Isolation and structure determination of a new lantibiotic cinnamycin B from Actinomadura atramentaria based on genome mining.
New lantibiotic cinnamycin B was isolated from the extract of Actinomadura atramentaria NBRC 14695(T), based on genome mining and chemical investigation. The partial structure of cinnamycin B was established by 2D NMR experiments, which indicated that cinnamycin B had same methyl lanthionine bridging pattern with cinnamycin. The reduction with NaBH4-NiCl2 afforded the reduced cinnamycin B, and MS/MS experiment indicated the presence of hydroxy asparatic acid in the molecule. Cinnamycin B showed an antibacterial activity against Streptomyces antibioticus with dosage of 5 μg (0.5μL, 10 mg/mL solution) at spot-on-lawn testing method. The gene cluster of cinnamycin B on the genome of A. atramentaria was identified and discussed in comparison with that of cinnamycin.


Wound botulism from heroin skin popping.
Following the introduction of black tar heroin mainly from Mexico in the 1980s, cases of wound botulism dramatically increased in the western United States. Contamination with spores of Clostridium botulinum of black tar heroin occurs along the distribution line. The heating of heroin powder to solubilize it for subcutaneous injection ("skin popping") does not kill the spores. The spores germinate in an anaerobic tissue environment and release botulinum toxin type A or B. Unless skin abscesses are found in the patient, the clinical diagnosis is often challenging. Facilitation of the compound muscle action potential by repetitive nerve stimulation at 20 to 50 Hz is an important and rapid diagnostic test. Definite diagnosis is made by detection of botulinum toxin in serum or isolation of C botulinum from the abscess. Early treatment with equine ABE botulinum antitoxin obtained from the Centers for Disease Control and Prevention often shortens the time on a ventilator.


Regional cerebral blood flow imaging: a quantitative comparison of 99mTc-bicisate with 133Xe using single photon emission computed tomography.
The aim of this study was to compare 99mTc-bicisate with 133Xe inhalation in regional CBF (rCBF) imaging. Five healthy volunteers and five patients were imaged with both techniques. Regional standardized values (SVs) of 99mTc-bicisate, uptake indexes (UIs), and asymmetry indexes (AIs) were compared quantitatively with, respectively, rCBF, flow indexes (FIs), and AIs. Areas with highest rCBF (sylvian and thalamic areas) appeared to be underestimated with 99mTc-bicisate, but significant correlations were found between SV and rCBF (n = 140, r = 0.468, p < 0.01) and for the 10 subjects between UI and FI and between AIs (p < 0.0001). There are therefore distinct regional differences in the cerebral distinction of 99mTc-bicisate and CBF, particularly in the thalamus and the temporal cortex. It is probable but not yet proved that an underestimation of high flow rates occurs with bicisate.


Characterization of Gordonia sp. strain CC-NAPH129-6 capable of naphthalene degradation.
A naphthalene-degrading isolate able to utilize naphthalene as a sole carbon source was identified as Gordonia sp. CC-NAPH129-6. Here a detail characterization of the naphthalene catabolic genes present in this strain was conducted. In nar region four structural genes (narAa, narAb, narB, narC), two regulatory genes (narR1, narR2), a rubredoxin encoding gene (rub1) and a gene (orf7) with unknown function were obtained. When compared with most of the members within naphthalene-degrading Rhodococcus, these naphthalene catabolic genes in strain CC-NAPH129-6 were organized into an operon-like gene cluster and present in the same order. This naphthalene gene cluster located in a 97-kb small plasmid of strain CC-NAPH129-6, as can be seen from the PFGE and Southern blot hybridization data. Besides, a partial transposase sequence containing an IS element structure with 12-nt inverted repeat at both ends was found, which was flanked by direct repeats downstream the narC gene in strain CC-NAPH129-6. This novel transposase gene sequence was unlike to the transposase sequence found between narR2 and rub1 genes in Rhodococcus opacus R7. The comparative analyses of the naphthalene catabolic genes, 16S rRNA and gyrB gene present in strain CC-NAPH129-6 and naphthalene-degrading Rhodococcus species imply that the naphthalene catabolic genes in strain CC-NAPH129-6 might be horizontally transferred from Rhodococcus members. This is the first report demonstrating that naphthalene catabolic genes organized into an operon-like gene cluster in the genus Gordonia, and this might provide evidence of the importance of this actinobacterial lineage in the bioremediation of oil-contaminated soils.


Adjuvanted versus non-adjuvanted standard-dose influenza vaccines in preventing all-cause hospitalizations in the elderly: a cohort study with nested case-control analyses over 18 influenza seasons.
The higher effectiveness of adjuvanted trivalent influenza vaccine (aTIV) versus non-adjuvanted (na) formulations in preventing all-cause hospitalization has been demonstrated for a single influenza season and in institutionalized elderly only. This study evaluated the relative vaccine effectiveness for aTIV vs. non-adjuvanted trivalent (naTIV) and/or quadrivalent (naQIV) influenza vaccines in preventing all-cause hospitalizations across 18 influenza seasons in primary care. Using Health Search Database, a nested case-control analysis was conducted in a cohort of older adults being vaccinated with aTIV or naTIV/naQIV. Conditional logistic regression was adopted to estimate the odds ratio (OR) of all-cause hospitalizations occurred during the epidemic period. Of 58,252 patients vaccinated with aTIV and naTIV/naQIV for the first time, 2,504 cases of all-cause hospitalization (3.46 per 1,000 person-weeks) during the 18 influenza seasons were identified. Compared with naTIV/naQIV, aTIV was associated with a 12% reduced the odds of all-cause hospitalizations (OR 0.88; 95% CI: 0.80-0.97). In an 18-season cohort of older adults, aTIV reduced the risk of all-cause hospitalizations when compared with naTIV/naQIV. Our findings confirm additional benefits for adjuvanted influenza vaccines in older adults.


