Development of an Fe2+ sensing system based on the inner filter effect between upconverting nanoparticles and ferrozine.
The ferrozine (FZ) assay is a vital oxidation state-specific colorimetric assay for the quantification of Fe2+ ions in environmental samples due to its sharp increase in absorbance at 562 nm upon addition of Fe2+. However, it has yet to be applied to corresponding fluoresence assays which typically offer higher sensitivites and lower detection limits. In this article we present for the first time its pairing with upconverting luminescent nanomaterials to enable detection of Fe2+via the inner filter effect using a low-power continuous wave diode laser (45 mW). Upon near infra-red excitation at 980 nm, the overlap of the upconversion emission of Er3+ at approximately 545 nm and the absorbance of the FZ:Fe2+ complex at 562 nm enabled measurement in the change of UCNP emission response as a function of Fe2+ concentration in a ratiometric manner. We first applied large, ultra-bright poly(acrylic acid) (PAA)-capped Gd2O2S:Yb3+,Er3+ UCNPs upconverting nanoparticles (UCNPs) for the detection of Fe2+ using FZ as the acceptor. The probe displayed good selectivity and sensitivity for Fe2+, with a low limit of detection (LoD) of 2.74 μM. Analogous results employing smaller (31 nm) PAA-capped hexagonal-phase NaYF4:Yb3+,Er3+ UCNPs synthesised in our lab were achieved, with a lower LoD towards Fe2+ of 1.43 μM. These results illustrate how the ratiometric nature of the system means it is applicable over a range of particle sizes, brightnesses and nanoparticle host matrices. Preliminary investigations also found the probes capable of detecting micromolar concentrations of Fe2+ in turbid solutions.


Fungal infections in the acquired immunodeficiency syndrome.
Defects in cell-mediated immunity caused by infection with the human immunodeficiency virus (HIV) render AIDS patients particularly susceptible to fungal pathogens. Signs and symptoms of serious infection may be nonspecific, and early diagnosis and institution of antifungal therapy is essential to decrease morbidity and mortality in this patient population. In a symptomatic individual, invasive procedures are often required to establish a microbiologic diagnosis, and histopathologic examination of tissue by light and electron microscopy is often the first indication of a serious fungal infection in an AIDS patient.


Are brief febrile seizures benign? A systematic review and narrative synthesis.
Febrile seizures affect 2%-5% of U.S. children and are considered benign although associated with an increased risk of epilepsy and, rarely, with sudden unexplained death. We compared rates of mortality, neurodevelopmental disorders, and neuropathology in young children with simple and complex febrile seizures to healthy controls. We systematically reviewed studies of 3- to 72-month-old children with simple or complex febrile seizures ≤30 min. We searched studies with outcome measures on mortality, neurodevelopment, or neuropathology through July 18, 2022. Bias risk was assessed per study design. Each outcome measure was stratified by study design. PROSPERO registration is CRD42022361645. Twenty-six studies met criteria reporting mortality (11), neurodevelopment (11), and neuropathology (13), including 2665 children with febrile seizures and 1206 seizure-free controls. Study designs varied: 15 cohort, 2 cross-sectional, 3 case-control, 5 series, and 1 case report. Mortality outcomes showed stark contrasts. Six cohort studies following children after febrile seizure (n = 1348) reported no deaths, whereas four child death series and 1 case report identified 24.1% (108/449) deaths associated with simple (n = 104) and complex (n = 3) febrile seizures ≤30 min. Minor hippocampal histopathological anomalies were common in sudden deaths with or without febrile seizure history. Most electroencephalography (EEG) studies were normal. Neuroimaging studies suggested increased right hippocampal volumes. When present, neurodevelopmental problems usually preexisted febrile-seizure onset. Risk bias was medium or high in 95% (18/19) of cohort and case-control studies vs medium to low across remaining study designs. Research on outcomes after simple or brief complex febrile seizures is limited. Cohort studies suffered from inadequate sample size, bias risk, and limited follow-up durations to make valid conclusions on mortality, neurodevelopment, and neuropathology. Sudden death registries, focused on a very small percentage of all cases, strongly suggest that simple febrile seizures are associated with increased mortality. Although most children with febrile seizures have favorable outcomes, longer-term prospective studies are needed.


Exploring two subdimensions of participation, involvement and engagement: A scoping review.
The conceptualisation of participation is an ongoing discussion with importance for measurement purposes. The aim of this study was to explore the two subjective subdimensions of participation, involvement and engagement. The purpose was related to measure development within the field of paediatric rehabilitation. In a scoping review, following the PRISMA-ScR, the databases MEDLINE, PubMed, Academic Research Complete, PsychINFO, and Business Source Complete were searched for publications that described engagement and/or involvement constructs. Thirty-nine publications met the inclusion criteria. Involvement could be conceptualised as an unobservable state of motivation, arousal, or interest towards a specific activity or product. Building a consensus over different fields of research, engagement can be seen as the individual's behavioural, cognitive and affective investment during role performance. This scoping review points in a direction that the two subdimensions of participation need to be separated, with involvement being a more stable internal state of interest towards an activity, and engagement referring to the specific behaviour, emotions, and thoughts meanwhile participating in a specific setting. Clear definition of concepts will enhance the development of measures to evaluate rehabilitation interventions in the field of occupational therapy and related fields.


Tomato Apical Leaf Curl Virus: A Novel, Monopartite Geminivirus Detected in Tomatoes in Argentina.
Plant viruses that are members of the Geminiviridae family have circular single-stranded DNA (ssDNA) genome and are responsible for major crop diseases worldwide. We have identified and characterized a novel monopartite geminivirus infecting tomato in Argentina. The full-length genome was cloned and sequenced. The genome-wide pairwise identity calculation that resulted in a maximum of 63% identity with all of other known geminiviruses indicated that it is a new geminivirus species. Biolistic infected plants presented interveinal yellowing, apical leaf curling and extreme root hypotrophy. Thus, the name proposed for this species is tomato apical leaf curl virus (ToALCV). The phylogenetic inferences suggested different evolutionary relationships for the replication-associated protein (Rep) and the coat protein (CP). Besides, the sequence similarity network (SSN) protein analyses showed that the complementary-sense gene products (RepA, Rep and C3) are similar to capulavirus while the viron-sense gene products (CP, MP and V3) are similar to topocuvirus, curtovirus and becurtovirus. Based on the data presented, ToALCV genome appears to have "modular organization" supported by its recombination origin. Analyses of the specificity-determining positions (SDPs) of the CP of geminiviruses defined nine subgroups that include geminiviruses that share the same type of insect vector. Our sequences were clustered with the sequences of topocuvirus, whose vector is the treehopper, Micrutalis malleifera. Also, a set of the highest scored amino acid residues was predicted for the CP, which could determine differences in virus transmission specificity. We predict that a treehopper could be the vector of ToALCV, but transmission assays need to be performed to confirm this. Given everything we demonstrate in this paper, ToALCV can be considered a type member of a new putative genus of the Geminiviridae family.


Effects of Aerobic Exercise on Rats with Hyperandrogenic Polycystic Ovarian Syndrome.
Hyperandrogenism is a key pathologic characteristic of polycystic ovarian syndrome (PCOS), and exercise can alleviate the accompanying inflammation and decrease the high androgen levels, but the mechanism is still unclear, so the purpose of this study is to explore the pathophysiologic characteristics of hyperandrogenic PCOS and the mechanism underlying its amelioration with aerobic exercise. Thirty-two female rats were randomly allocated to a normal control group (NC, n = 8), exercise control group (EC, n = 8), PCOS group (PC, n = 8), and PCOS plus exercise group (PE, n = 8). The PC and PE groups were injected with a dehydroepiandrosterone (DHEA) solution to induce the hyperandrogenic PCOS rat model. The EC and PE groups underwent a Masashi swimming protocol (120 min per session, 6 days/week, for 15 days). Results indicated that the concentrations of leptin (LP) in the EC group were significantly lower than those in the NC group (p < 0.05). Compared with the NC group, the levels of testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), LP, anti-Müllerian hormone (AMH), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and free fatty acids (FFA) were all significantly augmented in the PC group (all p < 0.05). In addition, compared with the NC group, the levels of adiponectin (ADP) were significantly decreased (p < 0.05), and the expression of aromatase cytochrome P450 (P450arom) in ovarian tissue was significantly elevated in the PC group (p < 0.05). The levels of T, FSH, LP, and FFA were also significantly increased in the PE group (p < 0.05). Compared with the PC group, the levels of T and LP in the PE group were significantly diminished (p < 0.05), and the levels of ADP were significantly increased in the PE group (p < 0.05). T was positively correlated with E2, FSH, AMH, LP, TNF-α, IL-6, and FFA levels, while ADP was negatively correlated with LP and E2. These results showed that hyperandrogenism, chronic low-grade inflammation, and leptin resistance may interact to influence the occurrence and development of PCOS. Aerobic exercise can alleviate the internal inflammation by relieving leptin resistance and may mitigate the sex hormone disorder and hyperandrogenism in rats with PCOS by affecting the hypothalamic-pituitary-ovarian axis.


Diagnostic Accuracy of Urine Lipoarabinomannan Testing in Early Morning Urine versus Spot Urine for Diagnosis of Tuberculosis among People with HIV.
The Fujifilm SILVAMP TB LAM (FujiLAM) assay offers improved sensitivity compared to Determine TB LAM Ag (AlereLAM) for detecting tuberculosis (TB) among people with HIV. Here, we examined the diagnostic value of FujiLAM testing on early morning urine versus spot urine and the added value of a two-sample strategy. We assessed the diagnostic accuracy of FujiLAM on cryopreserved urine samples collected and stored as part of a prospective cohort of adults with HIV presenting for antiretroviral treatment in Ghana. We compared FujiLAM sensitivity and specificity in spontaneously voided urine samples collected at inclusion (spot urine) versus in the first voided early morning urine (morning urine) and for a one (spot urine) versus two samples (spot and morning urine) strategy. Diagnostic accuracy was determined against both microbiological (using sputum culture and Xpert MTB/RIF testing of sputum and urine to confirm TB) and composite reference standards (including microbiologically confirmed and probable TB cases). Paired urine samples of spot and morning urine were available for 389 patients. Patients had a median CD4 cell count of 176 cells/μL (interquartile range [IQR], 52 to 361). Forty-three (11.0%) had confirmed TB, and 19 (4.9%) had probable TB. Overall agreement for spot versus morning urine test results was 94.6% (kappa, 0.81). Compared to a microbiological reference standard, the FujiLAM sensitivity (95% confidence interval [CI]) was 67.4% (51.5 to 80.9) for spot and 69.8% (53.9 to 82.8) for morning urine, an absolute difference (95% CI) of 2.4% (-10.2 to 14.8). Specificity was 90.2% (86.5 to 93.1) versus 89.0% (85.2 to 92.1) for spot and morning urine, respectively, a difference of 1.2% (-3.7 to 1.4). A two-sample strategy increased FujiLAM sensitivity from 67.4% (51.5 to 80.9) to 74.4% (58.8 to 86.5), a difference of 7.0% (-3.0 to 16.9), while specificity decreased from 90.2% (86.5 to 93.1) to 87.3% (83.3 to 90.6), a difference of -2.9% (-4.9 to -0.8). This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice. IMPORTANCE This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples for detecting tuberculosis among people with HIV. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice around FujiLAM.


