Multidrug-resistant bacteria in diabetic foot infections: Experience from a portuguese tertiary centre.
In recent years, the emergence of antibiotic resistant pathogens made increasingly difficult to establish appropriate empiric antimicrobial therapy protocols for acute diabetic foot infection (DFI) treatment. Early recognition of the population at-risk for multidrug-resistant (MDR) bacterial infection is of paramount importance in order to decrease large-spectrum antibiotic overuse. This study used retrospective cohort study in a multidisciplinary tertiary diabetic foot unit. Patients with severe DFI were included and divided according to their infection resistance profile (susceptible vs MDR bacteria). Data regarding their comorbidities and length of hospital stay were collected. The primary endpoint was to determine the risk factors for MDR infections and to evaluate if these were associated with an increased length of stay (LOS). A total of 112 microbial isolates were included. Predominance of Gram-positive bacteria was observed and 22.3% of isolated bacteria were MDR. Previous hospitalisation was associated with a higher likelihood of MDR infection. MDR bacterial infection was also associated with an increased LOS (P = .0296). Our study showed a high incidence of MDR bacteria in patients with a DFI, especially in those who had a recent hospitalisation. MDR infections were associated with a prolonged LOS and represent a global public health issue for which emergent measures are needed.


Prevalence and distribution of the c.1436C→T sequence variant of carnitine palmitoyltransferase 1A among Alaska Native infants.
To use genotype analysis to determine the prevalence of the c.1436C→T sequence variant in carnitine palmitoyltransferase 1A (CPT1A) among Alaskan infants, and evaluate the sensitivity of newborn screening by tandem mass spectrometry (MS/MS) to identify homozygous infants. We compared MS/MS and DNA analyses of 2409 newborn blood spots collected over 3 consecutive months. Of 2409 infants, 166 (6.9%) were homozygous for the variant, all but one of whom were of Alaska Native race. None of the homozygous infants was identified by MS/MS on the first newborn screen using a C0/C16 + C18 cutoff of 130. Among 633 Alaska Native infants, 165 (26.1%) were homozygous and 218 (34.4%) were heterozygous for the variant. The prevalence was highest in Alaska's northern/western regions (51.2% of 255 infants homozygous; allele frequency, 0.7). The CPT1A c.1436C→T variant is prevalent among some Alaska Native peoples, but newborn screening using current MS/MS cutoffs is not an effective means to identify homozygous infants. The clinical consequences of the partial CPT1A deficiency associated with this variant are unknown. If effects are substantial, revision of newborn screening, including Alaska-specific MS/MS cutoffs and confirmatory genotyping, may be needed.


Comparison of a high saturated fat diet with a high carbohydrate diet during pregnancy and lactation: effects on insulin sensitivity in offspring of rats.
Insulin resistance plays a critical role in metabolic syndrome and is influenced by the amount and saturation of dietary fat. Both prenatal over and under nutrition can program susceptibility to insulin resistance. The aim of the study was to explore the impact of dietary fat given to mothers during gestation on the insulin sensitivity of the offspring. Female Wistar rats were fed with diets rich in carbohydrate (CHO) or saturated fat (SAFA) during pregnancy. The male offspring was split into 5 subgroups: groups 1 (control) and 3 continued on CHO or SAFA after birth, respectively. Group 2 with mothers on CHO continued on the CHO diet during the nursing period and changed to SAFA postweaning. Group 4 with mothers on SAFA continued on SAFA during the weaning period and changed to CHO postweaning. For group 5 the offspring of mothers given SAFA diet was changed to nursing mothers on CHO diet immediately after birth and continued on the same diet postweaning. At the age of 16 weeks, a euglycemic hyperinsulinemic clamp was performed. The glucose infusion rate was lowered in the groups receiving the SAFA diet (group 2, 24.7 +/- 2.0 mg/kg per minute; group 3, 22.0 +/- 1.9 mg/kg per minute; P < .05) compared with group 1 (32.2 +/- 2.3 mg/kg per minute). We did not detect any alterations in the rate of glucose disappearance during the clamp for any of the groups compared with group 1. A diet high in SAFA given to mothers during gestation and/or the weaning period does not seem to have deleterious effects on the insulin sensitivity in the offspring.


Interstitial Granulomatous Dermatitis and Palisaded Neutrophilic Granulomatous Dermatitis: Retrospective Clinicopathological Analysis of 16 Cases.
Reactive granulomatous dermatitis (RGD) is a new entity, which is highly associated with systemic disorders. There is scarce data regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD). We aimed to evaluate clinical and histopathological characteristics of IGD and PNGD as unified entities under the term of RGD. Observational, retrospective, single-center study of patients diagnosed with IGD and PNGD between 2012 and 2021 were included in the study. Of 16 patients (14 females and 2 males) with RGD, 13 had IGD and 3 had PNGD with a mean age of 62.5 years. The most common clinical presentation was plaques 37.5% (N=6), followed by patches 25% (N=4). The most common localization of involvement was lower extremity 75% (N=12), followed by trunk and upper extremity. Multiple localization of involvement was determined in 75% (N=12) of patients. None of the patients had rope sign. Associated comorbidities such as autoimmune diseases and malignancies were detected in 68.7% (N=11) of patients. In majority of biopsies (87.5%; N=14), there were lymphohistiocytic cell infiltration. Other accompanying cells were scarce neutrophils 31.2% (N=5) and eosinophils 31.2% (N=5). All of the biopsies had interstitially located lymphohistiocytic cell infiltration surrounding with swollen and degenerated collagen. Palisaded pattern was determined in 18.7% (N=3) of patients and floating sign was seen in 18.7% (N=3) of biopsies. RGD is a rare entity and most patients with RGD had associated disorders such as autoimmunity or malignancy. There is overlapping between IGD and PNGD, therefore supporting the usage of umbrella term as reactive granulomatous dermatitis is compatible with the literature.


Synthesis of some 4-hydroxypiperazine and N.N.-dibenzylhydroxylamine esters with potential local anaesthetic activity.
In the synthetic approach to some new local anaesthetics, it was desirable to prepare esters of N1-methyl-N4-hydroxypiperazine and N.N-dibenzylhydroxylamine. Their local anaesthetic activity testing is in progress.


Synthesis and spectroscopic DNA binding studies of [Ru(phen)2(tbtc)]2+ and [Ru(2,9-dmp)2(tbtc)]2+.
A new polypyridyl ligand tbtc (tbtc=4,5,9,14-tetraaza-benzo[b]triphenylene-11-carboxylic acid methyl ester) and its complexes [Ru(phen)2(tbtc)]2+ (1) (phen=1,10-phenanthroline) and [Ru(2,9-dmp)2(tbtc)]2+ (2) (2,9-dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by element analysis, MS, and 1H NMR. The DNA binding properties of both complexes to calf thymus DNA (CT-DNA) were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode, and the DNA binding affinity of complex 1 is much greater than that of complex 2. This difference in binding affinity probably was caused by the different ancillary ligands. Also, when irradiated at 365 nm, complex 1 was found to be a more-effective DNA-cleaving agent than complex 2.


Caffeine exposure in utero increases the incidence of apnea in adult rats.
Caffeine abuse during pregnancy may be a factor in the development of long-term breathing abnormalities. Therefore, the objective of the present study was to monitor adult breathing patterns after in utero exposure to caffeine. This was done by isolating episodes of apnea of more than 6-s duration from the breathing data as obtained by the Cotwatch breathing monitors adapted for rat use. The breathing record obtained over 6 consecutive days was expressed as daily weighted apnea-hypopnea density (WAHD) values. It was shown that administration of caffeine in moderate (30 mg/kg daily) or high (60 mg/kg daily) doses throughout gestation resulted in a significant dose-dependent increase in the WAHD value. The experimental offspring were significantly growth retarded in utero and their subsequent growth rates were also affected. The caffeine-exposed pups grew more slowly with growth plateauing at the same age, resulting in smaller adults. A link was suggested between infants with apnea of prematurity, when occurring after the first week, and an increased risk for later apnea and sudden infant death syndrome.


Is the postoperative pedicle screw position after dorsal instrumentation with or without intraoperative cone beam CT imaging worse in patients with obesity than in normal-weight patients?
Intraoperative cone beam CT (CBCT) imaging in dorsal instrumentation facilitates pedicle screw positioning. However, in patients with obesity, the benefit may be reduced due to artifacts that affect image quality. The purpose of this study was to evaluate whether intraoperative CBCT leads to an improved postoperative screw position compared to conventional fluoroscopy independent of body weight. A total of 71 patients (18 patients with a BMI > 30 kg/m2, 53 patients with a BMI < 30 kg/m2) who underwent dorsal instrumentation with intraoperative CBCT imaging were included in study groups one (SG1) and two (SG2). Two control groups (CG1 and CG2) were randomly sampled to include 22 patients with a BMI > 30 kg/m2 and 60 patients with a BMI < 30 kg/m2 who underwent dorsal instrumentation without intraoperative CBCT imaging. The pedicle screw position in postoperative computed tomography was assessed using the Gertzbein-Robbins classification. In SG1 (BMI > 30 kg/m2), a total of 107 (83.6%) pedicle screws showed no relevant perforation (type A + B), and 21 (16.4%) pedicle screws showed relevant perforation (type C - E). In SG2 (BMI < 30 kg/m2), 328 (90.9%) screws were classified as type A + B, and 33 (9.1%) screws were classified as type C - E. In CG1 (BMI > 30 kg/m2), 102 (76.1%) pedicle screws showed no relevant perforation (type A + B), and 32 (23.9%) pedicle screws showed relevant perforation (type C - E). In CG2 (BMI < 30 kg/m2), 279 (76.9%) screws were classified as type A + B, and 84 (23.1%) screws were classified as type C - E. There were significant differences between the values of SG1 and SG2 (p = 0.03) and between the values of SG2 and CG2 (p < 0.0001). CBCT imaging in dorsal instrumentation can lead to an improved pedicle screw position among both patients with obesity and normal-weight patients. However, patients with obesity showed significantly worse pedicle screw positions postoperatively after dorsal instrumentation with intraoperative CBCT imaging than normal-weight patients.


Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19).
Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ("small immunoprotein") was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm(3). When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P<.0176]. In this preliminary trial, (131)I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment.


A monoclonal antibody against a CEA-related antigen expressed on HT29 colon tumour cells.
A new monoclonal antibody, that binds to CEA and with low cross-reactivity with NCA, has been raised to an antigen expressed on HT29 colon tumour cells. This antibody (H58) reacts strongly with high-molecular-weight protein (50 X 10(4)) isolated from a crude plasma membrane preparation of HT29 cells as well as binding to purified CEA of molecular size (20 X 10(4)) isolated both from those cells and liver metastases of colon tumour. H58 binds to an epitope sterically unrelated to the binding site of the previously described anti-CEA monoclonal antibody MA/1 and our routine anti-CEA polyclonal serum PKIG. Augmented binding of antibody to either the cell membrane preparation or conventional CEA can be achieved using a mixture comprising equal weights of specific immunoglobulin from H58 and MA/1. The value of solid-phase binding assays using microtitre plates for selecting potentially useful antibodies is discussed.


Markers of emotion regulation processes: A neuroimaging and behavioral study of reappraising abilities.
Emotion regulation (ER) is a core element for individual well-being, and dysregulated emotional states are prominent in several mental disorders. Moreover, dispositional use of adaptive ER strategies, such as cognitive reappraisal, is usually associated to better psychological outcomes and less emotional problems. Thus, identifying markers of emotion dysregulation could serve as a key point for developing treatments against risks of psychopathological outcomes. Neuroimaging techniques could represent a useful tool within these aims, focusing on neurobiological markers of psychopathological illness. Given the well known gender differences in using ER strategies, we examined behavioral and neuroimaging patterns associated with dispositional use of reappraisal among a non-clinical female sample. We found that the individual predisposition to use cognitive reappraisal as an emotion regulation strategy was associated with decreased levels of dysregulation. From a neurobiological perspective, difficulties in using reappraisal were associated with decreased resting-state functional connectivity (rs-FC) between the Middle Temporal Gyrus and occipito-parietal regions. Moreover, rs-FC between prefrontal and occipito-parietal brain regions was negatively associated with emotion dysregulation levels. Microstructural anomalies across white matter tracts connecting temporal, parietal, and occipital brain regions were associated to difficulties in using reappraisal. Our findings suggest that specific behavioral and neurobiological substrates are linked to reappraising abilities. Furthermore, the ability to implement adaptive ER strategies could serve as protective factor against developing emotion dysregulation.


Separation of membrane proteins by two-dimensional electrophoresis using cationic rehydrated strips.
Due to their poor solubility during IEF membrane proteins cannot be separated and analyzed satisfactorily with classical 2-DE. A more efficient method for such hydrophobic proteins is the benzyldimethyl-n-hexadecylammonium chloride (16-BAC)/SDS-PAGE, but the corresponding protocol is intricate and time-consuming. We now developed an easy-to-handle electrophoresis method in connection with a novel device which enables reproducible separation of ionic solubilized membrane proteins using individually rehydrated plastic sheet gel strips. These strips are suitable for the first dimension in a 2-D 16-BAC/SDS system and can be handled easily; this is demonstrated by the separation of membrane proteins of human embryonic kidney (HEK293) cells.


An Updated Algorithm for Radiographic Screening of Upper Cervical Instability in Patients With Down Syndrome.
Retrospective evaluation of cervical spine images from 2006-2012 for the purposes of "screening" children with Down syndrome for instability. To determine whether a full series of cervical spine images including flexion/extension lateral (FEL) radiographs was needed to avoid missing upper cervical instability. The best algorithm, measurements, and criteria for screening children with Down syndrome for upper cervical instability are controversial. Many authors have recommended obtaining flexion and extension views. We noted that patients who require surgical stabilization due to myelopathy or cord compression typically have grossly abnormal radiographic measurements on the neutral upright lateral (NUL) cervical spine radiograph. The atlanto-dental interval, space available for cord, and basion axial interval were measured on all films. The Weisel-Rothman measurement was made in the FEL series. Clinical outcome of those with abnormal measurements were reviewed. Sensitivity, specificity, and positive and negative predictive values of NUL and FEL radiographs for identifying clinically significant cervical spine instability were calculated. A total of 240 cervical spine series in 213 patients with Down syndrome between the ages of 4 months and 25 years were reviewed. One hundred seventy-two children had an NUL view, and 88 of these patients also had FEL views. Only one of 88 patients was found to have an abnormal atlanto-dental interval (≥6 mm), space available for cord at C1 (≤14 mm), or basion axial interval (>12 mm) on an FEL series that did not have an abnormal measurement on the NUL radiograph. This patient had no evidence of cord compression or myelopathy. Obtaining a single NUL radiograph is an efficient method for radiographic screening of cervical spine instability. Further evaluation may be required if abnormal measurements are identified on the NUL radiograph. We also propose new "normal" values for the common radiographic measurements used in assessing risk of cervical spine instability in patients with Down syndrome. Level IV.


Determination of uric acid in urine, saliva and calcium oxalate renal calculi by high-performance liquid chromatography/mass spectrometry.
A very simple and direct method for determination of uric acid, in various biological matrices, based on high-performance liquid chromatography and mass spectrometry is described. Chromatographic separations were performed with a stationary phase Zorbax Sax Column, an anion exchange resin, with 50% sodium citrate 1 mM at pH 6.5 and 50% acetonitrile as mobile phase delivered at a flow rate of 1 ml/min. The detector counted negative ions by monitoring m/z 167.1, which corresponds to the urate anion. The method does not use an internal standard but quality control samples were used. Intra-day precision ranged between 1.1 and 1.5%, whereas inter-day precision was between 1.3 and 2.8% (n=5) working with some selected standards. Recovery tests of added standard have been successfully performed in urine and saliva samples, thus showing an appropriate accuracy of the method. The limit of quantitation found was 70 microg/l. Different urine and saliva samples were analyzed using an alternative analytical methodology based on an enzymatic reaction and photometric detection at 520 nm, resulting both methods comparable at a 95% confidence level. The method has been also applied to the determination of trace amounts of uric acid in the core of some selected calcium oxalate renal calculi.


Maintaining soldier musculoskeletal health using personalised digital humans, wearables and/or computer vision.
The physical demands of military service place soldiers at risk of musculoskeletal injuries and are major concerns for military capability. This paper outlines the development new training technologies to prevent and manage these injuries. Narrative review. Technologies suitable for integration into next-generation training devices were examined. We considered the capability of technologies to target tissue level mechanics, provide appropriate real-time feedback, and their useability in-the-field. Musculoskeletal tissues' health depends on their functional mechanical environment experienced in military activities, training and rehabilitation. These environments result from the interactions between tissue motion, loading, biology, and morphology. Maintaining health of and/or repairing joint tissues requires targeting the "ideal" in vivo tissue mechanics (i.e., loading and strain), which may be enabled by real-time biofeedback. Recent research has shown that these biofeedback technologies are possible by integrating a patient's personalised digital twin and wireless wearable devices. Personalised digital twins are personalised neuromusculoskeletal rigid body and finite element models that work in real-time by code optimisation and artificial intelligence. Model personalisation is crucial in obtaining physically and physiologically valid predictions. Recent work has shown that laboratory-quality biomechanical measurements and modelling can be performed outside the laboratory with a small number of wearable sensors or computer vision methods. The next stage is to combine these technologies into well-designed easy to use products.


Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age.
The Bayley Scales of Infant Development, Second Edition (BSID II) are commonly used to assess outcomes of extremely low birth weight (ELBW) infants. We sought to assess the predictive validity of the BSID II Mental Developmental Index (MDI) for cognitive function at school age. Of 330 ELBW infants admitted in 1992-1995, 238 (72%) survived to the age of 8 years, of whom 200 (84%) were tested at both 20 months' corrected age (CA) and 8 years. Mean birth weight was 811 g, mean gestational age was 26.4 weeks, 41% were boys, and 60% were black. Measures included the BSID II at 20 months' CA and the Kaufman Assessment Battery for Children (KABC) Mental Processing Composite (MPC) at 8 years' postnatal age. BSID II MDI and MPC scores were compared and the predictive validity calculated for all 200 ELBW children and for the 154 ELBW neurosensory-intact subgroup. Predictors of stability or change in cognitive scores were examined via logistic regression adjusting for gender and sociodemographic status. For all ELBW children, the mean MDI was 75.6 +/- 16 versus a mean KABC of 87.8 +/- 19. For the neurosensory-intact subgroup, the mean MDI was 79.3 +/- 16 and the mean KABC was 92.3 +/- 15. Rates of cognitive impairment, defined as an MDI or KABC of <70, dropped from 39% at 20 months' CA to 16% at 8 years for the total ELBW population and from 29% to 7% for the neurosensory-intact subgroup. The positive predictive value of having an MPC of <70 given an MDI of <70 was 0.37 (95% confidence interval [CI]: 0.27, 0.49) for all ELBW infants, 0.20 (95% CI: 0.10, 0.35) for the neurosensory-intact subgroup, and 0.61 (95% CI: 0.42, 0.77) for the neurosensory-impaired subgroup. The negative predictive values were 0.98, 0.99, and 0.85 for the 3 groups, respectively. Neurosensory impairment at 20 months' CA predicted lack of improvement of cognitive function (odds ratio: 6.9; 95% CI: 2.4, 20.2). Children whose cognitive scores improved between 20 months and 8 years had significantly better school performance than those whose scores stayed at <70, but they did less well than those whose scores were persistently >70. The predictive validity of a subnormal MDI for cognitive function at school age is poor but better for ELBW children who have neurosensory impairments. We are concerned that decisions to provide intensive care for ELBW infants in the delivery room might be biased by reported high rates of cognitive impairments based on the use and presumptive validity of the BSID II MDI.