A protein-repellent and antibacterial nanocomposite for Class-V restorations to inhibit periodontitis-related pathogens.
The objectives of this study were to develop a bioactive dental composite and investigate the effects of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminohexadecyl methacrylate (DMAHDM) in Class V composite on mechanical properties, water sorption, protein adsorption, and inhibition of four species of periodontitis-related biofilms for the first time. The resin consisted of ethoxylated bisphenol A dimethacrylate (EBPADMA) and pyromellitic glycerol dimethacrylate (PMGDM). DMAHDM, MPC and nanoparticles of amorphous calcium phosphate (NACP) were incorporated into the resin. Four species (Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum) were tested for biofilm colony-forming units (CFU), live/dead, metabolic activity, and polysaccharide production. The results showed that adding DMAHDM and MPC to the composite did not compromise the mechanical properties (p>0.1), with acceptable water sorption values. Composite with 3% MPC reduced protein adsorption to 1/9 that of a commercial composite (p<0.05). For all four species, the composite with 3% DMAHDM+3% MPC had much greater reduction in biofilms than using DMAHDM or MPC alone (p<0.05). Biofilm CFU was reduced by about 4 orders of magnitude via 3% DMAHDM+3% MPC, compared to control. The inhibition efficacy for the four species was: P. gingivalis>P intermedia=A. actinomycetemcomitans>F. nucleatum. In conclusion, a novel bioactive composite with 3% DMAHDM and 3% MPC achieved the greatest reduction in biofilm growth, metabolic activity and polysaccharide of four periodontal pathogens. The new composite is promising for Class V restorations especially with subgingival margins to inhibit periodontal pathogens, combat periodontitis and protect the periodontium.


After weight loss, what skin removal procedure has the most effect using Body Q metrics?
Although postbariatric body contouring procedures have the ultimate goal of restoring quality of life, there currently exist minimal data assessing the effect of these procedures. To identify the most important body contouring procedure for quality of life (QoL). University Hospital, Online Questionnaire, Germany. A cross-sectional study was designed using a validated version of the internet-based Body Q questionnaire, which was distributed among patients using social media and patient events. A total of 460 patients (443 female, 17 male) participated and fulfilled inclusion criteria. Of those patients, 191 (41.5%) had already undergone surgery, and the rest served as the control group. Patients in a postoperative status had a significantly (P < .05) higher QoL regarding all body regions. Additionally, patients who underwent body contouring surgery showed significantly higher QoL in regard to sexuality, society, body image, and psychosocial metrics. Abdominoplasty represents the most important procedure for QoL. The control group showed the greatest dissatisfaction in the area of the inner thighs. Body contouring procedures have been shown to significantly restore and enhance a patient's QoL. Conducting contouring surgeries is specifically associated with an increase in body image satisfaction as well as patient acceptance of certain body regions.


Safety of piggyback intraocular lenses (polypseudophakia) in children: long-term outcomes of a 15-year, single-surgeon study.
To report the outcomes of piggyback (PB) intraocular lens (IOL) implantation, or temporary polypseudophakia, in children who have undergone cataract surgery and to assess their safety in pediatric patients. The medical records of consecutive patients who underwent PB IOL implantation at a single institution over a period of 15 years were reviewed retrospectively. Outcome measures were reoperation rate, complications, and outcome of planned explantation. A total of 48 eyes of 38 children received PB IOL implantation: 40 eyes at the time of cataract surgery and 8 eyes as a later secondary procedure. Of these, 38 eyes of 31 patients with primary PB IOL implantation had follow-up of >3 years and were included in the present analysis. Median age at cataract surgery with PB IOL implantation was 6.5 months (0.5 months to 2.4 years). Median follow-up was 12.5 years (range, 3.0-20.7). Four eyes required reoperation for adverse events related to PB IOL implantation (1 each for IOL tilt, pupillary capture, pupillary block glaucoma, and pupillary membrane). All 4 of these eyes were operated for cataract before 3 months of age. The sulcus-fixated PB IOL underwent a planned explantation in 33/38 eyes. Eight eyes needed intraocular pressure-lowering topical medications. Planned PB IOL explantation was uncomplicated in our series. Early complications occurred in 4 eyes, but late complications were not noted, and glaucoma developed at predictable rates for this population. Piggyback IOL placement in our cohort of young children appears to have an acceptable safety profile.


Magnetic resonance imaging bone edema is not a major feature of gout unless there is concomitant osteomyelitis: 10-year findings from a high-prevalence population.
Magnetic resonance imaging (MRI) is commonly used in autoimmune inflammatory arthritis to define disease activity and damage, but its role in gout remains unclear. The aim of our study was to identify and describe the MRI features of gout. Over a 10-year period we identified patients with gout who underwent MRI scanning of the hands or feet. Scans were reviewed for erosions, synovitis, tenosynovitis, tendinosis, bone edema, and tophi by a musculoskeletal radiologist and 2 rheumatologists in a blinded manner. MRI features in patients with uncomplicated gout were compared with features where concomitant osteomyelitis was diagnosed. A total of 47 patients with gout (51 scans) were included: 33 (70%) had uncomplicated gout and 14 (30%) had gout complicated by osteomyelitis. MRI features included tophi in 36 scans (71%), erosions in 35 (69%), bone edema in 27 (53%), synovitis in 15 (29%), tenosynovitis in 8 (16%), and tendinosis in 2 (4%). Uncomplicated gout and gout plus osteomyelitis did not differ for most MRI features. However, "severe bone marrow edema" was much more common in gout plus osteomyelitis, occurring in 14/15 scans (93%) compared with 3/36 scans (8%) in uncomplicated gout (OR 154.0, 95% CI 14.7-1612, p < 0.0001). Sensitivity and specificity of "severe bone edema" for concomitant osteomyelitis were 0.93 (95% CI 0.68-0.99) and 0.92 (95% CI 0.78-0.98), respectively. MRI reveals that gout affects the joints, bones, and tendons. Bone edema in patients with chronic tophaceous gout is frequently mild and this contrasts with the "severe bone edema" observed in patients with concomitant osteomyelitis.