Aquagenic Urticaria Diagnosed by the Water Provocation Test and the Results of Histopathologic Examination.
An 18-year-old male visited our department complaining of recurrent episodes of an itchy rash after hand washing, showering/bathing, drinking water, and getting rain-soaked. He was diagnosed with aquagenic urticaria after a water provocation test and histopathologic examination. Five months of antihistamine treatment successfully prevented further wheal formation. Aquagenic urticaria is a very unusual form of physical urticaria caused by contact with water. It manifests as pruritic small wheals surrounded by erythema within 30 minutes of exposure. The condition can be diagnosed by a water provocation test. Systemic antihistamines are the first-line treatment, with anticholinergics, phototherapy, or barrier cream used alternatively or additionally. Four cases of aquagenic urticaria have been reported in Korea, but no histopathologic evaluation was reported in the English or Korean literature. Herein, we provide both a case report of aquagenic urticaria diagnosed by the water provocation test and histopathologic examination results for this patient.


Surgical outcomes of 500 robot-assisted minimally invasive esophagectomies for esophageal carcinoma.
In 2003, robot-assisted minimally invasive esophagectomy (RAMIE) was first reported to overcome the technical limitations of minimally invasive esophagectomy. RAMIE requires repeated modifications to set up the robotic system, and sufficient experience is required to gain technical proficiency. This study aimed to identify the learning periods and the outcomes of RAMIE for esophageal carcinoma. We retrospectively reviewed 500 consecutive RAMIE cases for esophageal cancer from December 2008 to February 2021. The learning curve for RAMIE was identified using cumulative sum analysis. In a total of 500 RAMIE patients, the Ivor Lewis and McKeown operation were performed in 267 patients (53.4%) and 192 patients (38.4%), respectively. We classified learning periods into the learning phase (first 50 cases), the developing phase (51-150 case), and the stable phase (151-500 case). The rates of vocal cord palsy (42.0% vs. 28.4%) and anastomotic leakage (10.0% vs. 6.4%) were reduced after the learning phase. The mean total operative time (420 vs. 373 min), the mean length of stay (21.6 vs. 16.7 days), and the rate of anastomotic stricture (27.0% vs. 12.4%) were significantly reduced after reaching stable phase. In the stable phase, the proportion of the Ivor Lewis operation (26.0% vs. 67.1%), neoadjuvant chemoradiation therapy (14.0% vs. 25.7%), and bilateral cervical node dissection cases (12.0% vs. 22.0%) were significantly increased. Fifty procedures might be needed to achieve early proficiency, and extensive experience of more than 150 procedures is needed for quality stabilization.


Photophysical study of naphthalenophanes: evidence of adduct formation with molecular oxygen.
The photophysical properties of two atropisomeric naphthalenophanes (1 and 2) have been studied. Their structure only differs in the relative arrangement, syn (1) or anti (2), of the two aromatic units. The compounds emission is mainly excimeric and is strongly quenched in the presence of oxygen. Comparison of emission intensities obtained from steady state and from decay times provides clear evidence of the formation of ground state charge transfer complexes between oxygen and the naphthalenophanes 1 and 2. The calculated values for the association constants are on the order of 10(3) M(-1) (ethanol, room temperature) for both naphthalenophanes.


Roles of Amphipathicity and Hydrophobicity in the Micelle-Driven Structural Switch of a 14-mer Peptide Core from a Choline-Binding Repeat.
Choline-binding repeats (CBRs) are ubiquitous sequences with a β-hairpin core that are found in the surface proteins of several microorganisms such as S. pneumoniae (pneumococcus). Previous studies on a 14-mer CBR sequence derived from the pneumoccal LytA autolysin (LytA239-252 peptide) have demonstrated a switch behaviour for this peptide, so that it acquires a stable, native-like β-hairpin conformation in aqueous solution but is reversibly transformed into an amphipathic α-helix in the presence of detergent micelles. With the aim of understanding the factors responsible for this unusual β-hairpin to α-helix transition, and to specifically assess the role of peptide hydrophobicity and helical amphipathicity in the process, we designed a series of LytA239-252 variants affecting these two parameters and studied their interaction with dodecylphosphocholine (DPC) micelles by solution NMR, circular dichroism and fluorescence spectroscopies. Our results indicate that stabilising cross-strand interactions become essential for β-hairpin stability in the absence of optimal turn sequences. Moreover, both amphipathicity and hydrophobicity display comparable importance for helix stabilisation of CBR-derived peptides in micelles, indicating that these sequences represent a novel class of micelle/membrane-interacting peptides.


Ribosomal RNA genes in the amoebal and plasmodial forms of the slime mould Physarum polycephalum.
1. The degree of homology between ribosomal RNA isolated from microplasmodia and amoebae of the slime mould Physarum polycephalum has been determined by competive hybridisation of the RNA from the two sources to homologous DNA in solution. The extent of competition was measured both by hybridisation to saturation and by following the kinetics of hybrid formation. In each case competition was found to be 100%, indicating that the ribosomal RNAs from the two, quite different vegetative forms of the organism exhibit a high degree of homology and are probably transcribed from the same genes. 2. The relationship between the amount of nuclear DNA that codes for ribosomal RNA (rDNA) and ploidy has been investigated in three strains of P. polycephalum which exhibit a 1:2:5 variation in the amount of DNA per nucleus. Ribosomal RNA saturation values were determined by hybridisation to DNA isolated from prophase nuclei of plasmodia. The proportion of rDNA was found to be constant at 0.16--0.18% of the total genome in the three strains.


[Caspar Fraxinus's papers].
These 21 unpublished letters written by, to or about Gaspar Fraxinus were collected by Istvan Botta, Tivadar Vida and Tamás Grynaeus. Most of the letters were actually health reports written by Fraxinus to Count Nadasdy, though the doctor mentions various other subjects as well. We have followed the Hungarian practice in the publication. The numbers that precede the letters refer to their original date and put them in concordance with all the known Fraxinus letters. Where you find question marks with the numbers the exact date of the letter is uncertain. After the numbers there are also short summaries, and then comes the letter itself in its original language and spelling. Letters either in Latin or German have been translated into Hungarian by Tivadar Vida, and those written in old Hungarian were provided with a transcription that gives the modern spelling. Each unit is closed with the archival data: i.e. the name of the institution that has been trusted with the preservation, and the shelfmarks are indicated.


Human immunodeficiency virus type 1 infection induces cyclin T1 expression in macrophages.
The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for viral replication and activates RNA polymerase II transcriptional elongation through the association with a cellular protein kinase composed of Cdk9 and cyclin T1. Tat binds to this kinase complex through a direct protein-protein interaction with cyclin T1. Monocytes/macrophages are important targets of HIV-1 infection, and previous work has shown that cyclin T1 but not Cdk9 protein expression is low in monocytes isolated from blood. While Cdk9 expression is expressed at a high level during monocyte differentiation to macrophages in vitro, cyclin T1 expression is induced during the first few days of differentiation and is shut off after 1 to 2 weeks. We show here that the shutoff of cyclin T1 expression in late-differentiated macrophages involves proteasome-mediated proteolysis. We also show that cyclin T1 can be reinduced by a number of pathogen-associated molecular patterns that activate macrophages, indicating that up-regulation of cyclin T1 is part of an innate immune response. Furthermore, we found that HIV-1 infection early in macrophage differentiation results in sustained cyclin T1 expression, while infection at late times in differentiation results in the reinduction of cyclin T1. Expression of the viral Nef protein from an adenovirus vector suggests that Nef contributes to the HIV-1 induction of cyclin T1. These findings suggest that HIV-1 infection hijacks a component of the innate immune response in macrophages that results in enhancement rather than inhibition of viral replication.


Hormonal therapies for acne.
Acne is a common, worldwide problem that is usually multifactorial in etiology, but androgens may play a pivotal role in the development and severity of acne. Endocrinopathies, such as polycystic ovarian syndrome, ovarian tumors, or adrenal hyperplasia or tumors, may be detected in some patients with acne, especially if acne is sudden in onset, associated with hirsutism or menstrual irregularities, or associated with cushingoid facies, acanthosis nigricans, patterned hair loss, or deepened voice. In these instances, serum-free and total testosterone, dehydroepiandrosterone, luteinizing hormone, and follicle stimulating hormone should be tested. Appropriate referral and long-term follow-up is warranted in patients diagnosed with an endocrinopathy. Hormonal therapies for acne include systemic medications with various mechanisms: androgen receptor blockers, adrenal androgen production blockers, or ovarian androgen production blockers. Androgen receptor blockers include spironolactone, cyproterone acetate, chlormadinone, and flutamide; adrenal androgen production blockers include glucocorticoids; and ovarian production blockers include gonadotropin-releasing agonists and oral contraceptives. Practical guidelines are shared for the practicing physician treating hormonally related acne.


Effectiveness of Vitamin D Supplements in Reducing the Risk of Falls among Older Adults: A Meta-Analysis of Randomized Controlled Trials.
The role of vitamin D in reducing the risk of falls in older adults has not been clearly demonstrated. This study examined the effectiveness of vitamin D supplementation in reducing the risk of falls in older adults. Four databases (Cochrane Library, Embase, PubMed, and CINAHL) were searched without language restrictions or time limitations. These articles were comprehensively screened using EndNote version 20.1 software. A manual search of the reference lists of the identified studies was also performed. The analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The pooled evidence was analyzed using RevMan software version 5.4. Seventeen studies met inclusion criteria among 550 potentially relevant studies. The pooled analysis of 38,598 older adults showed that vitamin D supplementation decreased the odds of having at least one fall by 1% (odds ratio [OR]=1.01; 95% confidence interval [CI], 0.92-1.11; p=0.86); however, the difference was not statistically significant. Of eight studies with 19,946 older adults, the pooled analysis showed a 12% (OR=1.12; 95% CI, 0.97-1.29; p=0.11) decrease in the odds of having at least one fracture among older adults; however, the difference was also not statistically significant. Pooled subgroup analysis showed that neither low (<2,000 IU/day) nor high (≥2,000 and <4,000 IU/day) doses of vitamin D supplementation had any significant effect on the incidence of falls and fractures. Vitamin D supplementation had no beneficial effect in reducing fall and fracture incidence among older adults.