Non-targeted Tracer Fate Detection.
Stable isotopes have been used to trace atoms through metabolism and quantify metabolic fluxes for several decades. Only recently non-targeted stable isotope labeling approaches have emerged as a powerful tool to gain insights into metabolism. However, the manual detection of isotopic enrichment for a non-targeted analysis is tedious and time consuming. To overcome this limitation, the non-targeted tracer fate detection (NTFD) algorithm for the automated metabolome-wide detection of isotopic enrichment has been developed. NTFD detects and quantifies isotopic enrichment in the form of mass isotopomer distributions (MIDs) in an automated manner, providing the means to trace functional groups, determine MIDs for metabolic flux analysis, or detect tracer-derived molecules in general. Here, we describe the algorithmic background of NTFD, discuss practical considerations for the freely available NTFD software package, and present potential applications of non-targeted stable isotope labeling analysis.


Referral pattern to a university-based oral and maxillofacial cone beam CT service.
Despite the rising popularity of cone-beam computed tomography (CBCT) imaging in the field of dentistry, very few studies have addressed the questions of which dental specialties most frequently request CBCT images and which CBCT indications are most popular. This study attempts to answer both of these questions. CBCT request forms spanning a 1-year period were analyzed for data. Collected data included the specialty of the referring dentist and the referral reason. A total of 660 referral forms were analyzed. Oral and maxillofacial surgeons were the discipline to most commonly request CBCT examinations. Pretreatment evaluation of potential dental implant sites was the most common indication for requesting CBCT scans. All dental specialties refer patients for CBCT examinations but at different frequencies and for various reasons that pertain to their respective disciplines. Clinical significance: These findings should be the basis for customizing the availability and scope of imaging services and in developing and modifying educational programmes for dentists and dental specialists.


Esophageal rupture caused by explosion of an automobile tire tube: a case report.
There have been no reports in the literature of esophageal rupture in adults resulting from an explosion of an automobile tire. We report the first case of just such an occurrence after an individual bit into a tire, causing it to explode in his mouth. A 47-year-old Han Chinese man presented with massive hemorrhage in his left eye after he accidentally bit an automobile tire tube which burst into his mouth. He was diagnosed with esophageal rupture based on a chest computed tomography scan and barium swallow examination. Drainage of empyema (right chest), removal of thoracic esophagus, exposure of cervical esophagus, cardiac ligation and gastrostomy were performed respectively. After that, esophagogastrostomy was performed. Successful anastomosis was obtained at the neck with no postoperative complications 3 months after the surgery. The patient was discharged with satisfactory outcomes. We present this case report to bring attention to esophageal rupture in adults during the explosion of an automobile tire tube in the mouth.


Cement leakage in percutaneous vertebroplasty for spinal metastases: a retrospective study of risk factors and clinical outcomes.
The objective of this research was to investigate the risk factors of cement leakage in patients with metastatic spine tumors following percutaneous vertebroplasty (PVP). Sixty-four patients with 113 vertebrae were retrospectively reviewed. Various clinical indexes, including age, sex, body mass index (BMI), smoking history, drinking history, chemotherapy history, radiotherapy history, primary cancer, location, other metastases, collapse, posterior wall defects, the laterality of injection, and the injected cement volume were analyzed as potential risk factors. Multivariate analyses were conducted to identify the independent risk factors. The cement leakage was found 64 in 113 treated vertebrae (56.63%), in which the incidence of each type was shown as below: spinal canal leakage 18 (15.93%), intravascular leakage around the vertebrae 11 (9.73%), and intradiscal and paravertebral leakage 35 (30.97%). Tomita classification (P = 0.019) and posterior wall destruction (P = 0.001) were considered strong risk factors for predicting cement leakage in general. The multivariate logistic analysis showed that defects of the posterior wall (P = 0.001) and injected volume (P = 0.038) were independently related to the presence of spinal canal leakage. The postoperative visual analog scale (VAS) and activities of daily living (ADL) scores showed significant differences compared with the pre-operative parameters (P < 0.05). No significant differences were found in every follow-up time between the leakage group and the non-leakage group for pain management and improvement of activities in daily life. In our study, Tomita classification and the destruction of the posterior wall were independent risk factors for leakage in general. The defects of the posterior wall and injected volume were independently related to the presence of spinal canal leakage. The PVP procedure can be an effective way to manage the pain.


Immobilized beta2-adrenergic receptor: A powerful chromatographic platform for drug discovery and evaluation of drug-like property for natural products.
Drug discovery based on natural products like medicinal herbs remains challenging due to the technique limitations for rapidly screening and validating leads. To address the challenges, we employ the immobilized β2- adrenergic recepotor (β2-AR), an identified target of asthma, as the stationary phase in chromatographic column to screen compounds extracted from Stemonae Radix, Playtycodonis Radix, and Glycyrrhizae Radix et Rhizoma. To analyze binding properties of the extracted compounds to the immobilized receptors, we measured their retention behavior in the receptor chromatography and compared with six clinical asthma drugs. We identified tuberostemonine, platycodin D, and glycyrrhizic acid as the potential leads against asthma by our β2-AR chromatography coupled with mass spectrum (MS). The association constants of the three compounds to β2-AR were 2.85 × 10-5, 2.55 × 10-4, and 4.07 × 10-6 M with the dissociation rate constants of 6.91 ± 0.35, 11.88 ± 0.60, and 9.49 ± 0.64 min-1, respectively. Tuberostemonine, a pentacyclic Stemona alkaloids, presented the most optimum values of binding efficiency index (BEI) and surface efficiency index (SEI) as close to the diagonal of SEI-BEI optimization plane when it is compared with platycodin D, glycyrrhizic and the six clinical drugs. Our results suggest that tuberostemonine is a promising natural product to be developed for treating asthma because it exhibits better drug-like binding properties to β2-AR than the clinical drugs. As such, we demonstrate a chromatographic strategy to identify bioactive natural products based on the β2-AR immobilization, which can be widely adopted to screen natural products from mixture of herbal extracts.


Brown adipose tissue and alzheimer's disease.
Alzheimer's disease (AD), the most common type of senile dementia, is a chronic neurodegenerative disease characterized by cognitive dysfunction and behavioral disability. The two histopathological hallmarks in this disease are the extraneuronal accumulation of amyloid-β (Aβ) and the intraneuronal deposition of neurofibrillary tangles (NFTs). Despite this, central and peripheral metabolic dysfunction, such as abnormal brain signaling, insulin resistance, inflammation, and impaired glucose utilization, have been indicated to be correlated with AD. There is solid evidence that the age-associated thermoregulatory deficit induces diverse metabolic changes associated with AD development. Brown adipose tissue (BAT) has been known as a thermoregulatory organ particularly vital during infancy. However, in recent years, BAT has been accepted as an endocrine organ, being involved in various functions that prevent AD, such as regulating energy metabolism, secreting hormones, improving insulin sensitivity, and increasing glucose utilization in adult humans. This review focuses on the mechanisms of BAT activation and the effect of aging on BAT production and signaling. Specifically, the evidence demonstrating the effect of BAT on pathological mechanisms influencing the development of AD, including insulin pathway, thermoregulation, and other hormonal pathways, are reviewed in this article.


The role of DNA methylation in virus replication: inhibition of frog virus 3 replication by 5-azacytidine.
Frog virus 3 (FV3) DNA is the most highly methylated DNA of any known DNA virus; about 20% of the cytosine residues in FV3 DNA are methylated (D. Willis and A. Granoff, 1980, Virology 107, 250-257). To understand the role of DNA methylation in virus replication, we have examined the effect of 5-azacytidine, a drug that inhibits DNA methylation. 5-Azacytidine (10 microM) reduced the production of infectious FV3 by 100-fold or more and inhibited methylation of viral DNA by about 80%. Inhibition of DNA methylation did not affect viral gene expression since there was no detectable inhibition of virus-specific RNA or protein synthesis in 5-azacytidine-treated cells. In contrast, the size of the replicating DNA measured under completely denaturing conditions, was much smaller than that found during infection in the absence of drug. These results suggest that the undermethylated DNA was susceptible to endodeoxyribonuclease(s). Additionally, electron microscopic examination of FV3-infected, 5-azacytidine-treated cells revealed that preformed capsids remained empty or were only partially filled with viral DNA. Based on these data, it is suggested that methylation of DNA protects it from endonucleolytic cleavage and that the integrity of genomic DNA is required for its proper packaging into virions.


Epidermolysis Bullosa in children: the central role of the pediatrician.
Epidermolysis bullosa (EB) is a severe hereditary disease characterized by defective epithelial adhesion causing mucocutaneous fragility. The major types are EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and more than 35 EB subtypes. Another very rare type of EB is Kindler EB (KEB). Clinically, it is a very heterogeneous disease which ranges from localized to extensive skin lesions with frequent multisystem extra cutaneous involvement. The role of a pediatrician-dermatologist cooperation within a multidisciplinary team is fundamental for both the diagnosis and management contributing to these patients' better life expectancy. Aim of this study is to describe clinical and laboratory characteristics of the main EB subtypes focusing on nutritional and gastrointestinal aspects, providing information to aid the paediatric management of children with EB. This retrospective study reviewed the cases of 160 pediatric EB patients (76 male and 84 female): 31 patients affected by EBS (mean age ± SD: 4.37 ± 7.14), 21 patients affected by JEB (mean age ± SD: 9.26± 17.30) and 108 with DEB (mean age ± SD: 11.61 ± 13.48). All patients were admitted at the Bambino Gesù Children's Hospital in Rome, between June 2005 to June 2020. The reduced gastrointestinal absorption, chronic losses, esophageal stenosis and chronic inflammatory state, represent the basis of nutritional problems of EB patients. In particular, anemia represents one of the most important complications of DEB patients which could require transfusion-dependent patterns. Malnutrition, vitamin deficiencies and anemia have been related to growth delay in EB patients. A specific diet with a balance of all macronutrients is required and improving caloric intake with sugar limitations is fundamental to prevent dental caries and tooth decay typical of EB patients. While sepsis proved to be the major cause of morbidity and mortality in younger patients, squamous cell carcinoma was mostly observed in older patients, especially those affected by DEB. Patients with EB require regular monitoring for complications and sequelae with a frequency of evaluations which varies based on age and EB subtypes. Cooperation among medical teams involving paediatricians, dermatologists, specialist clinicians including nutritionists such as families and patient's association is fundamental to approach the disease and improve the quality of life of these patients.