Humoral immune response and delayed-type hypersensitivity in rabbits infected with Trypanosoma equiperdum.
Trypanosoma equiperdum is the causative agent of dourine, a parasitic venereal disease of equids. In this work, rabbits were infected with T. equiperdum strain OVI; serological tests (complement fixation test, ELISA and immunoblotting), used for the diagnosis of dourine in horses, were applied to study rabbit humoral immune response and to characterise T. equiperdum antigen pattern recognised by antibodies from infected rabbits. Moreover a protein extract of T. equiperdum strain OVI was produced and tested in skin tests on infected rabbits to detect the cell-mediated response induced by T. equiperdum, in order to evaluate its use in the field diagnosis of dourine. Sera of infected rabbits recognized in immunoblotting Trypanosoma protein bands with molecular weight below 37 kDa, providing a serological response comparable with that already observed in dourine infected horses. Moreover the trypanosome protein extract was capable to produce in vivo delayed-type hypersensitivity (DHT Type IV) in rabbits and proved itself to be non-toxic and non-sensitizing.


An exploration of microbial and associated functional diversity in the OMZ and non-OMZ areas in the Bay of Bengal.
Depletion of oxygen in certain marine areas creates oxygen minimum zones (OMZs), which can alter the species composition and abundance. We have carried out high-throughput 16S rRNA gene amplicon profiling from the Bay of Bengal (BOB) OMZ and non-OMZ areas. Typically, a total of 35 families of micro-organisms were identified as biomarkers for OMZ and non-OMZ regions in the BOB. Our analysis has identified families Pseudoalteromonadaceae, OM60 and Synechococcaceae to be abundant in oxygenated water, whereas organisms belonging to families Pelagibacteraceae and Caulobacteraceae, which are involved in sulphur and nitrogen metabolism, were prominent in the OMZ areas. Predictive functional analysis for these identified bacteria clearly that suggested an abundance of microbes with assimilatory sulphurreducing genes (cysl and csH) in the non-OMZ, while bacteria involved in dissimilatory sulphate reduction (known to carry aprA and aprB genes) were enriched in the OMZ areas. Comparative analysis with OMZ areas from Peru and Chile revealed that OMZ areas in the BOB are characterized by specific and distinctive bacterial diversity. Overall, the current analysis provides valuable documentation about the bacterial populations and their characteristics, which can generate pointers for their functional significance in the BOB.


Continuous glucose monitoring in cystic fibrosis - A practical guide.
Our ability to monitor blood glucose levels has become increasingly accurate over the last few decades. Continuous glucose monitoring (CGM) technology now allows providers and patients the ability to monitor glucose levels retrospectively as well as in real-time for diabetes management. CGM also provides the ability to study glucose patterns and trends for insight into the pathophysiology and natural history of disease. CGM captures a more complete picture of glucose profiles than traditional measures of glycemia such as the hemoglobin A1c or self-monitoring of blood glucose levels. This article provides a review of the history of glucose monitoring, a review of the literature pertaining to CGM with a focus on studies in patients with cystic fibrosis, and discusses practical uses of CGM technology and its application for the evaluation and management of cystic fibrosis related diabetes.


Sex and ethnic differences among South Tirolean suicides: a psychological autopsy study.
The aim of the research is to study whether any differences exist in the rates and characteristics of suicide by ethnicity and sex in South Tirol, Italy. Psychological autopsy interviews were conducted for suicides who died between March 1997 and July 2006. 332 individuals belonging to the three major South Tirolean ethnic groups (Germans, Italians, Ladins [Ladin is a Rhaeto-Romance language related to the Venetian and Swiss Romansh languages]) died by suicide. Around 23% of the victims had experienced suicidal behaviour among family members, and more than 31% of them had experienced trauma during their childhood. Germans were 1.37 times more at risk to commit suicide than Italians (95% CI: 1.04/1.80; z=2.26, p<.05). 69% of the suicides had attended school for less than 8 years: Germans (OR=4.62; 95% CI: 2.52/8.47; p<.001) and Ladins (OR=11.24; 95% CI: 2.99/42.30; p<.001) were more likely to have lower education than Italians. There were several differences by ethnicity and sex but no sex-by-ethnicity interactions. The study indicated that suicide, an alarming health and social problem in South Tirol, may require different preventive interventions for men and women and for those of different ethnicities.


A consultation with Canadian rural women with breast cancer.
Relatively little research has been carried out on the health and supportive care needs of rural women living with breast cancer. In this study, results from a Canadian focus group study are used to highlight issues of importance to rural women. A total of 276 rural women with breast cancer divided into 17 focus groups participated in the study conducted across Canada. A standardized protocol for discussion was employed. Issues of access to information, support and services were discussed, with women describing their experiences in trying to find appropriate programmes and services. The major theme identified through analysis of qualitative data was 'becoming aware of and/or gaining access to health care information, support and services.' Other major themes included: (1) dealing with isolation; (2) having to travel; (3) feeling the financial burden and (4) coping with changing work. Rural women with breast cancer have supportive care challenges related to their circumstances. A series of recommendations were generated through the consultation process which are contributing to the development of a national strategy focusing on the development and extension of programmes for rural women with breast cancer. Although the research on the project was not to specified standards, and suffered from less attention than community capacity building and advocacy, it proved to be of worth and revealed potential benefits from collaborations between researchers and community organizations.


Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation.
Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry.


Simultaneous determination of norepinephrine, dopamine, 5-hydroxytryptamine and their main metabolites in rat brain using high-performance liquid chromatography with electrochemical detection. Enzymatic hydrolysis of metabolites prior to chromatography.
In order to measure turnover rates of the noradrenergic, dopaminergic, and serotonergic transmitter systems in rat brain, a method was developed by which norepinephrine, dopamine, and 5-hydroxytryptamine, and their main metabolites 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid, could be measured simultaneously. High-performance liquid chromatography in the reversed-phase mode, including ion pairing, separated the transmitters and their metabolites well. By means of enzymatic hydrolysis of the sample prior to chromatography, it was also possible to measure the conjugated forms of the metabolites. Since there was no prepurification step, the hydrolysed supernatants of tissue homogenates were injected directly into the chromatographic system; additional selectivity tests were necessary. Peak identification was confirmed by comparison of hydrodynamic voltagrams and capacity factors at different pH values of the mobile phase of the components in the sample and the standard solution. The method is demonstrated by analysing mediobasal hypothalamic tissues of probenecid-treated rats.


Fetal head-to-trunk volume ratio in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation.
To determine the pattern of early growth disturbance in chromosomally abnormal fetuses by comparing the volume of the fetal head to that of the trunk. The fetal trunk and head volume was measured using three-dimensional (3D) ultrasound in 145 chromosomally abnormal fetuses at a median gestational age of 12 (range, 11 + 0 to 13 + 6) weeks. The head volume was measured separately and then subtracted from the total head and trunk volume to obtain the volume of the fetal trunk. The head-to-trunk ratios were then calculated and the Mann-Whitney U-test was used to determine the significance of differences from 500 chromosomally normal fetuses. The fetal head volume for crown-rump length (CRL) was significantly smaller than normal in trisomy 21, trisomy 13 and Turner syndrome (P < 0.001, P < 0.001 and P = 0.001, respectively), whereas no significant differences were found in trisomy 18 and triploidy (P = 0.139 and P = 0.070, respectively). The fetal trunk volume for CRL was significantly smaller in all chromosomal abnormalities (P < 0.001) except Turner syndrome (P = 0.134). The head-to-trunk ratio for CRL was significantly larger in trisomy 18, trisomy 13 and triploidy (P < 0.001), but normal in trisomy 21 (P = 0.221) and Turner syndrome (P = 0.768). In trisomy 21 and Turner syndrome, the growth deficit was symmetrical with the head and trunk being equally affected, whereas in triploidy and trisomies 18 and 13 there was asymmetrical growth restriction with the trunk being more severely compromised than the head.


Efficient multi-click approach to well-defined two-faced octasilsesquioxanes: the first perfect Janus nanocube.
The preparation of the first structurally well-defined Janus nanocube showing two chemically distinct opposed faces is described. The synthetic approach is based on a highly efficient and symmetry-controlled CuAAC functionalization of an octa-azido cubic silsesquioxane with a conformationally constrained tetra-alkyne with an appropriate spatial orientation of the triple bonds.


Interstitial Edema of the Interatrial Septum in Patients with Atrial Fibrillation and Chronic Heart Failure.
We studied the presence of interstitial edema of the interatrial septum in patients with chronic heart failure (CHF) with atrial fibrillation (n=23) or without rhythm disturbances (n=9). The intensity of the MRI signal of the interatrial septum, interventricular septum, and skeletal muscle by T2-weighted MRI and the enhancement index of interatrial septum (the ratio of the signal intensity of the interatrial septum to the signal intensity of the skeletal muscle) were evaluated. The enhancement index of interatrial septum ⩾2 was regarded as an MRI sign of myocardial edema. The enhancement index of interatrial septum in patients with persistent atrial fibrillation was 2.4 (2.21; 2.69) and was higher than in CHF patients with paroxysmal atrial fibrillation and in CHF patients without arrhythmias and surpassed the control values (p<0.05), which indicates the presence of MRI signs of edema of the myocardium of the interatrial septum. The obtained data confirm the presence of myocardial edema of the interatrial septum in CHF patients and persistent form of atrial fibrillation, which expands the understanding of the pathogenesis of this condition.


Usefulness of stress echocardiography for risk stratification of patients after percutaneous coronary intervention.
The prognostic value of stress echocardiography in patients with previous percutaneous coronary intervention (PCI) remains undefined. The aim of this study was to investigate the prognostic implication of stress echocardiography after PCI. The study group comprised 1,063 patients (794 men, 65 +/- 10 years of age) who underwent stress echocardiography with exercise (n = 105), dipyridamole (n = 780), or dobutamine (n = 178) after a median of 10 months from a successful PCI. Of these patients, 616 (58%) complained of chest pain and 447 (42%) were asymptomatic. Stress echocardiogram was positive for inducible ischemia in 328 patients (31%). During a median follow-up of 20 months, there were 167 events (61 deaths, 106 infarctions). Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03 to 1.09, p <0.0001), wall motion score index at rest (HR 3.91, 95% CI 2.19 to 6.99, p <0.0001), and ischemia at stress echocardiography (HR 1.82, 95% CI 1.05 to 3.16, p = 0.03). Five-year mortalities were 20% in patients with and 9% in those without ischemia (p = 0.006). Independent predictors of hard events were ischemia at stress echocardiography (HR 3.82, 95% CI 2.75 to 5.29, p <0.0001), age (HR 1.02, 95% CI 1.01 to 1.04, p = 0.009), wall motion score index at rest (HR 1.98, 95% CI 1.30 to 3.02, p = 0.002), multivessel disease at time of PCI (HR 1.45, 95% CI 1.05 to 2.02, p = 0.02), and female gender (HR 1.44, 95% CI 1.03 to 2.01, p = 0.03). Five-year hard event rates were 53% in patients with and 16% in those without ischemia (p <0.0001). Stress echocardiographic positivity added prognostic information to clinical and at-rest echocardiographic parameters in symptomatic and asymptomatic patients. Moreover, it identified a subset of patients at higher risk of developing hard events independent of the subtending coronary anatomy (multivessel or single vessel disease). In conclusion, stress echocardiography is effective in risk-stratifying patients with previous PCI. In particular, inducible ischemia is a strong and independent predictor of mortality and hard events.