Diagnosis of pulmonary diseases.
A broad spectrum of lung disease occurs in association with HIV infection. Included are both infectious and neoplastic processes and idiopathic disorders. To insure prompt, accurate, and efficient diagnosis, a logical, staged sequence of tests should be applied. Chest films and, in some instances, pulmonary function tests and gallium-67 citrate lung scans serve to provide objective indications of lung disease. Each of these tests is sensitive but nonspecific. Specific infecting organisms, particularly P. carinii, can be identified by examining sputum induced by inhalation of 3 per cent saline. Bronchoscopic procedures, including BAL and TBB, are highly sensitive and should be performed in patients having nondiagnostic sputum examinations. Tests involving antigen and antibody detection are of little use in the evaluation of individual patients. Detection of recurrent episodes of PCP is difficult because abnormalities in the usual screening tests may be residual from previous episodes. Finding P. carinii in sputum or bronchoscopic specimens soon (within 2 to 3 months) after a confirmed episode of PCP likely represents residual organisms rather than recrudescence of the infection. Empiric diagnosis of P. carinii should be employed only in limited circumstances when specific diagnostic studies are not available, are contraindicated, or are refused.


Spatial Analysis of Global Variability in Covid-19 Burden.
Since the first occurrence of coronavirus disease 2019 (Covid-19), a number of online tools have become available to assist with tracking Covid-19 prevalence. Yet we are unaware of resources that provide country-specific Covid-19 incidence data. We undertook a descriptive analysis of the global impact of Covid-19 using data reported on March 17, 2020. The prevalence of Covid-19 cases, fatalities attributed to Covid-19, and the case fatality rate for each of the 238 countries were accessed from the World Health Organization global Covid-19 tracking site, and we additionally calculated Covid-19 incidence based on country-specific population data. We determined the country-specific point prevalence and incidence of Covid-19 and associated deaths while using geocoded data to display their spatial distribution with geographic heat maps. The analysis included 193,197 Covid-19 cases and 7859 associated deaths. The point prevalence was highest in China (80,881), Italy (31,506), Iran (16,169), and Spain (11,312); no other country reported more than 10,000 cases. The incidence (per million population) was highest in San Marino (3389) followed by Iceland (645) and Italy (521); no other country had an incidence above 400 per million population. Countries with a high Covid-19 prevalence may not have a high incidence, and vice versa. Public health agencies that provide real-time infection tracking tools should report country-specific Covid-19 incidence metrics, in addition to prevalence data.


The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article.
We conducted a systematic review and meta-analysis to firstly obtain a reliable estimation of the prevalence of metabolically healthy obese (MHO) individuals in obesity, then assessed the risk of developing metabolic abnormalities (MA) among MHO individuals. At last, we evaluated the effects of traditional lifestyle interventions on metabolic level for MHO subjects. A systematic review and meta-analysis (PRISMA) guideline were conducted, and original studies were searched up to December 31, 2016. The prevalence of MHO in obesity from each study was pooled using random effects models. The relative risks (RRs) were pooled to determine the risk of developing MA for MHO compared with metabolically healthy normal-weight (MHNW) subjects. For the meta-analysis of intervention studies, the mean difference and standardized mean differences were both estimated for each metabolic parameter within each study, and then pooled using a random-effects model. Overall, 40 population-based studies reported the prevalence of MHO in obesity, 12 cohort studies and 7 intervention studies were included in the meta-analysis. About 35.0% obese individuals were metabolically healthy in the obese subjects. There were dramatic differences in the prevalence among different areas. However, 0.49 (95% confidence intervals [CI]: 0.38 to 0.60) of the MHO individuals would develop one or more MA within 10 years. Compared with MHNW subjects, the MHO subjects presented higher risk of incident MA (pooled RR = 1.80, 95%CI: 1.53-2.11). Following intervention, there was certain and significant improvement of metabolic state for metabolically abnormal obesity (MAO) subjects. Only diastolic blood pressure had reduced for MHO individuals after intervention. Almost one-third of the obese individuals are in metabolic health. However, they are still at higher risk of advancing to unhealthy state. Therefore, it is still needed to advise MHO individuals to maintain or adopt a healthy lifestyle, so as to counterbalance the adverse effects of obesity.


The age-dependent association between aortic pulse wave velocity and telomere length.
Age significantly modifies the relationship between aortic pulse wave velocity and telomere length. The differential relationships observed between aortic pulse wave velocity and telomere length in younger and older individuals suggest that the links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course. Ageing is associated with marked large artery stiffening. Telomere shortening, a marker of cellular ageing, is linked with arterial stiffening. However, the results of existing studies are inconsistent, possibly because of the confounding influence of variable exposure to cardiovascular risk factors. Therefore, we investigated the relationship between telomere length (TL) and aortic stiffness in well-characterized, younger and older healthy adults, who were pre-selected on the basis of having either low or high aortic pulse wave velocity (aPWV), a robust measure of aortic stiffness. Demographic, haemodynamic and biochemical data were drawn from participants in the Anglo-Cardiff Collaborative Trial. Two age groups with an equal sex ratio were examined: those aged <30 years (younger) or >50 years (older). Separately for each age group and sex, DNA samples representing the highest (n = 125) and lowest (n = 125) extremes of aPWV (adjusted for blood pressure) were selected for analysis of leukocyte TL. Ultimately, this yielded complete phenotypic data on 904 individuals. In younger subjects, TL was significantly shorter in those with high aPWV vs. those with low aPWV (P = 0.017). By contrast, in older subjects, TL was significantly longer in those with high aPWV (P = 0.001). Age significantly modified the relationship between aPWV and TL (P < 0.001). Differential relationships are observed between aPWV and TL, with an inverse association in younger individuals and a positive association in older individuals. The links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course.


[The microspectra of chromosome].
The spectra of radicle chromosome of broad bean, marrow cell chromosome and marrow cell micro-nucleus of small white mouse were measured within the range of visible light by microspectrum technique. The differences among the spectra were found.


Reduced-intensity conditioning umbilical cord blood transplantation in Nijmegen breakage syndrome.
NBS is a rare autosomal recessive congenital disorder associated with chromosome instability caused by a mutation in the NBN gene (8q21). Clinical manifestations include microcephaly, growth retardation, combined immunodeficiency, and a strong predisposition to develop (mainly lymphatic) malignancies. There is no specific treatment for patients with NBS, and the prognosis is generally poor. The therapeutic option for some patients with NBS may be HSCT. We present a case of safe and successful non-myeloablative UCB transplantation in the 19th month of the life of a female child with NBS concomitant with SCID.


Accuracy of MRI in diagnosing peripheral nerve disease: a systematic review of the literature.
MRI is increasingly being used to evaluate extracranial peripheral nerve disease in clinical practice. The objective of this study was to systematically review the accuracy of MRI in distinguishing normal from abnormal extracranial peripheral nerves. There is significant heterogeneity between studies investigating the accuracy of MRI. Studies have shown that nerve T2-weighted or STIR hyperintensity, nerve enlargement, and nerve flattening are associated with peripheral nerve disease.


Faith-based human services initiatives: considerations for social work practice and theory.
Faith-based human services initiatives present numerous challenges to professional social work. This article explores ways a theoretical integration of ecosystems and structuration perspectives may help social workers navigate complex ideological and practical implications of changing service delivery policies. The article highlights diversity among faith-related providers, with presentation of a services typology relevant to social work and ethical guidelines to inform decision making regarding referrals and collaborations. Examples from a qualitative study of faith-related services, values, and practices illustrate the typology and related practice issues.


Effects of earnings-supplement policies on adult economic and middle-childhood outcomes differ for the "hardest to employ".
Data from the Minnesota Family Investment Program and the New Hope demonstration were used to determine whether experimental effects of antipoverty policies differ by parents' risk for nonemployment. Using propensity score analysis, increases in employment and income were largest in the harder-to-employ halves of both samples. However, only children in the moderately hard-to-employ quartiles (50th to 75th percentile) consistently showed improvements in school and behavior outcomes. The very-hardest-to-employ 25% experienced decreases in school engagement, and increases in aggressive behaviors, despite substantial increases in parental employment and income. In this group, increases in maternal depression, reductions in regular family routines, and smaller increases in job stability and center-based child care occurred. These factors may have counteracted the potential benefits of increased income on children.


Solution structure as a function of pH of two central mismatches, C . T and C . C, in the 29 to 39 K-ras gene sequence, by nuclear magnetic resonance and molecular dynamics.
The DNA duplexes 5' d(GCCACCAGCTC) x d(GAGCTXGTGGC), where the base X is either cytosine or thymine, have been studied by one and two-dimensional nuclear magnetic resonance, energy minimization and molecular dynamics. The sequence studied corresponds to the region 29 to 39 of the K-ras gene and is a hot spot for mutations. The results show that both duplexes adopt a globally B-DNA-type structure. For the C x C mismatch, we observe a structural change as a function of pH with an apparent pK of 6.95. The neutral species has only one hydrogen bond between the two bases but shows two families of wobble structures where one base or the other is displaced in the major groove. The protonated species has two hydrogen bonds and two structures but of unequal populations. In both systems, the sugar puckers remain predominantly C2'-endo and no significant changes in the backbone structure are observed. The neutral C . T mismatch is stabilized by two hydrogen bonds but, surprisingly, it can also be protonated, although the apparent pK is much lower, 5.65. In this case, protonation does not result in an additional hydrogen bond but must be due to better base-stacking interactions for C+ x T. The NMR data show that the environment of the T imino proton is very similar for C x T and C+ x T, although the hydrogen bond acceptor would be expected to be a nitrogen atom in the former case and an oxygen atom in the latter. We propose that for both structures there is an intervening water molecule which in addition reduces backbone strain. We have also measured the fluctuations during molecular dynamics runs in these mismatches. All are greater than for Watson-Crick base-pairs and the C x C mismatch shows very pronounced mobility.