Black TiO2 nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis.
Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.


Heparin activates Wnt signaling for neuronal morphogenesis.
Wnt factors are secreted ligands that affect different aspects of the nervous system behavior like neurodevelopment, synaptogenesis and neurodegeneration. In different model systems, Wnt signaling has been demonstrated to be regulated by heparan sulfate proteoglycans (HSPGs). Whether HSPGs modulate Wnt signaling in the context of neuronal behavior is currently unknown. Here we demonstrate that activation of Wnt signaling with the endogenous ligand Wnt-7a results in an increased of neurite outgrowth in the neuroblastoma N2a cell line. Interestingly, heparin induces glycogen synthase kinase-3beta (GSK-3beta) inhibition, beta-catenin stabilization and morphological differentiation in both N2a cells and in rat primary hippocampal neuronal cultures. We also show that heparin modulates Wnt-3a-induced stabilization of beta-catenin. Several extracellular matrix and membrane-attached HSPGs were found to be expressed in both in vitro neuronal models. Changes in the expression of specific HSPGs were observed upon differentiation of N2a cells. Taken together, our findings suggest that HSPGs may modulate canonical Wnt signaling for neuronal morphogenesis.


High-Quality Artery Monitoring and Pathology Imaging Achieved by High-Performance Synchronous Electrical and Optical Output of Near-Infrared Organic Photodetector.
Near-infrared organic photodetectors (NIR-OPDs) are significant technologies in emerging biomedicine applications for uniquely wearable, noninvasive, low-cost advantages. However, biosignals are weak and changing rapidly so practical biodetection and bioimaging are still challenging for NIR-OPDs. Herein, high-performance NIR-OPDs with synchronous optical output are realized by recombining anode-injected electrons with photogenerated holes on emitters. Owing to high detection performance of 4.5 × 1012 Jones detectivity and 120 kHz -3 dB bandwidth, five arteries are monitored by transmission-type method and cardiac cycle is analyzed. Importantly, the synchronous optical output is direct emission demonstrating outstanding photon conversion efficiency approaching 20% and luminance signal-to-noise ratio over 8000. Consequently, pathology imaging is directly developed without complex readout circuits and arrays from which squamous metaplasia of cervix and carcinoma of large intestine are observed clearly. The NIR-OPD demonstrates strategies for high-performance synchronous electrical/optical output and directly imaging. Biomedicine applications implemented here are high level, representing important steps for NIR-OPDs toward providing clues for clinical diagnosis.


[Application of miniscrew for extraction of mesially impacted wisdom tooth adjacent to the inferior alveolar nerve canal].
To study the value of miniscrew for extraction of mesially impacted wisdom tooth adjacent to the inferior alveolar nerve canal. Fourteen mesially impacted wisdom teeth were proven to be adjacent to the inferior alveolar nerve canal by means of cone-beam CT scan. The treatment began with the miniscrew traction of the wisdom teeth. After 2-5 months, they were moved away from the canal and then extracted. After extraction, all 14 cases did not show any obvious side effect. Application of miniscrew traction is a valuable method for minimally invasive extraction of mesially impacted wisdom tooth that is adjacent to the inferior alveolar nerve canal.


Surgical management of aortopulmonary septal defect.
Fourteen patients with malseptation of the aortopulmonary trunk underwent operative repair from 1978 to 1988. Age ranged from 1 year to 35 years (mean age, 9.6 years). Five patients had type I, 6 had type II, and 3 had type III lesions. The hemodynamic disturbance in all patients was the consequence of a large left-to-right shunt (mean pulmonary/systemic flow ratio, 2.38:1) with increased pulmonary vascular resistance (mean value, 4.47 units/m2). Our initial surgical experience with closure under cardiopulmonary bypass through the transaortic route in 3 patients and the transpulmonary approach in two patients resulted in 3 deaths. In the 9 subsequent patients, division and repair of the defect in the great vessels yielded uniformly good results. During follow-up, which ranged from 3 months to 2 years, all 11 survivors had good clinical improvement and none showed residual defects on restudy. Pulmonary artery pressure and pulmonary vascular resistance decreased in all patients except 1.


Fatty acid and metabolomic profiling approaches differentiate heterotrophic and mixotrophic culture conditions in a microalgal food supplement 'Euglena'.
Microalgae have been recognized as a good food source of natural biologically active ingredients. Among them, the green microalga Euglena is a very promising food and nutritional supplements, providing high value-added poly-unsaturated fatty acids, paramylon and proteins. Different culture conditions could affect the chemical composition and food quality of microalgal cells. However, little information is available for distinguishing the different cellular changes especially the active ingredients including poly-saturated fatty acids and other metabolites under different culture conditions, such as light and dark. In this study, together with fatty acid profiling, we applied a gas chromatography-mass spectrometry (GC-MS)-based metabolomics to differentiate hetrotrophic and mixotrophic culture conditions. This study suggests metabolomics can shed light on understanding metabolomic changes under different culture conditions and provides a theoretical basis for industrial applications of microalgae, as food with better high-quality active ingredients.


Hidden blood loss and its influencing factors after minimally invasive percutaneous transpedicular screw fixation in thoracolumbar fracture.
Minimally invasive percutaneous transpedicular screw fixation (MIPTSF) is generally accepted as a minimally invasive treatment for thoracolumbar fracture. However, hidden blood loss (HBL) caused by this procedure is usually disregarded. This study aimed to investigate the amount of HBL and its influencing factors after MIPTSF in thoracolumbar fracture. Between October 2017 and December 2020, a total of 146 patients (106 males and 40 females, age range 21-59 years) were retrospectively examined, and their clinical and radiological data were recorded and analyzed. The Pearson or Spearman correlation analysis was used to investigate an association between patient's characteristics and HBL. Multivariate linear regression analysis was performed to elucidate the related clinical or radiological factors of HBL. A substantial amount of HBL (164.00 ± 112.02 ml, 40.65% of total blood loss (TBL)) occurred after transpedicular screw internal fixation. Multivariate linear regression analysis revealed that HBL was positively associated with TBL (p < .001), percentage of vertebral height loss (VHL) (p < .001), percentage of vertebral height restoration (VHR) (p < .001), numbers of fractured vertebrae (P = .013), and numbers of fixed vertebral segments (P = .002). A large amount of HBL was incurred in patients undergoing MIPTSF in thoracolumbar fracture. More importantly, TBL, percentage of VHL, percentage of VHR, the numbers of fractured vertebrae and fixed vertebral segments were independent risk factors for HBL.


Identification of metabolites from an active fraction of Cajanus cajan seeds by high resolution mass spectrometry.
Antioxidants are important food additives which prolong food storage due to their protective effects against oxidative degradation of foods by free radicals. However, the synthetic antioxidants show toxic properties. Alternative economical and eco-friendly approach is screening of plant extract for natural antioxidants. Plant phenolics are potent antioxidants. Hence, in present study Cajanus cajan seeds were analyzed for antioxidant activity, Iron chelating activity and total phenolic content. The antioxidant activity using DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay showed 71.3% inhibition and 65.8% Iron chelating activity. Total 37 compounds including some short peptides and five major abundant compounds were identified in active fraction of C. cajan seeds. This study concludes that C. cajan seeds are good source of antioxidants and Iron chelating activity. Metabolites found in C. cajan seeds which remove reactive oxygen species (ROS), may help to alleviate oxidative stress associated dreaded health problem like cancer and cardiovascular diseases.


Meeting physical activity guidelines and health-related fitness in youth.
National physical activity guidelines have been developed for Americans. Interest lies in the relationship between meeting the national physical activity guidelines and physical fitness outcomes in youth. Theoretically, those who meet the physical activity guidelines are more physically fit, which translates to better health and reduced risk. To examine the relationship between youth self-reported physical activity behaviors sufficient to meet DHHS Physical Activity Guidelines for Americans and an external health criterion: achievement of the FITNESSGRAM(®) Healthy Fitness Zone™ (HFZ). Logistic regression was used to examine achievement of the HFZ for three physical fitness measures (i.e., aerobic capacity, BMI, and muscle fitness) separately, and for all three combined, based on self-reported physical activity of 7 days per week for aerobic activity and ≥3 days per week of muscle-strengthening activity. One model examined the direct relationship between physical activity and fitness measures, and a second model assessed the same relationship while controlling for gender, age, ethnicity, economic status, and school. Data were collected during the 2009-2010 academic year and analyzed in 2012. Adolescents failing to meet national aerobic and muscle-strengthening physical activity guidelines have higher odds of not achieving healthy physical fitness levels of aerobic capacity, BMI, muscle fitness, and the combination of all three. An increase in the number of days of aerobic activity was related to decreased odds of being in the Needs Improvement Fitness Zone. The findings provide further support that meeting the national physical activity guidelines produces health benefits for youth.


'No Ebola…still doomed' - The Ebola-induced tourism crisis.
Many recent crisis and disasters affecting tourism have been studied, but few explicitly explore health related crisis in developing countries. This study analyses the effect of the Ebola Virus Disease Epidemic (EVDE) on The Gambia, where, despite no reported cases, EVDE had devastating consequences. A Rapid Situation Analysis is used to gain insights into responses to the EVDE, encompassing interviews with key stakeholders, field observations and follow up meetings with those involved in managing the crisis over 21 months. A crisis and disaster framework is used to understand the challenges encountered. Findings highlight the importance of consumer perception and preparedness and management failures' consequences, contributing to the broader debate on the indirect threat of epidemics on tourism in developing countries.