Hypothermic preservation of isolated rat lungs in modified bicarbonate buffer, EuroCollins solution or St Thomas' Hospital cardioplegic solution.
Inadequate preservation solutions limit lung storage times and, consequently, transplant programs. To address this problem we established an isolated, ventilated and perfused rat lung preparation. Here we report the effects of hypothermic storage in EuroCollins solution, St Thomas' Hospital cardioplegic solution and a modified bicarbonate buffer solution. Lungs from male Wistar rats (230-330 g) were perfused via the pulmonary artery with modified bicarbonate buffer (37 degrees C, 15 ml/min, constant flow) and ventilated by positive pressure (tidal volume:1.6-1.8 ml, 80 breaths/min). Vascular resistance (pulmonary artery pressure:perfusate flow ratio) and airways compliance (tidal volume:tracheal pressure ratio) were measured. After a control perfusion period (20 min), lungs were flushed with, then immersed in, bicarbonate buffer (4 degrees C) for varying periods (0-24 h). After storage, lung function was assessed during 20 min reperfusion. Having established a suitable period for study, storage in EuroCollins, St Thomas' Hospital cardioplegic solution or bicarbonate buffer were compared. Pulmonary compliance (ml/cmH2O) was significantly (P < 0.05) reduced in lungs stored for 6 h in modified bicarbonate buffer (0.026 +/- 0.008), EuroCollins solution (0.013 +/- 0.002) or St Thomas' Hospital solution (0.025 +/- 0.005) compared to unstored lungs (0.068 +/- 0.007). Vascular resistance, (1.32 +/- 0.13 cmH2O/ml per min) in unstored lungs, was similar in lungs stored in St Thomas' Hospital solution but increased significantly in lungs stored in modified bicarbonate buffer (3.22 +/- 0.78 cmH2O/ml per min) or EuroCollins solution (4.66 +/- 0.57 cmH2O/ml per min). Hypothermic storage of rat lungs for 6 h in modified bicarbonate buffer or St Thomas' Hospital solution causes less increase in vascular resistance on reperfusion than EuroCollins solution.


Cognitive behaviour therapy to prevent harmful compliance with command hallucinations (COMMAND): a randomised controlled trial.
Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer's motivation to comply. In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23-0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40-1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33-0·98, p=0·042). This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and compliance. UK Medical Research Council and the National Institute for Health Research.


Oscillometry and spirometry are not interchangeable when assessing the bronchodilator response in children and young adults born preterm.
The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes. Participants aged 6-23 born ≤32 (N = 288; 132 with bronchopulmonary dysplasia) and ≥37 weeks' gestation (N = 76, term-born controls) performed spirometry and oscillometry. A significant bronchodilator response (BDR) to 400 μg salbutamol was classified according to published criteria. A BDR was identified in 30.9% (n = 85) of preterm-born individuals via spirometry and/or oscillometry, with poor agreement between spirometry and oscillometry definitions (k = 0.26; 95% confidence interval [CI] 0.18-0.40, p < .001). Those born preterm with a BDR by oscillometry but not spirometry had increased wheeze (33% vs. 11%, p = .010) and baseline resistance (Rrs5 z-score mean difference (MD) = 0.86, 95% CI 0.07-1.65, p = .025), but similar baseline spirometry to the group without a BDR (forced expiratory volume in 1 s [FEV1 ] z-score MD = -0.01, 95% CI -0.66 to 0.68, p > .999). Oscillometry was more feasible than spirometry (95% success rate vs. 85% (FEV1 ), 69% (forced vital capacity) success rate, p < .001), however being born preterm did not affect test feasibility. In the preterm population, oscillometry is a feasible and clinically useful supportive test to assess the airway response to inhaled salbutamol. Changes measured by oscillometry reflect related but distinct physiological changes to those measured by spirometry, and thus these tests should not be used interchangeably.


Existence of memory in ion channels.
To explore the existence of memory in Ca(2+)-dependent K+ channels of cultured aortic smooth muscle cells (ASMC) and voltage-dependent K+ channels of clonal pheochromocytoma (PC12) cells. Calculating the sample auto-correlation functions based on the digitized signals or the 0-1 series corresponding to closing and opening of the channels after routine evaluation, rather than the sequence of sojourn times. The sample auto-correlations showed a decreasing trend with elapse of time, stable to repeated observations under the same conditions and sensitive to treatments. The attribute of memory exists in some single channels as an intrinsic feature of them, independent of any extrinsic assumptions on missing observations due to limited time resolution.


Why are psychotropic drugs prescribed to out-patients? A methodological study.
The prescription of psychotropic drugs at a multidoctor district health centre in northern Sweden in 1973, was analysed by means of problem-oriented medical records. Of the 22,000 inhabitants of the district 10,700 consulted the health centre. Psychotropic drugs were prescribed for 11.3% of the patients, corresponding to 5% of the inhabitants of the area. Sixty per cent of the patients received one psychotropic prescription and 90% not more than three. Two-thirds of prescriptions were for women. Hypnotics, sedatives and minor tranquillisers constituted 64% of all prescriptions, major tranquillisers 24% and antidepressants 12%. One fifth of the patients obtained drugs belonging to more than one of the major psychotropic groups during the year. Insomnia, psychoneurosis and depression made up two-thrids of the indications for psychotropic drug therapy. More than thirty different psychotropic drugs were prescribed for the two major indications. There was considerable variation in how the different doctors prescribed drugs for the same indication. Fifty-nine different drug products were prescribed, of which the commonest five constituted more than half of the total number. Individual doctors used from 22 to 38 different psychotropic drugs.


