this paper, we attempted to use whole cell and cell-attached patch-clamp recording technique and fura-2 fluorescence measurement to elucidate the effects of MeHg on rat alveolar macrophages. The results showed that extracellular application of MeHg induced a transient outward current I(O)(MeHg), 10-20 s in duration, 100-1000 pA in amplitude at -40 mV associated with a marked increase in conductance. The reversal potential depended distinctly on the external K(+) concentration. Removal of external Ca(2+) as well as bath applied verapamil caused a depression of I(O)(MeHg), and intracellular dialysis with 5 mM EGTA completely abolished I(O)(MeHg). Heparin (5 mg/ml) applied by intracellular dialysis greatly accelerated a run-down of I(O)(MeHg) induced by pressure ejection of MeHg. K(+) channel blockers such as quinine, and 4-aminopyridine especially low concentrations of dequalinium and apamin, but not tetraethylammonium inhibited I(O)(MeHg). Cell-attached single-channel recordings with the pipette solution containing 145 mM KCl revealed that the activation of single-channel currents with a conductance of 12 pS could be induced by application of MeHg outside the patch. Since MeHg increased [Ca(2+)](i), in a concentration-dependent manner which was partially blocked by either verapamil or Ca(2+)-free medium containing 1 mM EGTA, it is concluded that MeHg activates a Ca(2+)-dependent K(+) conductance by an increase of [Ca(2+)](i) through an influx from outside the cells as well as mobilization from intracellular store. A possibility that this membrane hyperpolarizing K(+) current may exhibit a functioning modulator in response to the harmful cytotoxic increase in [Ca(2+)](i) caused by MeHg was tested. Accordingly, this working hypothesis is verified by an increase of MeHg-induced cytotoxicity of cultured rat alveolar macrophages through a blockade of this Ca(2+)-activated K(+) channel by dequalinium.


Topological features of rugged fitness landscapes in sequence space.
The factors that determine the tempo and mode of protein evolution continue to be a central question in molecular evolution. Traditionally, studies of protein evolution focused on the rates of amino acid substitutions. More recently, with the availability of sequence data and advanced experimental techniques, the focus of attention has shifted toward the study of evolutionary trajectories and the overall layout of protein fitness landscapes. In this review we describe the effect of epistasis on the topology of evolutionary pathways that are likely to be found in fitness landscapes and develop a simple theory to connect the number of maladapted genotypes to the topology of fitness landscapes with epistatic interactions. Finally, we review recent studies that have probed the extent of epistatic interactions and have begun to chart the fitness landscapes in protein sequence space.


Projections of the individual vestibular end-organs in the brain stem of the squirrel monkey.
The central nervous system (CNS) projections of primary afferent neurons from individual vestibular receptors were studied using horseradish peroxidase (HRP) or biocytin labeling in 14 ears from 7 adult squirrel monkeys using the technique developed in the chinchilla (Lee et al., 1989, 1992). The specificity of labeling was verified by examining the location of the labeled fibers and cell bodies in the vestibular nerve and Scarpa's ganglion. Labeled fibers and cells were restricted to nerves and areas belonging to groups of cells in either the superior or the inferior ganglion of the vestibular nerve. In the vestibular nerve root, labeled primary afferent fibers also exhibited a receptor-dependent segregation at the entrance to the medulla. Fibers from the HSC and the SSC were found rostrally and those from the PSC and the SAC were found in the caudal area. The UTR fibers were situated intermediate between these two groups of fibers. (A bundle of fibers, probably vestibular efferents, was identified immediately rostrally and ventromedially to the UTR fibers.) The primary afferent fibers bifurcated into secondary ascending and descending fibers at the lateral border of the vestibular nuclei, forming a longitudinal rostrocaudal vestibular tract. The secondary fibers from individual end-organs occupied specific locations in the tract: the UTR fibers were dorsal to the SSC and the HSC fibers, PSC fibers were found most medially, and the SAC fibers occupied the lateralmost area. The secondary UTR fibers overlapped considerably with those of the SSC and the HSC. The orderly receptor-dependent segregation of fibers was more prominent in the descending tracts than in the ascending tracts. In the vestibular nuclei complex the location of the tertiary branches of various end-organs exhibited considerable overlap within the major vestibular nuclei (SN, superior nucleus; LN, lateral nucleus; MN, medial nucleus; DN, descending nucleus). There were still differences, however, in the projection pattern. Fibers from the SAC ran primarily in the lateral area, fibers from the SSC and the UTR were found ventromedially to the SAC fibers, and the HSC projected slightly medially to the fibers from the SSC. The PSC fibers projected most medially. The UTR and SAC sent numerous fibers to the cerebellum. Fibers from the semicircular canals projected through the rostrodorsal region of the SN and presumably also projected to the cerebellum. The precise termination of fibers was evaluated by studying the location of labeled boutons, which were identified in all major vestibular nuclei. Labeled boutons from all the receptors were in the rostral and central areas of the SN, and in the MN mainly in the rostral two-thirds. In the LN, boutons from all the receptors were in the rostroventral part, most of which were from the UTR and SAC. No labeled boutons were in the caudodorsal part of this nucleus. Labeled boutons in the DN primarily surrounded the descending tract fibers and were particularly prominent medially. In specimens in which superior vestibular nerve receptor organs were scratched vestibular efferent fibers were also labeled. These fibers traveled in the most ventral part of the vestibular nerve root and projected in the ventral aspect of the LN to labeled soma in the ipsilateral and contralateral brain stem. Specificity the in projection patterns of efferent fibers from different end-organs could not be ascertained.


Increased genetic susceptibility to intestinal-type gastric cancer is associated with increased activity of the RUNX3 distal promoter.
The runt-related transcription factor RUNX3 plays essential roles in various types of tumors, including gastric cancer. Epigenetic changes in the methylation of the RUNX3 proximal promoter, but not common genetic changes in RUNX3, have been associated with both changes in the gene expression and development of the cancer. A case-control association study was conducted by genotyping 865 unrelated Korean subjects. Subsequent functional studies were performed to reveal functional implication of genetic association. Several single-nucleotide polymorphisms (SNPs) in RUNX3 were significantly associated with susceptibility to intestinal-type gastric cancer (.0028 ≤ P ≤ .022) but not diffuse-type gastric cancer (.70 ≤ P ≤ .96). The risk-associated, minor variant of an intestinal-type gastric cancer-associated SNP in the RUNX3 distal promoter (rs7528484) significantly increased promoter activity in a CREB1-dependent manner. The distal promoter-derived, 33 kDa isoform of RUNX3 increased the activity of transcription factor nuclear factor kappa B (NF-κB), which had been activated by Helicobacter pylori infection, a risk factor for intestinal-type gastric cancer, and the expression of the interleukin-1β gene (IL1B), an NF-κB target genetically and functionally associated with gastric cancer. In contrast, the proximal promoter-derived, 44 kDa isoform of RUNX3 decreased both NF-κB activity and IL1B expression. In addition to epigenetic changes in the RUNX3 proximal promoter, genetic changes in the distal promoter may be associated with susceptibility to intestinal-type gastric cancer by increasing promoter activity. Functionally, 2 RUNX3 isoforms may contribute differentially to intestinal-type gastric cancer susceptibility, at least in part through regulating NF-κB activity and IL1B expression.