Expectations prior to epilepsy surgery: an exploratory comparison of men and women.
Although the clinical goal of resective epilepsy surgery is seizure freedom, patients have a wide set of expectations for this invasive procedure. The goal of this study was to evaluate potential gender differences in expectations among patients undergoing resective epilepsy surgery. Ratings of the importance of 12 potential impacts ("expectations") of resective surgery were analyzed in a seven-center cohort study including 389 adults aged 16 and older who underwent resective epilepsy surgery. Men and women both ranked anticipated changes in driving and memory as the most important presurgical expectations. Women rated driving, physical activity limitations, and economic worries as less important, and fatigue and pregnancy concerns as more important than did men (p's< or =0.05). Exploratory factor analysis indicated a different pattern of associations among the 12 importance items for men and women. Whether gender differences in presurgical values are associated with outcomes needs exploration.


Performance evaluation of FlowCytomix assays to quantify cytokines in patients with rheumatoid arthritis.
To compare the cytokine profile in RA patients and healthy control by using two methods-FlowCytomix assay and traditional ELISA. Cytokine levels were evaluated by FlowCytomix assay and ELISA in serum and supernatants of peripheral blood mononuclear cells (PBMC) cultures with and without stimulation by phytohaemagglutinin (PHA). The levels of IL-6, IL-1β, and TNF-α were significantly higher in sera of RA patients than those of healthy controls. The levels of IL-22, IL-6, IL-1β, TNF-α, and IL-10 were higher in unstimulated PBMC culture supernatant of RA patients than those of healthy controls. PHA stimulation significantly increased the production of proinflammatory cytokines from PBMC with RA patients. Compared with detectable cytokine levels in sera, cytokine concentration in the supernatant of PBMCs was remarkably higher. FlowCytomix and ELISA showed significant correlation in detecting cytokines. However, the FlowCytomix assay detected more cytokines than ELISA. The supernatant of PBMCs provide a fine condition for the study of cytokine production because of the lack of interference factors in sera. The FlowCytomix assay is more sensitive than ELISA in detecting cytokines from RA patients. Multiple cytokine signatures using FlowCytomix assay may represent a more realistic approach in the future of personalized medicine in RA.


SAIF plays anti-angiogenesis via blocking VEGF-VEGFR2-ERK signal in tumor treatment.
Shark cartilage was created as a cancer-fighting diet because it was believed to have an element that may suppress tumor growth. Due to overfishing, sharks have become endangered recently, making it impossible to harvest natural components from shark cartilage for therapeutic development research. Previously, we identified a peptide SAIF from shark cartilage with an-tiangiogenic and anti-tumor effects, successfully expressed it in Escherichia coli by using genetic engineering techniques. However, we did not elucidate the specific target of SAIF and its antiangiogenic molecular mechanism, which hindered its further drug development. Therefore, in this work, the exact mechanism of action was studied using various techniques, including cellular and in vivo animal models, computer-aided simulation, molecular target capture, and transcriptome sequencing analysis. With VEGF-VEGFR2 interaction and preventing the activation of VEGFR2/ERK signaling pathways, SAIF was discovered to decrease angiogenesis and hence significantly limit tumor development. The findings further demonstrated SAIF's strong safety and pharmaceutically potential. The evidence showed that SAIF, which is expressed by, is a potent and safe angiogenesis inhibitor and might be developed as a candidate peptide drug for the treatment of solid tumors such as hepatocellular carcinoma and other conditions linked with angiogenic overgrowth.


A suprasellar embryonal carcinoma producing alpha-fetoprotein and human chorionic gonadotropin; treated with combined chemotherapy followed by radiotherapy.
A case of primary suprasellar embryonal carcinoma that produced alpha-fetoprotein and human chorionic gonadotropin in a 12-year-old girl is reported. Partial removal of the tumor and cis-platinum-based combined chemotherapy followed by local radiotherapy resulted in a definite regression of the tumor and improvement from clinical signs and symptoms. After these treatments, the concentrations of alpha-fetoprotein and human chorionic gonadotropin in both serum and cerebrospinal fluid decreased to undetectable levels. Serum basic fetoprotein, another tumor marker, can be a tool for evaluating the clinical course following postoperative chemotherapy.


Continual monitoring of reaching in rat using magnetic induction law.
A method enabling the continual monitoring of movement has been developed based on the law of magnetic induction. The method was concretely applied in the handedness model of the rat. A sensing loop was implanted under the forearm skin of a rat. Electric voltage was induced by the movement of the sensing loop in a DC magnetic field. This voltage is proportional to the movement velocity and its polarity to the direction. The continuous character of the movement record allows convenient analysis and a more exact correlation with the bioelectric concomitants of the movement.


Microbubble-Mediated Cavitation Promotes Apoptosis and Suppresses Invasion in AsPC-1 Cells.
The aim of this study was to identify the potential and mechanisms of microbubble-mediated cavitation in promoting apoptosis and suppressing invasion in cancer cells. AsPC-1 cells were used and divided into four groups: control group, microbubble-only (MB) group, ultrasound-only (US) group and ultrasound plus microbubble (US + MB) group. Pulse ultrasound was used at a frequency of 360 kHz and a SPPA (spatial peak, pulse average) intensity of 1.4 W/cm2 for 1 min (duty rate = 50%). Then cells in the four groups were cultured for 24 h. Cell Counting Kit‑8 (Biosharp, Hefei, Anhui, China) revealed decreased cell viability in the US + MB group. Western blot confirmed that there were increased cleaved caspase‑3 and Bcl-2-associated X protein levels and decreased B‑cell lymphoma‑2 (Bcl-2) levels, as well as increased intracellular calcium ions and downregulated cleaved caspase-8, in the US + MB group. With respect to proliferation, cells in the US + MB group had lower expression of Ki67 and the weakened colony formation ability. The transwell invasion assay revealed that invasion ability could be decreased in AsPC-1 cells in the US + MB group. Further, it was found that cells in the US + MB group had lower levels of hypoxia-inducible factor-1α (HIF-1α) and vimentin and higher levels of E-cadherin compared with the other three groups. Finally, the US + MB cells had less invadopodium formation. In conclusion, these results suggest that microbubble-mediated cavitation promotes apoptosis and suppresses invasion in AsPC-1 cells.


Comparative adherence trajectories of oral disease-modifying agents in multiple sclerosis.
This study compared the adherence trajectories of fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) users with multiple sclerosis (MS) as there is limited evidence regarding the comparative adherence patterns of different oral disease-modifying agents (DMAs). A retrospective cohort study DATA SOURCE: 2015-2019 IBM MarketScan Commercial Claims Database. Adults (≥18 years) with MS (International Classification of Diseases [ICD]-9/10-Clinical Modification [CM]:340/G35) diagnosis and ≥1 DMA prescription. Incident FIN-, TER-, or DMF use based on the index DMA with 1 year of washout period. The DMA adherence trajectories based on the proportion of days covered (PDC) were examined using the Group-Based Trajectory Modeling (GBTM) one year after the treatment initiation. Generalized boosting models (GBM)-based inverse probability treatment weights (IPTW) were incorporated in multinomial logistic regression to assess the comparative adherence trajectories across oral DMAs with FIN group as a reference category. The study cohort consisted of 1913 patients with MS who were initiated with FIN (24.2%, n = 462), TER (24.0%, n = 458), and DMF (51.9%, n = 993) during 2016-2018. The adherence rate (PDC ≥ 0.8) among FIN, TER, and DMF users was found to be 70.8% (n = 327), 59.6% (n = 273), and 61.0% (n = 606), respectively. The GBTM grouped patients into three adherence trajectories: Complete Adherers-59.1%, Slow Decliners-22.6%, and Rapid Discontinuers-18.3%. The multinomial logistic regression model involving GBM-based IPTW revealed that DMF (adjusted odds ratio [aOR]: 2.32, 95% confidence interval [CI]:1.57-3.42) and TER (aOR: 2.50, 95% CI: 1.62-3.88) users had higher odds to be rapid discontinuers relative to FIN users. In addition, TER users were more likely (aOR: 1.50, 95% CI: 1.06-2.13) to be slow decliners compared with FIN users. Teriflunomide and DMF were associated with poorer adherence trajectories than FIN. More research is needed to evaluate the clinical implications of these adherence trajectories of oral DMAs to optimize the management of MS.


Study protocol for an open labelled randomised controlled trial of perioperative oral nutrition supplement in breast and colorectal cancer patients undergoing elective surgery.
While it is well established that perioperative use of oral nutrition supplement (ONS) improves nutrition status among severely malnourished surgical cancer patients, the evidence requires further substantiation for non-severely malnourished patients with cancer. This protocol paper presents the rationale and design of a randomised controlled trial to evaluate the effectiveness of preoperative as well as an extended 90-day postoperative use of ONS on nutritional and clinical outcomes among patients undergoing elective surgery for breast and colorectal cancer. Patients with primary breast and colorectal cancer undergoing elective surgery are recruited from two tertiary hospitals. Eligible patients are assigned into one of the three intervention arms: (i) Group SS will receive ONS in addition to their normal diet up to 14 days preoperatively and postoperatively up to discharge; (ii) Group SS-E will receive ONS in addition to their normal diet up to 14 days preoperatively, postoperatively up to discharge and for an extended 90 days after discharge; and (iii) Group DS will receive ONS in addition to their normal diet postoperatively up to discharge from the hospital. The ONS is a standard formula fortified with lactium to aid in sleep for recovery. The primary endpoints include changes in weight, body mass index (BMI), serum albumin and prealbumin levels, while secondary endpoints are body composition (muscle and fat mass), muscle strength (handgrip strength), energy and protein intake, sleep quality, haemoglobin, inflammatory markers (transferrin, high sensitivity C-reactive protein, interleukin-6), stress marker (saliva cortisol), length of hospital stay and postoperative complication rate. This trial is expected to provide evidence on whether perioperative supplementation in breast and colorectal cancer patients presenting with high BMI and not severely malnourished but undergoing the stress of surgery would be beneficial in terms of nutritional and clinical outcomes. ClinicalTrial.gov NCT04400552. Registered on 22 May 2020, retrospectively registered.