Sugar interaction with biologically active cis-PtCl2(NH3)2 (anticancer) and its inactive trans isomer.
The interaction of D-glucuronic and D-gluconic acids with cis- and trans-PtCl2(NH3)2 (cisplatin and transplatin) has been investigated in aqueous solution and solid complexes of the type cis-[PtL(NH3)2]L.H2O and trans-[PtL2(NH3)2]L.H2O, where L = D-glucuronate or D-gluconate anions, are isolated and characterized by means of Fourier transform-infrared and 1H-NMR spectroscopy, and molar conductivity and X-ray powder diffraction measurements. Spectroscopic and other evidence indicated that the sugar anions bind monodentately in trans-[PtL2(NH3)2].H2O and bidentately in cis-[PtL(NH3)2]L.H2O complexes through the carboxylate oxygen atoms and other sugar donor groups. The strong sugar intermolecular hydrogen-bonding network is altered to that of the sugar-OH...NH3(H2O)...OH-sugar, upon platinum-ammine interaction. The D-glucuronate anion has the beta-anomer configuration both in the free salt and in these platinum-sugar complexes.


Brief Report: Turkish Validity and Reliability of the HITS Intimate Partner Violence Screening Tool With Women.
The current study examined the validity and reliability of the Turkish version of the HITS (Hurt-Insult-Threaten-Scream) tool which was developed to screen for intimate partner violence. 154 Turkish women participated and completed the Turkish version of the HITS (HITS-TR). The validity of the language and factor structure were evaluated. The internal consistency coefficient of the scale was.89. Confirmatory factor analysis (CFA), revealed a single factor structure consisting of four items that explained 76% of the total variance. A CFA was performed with a modified model upon a second sample indicating high compatibility for the revised model with χ2/df = 1.262, a root mean square error of approximation.036, goodness of fit index of.996, adjusted goodness of fit index.998, root mean square residual of.006 and standardized root mean square residual of.008. It is concluded that the HITS-TR can be used as a valid and reliable screening tool for intimate partner violence in Turkish women.


Sister chromatid exchanges in balanced translocation carriers and in patients with unbalanced karyotypes.
Sister chromatid exchanges (SCEs) were studied in peripheral human leukocytes from 16 patients with balanced translocations or with unbalanced karyotypes, and from 4 controls. No difference was seen between these two groups of people in the mean number of SCEs per cell, or in the total number of SCEs observed for each pair of autosomes involved in the translocations studied. With this last number no difference from the expected number of SCEs, if one supposes that SCEs follow a random distribution, was seen.


Antidepressant-like effect of the ethanolic extract from Suanzaorenhehuan Formula in mice models of depression.
Suanzaorenhehuan Formula (SHF) is a Chinese herbal formula for the treatment of depression-like disorders. It contains four herbs: Semen Ziziphi spinosae, Cortex Albiziae, Radix Paeoniae Alba and Semen Platycladi. The present study is to investigate the antidepressant-like effect of the ethanolic extract of SHF and its possible mechanisms. Mouse models of depression including the tail suspension test (TST), forced swimming test (FST) and chronic unpredicted mild stress (CUMS) were used to evaluate the effects of SHF extract. The mechanisms were examined by measuring monoamine neurotransmitters in mice hippocampus and frontal cortex, testing monoamine oxidase enzyme (MAO) activities in brain of CUMS-exposed mice. After one-week treatment, SHF extract (50, 100 and 200mg/kg) induced a significant decrease on immobility time in TST. After two-week treatment, SHF extract (50, 100 and 200mg/kg) led to a reduction in the immobility period in TST and FST. The 5-HT levels in mice hippocampus were increased only after 200mg/kg SHF extract treatment. The noradrenaline (NE) levels were increased after 200mg/kg SHF extract treatment in mice hippocampus and frontal cortex. SHF extract (50, 100 and 200mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day CUMS exposure. These findings demonstrated that ethanolic SHF extract produced an antidepressant-like effect and the mechanism of action involves the serotonergic, noradrenergic and monoamine oxidase enzyme systems although underlying mechanism still remains to be further elucidated.