Purification and characterization of dihydrobenzophenanthridine oxidase from elicited Sanguinaria canadensis cell cultures.
Upon treatment of Papaveracea cells with fungal elicitors, the biosynthesis of benzo[c]phenanthridine alkaloids is induced. Dihydrobenzophenanthridine oxidase, which catalyzes a later step in the biogenesis of these alkaloids, is one of the enzymes whose activity is elevated in the process. Here we report the 211-fold purification of the oxidase from elicited Sanguinaria canadensis by a combination of ammonium sulfate fractionation, DEAE-Sephadex, CM-Sephadex, Sephadex G-200, and either phenyl Superose or gel filtration chromatography. The purified enzyme utilized molecular oxygen to oxidize dihydrosanguinarine to sanguinarine with concomitant formation of hydrogen peroxide. A pH optimum of 7.0, Vmax of 27 nkat/mg protein, and apparent Km of 6.0 microM for dihydrosanguinarine were determined. Dihydrochelerythrine was also found to be a substrate for the purified enzyme, displaying an apparent Km of 10 microM. However, neither dihydronorsanguinarine nor the indole alkaloid ajmalicine was oxidized, indicating that the enzyme has some substrate specificity. Apparent molecular weight estimates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the most purified enzyme preparation obtained contained a major component of 77 kDa and two minor components between 59 and 67 kDa that can be associated with oxidase activity. Purified enzyme preparations possessed activity that was inhibited by sodium diethyldithiocarbamate, sodium azide, potassium cyanide, 1,4-DL-dithiothreitol, and mercaptoethanol.


Results of multivessel percutaneous transluminal coronary angioplasty in persons aged 65 years and older.
Between 1981 and 1990, 1,373 patients, aged greater than or equal to 65 years (mean 71.2 +/- 4.9), underwent 1,640 multivessel percutaneous transluminal coronary angioplasty (PTCA) procedures. Of these, 224 patients (13.6%) had a left ventricular ejection fraction less than or equal to 40%, 412 (25.1%) had prior coronary artery bypass grafting (CABG) and 48 (2.9%) had left main artery dilatation. Of the 1,640 PTCA procedures, 697 were in patients with 2-vessel disease and 943 were in patients with 3-vessel disease. A mean 3.5 lesions were dilated per patient, with an overall angiographic success rate of 96%. Complete revascularization was achieved in 857 (52%). A total of 52 patients (3.2%) had a major in-hospital complication: 27 patients (1.6%) died, 24 (1.4%) had a Q-wave myocardial infarction, and 14 (0.8%) underwent emergent CABG. Stepwise logistic regression analysis identified ejection fraction less than or equal to 40% (p less than or equal to 0.001), 3-vessel disease (p less than or equal to 0.01), female gender (p less than or equal to 0.02), and PTCA between 1981 and 1985 (p less than or equal to 0.05) as independent predictors of mortality. Of the 1,373 patients, 1,023 have been followed for greater than or equal to 1 year (mean follow-up 32.5 +/- 21.3 months). There were 156 (15.2%) late deaths, 81 (7.9%) recurrent myocardial infarctions, and 162 (15.8%) coronary artery bypass operations. Actuarial survival, computed from the time of hospital discharge, was 92% at 1 year, 86% at 3 years and 78% at 5 years. Repeat PTCA was required in 371 patients (36.3%).(ABSTRACT TRUNCATED AT 250 WORDS)


Iterative Revision of the DSM: An Interim Report From the DSM-5 Steering Committee.
After the publication of DSM-5, the American Psychiatric Association moved to a model of iterative DSM revision. Proposals for changes-including addition and deletion of diagnostic categories-can be made whenever data become available to support these changes. Criteria for consideration of proposals and a multistage review process have been created. This Open Forum reports on the first 3 years' experience since the opening of the submission portal in late 2017. Changes to date include adoption of a new diagnostic category, clarification of existing diagnostic criteria and text, and inclusion of new nondiagnosis codes for suicidal and nonsuicidal self-injury.


Relationship between arterial blood gases and spirometry in acute exacerbations of chronic obstructive pulmonary disease.
Previous studies have established spirometric criteria for arterial blood gas analysis during acute asthmatic attacks. However, only general guidelines have been available regarding the need for blood gas analysis during an acute exacerbation of chronic obstructive pulmonary disease (COPD). We conducted a study to determine the relationship between arterial blood gases and spirometry in 70 emergency department patients during acute exacerbations of COPD. Arterial blood gas analysis and spirometry were performed on arrival at the emergency department. All of the patients with a pCO2 of more than 45 mm Hg had an FEV1 of less than 35% of the predicted normal. We found patients with a pO2 of less than 60 mm Hg who had an FEV1 as high as 54% of the predicted normal. There was no correlation between the FEV1 and pO2. Because spirometry was not reliable for identifying patients with significant hypoxemia, we conclude that arterial blood gas analysis is indicated for patients presenting to the ED with acute exacerbations of COPD. Spirometric criteria that have been used to eliminate the need for arterial blood gases in asthmatic patients cannot be applied safely to patients with COPD.


From Distress Screening to Uptake: An Italian Multicenter Study of Cancer Patients.
Little consideration is given to the referral and uptake of available supportive services after distress screening. However, identifying the reasons for accepting or refusing help is mandatory for implementing a screening policy. The present study explored the practical usefulness of and potential barriers to the application of distress management. 406 cancer patients were consecutively selected and asked to complete the Distress Thermometer (DT) and Problem Check List (PL). All patients with a DT score ≥6 were invited for a post-DT telephone interview with a trained psychologist. The 112 patients who refused to take part were more often older, retired, at a more advanced stage of illness, and with no previous experience of psychological intervention with respect to those who accepted. Of the 78 patients with a score ≥6 who were referred to the Psycho-Oncology Service, 65.4% accepted the telephone interview. Twenty-two patients rejected the initial invitation immediately for various reasons including logistic difficulties, physical problems, and feeling embarrassed about opening up to a psychologist. Our study confirms that screening per sé is insufficient to deal with the problem of distress and that more emphasis should be placed on implementing referral and treatment.