Neurobehavioral mechanisms underlying the effects of physical exercise break on episodic memory during prolonged sitting.
Episodic memory is the ability that enables individuals to recall and re-experience previous events and usually includes information concerning the spatial and temporal context. This study examined the effects of a physical exercise break during a period of prolonged sitting on episodic memory. Furthermore, we aimed to investigate whether alterations of functional connectivity patterns might contribute to the exercise-induced changes in episodic memory. Sixty healthy male college students were randomly assigned (1:1 ratio) to a prolonged-sitting group (PS group) or a physical-exercise-break group (PE group). The face-name paired-associate learning task was used to probe episodic memory. During the task, cortical hemodynamics in the prefrontal cortex were recorded using functional near-infrared spectroscopy (fNIRS). Changes in cortical hemodynamics were used to determine functional connectivity using graph-theoretical network analysis. There was no between-group difference in neurobehavioral outcomes at the pretest assessment. During the posttest assessment, compared with the PS group, higher nodal efficiency in the anterior prefrontal cortex (orbitofrontal and frontopolar cortices) was observed during the encoding phase (FDR corrected p values = 0.039), and higher nodal efficiency and degree centrality of orbitofrontal cortex were observed in the retrieval phase in the PE group (FDR corrected p values = 0.035). Moreover, the PE group showed closer temporal correlational interactions between the dorsolateral prefrontal cortex and the anterior prefrontal cortex in the left hemisphere during the episodic memory encoding phase (FDR corrected p values = 0.043), when compared to the PS group. Neither significant between-group difference in accuracy nor correlations between neural and behavioral outcomes were observed after the intervention. Our findings suggest that a physical exercise break during a prolonged sitting period has neither a beneficial nor a detrimental effect on behavioral performance concerning episodic memory. However, physical breaks do facilitate functional connectivity patterns of the prefrontal cortex while performing a episodic memory task.


Safety and Efficacy of Epitinib for EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Open-Label Multicentre Dose-Expansion Phase Ib Study.
Non-small-cell lung cancer (NSCLC) had poor prognosis in patients with brain metastasis. The trial evaluated the safety and efficacy of epitinib (HMPL-813), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), for EGFR-mutant NSCLC with brain metastasis. This open-label, dose-expansion phase Ib study (ClinicalTrials.gov: NCT02590952) was conducted at 7 Chinese centers and enrolled patients with EGFR-mutant advanced NSCLC with brain metastasis. Epitinib was administered at 120 mg or 160 mg, orally QD. The primary endpoint was safety and tolerability. Between April 2015 and April 2019, 72 patients were enrolled and received epitinib at 120 mg (n = 30) or 160 mg (n = 42). Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 13 (43.3%) patients in 120 mg group and 21 (50.0%) in 160 mg group. The objective response rate (ORR) was 53.6% (95% CI 33.9%-72.5%) in 120 mg group and 40.5% (25.6%-56.7%) in 160 mg group. The median duration of response in the 120 mg and 160 mg groups were 7.40 months (95% CI 3.70-7.40) and 9.10 months (6.50-12.00), respectively. The median progression-free survival were 7.40 months (95% CI 5.40-9.20) and 7.40 months (5.50-10.00), respectively. In patients with EGFR-mutant NSCLC with brain metastasis, epitinib was well tolerable with a promising efficacy. According to the comprehensive assessment on safety and efficacy, 160 mg QD could be the recommended phase 2 dose.


Optical Coherence Tomography Protocols for Screening of Hydroxychloroquine Retinopathy in Asian Patients.
To investigate the distribution of outer retinal changes in hydroxychloroquine (HCQ) retinopathy and explore optical coherence tomography (OCT) protocols to maximize the sensitivity of HCQ retinopathy detection in Asian patients. Diagnostic validity assessment. Setting: Institutional. Forty-eight eyes (24 patients) with HCQ retinopathy underwent 6-mm horizontal and vertical line scans and 6 × 6-mm2 volume scans using spectral-domain OCT (SD-OCT), and 9-mm line scans and 6 × 6-mm2 and 12 × 9-mm2 volume scans using swept-source OCT (SS-OCT). Distances from the fovea to the defective photoreceptors were measured in the temporal, nasal, superior, and inferior directions from line scan OCT images. The sensitivity of retinopathy detection, indicated by photoreceptor defects, was compared among protocols. Detection of photoreceptor defects and distances from the fovea to the defects. The average minimum distance from the fovea to an area of photoreceptor defects was 1.84 ± 1.26 mm (mean ± standard deviation). The distances were greater than 3 mm horizontally and vertically in 15 (31.3%) and 17 (35.4%) eyes with HCQ retinopathy, respectively, and only wide-field line or volume scans could detect defects in the eyes. The 9-mm line scans detected HCQ retinopathy significantly better than 6-mm scans (P < .001); the sensitivity of the wide volume scan was significantly greater than the standard volume scan (P = .001). The 12 × 9-mm2 volume scan detected retinopathy with the greatest sensitivity (100%). Our study recommends a wide-field OCT scan to screen Asian patients taking HCQ medications.


[Quantitative evaluation of the psychophysiological state of a person upon successful completion of work].
Ability of prediction successfulness of done work by the self-organizing maps was shown. Mathematical model which may be to appraise successfulness of done work by time of reaction on light signal and speed treat information was built. This model may be used for the estimate of the psychophysiological condition in the process of activity.


Radical Solution to the Alkylation of the Highly Base-Sensitive 1,1-Dichloroacetone. Application to the Synthesis of Z-Alkenoates and E,E-Dienoates.
A simple radical-based route to gem-α-dichloroketones, relying on the degenerative addition transfer of (S)-[3,3-dichloro-2-oxopropyl]-O-ethyl dithiocarbonate (xanthate), is described. The adducts can then be converted into Z-enoates by exposure to Et3N in methanol. In the case of certain substrates, it was possible to form skipped dienoic acid and methyl E,E-dienoates.


Preparation of hospitals for mass casualty incidents in Bavaria, Germany: care capacities for penetrating injuries and explosions in TerrorMASCALs.
In a terror attack mass casualty incident (TerrorMASCAL), compared to a "normal" MASCAL, there is a dynamic course that can extend over several hours. The injury patterns are penetrating and perforating injuries. This article addresses the provision of material and personnel for the care of special injuries of severely injured persons that may occur in the context of a TerrorMASCAL. To answer the research question about the preparation of hospitals for the care of severely injured persons in a TerrorMASCAL, a survey of trauma surgery departments in Bavaria (Germany) was conducted using a questionnaire, which was prepared in three defined steps based on an expert consensus. The survey is divided into a general, neurosurgical, thoracic, vascular and trauma surgery section. In the specialized sections, the questions relate to the implementation of and material and personnel requirements for special interventions that are required, particularly for injury patterns following gunshot and explosion injuries, such as trepanation, thoracotomy and balloon occlusion of the aorta. In the general section, it was noted that only a few clinics have an automated system to notify off-duty staff. When evaluating the data from the neurosurgical section, the following could be established with regard to the performance of trepanation: the regional trauma centers do not perform trepanation but nevertheless have the required material and personnel available. A similar result was recorded for local trauma centers. In the thoracic surgery section, it could be determined that almost all trauma centers that do not perform thoracotomy have the required material available. This group of trauma centers also stated that they have staff who can perform thoracotomy independently. The retrograde endovascular aortic occlusion procedure is possible in 88% of supraregional, 64% of regional and 10% of local trauma centers. Pelvic clamps and external fixators are available at all trauma centers. The results of the survey show potential for optimization both in the area of framework conditions and in the care of patients. Consistent and specific training measures, for example, could improve the nationwide performance of these special interventions. Likewise, it must be discussed whether the abovementioned special procedures should be reserved for higher-level trauma centers.


Small angle X-ray scattering study of meso-tetrakis (4-sulfonatophenyl) porphyrin in aqueous solution: a self-aggregation model.
The aggregate morphology of meso-tetrakis(4-sulfonatophenyl) porphyrin (TPPS(4)) in aqueous solution is investigated by using small angle x-ray scattering (SAXS) technique. Measurements were performed at pH 4.0 and 9.0 to monitor the pH influence on the structural parameters of the aggregates. Radii of gyration were obtained from distance distribution functions p(r) analysis. The experimental data of TPPS(4) at pH 4.0 showed well-defined oscillations characteristic of large aggregates in contrast to the SAXS curve of 5 mM TPPS(4) at pH 9.0, where both a significant decrease in the intensity and the disappearance of the oscillation peaks suggest the dissociation of the aggregate. A 340-A long "hollow" cylinder with shell thickness of 20 A, compatible to the porphyrin molecule dimension, represents well the scattering curve of the aggregates at pH 4.0. According to the fitting parameters, 26 porphyrin molecules self-associate into a ringlike configuration in the plane of the cylinder cross-section. The total number of porphyrin molecules in the whole aggregate was also estimated as approximately 3000. The model compatible to SAXS data of a hollow cylinder with J-aggregation in the cross-section and H-aggregation (columnar stacking) between the cylinder layers is consistent with optical absorption spectroscopic data both in the literature and obtained in this work.


Severe gyration and migration disorder in fetofetal transfusion syndrome: two case reports and a review of the literature on the neurological outcome of children with lesions on neuroimaging.
Fetofetal transfusion syndrome is a dreaded cause of morbidity and mortality in monochorionic pregnancies. We present two pairs of twins one of which we have followed for more than 6 years. The donors suffer from cerebral palsy, orofacial, and motor problems, and both are significantly smaller than their recipient twins. Interestingly, cranial MRI revealed medial frontal lobe polymicrogyria, ventriculomegaly, and decreased thickness in both parietal lobes in both donors. We suggest this as a possible feature of fetofetal transfusion syndrome. A minireview of the literature on neuroimaging and neurodevelopmental outcome in fetofetal transfusion syndrome is presented. While the close resemblance of the imaging features of both cases is likely incidental further study of a connection between migration and gyration disorders and fetofetal transfusion syndrome is warranted.