Evaluating the role of dietary plant extracts to allow adaptation to thermal stress in a cold stream ornamental fish, Botia rostrata (Günther, 1868).
Increases in ambient temperature affect the biochemical status of fish, and dietary supplementation with bioactive phytoconstituents may promote resilience against environmental stress. This study evaluated the impact of three plant extracts on the biochemical status of a cold stream fish Botia rostrata (Günther, 1868) under high temperatures. After 1 month dietary supplementation separately with Mucuna pruriens methanol extract (0.25 g/kg feed), Tribulus terrestris ethanol extract (0.5 g/kg feed) and Basella alba ethanol extract (1.0 g/kg feed), juvenile fish (Wt. 4.3 ± 0.5g) were exposed to different sublethal heat stress [28 ± 0.5 °C (T1), 32 ± 0.5 °C (T2), 36 ± 0.5 °C (T3)]. Control fish were fed a diet without any plant extract and maintained at 24 ± 0.5 °C. Serum and muscle tissues were collected to measure different biochemical parameters, muscle metabolic enzymes and molecular chaperons before and after heat stress. Before stress, the group fed the Mucuna diet showed significant (P < 0.05) increases in serum glucose [+10.92%], protein [+18.93%], muscle heat shock protein (HSP) 90 [+8.6%] compared to the control group. No significant change (P > 0.05) of stress parameters was observed between control, Tribulus and Basella fed fish. The control group exposed to T3 showed significant differences (P < 0.05) in protein [-26.19%], lactate dehydrogenase [+93.69%], fructose 1,6 bisphosphate [-35.19%], phosphorylase 'a' [+35.72%], HSP60 [+69.54%], HSP70 [+84.85%], HSP90 [+92.07%], heat shock factor (HSF) 1 [+88.48%] suggesting susceptibility of Botia to this temperature. Among the three plant extracts, Mucuna methanol extract was effective to enhance resistance against temperature-induced biochemical alterations. After exposure to T3, only the fish fed Mucuna diet showed no mortality. Fish fed Mucuna diet exposed to 36 ± 0.5 °C showed significantly higher (P < 0.05) glucose [+42.82%], protein [+11.98%], citrate synthase [+59.81%], phosphorylase 'a' [+14.96%], Glucose 6 phosphate dehydrogenase [+60.87%], HSP60 [+34.13%], HSP70 [+41.42%], HSP90 [+65.91%], HSF1 [+61.32%] compared to those in Mucuna fed fish maintained at 24 ± 0.5 °C. These results highlight temperature-induced biochemical alterations in Botia and point towards the potential use of Mucuna in overcoming such adverse high thermal stress.


How school life with international students develops the intercultural competence of domestic dental students.
Reflecting multicultural society, the diversity of the healthcare professional students' ethnicities and cultures is promoted around the world. However, most of the healthcare professional education in Japan had been targeted mainly at students who follow the Japanese language and culture. The aim of this study is to clarify what Japanese dental students have culturally experienced and how they developed intercultural competence during their school life with international dental students in Japan. We conducted semi-structured interviews with 18 of the sixth-grade students in standard Japanese undergraduate dental programmes who shared required classes in Japan with non-Japanese-speaking international dental students in preclinical programmes. Based on the qualitative analysis of the interviews, we administered a questionnaire survey to 82 dental trainees (the seventh grade) in clinical training programmes who just graduated from various Japanese dental schools. Then, the answers of the questionnaire were statically analysed. The interview identified a total of 37 constituent elements regarding "students' attitudes and experiences in school days" and "perceptions and motivations." Analysis of the questionnaire showed that the group experiencing a learning environment with international students had various communication with and respect for their various classmates and had the ambition to develop themselves. Especially, the participants who had international experiences both in and out of classrooms showed more active attitude on intercultural communication. Overall, for Japanese dental students, daily contact with international students gave direct and indirect cross-cultural experiences and recognitions. In particular, the Japanese students were stimulated active perceptions. The findings of this study can be used for future discussion about the cross-cultural education and collaboration of healthcare professionals not only within Japan but also around the world.


Dynamic nonlinear effects of urbanization on wastewater discharge based on inertial characteristics of wastewater discharge.
This study examines the impact of urbanization on wastewater discharge (WD) in 30 provinces in mainland China, considering the inertia characteristics of WD. Various models, including the Tapio decoupling model, dynamic curve relationship model, dynamic threshold effect model, and dynamic quantile model, are employed to analyze the decoupling relationship, curve relationship, threshold relationship, and quantile relationship, respectively. The research findings indicate a shift in the relationship between urbanization and total wastewater discharge (TWD) from expansionary negative decoupling to strong decoupling. Regarding household wastewater discharge (HWD), the relationship is primarily characterized by expansionary negative decoupling and weak decoupling, while industrial wastewater discharge (IWD) is mainly associated with strong decoupling. Urbanization does not exhibit an (inverted) N-shaped relationship with TWD, IWD, and HWD, but it does show an inverted U-shaped relationship with TWD and HWD. The study also reveals that urbanization has a dynamic threshold effect and regional heterogeneity on HWD, but not on TWD and IWD. As the quantile increases, the positive impact of urbanization on TWD and HWD decreases, while the negative impact on IWD increases.


Using molecular markers to identify two major loci controlling carotenoid contents in maize grain.
Maize is an important source of pro-vitamin A; beta-carotene, alpha-carotene and beta-cryptoxanthin, and the non-pro-vitamin A carotenoids including lutein and zeaxanthin. In the present study, a recombinant inbred (RI) population with 233 RI lines derived from a cross between By804 and B73 was employed to detect QTL for these nutritionally important components in maize grain. High Performance Liquid Chromatography was used to measure amounts of individual carotenoids over 2 years. A genetic linkage map was constructed with 201 molecular markers. In all, 31 putative QTL including 23 for individual and 8 for total carotenoids were detected on chromosome(s) 1, 3, 5, 6, 7, 8 and 10. The notable aspect of this study was that much of the phenotypic variation in contents of carotenoids could be explained by two loci (y1 and y9), and the QTL for carotenoids elucidated the interrelationships among these compounds at the molecular level. A gene targeted marker (Y1ssr) in the candidate gene phytoene synthase 1 (psy1) tightly linked to a major QTL explaining 6.6-27.2% phenotypic variation for levels of carotenoids was identified, which may prove useful to expedite breeding for higher level of carotenoids in maize grain. This functionally characterized gene (psy1) could also be exploited for further development of functional marker for carotenoids in maize. The QTL cluster located at y9 locus may also be used for pyramiding favorable alleles controlling contents of carotenoids from diverse maize germplasm.


A new dynamic testing apparatus to study glenohumeral joint motion.
A dynamic shoulder testing apparatus has been developed to examine unconstrained glenohumeral joint motion in human cadaveric full upper extremities. Six computer-controlled hydraulic cylinders are used to simulate muscle action, while the corresponding tendon excursions and six-degree of freedom joint motion are measured. Trials showed that the testing apparatus creates highly reproducible glenohumeral joint motion in the scapular plane. The apparatus can be used to examine the function of the shoulder musculature and capsuloligamentous structures during normal and pathologic motion at the glenohumeral joint.