Male sterility thermal thresholds in Drosophila: D. simulans appears more cold-adapted than its sibling D. melanogaster.
Numerous different criteria may be used for analysing species thermal adaptation. We compared male sterility thresholds in the two most investigated cosmopolitan siblings, D. melanogaster and D. simulans. A survey of various populations from Europe and North Africa evidenced consistent differences between the two species, and a detailed analysis was made on flies from Marrakech. Sharp sterility thresholds were observed in both species but at different temperatures: D. simulans appeared more tolerant to cold than its sibling (difference 1 degrees C) but more sensitive to heat (difference 1.5 degrees C). When transferred to an optimum temperature of 21 degrees C, D. simulans males, sterilized by a low temperature, recovered more rapidly than males of D. melanogaster; the reverse was true on the high temperature side. The analysis of progeny number also revealed the better tolerance of D. simulans males to cold but a lesser tolerance to heat. From these observations, we might expect that D. simulans should be more successful in cold temperate countries than its sibling, while ecological observations point to the contrary. Our data clearly show the difficulty of comparing ecophysiological data to field observations, and also the need of extensive comparative life history studies in closely related species.


Dental Anomalies in Consanguineous Marriage: A Clinical-Radiological Study.
This study aimed to evaluate nonsyndromic developmental dental anomalies (DDAs) in individuals born from consanguineous and nonconsanguineous marriages and the possible effects of these marriages on self-reported systemic diseases. The study comprised a total of 880 patients aged 16 years or older who applied to our clinic for various dental problems. Based on detailed anamnesis, the patients were divided into 2 groups: individuals born from consanguineous (study group, n = 445) and nonconsanguineous (control group, n = 435) marriages. The parents' consanguinity type was also recorded, as well as the presence of any self-reported systemic diseases. The number, size, erupted, and morphological DDA types were investigated with both clinical and radiological examinations. All data from the 2 groups were recorded, and a statistical analysis was performed. There was a statistically significant relationship between the consanguineous marriage and the size (microdontia), and morphological (dilaceration and taurodontism) DDA types. Additionally, a significant relationship was found between consanguineous marriage and self-reported systemic disease but not between the parents' consanguinity type and systemic disease. The results of this study suggest that consanguineous marriage affects DDAs.


Extraosseous extradural tuberculous granuloma of the cervical spine: a case report and review of intraspinal granulomatous infections.
A 70-year-old woman presented with a 5-month history of tetraparesis. Her cerebrospinal fluid and roentgenographic examination of the cervical spine were both normal. Myelography showed an extradural type of spinal cord compression at the C7 level. At operation, an extraosseous extradural mass of granulation tissue was removed, which proved on histological and bacteriological examination to be a tuberculous granuloma.


[Measurement of trace elements in blood serum by atomic absorption spectroscopy with electrothermal atomization].
Describes a method for measuring trace elements Cr, Mn, Co, Fe, Cu, Zn, and Mo in the blood serum using non-flame atomization (KAC 120.1 complex). Optimal conditions for preparing the samples were defined, temperature regimens for analysis of each element selected, and original software permitting automated assays created. The method permits analysis making use of the minimal samples: 0.1 ml per 10 parallel measurements, which is 100 times less than needed for atomic absorption spectroscopy with flame atomization of liquid samples. Metrological characteristics of the method are assessed.


Dermoscopy of the iris: identification of Lisch nodules and contribution to the diagnosis of Neurofibromatosis type 1.
Neurofibromatosis is a common genodermatosis, whose diagnosis often involves the participation of a dermatologist. A case of a 38-year-old female patient with four café-au-lait macules and eleven neurofibromas on clinical examination is presented. Dermoscopy allowed the identification of Lisch nodules in the iris, bilaterally. The combination of these findings allowed the diagnosis of neurofibromatosis type 1, according to NIH criteria. Lisch nodules are melanocytic hamartomas of the iris, which must be evaluated through a visual augmentation method, usually employed in ophthalmology. Alternatively, dermoscopy can be used and contribute to the early diagnosis of neurofibromatosis type 1.


Psychological impact of BRAF mutational status in advanced melanoma patients.
The aim of the study was to highlight the psychological aspects involved in patients with advanced melanoma and to describe the differences between subjects who are positive and negative for the BRAFv600e genetic mutation, a variable that leads to a different medical approach to cancer therapy. The hypothesis is that following knowledge of the genetic mutation and the therapeutic possibilities inherent to it, mutation positive patients (BRAF+) exhibit fewer negative psychological reactions than negative patients (BRAF-) at the time of diagnosis. The tests used (SF-12, MHQ) were administered at the time of diagnosis and after three months. The main findings suggest a greater impairment of quality of life at T1 than at T0, regardless of the mutation; BRAF mutated patients show more favorable scores at diagnosis and a reversal of the trend at three months after diagnosis. The results obtained, in line with the literature under review, show a significant general psychological distress in the present oncological sample, suggesting the importance of a psychological, as well as medical, care of the patient and the family.


Assessment of Hypoxia and Physiological Stress Evinced by Usage of N95 Masks among Frontline Dental Healthcare Workers in a Humid Western Coastal Region of India-A Repeated Measure Observational Study.
To assess the oxygen saturation in DHCWs using N95 and 3 ply surgical masks and determine the presence of any other subjective discomfort in them. A repeated measure observational study conducted at the Tertiary Care Dental Institute situated in Goa, a western coastal region of India recording humid conditions year around. Participants constituted 60 frontline DHCWs wearing N95 masks and 60 DHCWs working in non-clinical setting wearing surgical masks. After completion of a self-administered questionnaire their oxygen saturation and pulse rate were monitored at baseline, 60mins and 120mins using pulse oximetry. Statistical Analysis: Mann Whitney u test compared oxygen saturation between the two groups. Friedmann and Wilcoxon signed rank test with Bonferroni correction computed differences within group at various time intervals. Binary logistic and linear regression was used to compare the study variables with outcome measure. p value was set at < 0.05. Oxygen saturation reported a significant drop post one hour of wearing N95 masks which increased in the second hour. Prolonged use of N95 mask in humid environment adds to the body's physiological burden or perceptions of discomfort and exertion. Efforts need to be taken to address this for better compliance to the use of these protective gears.