Saccharomyces cerevisiae-Based Probiotics as Novel Antimicrobial Agents to Prevent and Treat Vaginal Infections.
Vaginal infections affect 70% of women during their lifetimes and account for millions of annual doctors' visits. These infections are predominantly represented by vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV). Although standard antimicrobial agents remain the major strategy for the prevention and treatment of vaginal infections, both VVC and BV are difficult to treat due to high rates of resistance and recurrence, high probability of complications, and negative effects on the vaginal microbiota. This review focuses on a new approach of yeast-based probiotics for the prevention and/or treatment of these common vaginal infections.


[Renovascular hypertension--diagnosis and therapy].
Atherosclerotic renal artery stenosis accounts for most cases of renovascular hypertension (RVH). Hypertensive patients with clinical features suggesting RVH should be submitted to further noninvasive evaluation including duplex Doppler ultrasonography, CT- or MR angiography. Invasive evaluation by contrast-enhanced angiography confirms the diagnosis of renal artery stenosis. However, neither diagnostic test reliably predicts the course of hypertension after revascularisation. The therapeutic approach in hypertensive patients with hemodynamically important renal artery stenosis includes medical or invasive therapy (renal percutaneous transluminal angioplasty, PTRA; renal arterial stent placement, PTRAS; surgical revascularisation). Randomized trials comparing invasive and conservative approaches demonstrated no differences in blood pressure control or renal function. Only patients with clear clinical indications should be submitted to interventional procedures as PTRA, PTRAS and surgical vascular intervention.


In vitro proliferation and production of cytokine and IgG by human PBMCs stimulated with polysaccharide extract from plants endemic to Gabon.
Polysaccharides were extracted from seven plants endemic to Gabon to study their potential immunological activities. Peripheral blood mononuclear cell (PBMC) (5×10⁵ cells/mL) proliferation, cytokine and immunoglobulin G (IgG) assays were performed after stimulation with different concentrations of polysaccharide fractions compared with lipopolysaccharides (LPS) and concanavalin A (ConA) from healthy volunteers. The culture supernatants were used for cytokine and IgG detection by enzyme-linked immunosorbent assay (ELISA). The results show that pectin and hemicellulose extracts from Uvaria klainei, Petersianthus macrocarpus, Trichoscypha addonii, Aphanocalyx microphyllus, Librevillea klaineana, Neochevalierodendron stephanii and Scorodophloeus zenkeri induced production levels that were variable from one individual to another for IL-12 (3-40 pg/mL), IL-10 (6-443 pg/mL), IL-6 (7-370 pg/mL), GM-CSF (3-170 pg/mL) and IFN-γ (5-80 pg/mL). Only hemicelluloses from Aphanocalyx microphyllus produce a small amount of IgG (OD=0.034), while the proliferation of cells stimulated with these polysaccharides increased up to 318% above the proliferation of unstimulated cells. However, this proliferation of PBMCs was abolished when the pectin of some of these plants was treated with endopolygalacturonase (p<0.05), but the trend of cytokine synthesis remained the same, both before and after enzymatic treatment or saponification. This study suggests that these polysaccharides stimulate cells in a structure-dependent manner. The rhamnogalacturonan-I (RGI) fragment alone was not able to induce the proliferation of PBMC.


Biomass-mediated ZSM-5 zeolite synthesis: when self-assembly allows to cross the Si/Al lower limit.
A family of Al-rich ZSM-5 zeolites with Si/Al = 8 ± 0.5 was prepared according to a biomass-mediated supramolecular approach. A combination of advanced characterisation techniques and periodic density functional theory (DFT) calculations unraveled the purity and stability of un-expected Al-enriched ZSM-5 structures, hence allowing to cross the frontier of Si/Al lower limit. In addition, these Al-rich ZSM-5 zeolites demonstrated high catalytic activity in n-hexane cracking and methanol conversion into hydrocarbons, being in line with the presence of numerous Brønsted acid sites.


Drug use during early pregnancy: cross-sectional analysis from the Childbirth and Health Study in Primary Care in Iceland.
To analyse drug use in early pregnancy with special focus on socio-demographic factors associated with psychotropic and analgesic drug use. Cross-sectional study. A total of 1765 women were invited via their local health care centres, and 1111 participated at 11-16 weeks of pregnancy by filling out a postal questionnaire concerning socio-demographic and obstetric background, stressful life events, and drug use. Drug use prior to and early on in pregnancy, socio-demographic factors, smoking, and adverse life events were investigated. Drug categories screened for were psychotropics (collective term for antidepressants, relaxants, and sleep medication), analgesics, hormones, nicotine, vitamins/minerals, and homeopathic medicine. Drug use from the aforementioned drug categories, excluding vitamins/minerals and homeopathic medicine, was reduced by 18% during early pregnancy, compared with six months prior to conception (49% vs. 60%). Psychotropic drug use during early pregnancy was associated with elementary maternal education (p < 0.5), being unemployed (p < 0.001), being single/divorced/separated (p < 0.01), smoking prior to or during pregnancy (p < 0.01), forced to change job/move house (p < 0.001), and psychotropic drug use six months prior to pregnancy (p < 0.001). No items on the stressful life events scale were associated with increased analgesic use, which increased only with multiparity. Use of analgesics and psychotropic drugs seems common in pregnancy. Our results indicate that lack of a support network, stressful life events, and lower status in society may predispose women to more drug use. GPs and midwives responsible for maternity care could take this into account when evaluating risk and gain for women and foetuses in the primary care setting.


Increased Lean Body Mass After Bodyweight-Based High Intensity Interval Training in Overweight and Obese Men.
Purpose: The effects of 8 weeks of bodyweight exercise-based, high-intensity interval training (BWHIIT) on body composition and blood-based markers of metabolic health were investigated in overweight and obese, sedentary young men. Methods: In a parallel group, PRE-POST design, n = 30 men (age, 25.7 ± 4.3 y; body mass index, 27.7 ± 2.1 kg m-2; 26.1 ± 5.2% body fat) were randomized to BWHIIT (n = 20) or a control group (CON; n = 10). BWHIIT consisted of supervised, group-based training sessions (~30 minutes) performed 3 times weekly. Each session consisted of 6 high-intensity bodyweight-based exercises, with each exercise being performed for 4 minutes in the manner of 8 sets of 20 seconds of exercise, 10 seconds of rest. Prior to commencing training (PRE), and 36 h after the final training session (POST), an overnight fasted blood sample was drawn, and body composition was assessed by dual-energy X-ray absorptiometry. Eighteen participants completed the intervention (CON, n = 9; BWHIIT, n = 9). Results: Lean body mass (LBM) was increased at POST in BWHIIT compared to CON (P = .011, η2p = .359), with the mean (95% confidence limits) increase in LBM from PRE to POST within BWHIIT being 1.23 (0.55, 1.92) kg. Body mass and fat mass were unchanged in both groups from PRE to POST. BWHIIT had no effect on serum concentrations of total cholesterol, HDL-C, LDL-C, triglycerides, NEFA, hsCRP, or glucose. Conclusion: Eight weeks of bodyweight exercise-based high intensity interval training by overweight and obese sedentary young men increased LBM by ~2%, but fat mass and blood-based markers of metabolic health were unchanged.


A correlation between symptom severity and unbalanced reactive IgA production in Japanese cedar pollinosis patients.
To better understand the unbalanced immunoglobulin production that occurs in pollinosis, we measured the levels of IgG, IgA, and IgE reactive to either Japanese cedar pollen, Cry j 1 protein, or Cry j 2 protein in the sera of pollinosis patients. As expected, the levels of these immunoglobulins (Igs) reactive to the three antigens were significantly higher in the patients than in the controls, and the RAST scores correlated with the levels of these Igs. Only the levels of IgA reactive to the Cry j 2 protein and IgG reactive to the Japanese cedar pollen antigen did not correlate with the RAST scores. We classified the patients into mild and severe, based on the severity of their allergic symptoms, and compared their levels of Igs. As expected, the levels of IgE reactive to Japanese cedar pollen and Cry j 1 of the severe group were significantly higher than those of the mild group. It is of note that the ratio of anti-Cry j 1 IgE to anti-Japanese cedar pollen IgA was significantly higher in the patients with severe symptoms suggesting that decreased IgA production could be responsible for the severity of pollinosis.


Effects of acetylcholine and substance P on electrical activity of intact toad gastric muscles.
By using isolated gastric muscle cells of Bufo marinus, others have studied the mechanism of action of muscarinic agonists and substance P (SP). To compare responses of isolated cells with those of intact muscles, we have studied the effects of acetylcholine (ACh) and SP on membrane potentials of circular muscle cells in strips of intact muscle from the toad gastric corpus region. These cells had average resting potentials of -69 +/- 0.7 mV. Membrane potential rhythmically depolarized, producing slow waves at an average frequency of 1/min and average amplitude of 25 +/- 2.2 mV. The major effect of ACh (10(-7) to 10(-4) M) was chronotropic; the frequency of slow waves was increased by 88 +/- 11% by 10(-6) M ACh. The amplitudes and rates of rise of slow waves were decreased by ACh. SP had effects similar to ACh; its major effect was chronotropic. The data suggest that ACh and SP primarily affect the pacemaker mechanism in gastric muscles. Since rhythmicity is apparently not expressed in isolated gastric myocytes, it is possible that this effect of these agonists may have been missed in studies of dispersed cells. Our data suggest that the excitatory effects of ACh and SP on contractions may be due to summation of Ca2+ signals, a partial tetanus-like effect.


Homo- and heterometallic chiral dynamic architectures from allyl-palladium(II) building blocks.
New chiral tetranuclear square-like homo- and heterometallamacrocycles containing allyl-palladium and either {Pd(P-P)*} or {Pt(P-P)*} optically pure moieties (P-P* = (2S,3S)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphanyl)butane ((S,S)-DIOP) and (2S,4S)-2,4-bis(diphenylphosphanyl)pentane ((S,S)-BDPP)) have been obtained by the self-assembly of [Pd(η3-2-Me-C3H4)(4-PPh2py)2]+ and [M(P-P)*(H2O)2]2+ building blocks in a 1 : 1 molar ratio. The supramolecular assemblies thus prepared [{Pd(η3-2-Me-C3H4)}2(4-PPh2py)4{M(P-P)*}2](CF3SO3)6 (M = Pd, Pt) have been fully characterised by multinuclear NMR spectroscopy and MS spectrometry. The structures display remarkable differences on their dynamic behaviour in solution that depend on the lability and thermodynamic strength of M-py bonds. The structural characteristics of the new metallamacrocyles obtained have also been unambiguously established by XRD analysis. The architectures have been assayed as catalytic precursors in the asymmetric allylic alkylation reaction.