Adenylate kinase activity in cerebrospinal fluid of schizophrenic and certain other psychiatric symptomatologies.
Adenylate kinase activity in the cerebrospinal fluid (CSF) was investigated in 29 patients with psychiatric symptomatologies. Such activity was demonstrated in 18 of the 19 individuals with schizophrenic or other psychotic or borderline psychotic symptomatology. No activity was seen in the remaining 10 patients with non-psychotic nervous and/or functional somatic complaints, nor in the 20 persons whose CSF was examined in connection with spinal anaesthesia, nor in four who were treated with neuroleptic drugs on nonpsychiatric indications. The findings are compatible with the assumption that in persons with psychotic or borderline psychotic symptomatology a lowered membrane electrochemical potential may be associated with some of the symptoms exhibited.


Nasal symptoms, airway obstruction and disease severity in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of the lung in association with airflow obstruction. There is increasing evidence of upper airway involvement in COPD and we have reported that this nasal inflammation is proportional to that in the lung. Given recognized relationships between lower airway inflammation and spirometric indices such as the Forced Expiratory Volume in one second (FEV(1)), we hypothesized that there may be a relationship between nasal obstruction and FEV(1) in COPD. We also sought to investigate relationships between nasal symptoms and nasal patency in COPD. We assessed the nasal and pulmonary airways, using acoustic rhinometry and spirometry respectively, in 51 patients with COPD. The presence of chronic nasal symptoms in COPD was associated with reduced nasal patency (6.04 cm(2) symptoms vs. 9.55 cm(2) no symptoms, at the second minimum cross-sectional area, P = 0.049). Nasal patency in COPD was inversely proportional to pulmonary airflow obstruction, and therefore to COPD disease severity (e.g. FEV(1)% predicted vs. second minimum cross-sectional area, r = 0.36, P = 0.009). The degree of nasal airway obstruction in COPD reflects the impairment to pulmonary airflow, and is greater in the presence of chronic nasal symptoms. This study provides further evidence of pan-airway involvement in COPD.


Exogenous melatonin improves corn (Zea mays L.) embryo proteome in seeds subjected to chilling stress.
Melatonin (MEL; N-acetyl-5-methoxytryptamine) plays an important role in plant stress defense. Various plant species rich in this indoleamine have shown a higher capacity for stress tolerance. Moreover, it has great potential for plant biostimulation, is biodegradable and non-toxic for the environment. All this indicates that our concept of seed enrichment with exogenous MEL is justified. This work concerns the effects of corn (Zea mays L.) seed pre-sowing treatments supplemented with MEL. Non-treated seeds (nt), and those hydroprimed with water (H) or with MEL solutions 50 and 500 μM (HMel50, HMel500) were compared. Positive effects of seed priming are particularly apparent during germination under suboptimal conditions. The impact of MEL applied by priming on seed protein profiles during imbibition/germination at low temperature has not been investigated to date. In order to identify changes in the corn seed proteome after applying hydropriming techniques, purified protein extracts of chilling stressed seed embryos (14 days, 5°C) were separated by two-dimensional electrophoresis. Then proteome maps were graphically and statistically compared and selected protein spots were qualitatively analyzed using mass spectrometry techniques and identified. This study aimed to analyze the priming-induced changes in maize embryo proteome and at identifying priming-associated and MEL-associated proteins in maize seeds subjected to chilling. We attempt to explain how MEL expands plant capacity for stress tolerance.


Urethral stricture secondary to self-instrumentation due to delusional parasitosis: a case report.
Delusional parasitosis is a rare psychiatric disorder which often presents with dermatological problems. Delusional parasitosis, which involves urethral self-instrumentation and foreign body insertion, is exceptionally rare. This is the first case report to date that provides a detailed presentation of the urological manifestation of delusional parasitosis with complications associated with repeated self-instrumentation and foreign body insertion, resulting in stricture formation and requiring perineal urethrostomy. A 45-year-old Irish man was electively admitted for perineal urethrostomy with chronic symptoms of dysuria, haematuria, urethral discharge, and intermittent urinary retention. He reported a 4-year history of intermittent pain, pin-prick biting sensations, and burrowing sensations, and held the belief that his urethra was infested with ticks. He also reported a 2-year history of daily self-instrumentation, mainly injecting an antiseptic using a syringe in an attempt to eliminate the ticks. He was found to have urethral strictures secondary to repeated self-instrumentation. A foreign body was found in his urethra and was removed via cystoscopy. On psychiatric assessment, he displayed a fixed delusion of tick infestation and threatened to surgically remove the tick himself if no intervention was performed. The surgery was postponed due his mental state and he was started on risperidone; he was later transferred to an acute in-patient psychiatric unit. Following a 3-week admission, he reported improvement in his thoughts and distress. Delusional parasitosis is a rare psychiatric disorder. Self-inflicted urethral foreign bodies in males are rare and have high comorbidity with psychiatric disorders; hence, these patients have a low threshold for referral for psychiatric assessment. The mainstay treatment for delusional parasitosis is second-generation antipsychotic drugs.


Intraprostatic injection of tranexamic acid to control refractory bleeding while maintaining therapeutic anticoagulation.
Tranexamic acid (TXA) has been used to manage menstrual bleeding and reduce bleeding during orthopedic procedures, but has not been widely used in urology. We present a patient with refractory gross hematuria with required therapeutic anticoagulation who failed multiple other measures to control prostatic bleeding. This patient's hematuria abated with endoscopic localized injection of tranexamic acid into the prostate. The effects were durable with no bleeding recurrence reported while maintaining therapeutic anticoagulation.


Association of thoraco-lumbar fascia length in individuals with non-specific low back pain - an observational study.
The purpose of the study was to assess the length of TLF and to evaluate the strength of muscles attached to it in subjects with and without nonspecific low back pain (NSLBP). 31 patients with NSLBP and 31 healthy individuals were included in the study. In each subject the TLF length was assessed by quantifying lumbar rotation using Back range of motion (BROM-II) instrument. The endurance of transverses abdominis was assessed using the pressure biofeedback unit while the strength of Latissimus dorsi, internal and external oblique's were assessed using MMT. Outcome measure such as Range of Motion (ROM) was compared across the group using independent sample T-test. While the muscle strength of Latissimus dorsi and oblique's were compared across the group using Man-whitney U- test. Transverse abdominis endurance was tested using chi-square test. There was statistically significant difference in the length of TLF of subjects with NSLBP when compared with subjects without NSLBP. When the strength of Latissimus dorsi muscle, transverses abdominis muscle and internal and external oblique's muscle was assessed no significant (p value > 0.05) difference was found in either group. There was statistically significant reduction in length of TLF but there was no difference in the strength of Latissimus dorsi, internal and external oblique's or endurance of transverses abdominus attached to the TLF in individuals with NSLBP and without low back pain. This study will help in determining the inclusion of TLF and the associated structures in evaluation and management of subjects with NSLBP.


Progesterone promotes oocyte maturation, but not ovulation, in nonhuman primate follicles without a gonadotropin surge.
During the periovulatory interval, intrafollicular progesterone (P) prevents follicular atresia and promotes ovulation. Whether P influences oocyte quality or maturation and follicle rupture independent of the midcycle gonadotropin surge was examined. Rhesus monkeys underwent controlled ovarian stimulation with recombinant human gonadotropins followed by a) experiment 1: an ovulatory bolus of hCG alone or with a steroid synthesis inhibitor (trilostane, TRL), or TRL + the progestin R5020; or b) no hCG, but rather sesame oil (vehicle), R5020, or dihydrotestosterone (DHT). In experiment 1, the majority of oocytes remained immature (65% +/- 20%) by 12 h post-hCG. However, the percentage of degenerating oocytes increased (P < 0.05) with TRL (42% +/- 22% vs. 0% controls), but was reduced (P < 0.05) by progestin replacement (15% +/- 7%). By 36 h post-hCG, the majority of oocytes in all three groups reached metaphase II (MI). In experiment 2, no evidence of follicle rupture was observed in the vehicle, R5020, or DHT groups. Despite the absence of hCG, a significant (P < 0.05) percentage of oocytes resumed meiosis to metaphase I in R5020- (41 +/- 9) and DHT- (36 +/- 15) but not vehicle- (4 +/- 4) treated animals. Only oocytes from R5020-treated animals continued meiosis in vivo to MII. More (P < 0.05) oocytes fertilized in vitro with R5020 (40%) than with vehicle (20%) or DHT (22%). Thus, P is unable to elicit ovulation in the absence of an ovulatory gonadotropin surge; however, P and/or androgens may prevent oocyte atresia and promote oocyte nuclear maturation in primate follicles.


Distribution of glutamine synthetase and an inverse relationship between glutamine synthetase expression and intramuscular glutamine concentration in the horse.
Glutamine plays important roles in the interorgan transport of nitrogen, carbon and energy but little is known about glutamine metabolism in the horse. In this study we determined the tissue distribution of glutamine synthetase expression in three Standardbred mares. Expression of glutamine synthetase was highest in kidney and mammary gland, and relatively high in liver and adipose tissue. Expression was lower in gluteus muscle, thymus, colon and lung, and much lower in small intestine, pancreas and uterus. The pattern of glutamine synthetase expression in the horse is similar to that of other herbivores and it is likely that skeletal muscle, liver, adipose tissue and lungs are the major sites of net glutamine synthesis in this species. Expression did not differ between adipose tissue depots but did vary between different muscles. Expression was highest in gluteus and semimembranous muscles and much lower in diaphragm and heart muscles. The concentration of intramuscular free glutamine was inversely correlated with expression of glutamine synthetase (r=-0.81, p=0.0017). The concentration of free glutamine was much higher in heart muscle (21.6+/-0.9 micromol/g wet wt) than in gluteus muscle (4.19+0.33 micromol/g wet wt), which may indicate novel functions and/or regulatory mechanisms for glutamine in the equine heart.