Strategic combination of metal-organic frameworks and C3N4 for expeditious photocatalytic degradation of dye pollutants.
The potential of fabricated silver and bismuth Co-N-doped imidazolate embedded into graphitic nitride BiO-Ag(0)/C3N4@ZIF-67 for the degradation of Methylene blue (MB) and Congo red (CR) dyes have been reported. The synthesized materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy photoluminescence (PL) spectroscopy, and electrochemical impedance spectroscopy (EIS). The band gaps of ZIF-67, C3N4 and composites were calculated using Tauc plot. Besides, it was revealed that incorporation of silver, bismuth, and C3N4 reduced the band gap energy to 2.2 eV. The introduction of metallic species in the precursors promoted better charge separation behavior towards photogenerated electron and hole in the heterojunction composite. Two perilous organic dyes; MB and CR were degraded under natural sunlight irradiation. The photocatalytic efficiency of BiO-Ag(0)/C3N4@ZIF-67 for the removal of CR and MB significantly increased compared to bare ZIF-67. The enhanced photocatalytic activity of BiO-Ag(0)/C3N4@ZIF-67 is attributed to the higher surface area and Plasmon effect of noble silver metal. The solar light-triggered degradation of MB and CR yielded efficient efficiency of 96.5 and 90% for 10 mg/L of dye solution each. Additionally, the effect of pH was evaluated for optimizing degradation of CR and MB dyes. The kinetics studies of both CR and MB were clarified according to Langmuir model. The reusability and quenching investigation of active species were carried out to discover find catalytic potential of the composite. Besides, possible dye degradation mechanism was proposed for BiO-Ag(0)/C3N4@ZIF-67. The obtained results indicated that solar-light triggered photocatalyst BiO-Ag(0)/C3N4@ZIF-67 can be employed as a promising approach for photocatalytic elimination of organic pollutants.


Transbilayer distribution of phospholipid fatty acyl chains in photoreceptor membrane.
The transverse distribution of the fatty acyl chains of the major phospholipids over the two faces of the photoreceptor membranes has been determined in bovine rod outer segment (stacked disk) preparations. For this purpose, the fatty acid composition of the phospholipids has been analyzed before and after treatment with trinitrobenzenesulfonic acid and phospholipase D. The latter agents are used under conditions in which they have been demonstrated to attack only the outer (cytoplasmic) face of the membrane. After treatment with trinitrobenzenesulfonic acid or phospholipase D, the fatty acid composition of the unreacted phospholipids is the same as that before treatment, regardless of the extent of modification or hydrolysis attained. The fatty acid composition of phosphatidic acid, resulting from phospholipase D action, also remains unchanged during progressive hydrolysis. These results indicate that the fatty acyl chains of the major phospholipids have the same composition on either side of the disk membrane. Together with our previously published evidence for the distribution of the major phospholipids in rod outer segment disk membranes, this means that both the phospholipids and their fatty acyl chains have a remarkably symmetrical distribution over the two membrane faces. On the basis of literature data it is concluded that this approximate symmetry reflects the high mobility of the entire phospholipid pool of disk membranes, thus including appreciable transbilayer movements of the phospholipids.


Identification and partial purification of fibroblast growth factor from the brains of developing rats and leucodystrophic mutant mice.
High titres of fibroblast growth factor activity (assessed by mitogenicity for Balb/c 3T3 fibroblast cells in vitro) have been extracted from the brains of foetal and neonatal rats long before myelinogenesis commences, from the brains of hypomyelinated, leucodystrophic, murine mutants and from normal adult rats. Partial purification, by ion-exchange chromatography and gel filtration, indicates that the brain fibroblast growth factor activity from these sources is associated with very similar basic protein fractions. These results, together with the observation that none of the samples of partially purified basic fibroblast growth factor elicits the experimental allergic encephalomyelitis response attributed to myelin basic protein in the rat, suggest that basic fibroblast growth factor is not a degradation product of myelin basic protein.


Nanosilver Colloids-Filled Photonic Crystal Arrays for Photoluminescence Enhancement.
For the improved surface plasmon-coupled photoluminescence emission, a more accessible fabrication method of a controlled nanosilver pattern array was developed by effectively filling the predefined hole array with nanosilver colloid in a UV-curable resin via direct nanoimprinting. When applied to a glass substrate for light emittance with an oxide spacer layer on top of the nanosilver pattern, hybrid emission enhancements were produced from both the localized surface plasmon resonance-coupled emission enhancement and the guided light extraction from the photonic crystal array. When CdSe/ZnS nanocrystal quantum dots were deposited as an active emitter, a total photoluminescence intensity improvement of 84% was observed. This was attributed to contributions from both the silver nanoparticle filling and the nanoimprinted photonic crystal array.


Disease of the left main coronary artery. Surgical treatment and long-term follow up in 267 patients.
Of 4,196 patients undergoing coronary angiography, 297 (7 percent) had left main coronary arterial narrowing. In 188 (4.5 percent) the narrowing was greater than or equal to 70 percent and in 109 (3 percent) it was between 50 and 69 percent. Three patients (1 percent) died at cardiac catheterization. Saphenous vein bypass graft surgery was performed in 267 patients with an operative mortality of 7 percent: in 179 patients the left main coronary narrowing was greater than or equal to 70 percent (operative mortality 9 percent), and in 88 between 50 and 69 percent (mortality rate 2 percent). There was an average of 2.6 grafts per patient. The course of these patients was followed up for 4 3/4 years. At 1 year there was a 92.2 percent survival rate. The rate of survival at 2, 3 and 4 3/4 years, was 91, 89 and 86 percent, respectively. After saphenous vein bypass graft surgery, 75 percent of patients are angina-free and 22.4 percent are in improved condition. Grafts were studied in 51 patients and 85 percent of 128 grafts were found to be patent. It appears that there is improvement in survival and a reduction of symptoms after saphenous vein bypass graft surgery in patients with left main coronary arterial narrowing.


Combination of lentivector immunization and low-dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity.
In the last two decades, anti-cancer vaccines have yielded disappointing clinical results despite the fact that high numbers of self/tumor-specific T cells can be elicited in immunized patients. Understanding the reasons behind this lack of efficacy is critical in order to design better treatment regimes. Recombinant lentivectors (rLVs) have been successfully used to induce antigen-specific T cells to foreign or mutated tumor antigens. Here, we show that rLV expressing a murine nonmutated self/tumor antigen efficiently primes large numbers of self/tumor-specific CD8(+) T cells. In spite of the large number of tumor-specific T cells, however, no anti-tumor activity could be measured in a therapeutic setting, in mice vaccinated with rLV. Accumulating evidence shows that, in the presence of malignancies, inhibition of T-cell activity may predominate overstimulation. Analysis of tumor-infiltrating lymphocytes revealed that specific anti-tumor CD8(+) T cells fail to produce cytokines and express high levels of inhibitory receptors such as programmed death (PD)-1. Association of active immunization with chemotherapy or antibodies that block inhibitory pathways often leads to better anti-tumor effects. We show here that combining rLV vaccination with either cyclophosphamide or PD-1 and PD-L1 blocking antibodies enhances rLV vaccination efficacy and improves anti-tumor immunity.