Enhanced marrow [18F]fluorodeoxyglucose uptake related to myeloid hyperplasia in Hodgkin's lymphoma can simulate lymphoma involvement in marrow.
[18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for the clinical staging of lymphomas and for assessment of response to therapy. We report the case of a woman with classic Hodgkin's lymphoma who had marked FDG uptake by tumor and bone marrow suggestive of diffuse marrow involvement by lymphoma. However, iliac crest bone marrow examination showed marked myeloid hyperplasia without evidence of lymphoma involvement. We discuss the implications for interpretation of FDG-PET imaging of bone marrow in lymphomas.


Comparison of the Moisture Adsorption Properties of Starch Particles and Flax Fiber Coatings for Energy Wheel Applications.
The adsorption-desorption behavior of flax fibers (FFs) is reported in this paper. FFs are a potential desiccant material for air-to-air energy wheels, which transfer heat and moisture in building heating, ventilation, and air conditioning (HVAC) systems. The raw FFs sample was subjected to physical modification, followed by complementary material characterization to understand the relationship between its structure and its moisture uptake performance. The surface and textural properties of the modified FFs were determined by gas adsorption (N2, H2O) and gravimetric liquid water swelling studies and further supported by spectroscopic (infrared and scanning electron microscopy) results. A FF-coated small-scale energy exchanger was used to determine the moisture transfer (or latent effectiveness; εl) using single-step and cyclic testing. The FF-coated exchanger had εl values of ∼10 and 40% greater compared to similar exchangers coated with starch particles (SPs) and silica gel (SG) reported in a previous study. The enhanced surface and textural properties, along with the complex compositional structure of FFs and its greater propensity to swell in water, account for the improved performance over SPs. Thus, FFs offer an alternative low-cost, environment-friendly, and sustainable biodesiccant for air-to-air energy wheel applications in buildings. The current study contributes to an improved understanding of the structure-function relationship of biodesiccants for such energy wheel applications.


Accuracy, stability, and corrective behavior in a visuomotor tracking task: a preliminary study.
Visuomotor tracking tasks have been used to elucidate the underlying mechanisms that allow for the coordination of a movement to an environmental event. The main purpose of the present study was to examine the relationship between accuracy and stability of tracking performance and the amount of corrective movements that emerge for various coordination patterns in a unimanual visuomotor tracking task. Participants (N = 6) produced rhythmic elbow flexion-extension motions and were required to track an external sinusoidal signal at five different relative phases, 0°, 45°, 90°, 135°, and 180°. Differential accuracy and stability were found among the five tracking patterns with the 0° relative phase pattern being the most accurate and stable pattern. Corrective movements were correlated with changes in accuracy only for the 0° relative phase pattern, with more corrections emerging for less accurate performance. The amount of corrective movements decreased as the stability of tracking performance increased for the 0°, 45°, and 135° patterns. For the 90° and 180° tracking patterns, the amount of corrective movements was not correlated with pattern accuracy or pattern stability. The results demonstrate that corrective behaviors are an important motor process in maintaining the stability of stable perception-action coordination patterns, while offering little benefit for unstable perception-action patterns.


Reliability of Waveform Analysis as an Adjunct to Loss of Resistance for Thoracic Epidural Blocks.
The epidural space is most commonly identified with loss of resistance (LOR). Although sensitive, LOR lacks specificity, as cysts in interspinous ligaments, gaps in ligamentum flavum, paravertebral muscles, thoracic paravertebral spaces, and intermuscular planes can yield nonepidural LOR. Epidural waveform analysis (EWA) provides a simple confirmatory adjunct for LOR. When the needle is correctly positioned inside the epidural space, measurement of the pressure at its tip results in a pulsatile waveform. In this observational study, we set out to assess the sensitivity, specificity, as well as positive and negative predictive values of EWA for thoracic epidural blocks. We enrolled a convenience sample of 160 patients undergoing thoracic epidural blocks for thoracic surgery, abdominal surgery, or rib fractures. The choice of patient position (sitting or lateral decubitus), approach (midline or paramedian), and LOR medium (air or normal saline) was left to the operator (attending anesthesiologist, fellow, or resident). After obtaining a satisfactory LOR, the operator injected 5 mL of normal saline through the epidural needle. A sterile tubing, connected to a pressure transducer, was attached to the needle to measure the pressure at the needle tip. A 4-mL bolus of lidocaine 2% with epinephrine 5 μg/mL was then administered and, after 10 minutes, the patient was assessed for sensory blockade to ice. The failure rate (incorrect identification of the epidural space with LOR) was 23.1%. Of these 37 failed epidural blocks, 27 provided no sensory anesthesia at 10 minutes. In 10 subjects, the operator was unable to thread the catheter through the needle. When compared with the ice test, the sensitivity, specificity, and positive and negative predictive values of EWA were 91.1%, 83.8%, 94.9%, and 73.8%, respectively. Epidural waveform analysis (with pressure transduction through the needle) provides a simple adjunct to LOR for thoracic epidural blocks. Although its use was devoid of complications, further confirmatory studies are required before its routine implementation in clinical practice.


Opioid Prescribing for Proximal Row Carpectomy versus Four-Corner Arthrodesis.
Background Proximal row carpectomy (PRC) and four-corner arthrodesis (4-CA) represent motion-sparing procedures for addressing degenerative wrist pathologies. While both procedures demonstrate comparable functional outcomes, postoperative pain presents a surgical challenge that often necessitates the use of opioids. Objectives The aim of this study was to (1) compare opioid prescribing patterns surrounding PRC and 4-CA, (2) identify risk factors predisposing patients to increased perioperative and prolonged postoperative opioids, and (3) examine the association between opioids and perioperative health care utilization. Patients and Methods PearlDiver Patients Records Database was used to retrospectively identify patients undergoing primary PRC and 4-CA between 2010 and 2018. Patient demographics, comorbidities, prescription drug usage, and perioperative health care utilization were evaluated. Perioperative opioid prescriptions and post-operative opioid prescriptions were recorded. Logistic regression analysis evaluated the association of patient risk factors. Results There was no significant difference in perioperative (PRC [odds ratio {OR}: 0.84, p = 0.788]; 4-CA [OR: 0.75, p = 0.658]) or prolonged postoperative opioid prescriptions (PRC [OR: 0.95, p = 0.927]; 4-CA [OR: 0.99, p = 0.990]) between PRC and 4-CA. Chronic back pain and use of benzodiazepines or anticonvulsants were associated with increased risks of prolonged postoperative opioids. Prolonged postoperative opioids presented increased risks of emergency department visits (OR: 2.09, p = 0.019) and hospital readmissions (OR: 10.2, p = 0.003). Conclusion No significant differences exist in the prescription of opioids for PRC versus 4-CA. Both procedures have high amounts of prolonged postoperative opioid use, which is associated with increased risks of emergency department visits and hospital readmissions. Level of Evidence This is a level III, retrospective comparative study.


Effects of wax treatment on the physiology and cellular structure of harvested pineapple during cold storage.
Pineapple (Ananas comosus (L.) Merr. cv. 'Paris') is sensitive to low temperature and highly susceptible to blackheart during cold storage, which causes serious fruit decay. This work investigated the effect of wax treatment (Sta-Fresh 2952, 60 g/L) on blackheart of pineapple under chilling stress. Wax treatment significantly reduced blackheart symptoms after 14 days of storage and markedly delayed changes in firmness and flesh color during the whole period of storage. The weight loss of wax-treated fruit (2.6%) was less than the control (3.1%) at the 24th day of storage. The treatment decreased the activities of PG and EGase for maintaining cell wall stability during the later period of storage. In the control fruit, the structure of flesh cells was significantly damaged under chilling stress, with looser cell wall, absence of middle lamella, loss of membrane integrity, and many cells near the vascular tissue collapsed. The subcellular elements could be barely observed in the control after storage. These destructive symptoms were significantly alleviated in the wax-treated fruit. The results suggest that wax treatment could reduce blackheart of pineapple under chilling stress via maintenance of cell integrity.


Early atherogenesis in White Carneau pigeons. I. Leukocyte margination and endothelial alterations at the celiac bifurcation.
The addition of 0.2% or more cholesterol to the diet of young White Carneau pigeons produced atherosclerotic lesions within 10 weeks in a 2-sq mm area of the lower thoracic aorta. Concurrent with lesion development, a shift in the shape of endothelial cells from fusiform to polygonal was noted. This shift changed the ratio of endothelial cell width to length from 0.34 in pigeons receiving a control diet to 0.50 in pigeons receiving cholesterol. In contrast, endothelial cells in an atherosclerosis-resistant region 6 cm superior to the test region retained their fusiform shape despite the addition of cholesterol to the pigeon's diet. Cholesterol diets also increased adherence of leukocytes to the luminal surface of the aorta. This was most prevalent at the edge of large lesions (2430 +/- 180 cells/sq mm) and over small lesions (2240 +/- 150 cells/sq mm). Leukocyte adherence was also increased in the central region of large lesions (960 +/- 140 cells/sq mm). In addition, leukocyte activation, as evidence by crawling or spreading cells, was increased almost twofold over small lesions and the edge of large lesions when compared with adherent cells over nonlesion areas.


The intravenous furosemide test: a simple way to evaluate renin responsiveness.
To identify patients with low-renin hypertension, we measured plasma renin activity after the administration of 40 mg of furosemide intravenously and 30 minutes of upright posture in 127 normotensive subjects and 363 patients with essential hypertension. Plasma renin activity 30 minutes after intravenous furosemide was found to be closely correlated to the level found after either 2 or 4 h of standing or 3 days of a low-salt diet plus 2 h of upright posture. Renin responsiveness was significantly lower in hypertensive patients, blacks, and women, compared with normotensive subjects, whites, and men respectively. The level of plasma renin activity in most normal white subjects was greater than 1.0 ng/ml - h and in most normal blacks was greater than 0.5 ng/ml - h. It was below those levels in 23% of white hypertensive and 25.2% of black hypertensive patients respectively. The mean level of plasma renin activity fell with increasing age of hypertensive patients. This procedure is recommended as a safe, easy, and reliable test for assessing renin responsiveness and identifying the low-renin state.