The application of the Yerkes-Dodson law in a childhood weight management program: examining weight dissatisfaction.
To determine the effect of dissatisfaction with one's weight on outcomes in a weight management program. Participants included 149 children between the ages of 11 and 14 years who were enrolled in an intensive weight loss intervention. All participants had a body mass index (BMI) ≥ 85th percentile. Children were divided into tertiles based on their level of weight dissatisfaction as assessed by the Kids' Eating Disorder Survey. Analysis revealed significant differences across levels of weight dissatisfaction categories for weight loss. Specifically, children in the moderate dissatisfaction group lost weight while participants in low and high groups gained weight over 6 months. As the Yerkes-Dodson law would predict, these findings suggest that moderate levels of weight dissatisfaction are associated with improved outcomes in a weight management program.


Coeliac disease.
Coeliac disease is a genetically-determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten. Patients with the disease might have mainly non-gastrointestinal symptoms, and as a result patients present to various medical practitioners. Epidemiological studies have shown that coeliac disease is very common and affects about one in 250 people. The disease is associated with an increased rate of osteoporosis, infertility, autoimmune diseases, and malignant disease, especially lymphomas. The mechanism of the intestinal immune-mediated response is not completely clear, but involves an HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium. An important component of the disease is the intraepithelial lymphocyte that might become clonally expanded in refractory sprue and enteropathy-associated T-cell lymphoma. Study of the mechanism of the immune response in coeliac disease could provide insight into the mechanism of inflammatory and autoimmune responses and lead to innovations in treatment.


Brief Report: Task-Shifting "Gold Standard" Clinical Assessment and Safety Planning for Suicide Risk Among People Living With HIV: A Feasibility and Fidelity Evaluation in Tanzania.
Suicide is a leading cause of death among people living with HIV (PLWH) worldwide, with suicide deaths occurring twice as frequently among PLWH than among the general public. In Tanzania, resources for mental health care are sorely lacking, with 55 psychiatrists and psychologists providing treatment for 60 million people. In light of this shortage, nonspecialists play a crucial role. The objective of this study was to assess feasibility of implementing task-shifted screening, assessment, and safety planning for suicide risk among PLWH. Two adult HIV clinics in Kilimanjaro, Tanzania. Registered professional nurses in the HIV clinics were trained to administer brief screening of suicidal ideation in the past month. Patients experiencing suicidal ideation were referred to bachelor's-level counselors for further assessment and safety planning, supervised by specialist providers who reviewed audio recordings for quality assurance. During 180 days of implementation, nurses screened patients attending 2745 HIV appointments. Sixty-one (2.2%) endorsed suicidal ideation and were linked to further assessment and safety planning. We cross-checked screening with clinic attendance logs on 7 random days and found high fidelity to screening (206 of 228 screened, 90%). Quality assurance ratings demonstrated key assessment pieces were consistently completed (mean = 9.3/10 possible), with "Good" to "Excellent" counseling skills (mean = 23.7/28) and "Good" to "Excellent" quality (mean = 17.1/20), including appropriate referral for higher levels of care. Brief screening can be implemented and paired with task-shifted counseling to facilitate high-quality assessment of suicide risk. This model shows excellent potential to extend mental health services for PLWH in low-resource settings.


Stenting of bifurcation lesions using the Bestent: a prospective dual-center study.
Treatment of bifurcation lesions remains a technical challenge. Among 13 stents previously tested in a bench study, the Bestent seemed of particular interest in this indication as it provided good access to the side branch after stent implantation in the main branch associated with a satisfactory coverage of the lesion after kissing balloon inflation. The use of Bestent implanted in the main branch or both branches for treatment of bifurcation lesions involving a side branch > or = 2.2 mm in diameter was prospectively evaluated in a dual-center prospective study with a prospective 6-month clinical follow-up. All angiographic documents were analyzed by an independent corelab (CORISIS). Between 11 September 1997 and 21 February 1998, 96 patients were consecutively included (mean age, 63.7 +/- 11.4 years; 81.3% male; 58.3% with unstable angina and 6.3% acute myocardial infarction). The lesion involved the left anterior descending-diagonal coronary bifurcation in 55% of cases, left circumflex-marginal 23%, posterior descending-postero-lateral 12%, distal left main 6%, and others 4%. The main branch (proximal reference diameter: 3.43 +/- 0.45 mm) was stented in 98% of cases and the side branch (2.72 +/- 0.38 mm) in 38% (both branches in 34% of cases). T-stenting or provisional T-stenting was used in 88% of cases and final kissing balloon inflation was performed in 78% of cases. Procedural success was obtained in 100% of cases in the main branch and 98% in both branches. Major cardiac and cerebral events (MACCE) during hospitalization occurred in 4.2% of cases, non-Q-wave myocardial infarction (MI) in 3.1%, Q-wave MI in 1.0%, repeat PTCA in 2.1%; there were no major access site complication, no emergency coronary artery bypass grafting operation, no death. At 6-month follow-up, total MACCE rate was 14.6% (Q-wave MI, 3.1%; non-Q-wave MI, 3.1%; target vessel revascularization, 9.4%; death, 2.1%). Patients with target vessel revascularization (TVR) had restenosis of both branches in 22.2% of cases, main branch in 22.2%, and side branch in 55.6%. This study shows that using a simple strategy of provisional T-stenting of the side branch in the majority of cases, the Bestent can be used for treating bifurcation lesions with a high rate of success and an acceptable rate of TVR at 6-month follow-up.


Meta-analysis of cytochrome P4501A1 MspI gene polymorphism and childhood acute leukemia.
To investigate the relationship between cytochrome P4501A1 (CYP1A1) Msp I gene polymorphism and childhood acute leukemia (AL). Relevant literature was extensively searched and screened by Pubmed and Wanfang Database, Chinese Science Journal Database and Chinese Journal Net. Various data consolidation, combined OR values and their 95% CI were tested by RevMan 4.2; Funnel plots were used for the bias analysis. Six related literatures were found to meet the requirements. According to heterogeneity results, there was no significant difference in homozygous types(P>0.05), while there was significant difference in two others types (P all<0.05). For wild CYP1A1MspI homozygous for the reference group, Combined OR of heterozygous mutation, homozygous, heterozygous + homozygous mutation in AL and control groups were 1.18, 0.96, and 1.10 respectively. Subgroup analysis: Z values of CYP1A1MspI homozygous, heterozygous + homozygous in the acute lymphoblastic leukemia (ALL) and the control group were 0.10 and 0.76 respectively, Z values in non-acute lymphoblastic leukemia and control group were 0.74 and 0.75. There is no correlation between CYP1A1MspI gene polymorphism and the susceptibility of childhood AL.


Influence of reaction time and temperature on product formation and characteristics associated with the hydrothermal carbonization of cellulose.
Studies have demonstrated that hydrothermal carbonization of biomass and waste streams results in the formation of beneficial materials/resources with minimal greenhouse gas production. Data necessary to understand how critical process conditions influence carbonization mechanisms, product formation, and associated environmental implications are currently lacking. The purpose of this work is to hydrothermally carbonize cellulose at different temperatures and to systematically sample over a 96-h period to determine how changes in reaction temperature influence product evolution. Understanding cellulose carbonization will provide insight to carbonization of cellulosic biomass and waste materials. Results from batch experiments indicate that the majority of cellulose conversion occurs between the first 0.5-4h, and faster conversion occurs at higher temperatures. Data collected over time suggest cellulose solubilization occurs prior to conversion. The composition of solids recovered after 96h is similar at all temperatures, consisting primarily of sp(2) carbons (furanic and aromatic groups) and alkyl groups.


Efficacy and Safety of Intravitreal Sirolimus for Noninfectious Uveitis of the Posterior Segment: Results from the Sirolimus Study Assessing Double-Masked Uveitis Treatment (SAKURA) Program.
To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale). Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 μg (n = 208), 440 μg (n = 208), or 880 μg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-μg group was terminated after interim results found no significant difference in efficacy compared with the 440-μg dose. The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events. A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 μg compared with 44 μg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-μg and 44-μg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-μg and 44-μg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-μg and 44-μg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups. Intravitreal sirolimus 440 μg improved ocular inflammation, as measured by VH, compared with the 44-μg dose, with minimal impact on IOP, while preserving BCVA.


Thoracic Aortic Syndromes.
Aortic dissection (AD) is a lethal, treatable disruption of the aortic vessel wall. It often presents without classic features, mimicking symptoms of other conditions, and diagnosis is often delayed. Established high-risk markers of AD should be sought and indicate advanced aortic imaging with CT, MRI, or TEE. Treatment is immediate surgical evaluation, aggressive symptom relief, and reduction of the force of blood against the aortic wall by control of heart rate, followed by blood pressure.


Lactulose/mannitol test and specificity, sensitivity, and area under curve of intestinal permeability parameters in patients with liver cirrhosis and Crohn's disease.
The purpose of this study was to investigate and compare the specificity, sensitivity, and area under curve (AUC) of the lactulose/mannitol ratio, lactulose/creatinine ratio, and lactulose recovery and their diagnostic value for intestinal permeability assessment within the absorption lactulose/mannitol (L/M) test. The value of the lactulose/mannitol ratio, lactulose/creatinine ratio, and the percentage of lactulose recovery in Crohn's disease (0.0763 +/- 0.0369; 99.62 +/- 67.87; 1.0478 +/- 0.6148) and in liver cirrhosis (0.0517 +/- 0.0365; 54.65 +/- 53.26; 0.838 +/- 0.929) were significantly different from the values measured in the control group (0.0123 +/- 0.0081; 10.95 +/- 7.07; 0.2438 +/- 0.1568), P < 0.0001-0.002). In Crohn's disease, specificity, sensitivity, and AUC were 100%, 89.5%, and 0.987, respectively, of the lactulose/mannitol ratio at a cut-off level of 0.022. In liver cirrhosis, the test characteristics were 88.5%, 84.2%, and 0.910 at a cut-off level of 0.018. The lactulose/mannitol ratio was evaluated to have the highest diagnostic value to assess intestinal permeability.