Evaluating posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.
The objective of this study was to evaluate the efficacy of various posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probability of target attainment (PTA) and cumulative fraction of response (CFR) in terms of area under the concentration-time curve/minimum inhibition concentration (AUC/MIC) targets of posaconazole. According to the results of the PTA analysis, currently recommended clinical dosing regimens of the delayed-release tablet and intravenous (i.v.) solution were appropriate in prophylaxis against Aspergillus spp. with MICs ≤ 0.125 µg/mL. However, only high-dose regimens of the delayed-release tablet could achieve the target PTA in the treatment against Aspergillus spp. at an MIC of 0.125 µg/mL. Furthermore, the CFR was calculated for each dosing regimen. For the oral suspension, none of the simulated dosing regimens was effective against Aspergillus spp. For the delayed-release tablet and i.v. solution, the recommended dosing regimens were effective for prophylaxis of invasive fungal infections by four Aspergillus spp. (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans and Aspergillus terreus). However, these recommended dosing regimens were only effective for the treatment of A. terreus infection. Therefore, the high-dose regimen (200 mg oral every 12 h) of the delayed-release tablet should be recommended to achieve optimal therapeutic efficacy against four Aspergillus spp. (A. flavus, A. fumigatus, A. nidulans and A. terreus). These PK/PD-based simulations rationalise and optimise the dosing regimens of the different posaconazole formulations against Aspergillus spp. in adults.


Routine, rapid HIV testing of medicine service admissions in the emergency department.
We identify undiagnosed HIV among adult emergency department (ED) patients awaiting medicine admission through rapid testing, expedite their redirection to the inpatient HIV service, and improve linkage to ambulatory HIV care. Two ED health educators offered rapid testing to patients aged 18 to 64 years from the high-acuity ED area from which most medicine admissions originate. Heath educators obtained consent, obtained fingerstick blood, and performed point-of-care testing. Patients with reactive results received counseling, confirmatory testing, and appointments at the affiliated HIV clinic. Between March 1, 2008, and February 28, 2009, 4,755 patients received testing. Thirty patients (0.6%) had received a new diagnosis of HIV; 26 were admitted and redirected to the HIV service. Characteristics of HIV positive patients were mean age 38 years, 87% men, 64% black, and 33% Hispanic; 76% had CD4 counts less than 200 cells/mm(3); 67% had HIV-related diagnoses; and 93% reported for ambulatory HIV care in a median of 10 days. During 2 preceding years, these patients had a mean of 3 previous health system visits without testing. During a 6-month quality assurance interval of the 5,340 ED medicine admissions, 31% of patients were eligible for testing, of whom 88% received testing (1% positive) and 12% declined; 29% of the 5,340 were not approached for testing; and 40% were deemed ineligible. Common reasons for ineligibility included older age, recent previous test, and known HIV-positive status. Patients who receive a diagnosis of HIV in our ED before admission are extremely ill, most having AIDS. Targeted HIV screening of ED patients awaiting hospital admission facilitated timely diagnosis and reliable linkage to inpatient and outpatient HIV care.


A model of cell electromagnetic susceptibility associated with the membrane electric field.
A phenomenological model of the microwave enhancement of membrane conductance is presented based on the nonlinear calmodulin polarization produced by the strong membrane electric field.


Using quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify low level monoclonal proteins.
Mass spectrometry has recently been proposed as a novel sensitive screening tool for monoclonal gammopathies. In a small study we have tested the ability of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify low level monoclonal immunoglobulins not currently detected by the initial serum protein electrophoresis (SPEP) screen. QIP-MS positively identified the primary monoclonal immunoglobulins in all 11 patient samples alongside additional monoclonal immunoglobulins in a subset of patient samples. We conclude that QIP-MS has clinical utility as a first-line screening tool for monoclonal gammopathy investigation, identifying monoclonality in patients with higher sensitivity and resolution compared to the current standard methods.


The substituted benzamides and their clinical potential on dysthymia and on the negative symptoms of schizophrenia.
In this paper the historical and scientific background that led to the use of substituted benzamides in two apparently unrelated clinical conditions namely dysthymic disorder and schizophrenia will be reviewed, in order to understand if a common mechanism of action may support this dual therapeutic indication. The dopaminergic antidepressant action of substituted benzamides such as sulpiride, has been proposed, since the late 1970s, by several authors and extensively explored in preclinical experiments by our group. In Italy the first marketing authorization obtained for the new substituted benzamide amisulpride, was with the sole indication of dysthymia and therefore a solid clinical experience exists in the use of substituted benzamides in mild forms of depression, with more than 1 000 000 patients being treated in the last 7 years. The proposed mechanism of action of substituted benzamides implies a selective modulation of the dopaminergic system in the mesocorticolimbic area, important for cognitive processing of internal and external cues, related to survival. The selective antagonism of dopamine D2-D3 receptors has been evoked to explain, in small to moderate doses (ie 50-100 mg day(-1)), the antidepressant effect and, in moderate to medium doses (100-400 mg day(-1)), the reported efficacy on negative symptoms of schizophrenia. Thus, substituted benzamides could represent the first class of atypical antipsychotics successfully employed for both depressive states and schizophrenia. Interestingly, recent evidence in the literature suggests that depressive episodes belonging to the bipolar spectrum are among "alternative indications" of other atypical antipsychotics such as olanzapine and risperidone.


Giant excised cardiac sarcolemmal membrane patches: sodium and sodium-calcium exchange currents.
A tightly-sealed cardiac sarcolemmal patch preparation of large diameter (10-16 microns with 5-25 G delta seals) has been developed to study regulation of selected electrogenic mechanisms. Formation of a large readily accessible membrane surface area is achieved by incubating freshly isolated myocytes in a high KCl/zero calcium solution, which promotes separation of sarcolemma from myofilaments. The formation of large-diameter, high resistance seals is facilitated by depositing a neutral hydrocarbon film on electrode tips. Sodium currents in excised patches are stable for patch life-times of 15-40 min with peak current densities of 120 to 350 microA/cm2. Outward sodium-calcium exchange current is identified by its specific dependence on external calcium and internal sodium, inhibition by cobalt and dichlorobenzamil, and activation by less than 0.1 microM internal free calcium. Maximum exchange current density is greater than 20 microA/cm2.


[μ-Bis(di-o-tolyl-phosphan-yl)methane-1:2κP:P']nona-carbonyl-1κC,2κC,3κC-[diphen-yl(phenyl-sulfanylmeth-yl)phosphane-3κP]-triangulo-triruthenium(0) dichloro-methane 0.25-solvate.
In the title compound, [Ru(3)(C(29)H(30)P(2))(C(19)H(17)PS)(CO)(9)]·0.25CH(2)Cl(2), the atoms of the dichloro-methane solvent mol-ecule have a fractional site occupancy of 0.25; the dichloro-methane mol-ecule is disordered about an inversion centre. The bis-(di-o-tolyl-phosphan-yl)methane ligand bridges an Ru-Ru bond and the monodentate phosphane ligand bonds to the third Ru atom; its S-bonded phenyl ring is disordered over two orientations in a 0.53 (4):0.47 (4) ratio. All the P atoms are equatorial with respect to the Ru(3) triangle: each Ru atom also bears one equatorial and two axial terminal carbonyl ligands. The dihedral angles between the two benzene rings attached to each P atom of the diphenyl-phosphanyl ligand are 68.4 (2) and 71.5 (2)°. In the crystal, mol-ecules are linked into [001] chains via inter-molecular C-H⋯O hydrogen bonds. Weak inter-molecular C-H⋯π inter-actions also occur.