Coordination of Rho family GTPase activities to orchestrate cytoskeleton responses during cell wound repair.
Cells heal disruptions in their plasma membrane using a sophisticated, efficient, and conserved response involving the formation of a membrane plug and assembly of an actomyosin ring. Here we describe how Rho family GTPases modulate the cytoskeleton machinery during single cell wound repair in the genetically amenable Drosophila embryo model. We find that Rho, Rac, and Cdc42 rapidly accumulate around the wound and segregate into dynamic, partially overlapping zones. Genetic and pharmacological assays show that each GTPase makes specific contributions to the repair process. Rho1 is necessary for myosin II activation, leading to its association with actin. Rho1, along with Cdc42, is necessary for actin filament formation and subsequent actomyosin ring stabilization. Rac is necessary for actin mobilization toward the wound. These GTPase contributions are subject to crosstalk among the GTPases themselves and with the cytoskeleton. We find Rho1 GTPase uses several downstream effectors, including Diaphanous, Rok, and Pkn, simultaneously to mediate its functions. Our results reveal that the three Rho GTPases are necessary to control and coordinate actin and myosin dynamics during single-cell wound repair in the Drosophila embryo. Wounding triggers the formation of arrays of Rho GTPases that act as signaling centers that modulate the cytoskeleton. In turn, coordinated crosstalk among the Rho GTPases themselves, as well as with the cytoskeleton, is required for assembly/disassembly and translocation of the actomyosin ring. The cell wound repair response is an example of how specific pathways can be activated locally in response to the cell's needs.


Treatment of cystoid macular edema after cataract surgery.
The purpose of this review was to determine the optimum pharmacologic treatment for cystoid macular edema (CME) after cataract surgery in nondiabetic and diabetic patients. The Cochrane Library, Medline, and Embase databases were searched, and all randomized controlled trials (RCTs) that compared at least 2 pharmacologic strategies for CME after cataract surgery were included. Studies were excluded if preoperative CME or other risk factors for developing CME postoperatively were present. Ten RCTs were included in the systematic review. Five trials included at least 30 participants. Three RCTs showed a greater visual acuity improvement in patients treated with topical nonsteroidal antiinflammatory drugs (NSAIDs) than with a placebo. Other studies comparing the efficacy of topical NSAIDs, topical corticosteroids, sub-Tenon corticosteroids, oral NSAIDs, and oral acetazolamide did not report significant differences between treatment groups. Therefore, large RCTs are needed to provide evidence-based recommendations for the optimum treatment of CME after cataract surgery.


Endothelial Cell Loss after Phacoemulsification according to Different Anterior Chamber Depths.
Purpose. To compare the loss of corneal endothelial cells after phacoemulsification according to different anterior chamber depths (ACDs). Methods. We conducted a prospective study on 135 eyes with senile cataracts. Eyes with nuclear density grades of 2 to 4 were divided into three groups according to ACD: ACD I, 1.5 < ACD ≤ 2.5 mm; ACD II, 2.5 < ACD ≤ 3.5 mm; or ACD III, 3.5 < ACD ≤ 4.5 mm. Intraoperative mean cumulative dissipated energy (CDE) was measured. Clinical examinations included central corneal thickness (CCT) and endothelial cell count (ECC) preoperatively and 2 months postoperatively. Results. There were no significant differences in CDE among the ACD groups (P > 0.05). Endothelial cell loss was significantly higher in ACD I than in ACD III in grades 3 and 4 cataract density groups 2 months after phacoemulsification (P < 0.05). There were also more changes in CCT in all of the cataract density groups in the ACD I group compared to the ACD II and III groups 2 months postoperatively, but the difference was not statistically significant. Conclusions. Eyes with shallow ACDs, especially those with relatively hard cataract densities, can be vulnerable to more corneal endothelial cell loss in phacoemulsification surgery.


Genome maintenance and mutagenesis in embryonic stem cells.
Widespread loss of heterozygosity (LOH) in cancer cells is often thought to result from chromosomal instability caused by mutations affecting DNA repair/genome maintenance; however, the origin of LOH in most tumors is unknown. In a recent study, we examined the ability of carcinogenic agents to induce LOH in diploid mouse embryo-derived stem (ES) cells. Brief exposures to nontoxic levels of several carcinogens stimulated genome-wide LOH, with maximum per-gene frequencies approaching one percent. These results suggest that LOH contributes significantly to the carcinogenicity of a variety of mutagens, and that genome-wide LOH may result from prior exposure to genotoxic agents rather than from a state of chromosomal instability during the carcinogenic process. Mechanisms in stem cells that influence carcinogen-induced LOH are likely to play central roles in the etiology of nonhereditary cancers that often arise after extensive carcinogen exposures.


Bisphenol A affects endocrine physiology and biotransformation enzyme activities of the field vole (Microtus agrestis).
Bisphenol A (BPA), an environmental estrogen, was given subcutaneously for 4 days to 48 field voles at three doses (10, 50, or 250 mg kg(-1) day(-1)). Plasma sex steroids, thyroxine, weight-regulatory hormones, and liver biotransformation enzymes were determined. There was no mortality in the control group but the mortality in the BPA-exposed animals was significant. BPA increased the plasma testosterone concentrations at 250 mg BPA kg(-1) day(-1). The plasma ghrelin levels measured from pooled plasma increased and at the same time the leptin levels measured from pooled plasma decreased at 50 or 250 mg BPA kg(-1) day(-1). The liver 7-ethoxyrufin-o-deethylase activity decreased slightly at all doses, as did the liver cytosolic glutathione S-transferase activity at 250 mg BPA kg(-1) day(-1). The results show that wild mammals such as the field vole could be more susceptible to BPA than laboratory rodents. More studies on wild mammals are needed to determine the risks of endocrine disruptors in natural ecosystems.


An experimental evaluation of the generalized sinusoidal frequency modulated waveform for active sonar systems.
This paper experimentally evaluates the Generalized Sinusoidal Frequency Modulated (GSFM) waveform, a generalization of the Sinusoidal Frequency Modulated (SFM) waveform. The Instantaneous Frequency (IF) of the GSFM resembles the time/voltage characteristic of a Linear Frequency Modulated (LFM) chirp waveform. Consequently, the GSFM possesses an Ambiguity Function (AF) that resembles a thumbtack shape. Practical sonar system design must consider two factors beyond the AF. The Spectral Efficiency (SE), defined as the ratio of energy in an operational frequency band to the total waveform energy, is another important metric for waveform design. The Peak-to-Average-Power Ratio (PAPR) quantifies how close the waveform is to constant amplitude. These measures predict a waveform's energy efficiency and ability to be accurately replicated on practical piezoelectric transducers, which have limits on both their bandwidth and maximum transmit power. This paper explores these design considerations for the GSFM waveform and evaluates its performance against a host of other well established waveforms using simulated and experimental acoustic data. The GSFM possesses superior SE, PAPR, and overall energy efficiency when compared to other thumbtack waveforms.


Water Vapor Sorption in Hybrid Pillared Square Grid Materials.
We report water vapor sorption studies on four primitive cubic, pcu, pillared square grid materials: SIFSIX-1-Cu, SIFSIX-2-Cu-i, SIFSIX-3-Ni, and SIFSIX-14-Cu-i. SIFSIX-1-Cu, SIFSIX-3-Ni, and SIFSIX-14-Cu-i were observed to exhibit negative water vapor adsorption at ca. 40-50% relative humidity (RH). The negative adsorption is attributed to a water-induced phase transformation from a porous pcu topology to nonporous sql and sql-c* topologies. Whereas the phase transformation of SIFSIX-1-Cu was found to be irreversible, SIFSIX-3-Ni could be regenerated by heating and can therefore be recycled. In contrast, SIFSIX-2-Cu-i, which is isostructural with SIFSIX-14-Cu-i, exhibited a type V isotherm and no phase change. SIFSIX-2-Cu-i was observed to retain both structure and gas sorption properties after prolonged exposure to heat and humidity. The hydrolytic stability of SIFSIX-2-Cu-i in comparison to its structural counterparts is attributed to structural features and therefore offers insight into the design of hydrolytically stable porous materials.


High-throughput bioluminescence screening of ubiquitin-proteasome pathway inhibitors from chemical and natural sources.
To discover original inhibitors of the ubiquitin-proteasome pathway, the authors have developed a cell-based bioluminescent assay and used it to screen collections of plant extracts and chemical compounds. They first established a DLD-1 human colon cancer cell line that stably expresses a 4Ubiquitin-Luciferase (4Ub-Luc) reporter protein, efficiently targeted to the ubiquitin-proteasome degradation pathway. The assay was then adapted to 96- and 384-well plate formats and calibrated with reference proteasome inhibitors. Assay robustness was carefully assessed, particularly cell toxicity, and the statistical Z factor value was calculated to 0.83, demonstrating a good performance level of the assay. A total of 18,239 molecules and 15,744 plant extracts and fractions thereof were screened for their capacity to increase the luciferase activity in DLD-1 4Ub-Luc cells, and 21 molecules and 66 extracts inhibiting the ubiquitin-proteasome pathway were identified. The fractionation of an active methanol extract of Physalis angulata L. aerial parts was performed to isolate 2 secosteroids known as physalin B and C. In a cell-based Western blot assay, the ubiquitinated protein accumulation was confirmed after a physalin treatment confirming the accuracy of the screening process. The method reported here thus provides a robust approach to identify novel ubiquitin-proteasome pathway inhibitors in large collections of chemical compounds and natural products.


[Spinal injection : risks and side effects].
The efficacy of spinal injection for chronic spinal pain is dubious for most conditions. They are however frequently prescribed. Side effects are poorly reported in the literature. In addition to benign and transient problems, serious and lethal side effects have been reported due to infection, hematoma or central and spinal cord infarctions which could be related to intravascular injection of corticoids. Although their frequency is excessively low, they should be discussed with every patient before prescription and should be mentioned in the consent form.