Chemical peelings for the treatment of actinic keratosis: a systematic review and meta-analysis.
Actinic keratosis (AK) is a common precancerous lesion of the skin that may be treated with chemical peelings. Despite their long-standing usage and clinical experience, no evidence-based recommendation regarding the efficacy and safety of chemical peelings for AK exists. To systematically review and synthesize the current knowledge on chemically exfoliative peelings as interventions for AK. We performed a systematic literature research in Medline, Embase and CENTRAL and hand-searched pertinent trial registers for eligible records until 5 August 2019. Results from individual studies were pooled using a random-effects model or described in a qualitative synthesis. The risk of bias was estimated with the tools provided by the Cochrane Collaboration (randomized and non-randomized trials) and the Evidence Project (single-arm trials). Four randomized controlled trials, two non-randomized controlled trials and two single-arm studies with a total sample size of n = 170 patients were included. Trichloroacetic acid (TCA) plus Jessner's solution showed significantly lower participant complete clearance (RR 0.36, 95% CI: 0.14-0.90, two studies, I2 = 0%, P = 0.03) and lower lesion clearance (RR 0.92, 95% CI: 0.85-0.99, one study, P = 0.03) compared to 5-fluorouracil (5-FU) 5% cream. TCA as monotherapy showed lower lesion complete clearance (RR 0.75, 95% CI: 0.69-0.82, two studies, I2 = 7%, P < 0.001) and lower mean lesion reduction per patient compared to conventional photodynamic therapy (cPDT) (MD -20.48, 95% CI: -31.55 to -9.41, two studies, I2 = 43%, P = 0.0003). Pain was more pronounced in patients treated with cPDT in comparison with TCA (MD -1.71 95% CI: -3.02 to -0.41, two studies, I2 = 55%, P = 0.01). In the single-arm studies, 5-FU plus glycolic acid showed 92% lesion clearance and phenol peeling 90.6% participant complete clearance. All studies showed a high risk for bias. Future high-quality studies and a standardization of peeling protocols are warranted to determine the value of chemical peelings in the treatment of AK.


A fuzzy approach to support decision-making in the triage process for suspected COVID-19 patients in Brazil.
Triage is a fundamental process in hospitals and emergency care units, as it allows for the classification and prioritization of patient care based on the severity of their clinical conditions. In Brazil, the triage of suspected COVID-19 cases is performed using a specific protocol, which involves manual steps, requiring the completion of four different forms, by four health care professionals. Aiming to investigate the possibility of improving the triage processes in Brazil, this article proposes the use of computational techniques for decision-making based on fuzzy inference systems. We argue that fuzzy set theory is appropriate to the problem because it allows the use of natural language to express the patient's symptoms, making it easier for health care professionals. After modelling the problem in a fuzzy system we applied a pilot test. The model includes symptoms that health professionals currently use to analyse COVID-19 cases. The results suggest that the model presents convergence with the sample data, highlighting its potential application in supporting triage for the classification of the severity of COVID-19 cases. Among the benefits of the proposed model, we emphasize contributions as the reduction of the time and number of professionals required for triage as well as the reduction of exposure of health care professionals and other patients suspected of carrying the virus. In this context, this research provides an opportunity to obtain social contributions regarding the services in public hospitals improvement.


New, long-acting, potent bradykinin antagonists.
1. Three new bradykinin (BK) antagonists, D-Arg0-Hyp3-Thi5-D-Tic7-Oic8-BK (compound I), D-Arg0-Hyp3-D-Tic7-Oic8-BK (compound II), and Arg(Tos)1-Hyp3-Thi5-D-Tic7-Oic8-BK (compound III), were tested against the effects of BK in 9 bioassay preparations including visceral smooth muscles, vasoconstriction, plasma protein extravasation, release of prostaglandin E2, bronchoconstriction, and stimulation of afferent C-fibre nociceptors. In some of these tests the effects of the new compounds were compared with those of the antagonist D-Arg0-Hyp2-Thi5,8-D-Phe7-BK (compound IV), described by Stewart & Vavrek (1987). 2. For all bioassays the general rank order of potency of the compounds was found to be I greater than II greater than III much greater than IV. The new antagonists were long-acting; in some bioassays their effects outlasted the duration of the experiment. 3. The inhibitory effects of the new BK antagonists were specific for BK; actions of noradrenaline, angiotensin II, acetylcholine or histamine were unaffected by the antagonists. They did not stimulate the release of histamine or prostaglandins. An agonistic effect was observed only with very high concentrations of compounds I and II in the plasma protein extravasation test. 4. The long duration of action of the new BK antagonists is probably due to a high and long-lasting affinity to the BK receptors. A high resistance of the antagonists to enzymatic destruction may be another reason. 5. The new BK antagonists will be valuable tools for the investigation of the pathophysiological role of BK. In addition they may offer a potential for therapeutic applications.


Dose- and time-dependent estradiol modulation of morphine antinociception in adult female rats.
To clarify the activational role of ovarian hormones on pain and analgesia, the present study determined whether estradiol (E2) modulation of nociception and morphine antinociception in adult female rats depends on (1) the dose of E2 and (2) the interval between E2 treatment and nociceptive testing. Female rats were ovariectomized (OvX) and either oil vehicle (0), or E2 (0.25, 2.5 or 25 microg/0.1 ml vehicle) was injected s.c. two consecutive days of every four days for five cycles before testing. Either 4, 24, 48 or 96 h after the last injection, nociception was evaluated on the 50 degrees C hotplate and warm water tail withdrawal tests before and after escalating doses of s.c. morphine. Lordosis behavior and uterine weight were assessed in other rats at the same E2 doses and time points. E2 significantly lengthened latency to respond on the hotplate test at 24 h after the last injection, but had no significant effect on tail withdrawal latencies. The lower doses of E2 significantly increased morphine antinociceptive potency at 4-24 h on one or both tests, but the intermediate E2 dose significantly decreased morphine potency at 48 h on the hotplate test. Thus, E2 modulation of morphine antinociception in the adult female rat is bidirectional, and occurs at E2 doses producing cyclic changes in sexual behavior, uterine weight and vaginal cytology that are similar to those observed in gonadally intact, cycling females.


[Immunologic mechanism following liver transplantation. An experimental study in the rat].
To investigate the immunological status of hepatic grafts we transplanted livers from different inbred rats orthotopically on 58 LEW rats; rearterialization of the grafts was achieved with an hepatico aortal segment of the donor. Survival time depended on the donor strain; LBNF1-allografts survived in 67% (n = 12), WiS- in 60% (n = 20) and BUF- in 43% (n = 14) indefinitely. In the DA-to-LEW-combination we found no long-term survivor. Liver perfusates (LP) were prepared from 10 BDE and 10 LEW; after keeping the livers for 6 h at room temperature we perfused via portal vein with 2 ml/g Ringer's solution five times. The treatment of BDE-kidney recipients (LEW) with LP showed prolonged survival; at 5 days application 10.2 +/- 1.3 d (control: 6.5 +/- 0.5 d; P less than 0.001), at 10 days treatment 15.3 +/- 7.3 d. In vitro LP inhibited the PHA-stimulation of LEW lymphoid cells in more than 90% and the ConA-stimulation of LEW spleen cells in more than 95%. In MLC LP showed strong inhibitory effect (inhibition rate greater than 97%) even when different combinations of responding and stimulating cells were used. We assume that an unspecific immunosuppressive hepatic factor is released from ischemic damaged liver grafts which is able to prevent rejection in the induction phase. In WiS-liver recipients surviving for more than 4 months GvHR was tested after splenectomy with spleen cells. All tests showed a grade III reaction. Donor-specific skin grafts which were transplanted on these recipients survived indefinitely while third party skin grafts were regularly rejected (7.6 +/- 0.5 d). We therefore can conclude that the cellular immunosurveillance is intact, but the immunological response against donor-specific antigens is reduced. With transfer of serum from long-term-surviving WiS-liver recipients (greater than 6 months) WiS-kidney grafted LEW were able to survive also prolonged (20.7 +/- 3.4 d, control 6.2 +/- 1.0 d; P less than 0.001). Lymphoid cell transfer (1 X 10(8)) did did not result in significant prolongation of survival time (8.0 +/- 2.0 d). These observations suggest that in the steady phase specific humoral transfer factors are responsible for prolonged survival of hepatic grafts.


Number and phenotype of rheumatoid arthritis patients' CD4+CD25hi regulatory T cells are not affected by adalimumab or etanercept.
To analyse the therapeutic effects of etanercept (ETA) or adalimumab (ADA) on the numbers and phenotypes of CD4+CD25hi Tregs in RA patients. RA patients received ADA (n = 28) or ETA (n = 20) and stable-dose MTX or LEF. Therapeutic responses were assessed with the 28-joint DAS (DAS-28) criteria after 12 weeks of treatment. Treg numbers and phenotypes, determined by flow cytometry using different gating strategies, were compared between responders and non-responders before and after 6 and 12 weeks of treatment. The percentages of good, moderate and non-responders among patients given ADA or ETA, respectively, were 46.5, 35.7 and 17.8% or 30, 20 and 50%, with respective mean (s.d.) pre-treatment CD4+CD25hi Treg percentages of 5.5 (0.04)% or 4.95 (0.02)%. Overall, for patients with active RA given ADA or ETA, neither TNF-α-blocking agent had an effect on Tregs percentage and absolute number. Moreover, CD4+CD25hi Treg counts remained unaffected in RA responders to ADA or ETA, compared with RA non-responders. Furthermore, the CD4+CD25hiCD45RA+, CD4+CD25hiCD45RO+ and CD4+CD25hiCD62L+ cell populations were unchanged by TNF-α-blocking agents. Neither ADA nor ETA modified the percentages or absolute numbers of circulating CD4+CD25hi Tregs and their phenotypes after being administered for 6 and 12 weeks to RA patients. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00234234.


Multivalent Nanobody Conjugate with Rigid, Reactive Oxygen Species Scavenging Scaffold for Multi-Target Therapy of Alzheimer's Disease.
Efficient therapeutic strategies that concurrently target both Aβ aggregation and oxidative stress in the Alzheimer's disease (AD) microenvironment emerge as a cutting-edge tool to combat the intricate pathogenesis of AD. Here, a multivalent nanobody conjugate with rigid, reactive oxygen species (ROS) scavenging scaffold is developed to achieve simultaneous Aβ amyloidogenesis mitigation, ROS elimination, and Aβ plaque clearance. Grafting Aβ segment (33-GLMVGGVVIA-42) into the third complementary-determining region of a parent nanobody generates an engineered nanobody NB that can recognize Aβ and inhibit its aggregation through homotypic interactions. NB is further genetically modified with a fragment of human interleukin-1β (163-VQGEESNDK-171), so that the obtained fusion nanobody NBIL can also facilitate the Aβ clearance by microglia. Linking NBIL covalently onto a rigid, ROS scavenging scaffold poly(deca-4,6-diynedioic acid) (PDDA) creates the multivalent nanobody conjugate PNBIL, which not only boosts the binding affinity between NBIL and Aβ aggregates for nearly 100 times but also possesses a long-term capability of oxidative stress alleviation, inflammation reduction, and neuron protection. PNBIL has significantly attenuated symptoms on two AD mouse models through amyloidogenesis inhibition and AD microenvironment modulation, validating that the multivalent nanobody conjugate design based on combinatory nanobody and molecular engineering is a promising approach of multi-target therapeutic strategies.


Protocol for live enhanced resolution confocal imaging of dendritic spinule dynamics in primary mouse cortical neuron culture.
Dendritic spinules are fine membranous protrusions of neuronal spines that play a role in synaptic plasticity, but their nanoscale requires resolution beyond conventional confocal microscopy, hindering live studies. Here, we describe how to track individual spinules in live dissociated cortical pyramidal neurons utilizing fluorescence labeling, optimized confocal imaging parameters, and post-acquisition iterative 3D deconvolution, employing NIS Elements software. This approach enables investigations of spinule structural dynamics and function without using super-resolution microscopy, which involves special fluorophores and/or high laser power. For complete details on the use and execution of this protocol, please refer to Zaccard et al. (2020).


Intracranial bleeds after minor and minimal head injury in patients on warfarin.
There is little evidence to guide physicians on management of patients who sustain head injuries while on warfarin. Our objective was to determine the rate of intracranial bleeding in anticoagulated patients with minor and minimal head injuries and the association with clinical features and international normalized ratio (INR). We conducted a historical cohort study of adult patients, taking warfarin, at two tertiary care emergency departments over 2 years with minor (Glasgow Coma Score 13-15, with loss of consciousness, amnesia, or confusion) or minimal (Glasgow Coma Score 15 without loss of consciousness, amnesia, or confusion) head injuries. Patients with penetrating injuries, INR < 1.5, or a new focal neurological deficit were excluded. Our outcome, intracranial bleeding, was determined by the radiologist's final computed tomography (CT) report for imaging performed within 2 weeks. There were 176 patients enrolled, of which 157 (89.2%) had CT and 28 (15.9%) had intracranial bleeding. Comparing patients with and without intracranial bleeding found no significant differences in INR, and loss of consciousness was associated with higher rate of intracranial bleeding. The rate of intracranial bleeding in the minor and minimal head injury groups was 21.9% and 4.8%, respectively. The rate of intracranial bleeding in patients on warfarin is considerable. Loss of consciousness is associated with high rates of intracranial bleeding. This study supports a low threshold for ordering CT scans for anticoagulated patients with head injuries.