Phosphorylation state of HMG CoA reductase affects its catalytic activity and degradation.
The expressed catalytic activity of liver microsomal HMG CoA reductase, the limiting enzyme in cholesterol synthesis, is reversibly diminished by phosphorylation in vitro. In intact hepatocytes the expressed activity of HMG CoA reductase is enhanced by incubation of cells with insulin, and diminished by treatment with glucagon or with mevalonate. In the latter situations the level of total reductase activity falls following initial inactivation (phosphorylation) of the enzyme. This observation suggested that the phosphorylated form of HMG CoA reductase is more sensitive to proteolysis. HMG CoA reductase is a 97,000 dalton (97 K) integral protein of the endoplasmic reticulum with a cytosolic domain that includes the catalytic site and serine residues that may be reversibly phosphorylated. In vitro the Ca2+-activated proteolytic enzyme, calpain, generates two catalytically-active fragments: a membrane bound 62 K and a soluble 53 K form of the enzyme which are quantified by specific immunoblot procedures. Cleavage of the native 97 K HMG CoA reductase is enhanced by pretreatment (inactivation) of microsomes with ATP (Mg2+) and liver reductase kinase compared to microsomes pretreated with protein phosphatase. This is reflected in a loss of 97 K reductase and an increase in the soluble 53 K form of the enzyme. Degradation of HMG CoA reductase in hepatocytes is partially blocked by lysosomotropic agents and insulin. A steady state model for the turnover of proteins subject to reversible phosphorylation has been developed which recognizes fractional degradative rate constants for the phosphorylated and dephosphorylated species.


Hybrid Repair Techniques for Complex Aneurysms and Dissections Involving the Aortic Arch and Thoracic Aorta.
Aortic aneurysms involving the ascending aorta, aortic arch, and descending thoracic aorta have been a challenging entity to surgically treat for over 60 years. Despite the mortality of the disease, early open surgical procedures also had significant morbidity and mortality. The inherent risk in treating multiple anatomic segments simultaneously led to the innovation of the staged elephant trunk (ET) approach by Borst in 1983. To avoid the thoracotomy and associated complications related to the second stage of the procedure, an endovascular completion paradigm was begun by Volodos in 1991. This theoretical hybrid technique combinined shorter and less elaborate open supra-aortic trunk debranching with less invasive endovascular exclusion and has grown since then in terms of different approaches and case volume. The rise of thoracic endovascular aortic repair (TEVAR) combined with debranching bypass has allowed certain lesions to be treated without a large scale intrathoracic open surgical procedure. The complexity and extensiveness of certain lesions, however, has necessitated a hybrid approach such as the frozen elephant trunk (FET) and the standard ET with second stage TEVAR. The former has been used to treat multifocal degenerative aneurysms, chronic dissections with aneurysm, and acute extensive dissections. After conventional proximal aortic replacement, a stent-graft (SG) is delivered antegrade through the transected arch where it is sutured proximally and then "frozen" distally via endovascular means. The FET has the advantage of avoiding a second stage, but potentially introduces a greater rate of spinal cord ischemia compared to the standard elephant trunk. Improvements on the FET procedure have included the development of more advanced hybrid SG such as the Vascutek® Thoraflex™ Hybrid graft (Vascutek Ltd, Scotland, UK), which consists of a distal en,dograft sealed to a proximal four-branched Vascutek Gelweave™ Vascutek Ltd, Scotland, UK) and incorporated sewing collar. While open surgery continues to be a component of complex aortic arch aneurysms, the development of hybrid devices that can bridge the gap between open and endovascular surgery will continue to flourish.


A Virtual Instructional Design Improved Breaking Bad News in Obstetrics and Gynecology Residents.
Breaking bad news to the patient is challenging, especially for the physicians and the residents, due to the lack of structured and practical training. This study aimed to design and evaluate a novel virtual instructional design for improving obstetrics and gynecology (Ob/Gyn) residents breaking bad news skills. Virtual instructional design was performed based on the ADDIE model (Analysis, Design, Development, Implementation and Evaluation) from September 2020 to July 2021 at the Department of Ob/Gyn, a referral hospital affiliated with Tehran University of Medical Sciences, Tehran. Iran. The five steps of ADDIE virtual instructional design were applied sequentially. Totally 33 of the Ob/Gyn residents included in the study that 77% needed specific training. The awareness of the performance of the residents in seven areas including interview context, strategy, planning, professionalism, empathy, knowledge, and receiving information needed to be trained for breaking bad news. The content of the virtual training package was designed based on the prior assessment needs in four multimedia lectures of professors, one short educational video, a 65-page file that combines text and images in 4 parts. The pre-test and post-test mean scores (SD) were 9.45 (2.0) and 10.67 (1.7), respectively (p-value≤0.001) in the cognitive and attitudinal domain. In the final step, the final corrections were made in the virtual training package. Interestingly, the satisfaction of residents' attitudes was 96.5%. Most Ob/Gyn residents do not have the necessary perception and skills to deliver bad news to the patients. Designing an appropriate virtual training package for improving communication skills is associated with satisfaction. Thus, the efficacy of the training program should be implemented for all Ob/Gyn residents.


Selected aspects of europeization of pharmaceutical law.
As one of its aspects, the process of European integration has an influence on the legal orders of the Member States, which is often referred to in the literature as the europeization of law. Upon Poland's accession to the structures of the European Union, there have also been radical changes to the Polish legal system. According to the concept of the sources of law in the Polish Constitution and to the judicial decisions of the European Court of Justice, Community law now takes priority over national law, even over acts of parliament. Pharmaceutical law represents one of the areas where the harmonization process has been taking place. It shapes the principles and the manner according to which medicinal products are approved for marketing, the conditions of clinical trials, as well as the conditions of drug manufacture and advertisement. It also determines the rules of trading in medicinal products, the running of pharmaceutical wholesalers and pharmacies, as well as the duties and rights of the Pharmaceutical Inspectorate. This paper provides a summary of research on the impact of Community law on Polish pharmaceutical law, i.e. on the europeization process, and on the consequences of this process for the Polish pharmaceutical market and for research and development.


Dual-energy computed tomography for non-invasive prediction of the risk of oesophageal variceal bleeding with hepatitis B cirrhosis.
Oesophageal variceal bleeding (OVB) is a fatal complication of cirrhosis and/or portal hypertension. We aimed to develop a non-invasive prediction model for the risk of OVB using dual-energy computed tomography (CT). 317 oesophageal varices (OV) patients with hepatitis B virus-related cirrhosis were retrospectively assessed from January 2018 to December 2018. All patients underwent dual-energy CT scans within 14 days before endoscopy. 222 of 317 patients (174 OVB-negative patients and 48 OVB-positive patients) were included in the training cohort and 95 patients (74 OVB-negative patients and 21 OVB-positive patients) were included in the validation cohort chronologically. A model with the selected conventional CT features and a model with the conventional CT and dual-energy CT features were developed. The prediction accuracy was evaluated using the receiver operating characteristic (ROC) curve. The accuracy and reproducibility of the models for OVB risk prediction of cirrhosis were validated by the validation cohort. The areas under the curve (AUC) of the two models were compared with Delong test. Diameter of oesophageal vein (OV(mm)), diameter of splenic vein (SPV(mm)), ascites (AS), iodine concentration in short gastric vein (SGV(HU)), iodine concentration in spleen (SP(HU)) were independent predictors of OVB risk (P < 0.05). Then, we developed a model with the selected conventional CT features [OV(mm), SPV(mm), AS] and a model with the conventional CT and dual-energy CT features [OV(mm), SPV(mm), AS, SGV(HU), SP(HU)]. The AUCs of the model built with the conventional CT and dual-energy CT features were higher than the model built only with the conventional CT features in the training (0.839 vs 0.809) and validation cohorts (0.798 vs 0.738). The non-invasive prediction model developed with the conventional CT and dual-energy CT features may have added value in noninvasively predicting OVB than the model built only with the conventional CT features and may have significant clinical implications on early prevention and treatment of OVB. Combination of dual-energy CT with conventional CT may have added value for non-invasive prediction of OVB compared to conventional CT.


Large discrete jumps observed in the transition between Chern states in a ferromagnetic topological insulator.
A striking prediction in topological insulators is the appearance of the quantized Hall resistance when the surface states are magnetized. The surface Dirac states become gapped everywhere on the surface, but chiral edge states remain on the edges. In an applied current, the edge states produce a quantized Hall resistance that equals the Chern number C = ±1 (in natural units), even in zero magnetic field. This quantum anomalous Hall effect was observed by Chang et al. With reversal of the magnetic field, the system is trapped in a metastable state because of magnetic anisotropy. We investigate how the system escapes the metastable state at low temperatures (10 to 200 mK). When the dissipation (measured by the longitudinal resistance) is ultralow, we find that the system escapes by making a few very rapid transitions, as detected by large jumps in the Hall and longitudinal resistances. Using the field at which the initial jump occurs to estimate the escape rate, we find that raising the temperature strongly suppresses the rate. From a detailed map of the resistance versus gate voltage and temperature, we show that dissipation strongly affects the escape rate. We compare the observations with dissipative quantum tunneling predictions. In the ultralow dissipation regime, two temperature scales (T 1 ~ 70 mK and T 2 ~ 145 mK) exist, between which jumps can be observed. The jumps display a spatial correlation that extends over a large fraction of the sample.


High thermoelectric performance of half-Heusler ZrXPb (X= Ni, Pd, and Pt) compounds from first principle calculation.
Half-Heusler compounds have distinguished themselves as outstanding thermoelectric materials on account of high temperature stability and large thermopower. However, the dimensionless figure of merit of traditional half-Heusler alloys remains low. In this study, we investigate the thermoelectric performance of novel ZrXPb (X= Ni, Pd, and Pt) ternary compounds by semi-classical Boltzmann transport theory combining with deformation potential. The n-type ZrNiPb and ZrPtPb exhibits obviously largeZTvalues of 1.71 around 650 K and 1.75 around 1200 K, with 1.17 × 1020 cm-3and 3.43 × 1020 cm-3, respectively. The electron and phonon structure calculations demonstrate that for the n-type ZrXPb (X= Ni, Pd, and Pt) compounds, doping at Pb site can not only modify the carrier concentrations but also significantly decrease the lattice thermal conductivity. These investigations are expected to be beneficial to the exploration of novel highZTthermoelectric materials.