Subgroups Defined by the Montreal Cognitive Assessment Differ in Functional Gain During Acute Inpatient Stroke Rehabilitation.
To validate subgroups of cognitive impairment on the Montreal Cognitive Assessment (MoCA)-defined as normal (score of 25-30), mildly impaired (score of 20-24), and moderately impaired (score less than 19)-by determining whether they differ in rehabilitation gain during inpatient stroke rehabilitation. Observational study. Linear regression models were conducted and predictors included MoCA subgroups and relevant baseline demographic and clinical covariates. Separate models included the cognitive subscale of the FIM instrument as a predictor. Inpatient rehabilitation facility of an urban, academic medical center. Inpatients (N=334) with mild-moderate strokes who were administered the MoCA on admission. Not applicable. The mean relative functional gain (mRFG) and mean relative functional efficiency (mRFE, which adjusts for length of stay) on the FIM total. MoCA subgroups significantly predicted mRFG and mRFE after accounting for age, sex, education, stroke severity, and recurrent vs first stroke. The normal group exhibited greater mRFG and mRFE than the mildly impaired group, while the moderately impaired group had significantly worse mRFG and mRFE than the mildly impaired group. The moderately impaired group had a significantly smaller proportion of individuals who made a clinically meaningful change on the total-FIM than the mildly impaired and normal groups. MoCA subgroups better accounted for mRFG and mRFE than a standard-of-care cognitive assessment (cognitive-FIM). Use of MoCA-defined subgroups can assist providers in predicting functional gain in survivors of stroke being treated in inpatient rehabilitation.


An atherosclerotic plaque-targeted single-chain antibody for MR/NIR-II imaging of atherosclerosis and anti-atherosclerosis therapy.
Oxidation-specific epitopes (OSEs) are rich in atherosclerotic plaques. Innate and adaptive immune responses to OSEs play an important role in atherosclerosis. The purpose of this study was to develop novel human single-chain variable fragment (scFv) antibody specific to OSEs to image and inhibit atherosclerosis. Here, we screened a novel scFv antibody, named as ASA6, from phage-displayed human scFv library. ASA6 can bind to oxidized LDL (Ox-LDL) and atherosclerotic plaques. Meanwhile, ASA6 can also inhibit the uptake of Ox-LDL into macrophage to reduce macrophage apoptosis. The atherosclerotic lesion area of ApoE-/- mice administrated with ASA6 antibody was significantly reduced. Transcriptome analysis reveals the anti-atherosclerosis effect of ASA6 is related to the regulation of fatty acid metabolism and inhibition of M1 macrophage polarization. Moreover, we conjugated ASA6 antibody to NaNdF4@NaGdF4 nanoparticles for noninvasive imaging of atherosclerotic plaques by magnetic resonance (MR) and near-infrared window II (NIR-II) imaging. Together, these data demonstrate the potential of ASA6 antibody in targeted therapy and noninvasive imaging for atherosclerosis.


Precursor biosynthesis regulation of lignin, suberin and cutin.
The extracellular matrix of plants can contain the hydrophobic biopolymers lignin, suberin and/or cutin, which provide mechanical strength and limit water loss and pathogen invasion. Due to their remarkable chemical resistance, these polymers have a high potential in various biotechnological applications and can replace petrol-based resources, for example, in the packing industry. However, despite the importance of these polymers, the regulation of their precursor biosynthesis is far from being fully understood. This is particularly true for suberin and cutin, which hinders efforts to engineer their formation in plants and produce customised biopolymers. This review brings attention to knowledge gaps in the current research and highlights some of the most recent findings on transcription factors that regulate lignin, suberin and cutin precursor biosynthesis. Finally, we also briefly discuss how some of the remaining knowledge gaps can be closed.


Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope-specific IgE antibody profiling.
IgE-epitope profiling can accurately diagnose clinical peanut allergy. We sought to determine whether sequential (linear) epitope-specific IgE (ses-IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double-blind, placebo-controlled food challenges utilizing PRACTALL dosing. Sixty four ses-IgE antibodies were quantified in blood samples using a bead-based epitope assay. A pair of ses-IgEs that predicts Cumulative Tolerated Dose (CTD) was determined using regression in 75 subjects from the discovery cohort. This epitope-based predictor was validated on 331 subjects from five independent cohorts (ages 4-25 years). Subjects were grouped based on their predicted values and probabilities of reactions at each CTD threshold were calculated. In discovery, an algorithm using two ses-IgE antibodies was correlated with CTDs (rho = 0.61, p < .05); this correlation was 0.51 (p < .05) in validation. Using the ses-IgE-based predictor, subjects were assigned into "high," "moderate," or "low" dose-reactivity groups. On average, subjects in the "high" group were four times more likely to tolerate a specific dose, compared with the "low" group. For example, predicted probabilities of tolerating 4, 14, 44, and 144 or 444 mg in the "low" group were 92%, 77%, 53%, 29%, and 10% compared with 98%, 95%, 94%, 88%, and 73% in the "high" group. Accurate predictions of food challenge thresholds are complex due to factors including limited responder sample sizes at each dose and variations in study-specific challenge protocols. Despite these limitations, an epitope-based predictor was able to accurately identify CTDs and may provide a useful surrogate for peanut challenges.


Human leukocyte migration inhibitory factor (LIF). IV. 3',5'-cGMP protects LIF against inactivation by the esterase inhibitor phenylmethylsulfonyl fluoride.
Recently reported experiments suggest that human leukocyte migration inhibitory factor (LIF) has properties of an esterase and a protease with substrate specificities directed against arginine esters and amides. Also reported previously, the synthetic phosphodiester bis-p-nitrophenyl phosphate (BNPP) but not various phosphomonoesters preserve LIF activity in the presence of the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF). In this paper I demonstrate that guanosine 3'5'-cyclic monophosphoric acid (3',5'-cGMP), a naturally occurring phosphodiester, at concentrations in excess of 10(-5)M also protects LIF against PMSF inactivation. The effect seems specific for the diester bond, its position in the nucleotide, and the guanine base. The possibility that LIF may be a multifunctional or an allosteric enzyme regulated by 3',5'-cGMP is discussed.


Causes of death in the native sheep of North Ronaldsay, Orkney. II. Lambs.
Investigation showed that the common causes of death in North Ronaldsay lambs were trauma due to behavioural patterns and starvation/hypothermia due in part to poor condition of the ewes.