Forced resting by high dietary zinc: tissue zinc accumulation and reproductive organ weight changes.
An experiment was conducted to investigate the effects of high dietary zinc, as a means of inducing a forced-rest, on selected organ accumulation of zinc and reproductive function in terms of ovary and oviduct weight in the laying hen. Single Comb White Leghorn hens laying approximately at 60% production were fed either 10,000 ppm zinc as zinc oxide (10 Zn) or 20,000 ppm zinc (20 Zn) for a period of 4 days. At the initiation of the experiment (Day 0), five hens were killed and organs obtained for analysis. On 4, 10, 16, and 22 days afterward, similar samples were obtained from 5 hens per treatment. Ovary and oviduct weights were determined and zinc analysis performed on the latter as well as liver, kidney, and pancreas. The brief 4-day feeding of either high zinc diet caused a marked 80% reduction in ovary weight by Day 10. The oviduct, although less affected, was still reduced approximately 60% in weight after feeding either 10 Zn or 20 Zn for 4 days. The oviduct exhibited a statistically significant elevation in zinc concentration on Day 4 but was normal by Day 10 (6 days following the refeeding of a normal diet) and not different between treatments. There was extensive accumulation of zinc in kidney, liver, and especially pancreas after 4 days of feeding either 10 Zn or 20 Zn. The level of dietary zinc had no effect on the extent of accumulation in any tissue. The depletion of tissue zinc roughly corresponded to the magnitude of increase in the concentration of zinc observed at Day 4. Possible ramifications of the dramatic increase observed in pancreatic zinc were discussed. We concluded that feeding either 10 Zn or 20 Zn as a means of inducing a forced rest effects a marked and rapid reduction in ovary and oviduct weight as well as an extensive increase in renal, hepatic, and especially pancreatic zinc.


Potential latentiation forms of biologically active compounds based on action of leucine aminopeptidase. Dipeptide derivatives of the tricycloaliphatic alpha-amino acid, adamantanine.
Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leucyladamantanine appeared to be absorbed in vivo as evidenced by its appearance in the uring following intraperitoneal administration, they were not hydrolyzed by a purified preparation of leucine aminopeptidase in vitro. Indeed, they were inhibitors of this enzyme. Adamantanylglycine, adamantanyl-L-leucine, and adamantanyl-L-phenylalanine were also not hydrolyzed by leucine aminopeptidase.


Brazilein inhibits neuronal inflammation induced by cerebral ischemia and oxygen-glucose deprivation through targeting NOD2 expression.
Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.


Chronic Diseases Associated With Mortality in British Columbia, Canada During the 2021 Western North America Extreme Heat Event.
Western North America experienced an unprecedented extreme heat event (EHE) in 2021, characterized by high temperatures and reduced air quality. There were approximately 740 excess deaths during the EHE in the province of British Columbia, making it one of the deadliest weather events in Canadian history. It is important to understand who is at risk of death during EHEs so that appropriate public health interventions can be developed. This study compares 1,614 deaths from 25 June to 02 July 2021 with 6,524 deaths on the same dates from 2012 to 2020 to examine differences in the prevalence of 26 chronic diseases between the two groups. Conditional logistic regression was used to estimate the odds ratio (OR) for each chronic disease, adjusted for age, sex, and all other diseases, and conditioned on geographic area. The OR [95% confidence interval] for schizophrenia among all EHE deaths was 3.07 [2.39, 3.94], and was larger than the ORs for other conditions. Chronic kidney disease and ischemic heart disease were also significantly increased among all EHE deaths, with ORs of 1.36 [1.18, 1.56] and 1.18 [1.00, 1.38], respectively. Chronic diseases associated with EHE mortality were somewhat different for deaths attributed to extreme heat, deaths with an unknown/pending cause, and non-heat-related deaths. Schizophrenia was the only condition associated with significantly increased odds of EHE mortality in all three subgroups. These results confirm the role of mental illness in EHE risk and provide further impetus for interventions that target specific groups of high-risk individuals based on underlying chronic conditions.


The effect of plate design, bridging span, and fracture healing on the performance of high tibial osteotomy plates: An experimental and finite element study.
Opening wedge high tibial osteotomy (HTO) is an established surgical procedure for the treatment of early-stage knee arthritis. Other than infection, the majority of complications are related to mechanical factors - in particular, stimulation of healing at the osteotomy site. This study used finite element (FE) analysis to investigate the effect of plate design and bridging span on interfragmentary movement (IFM) and the influence of fracture healing on plate stress and potential failure. A 10° opening wedge HTO was created in a composite tibia. Imaging and strain gauge data were used to create and validate FE models. Models of an intact tibia and a tibia implanted with a custom HTO plate using two different bridging spans were validated against experimental data. Physiological muscle forces and different stages of osteotomy gap healing simulating up to six weeks postoperatively were then incorporated. Predictions of plate stress and IFM for the custom plate were compared against predictions for an industry standard plate (TomoFix). For both plate types, long spans increased IFM but did not substantially alter peak plate stress. The custom plate increased axial and shear IFM values by up to 24% and 47%, respectively, compared with the TomoFix. In all cases, a callus stiffness of 528 MPa was required to reduce plate stress below the fatigue strength of titanium alloy. We demonstrate that larger bridging spans in opening wedge HTO increase IFM without substantially increasing plate stress. The results indicate, however, that callus healing is required to prevent fatigue failure.Cite this article: A. R. MacLeod, G. Serrancoli, B. J. Fregly, A. D. Toms, H. S. Gill. The effect of plate design, bridging span, and fracture healing on the performance of high tibial osteotomy plates: An experimental and finite element study. Bone Joint Res 2018;7:639-649. DOI: 10.1302/2046-3758.712.BJR-2018-0035.R1.


[A reactivity to polyclonal stimulation of immunogenesis with salmozan after its repeated administration].
The injection of 100 micrograms of salmozan (polysaccharide isolated from Salmonella typhi somatic O-antigen) or 50 micrograms of Escherichia coli lipopolysaccharide into mice induced a considerable increase in the number of antibody-forming cells in the spleen in response to the injection of sheep red blood cells (SRBC) 2-3 days later. This polyclonal effect was essentially weaker if the animals previously received 500 micrograms of salmozan (9-10 days prior to the injection of SRBC). The absence of reactivity was not linked with antibodies to salmozan or with some other serum factor. The lymphocytes of nonreactive mice proved to be capable of polyclonal response in the adoptive system, and at the same time the polyclonal response of intact lymphocytes to salmozan in the body of nonreactive irradiated mice was essentially weakened. The features making the above phenomenon similar to, as well as different from, the so-called "endotoxin tolerance" are analyzed.


Antigenicity of beta-lactam antibiotic preparations: production of IgE antibodies to beta-lactam antibiotic and their cross-reaction within the antibiotic group.
BALB/C mice were immunized with conjugate of benzylpenicillin or ampicillin with Ascaris suum extract. The mice developed IgE antibodies to penicillin, which were found to react with commercially available penicillin preparations in the PCA system. Elimination of polymerized penicillin by Sephadex chromatography from tested preparations could not diminish their activities to elicit PCA. High pressure liquid chromatographic (HPLC) separation of PcG preparation yielded fractions unable to elicit PCA. On the other hand, all fractions from ABPC retained the activity even after the HPLC purification. A comparative estimation of cross-reactivity of IgE and IgE antipenicillin antibodies showed that IgE antibodies cross-reacted with a variety of beta-lactam antibiotics in a high degree.


Measuring the spatial distribution of multiply scattered light using a de-scanned image sensor for examining retinal structure contrast.
An optical platform is presented for examining intrinsic contrast detection strategies when imaging retinal structure using ex vivo tissue. A custom microscope was developed that scans intact tissue and collects scattered light distribution at every image pixel, allowing digital masks to be applied after image collection. With this novel approach at measuring the spatial distribution of multiply scattered light, known and novel methods of detecting intrinsic cellular contrast can be explored, compared, and optimized for retinal structures of interest.


Using Nicotine in A Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition.
Smoking and exposure to silica are common among occupational workers, and silica is more likely to injure the lungs of smokers than non-smokers. The role of nicotine, the primary addictive ingredient in cigarettes, in silicosis development is unclear. The mouse model employed in this study was simple and easily controlled, and it effectively simulated the effects of chronic nicotine ingestion and repeated exposure to silica on lung fibrosis through epithelial-mesenchymal transition in human beings. In addition, this model can help in the direct study of the effects of nicotine on silicosis while avoiding the effects of other components in cigarette smoke. After environmental adaptation, mice were injected subcutaneously with 0.25 mg/kg nicotine solution into the loose skin over the neck every morning and evening at 12 h intervals over 40 days. Additionally, crystalline silica powder (1-5 µm) was suspended in normal saline, diluted to a suspension of 20 mg/mL, and dispersed evenly using an ultrasonic water bath. The isoflurane-anesthetized mice inhaled 50 µL of this silica dust suspension through the nose and were awoken via chest massage. Silica exposure was administrated daily on days 5-19. The double-exposed mouse model was exposed to nicotine and then silica, which matches the exposure history of workers who are exposed to both harmful factors. In addition, nicotine promoted pulmonary fibrosis through epithelial-mesenchymal transformation (EMT) in mice. This animal model can be used to study the effects of multiple factors on the development of silicosis.


Minimally invasive lobectomy versus stereotactic ablative radiotherapy for stage I non-small cell lung cancer.
A minimally invasive lobectomy (MIL) is the standard treatment for stage I non-small cell lung cancer (NSCLC) in medically operable patients. Stereotactic ablative radiotherapy (SABR) is recommended for inoperable patients and has been proposed as a potential alternative for operable patients as well. Here, we present the results of a feasibility study in preparation for a nationwide retrospective cohort study, comparing outcomes between both treatment modalities. In this retrospective cohort study, data from patients with clinical stage I NSCLC treated with MIL or SABR in 2014-2015 were retrieved from databases from 12 Dutch hospitals. Progression-free survival (PFS), overall survival (OS) and lung cancer-specific survival (LCSS) were compared between MIL and SABR. A total of 597 patients with clinical stage I NSCLC treated with MIL (n = 356) or SABR (n = 241) were included. In total, 106 (30%) patients had died in the MIL group and 142 (59%) in the SABR group. After MIL and SABR, unadjusted 5-year PFS was 63% and 30%, OS was 72% and 38% and LCSS was 81% and 76%, respectively. Propensity score-weighted analyses did not show significant differences between MIL and SABR in OS [hazard ratios (HR) 0.74 (95% confidence interval (CI) 0.43-1.29)], PFS [HR 0.74 (95% CI 0.42-1.32)] or LCSS [HR 0.81 (95% CI 0.42-1.59)]. Unadjusted analyses revealed superior OS and PFS for MIL and similar LCSS, but this feasibility study was not sufficiently powered to demonstrate significant differences using propensity score methodology. Therefore, this study is currently being extended to include more than half of Dutch hospitals in order to enlarge the population to ≥1880 patients, not only to determine the best treatment for patients with stage I NSCLC overall, but also to assess the preferred treatment for patient groups with specific characteristics.