Pilot testing of a self-care education intervention for patients with heart failure.
A key component of the structured approach to the management of chronic heart failure (CHF) is effective patient education. Patient education is a precursor to performing appropriate health-related behaviours that can decrease rehospitalizations. To pilot test an educational intervention and to determine the efficacy of a self-care manual combined with a DVD for patients with CHF. Outcomes of interest included heart failure-related knowledge and self-care behaviours. This pilot study enrolled a sample of 38 patients with CHF. A pre-test/post-test design was conducted to assess changes in knowledge and self-care abilities. Knowledge was assessed with the Dutch Heart Failure Knowledge Scale and self-care behaviours were assessed using the Self-Care of Heart Failure Index. Of the 38 participants 71% were male, 50% were aged between 65 and 74 years, and 31.6% had not completed Year 10 education. There was a statistically significantly difference in the pre- and post-test scores for knowledge (p < 0.0001). Self-care showed positive improvement between pre- and post-test scores; maintenance (p = 0.027), management (p < 0.0001) and confidence (p = 0.051). This pilot study has indicated that a patient-centred self-care manual combined with a DVD is beneficial and is associated with an improvement in patients' knowledge and self-care abilities. Healthcare professionals should utilize multimedia educational resources specifically designed to meet the learning needs of patients with CHF.


[Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal tract and non-digestive organs in rats of different ages].
It is stated that Livagen (Lys-Glu-Asp-Ala) is a weakly hydrolyzed peptide. Peptide hydrolases of small intestine do not hydrolyze Livagen even to a small extent. Under in vitro conditions Livagen reduces glycil-L-leucinedipeptidase activity in small intestine by 50%. After two weeks of Livagen administration per os in rats the digestive enzymes activity in young animals reduces, while in old animals it increases. It should be mentioned that the activity of enzymes in old rats after Livagen administration in the majority of cases approaches to the level of the activity in young animals of control group.


A comparison of anesthetic outcomes between activation and removal of epidural catheters for patients who underwent unscheduled intrapartum cesarean delivery.
We hypothesized that patients who underwent unscheduled intrapartum cesarean delivery and had removal of an indwelling epidural catheter followed by an attempt of a new regional anesthetic would be more likely to have regional anesthesia without conversion to general anesthesia or administration of additional anesthetic medication compared to patients who had activation of an epidural catheter. Patients who had an unscheduled intrapartum cesarean delivery from July 1, 2019, through June 30, 2021, who had an indwelling labor epidural catheter were included. Patients were propensity matched based on obstetric indication for cesarean delivery and number of physician-administered rescue analgesia boluses administered during labor. A multivariate proportional odds regression was performed. After adjusting for parity, depression, last neuraxial labor analgesic technique, physician-administered rescue analgesia boluses, and duration from neuraxial placement to entering the operating room for cesarean delivery, patients who had removal of their epidural catheters were more likely to have regional anesthesia without conversion to general anesthesia or administration of additional anesthetic medication (odds ratio 4.298; 95% confidence interval 2.448, 7.548; P < 0.01). Removal of epidural catheters was associated with a greater chance of avoiding conversion to general anesthesia or administration of additional anesthetic medication.


Comparing dietary macronutrient composition and food sources between native and diasporic Ghanaian adults.
Dietary acculturation may contribute to the increased burden of non-communicable diseases (NCDs) in diasporic populations of African ancestry. To assess nutritional composition and the contribution that traditional foods make to the diets of native and UK-dwelling Ghanaian adults. An observational study of Ghanaian adults living in Accra (n=26) and London (n=57) was undertaken. Three-day food records were translated to nutrient data using culturally sensitive methods and comparisons were made for energy, macronutrients, and dietary fibre between cohorts. The contribution of traditional foods to dietary intake was measured and the foods contributing to each nutrient were identified. Compared to native Ghanaians, UK-Ghanaians derived a significantly higher proportion of energy from protein (16.9±3.9 vs. 14.1±2.8%, p=0.001), fat (29.9±7.9 vs. 24.4±8.5%, p=0.005), and saturated fat (8.5±3.4 vs. 5.8±3.7%, p<0.001) and a significantly lower energy from carbohydrate (52.2±7.7 vs. 61.5±9.3%, p<0.001). Dietary fibre intake was significantly higher in the UK-Ghanaian diet compared to the native Ghanaian diet (8.3±3.1 vs. 6.7±2.2 g/1,000 kcal, p=0.007). There was significantly less energy, macronutrients, and fibre derived from traditional foods post-migration. Non-traditional foods including breakfast cereals, wholemeal bread, and processed meats made a greater contribution to nutrient intake post-migration. Our findings show the migrant Ghanaian diet is characterised by significantly higher intakes of fat, saturated fat, and protein and significantly lower intakes of carbohydrate; a macronutrient profile which may promote increased risk of NCDs amongst UK-Ghanaians. These differences in the nutrient profile are likely to be modulated by the consumption of 'Western' foods observed in migrant communities.


Contributions and Limitations of Mitochondria-Targeted and Non-Targeted Antioxidants in the Treatment of Parkinsonism: an Updated Review.
As conventional therapeutics can only treat the symptoms of Parkinson's disease (PD), major focus of research in recent times is to slow down or prevent the progression of neuronal degeneration in PD. Non-targeted antioxidants have been an integral part of the conventional therapeutics regimen; however, their importance have lessened over time because of their controversial outcomes in clinical PD trials. Inability to permeate and localize within the mitochondria remains the main drawback on the part of non-targeted antioxidants inspite of possessing free radical scavenging properties. In contrast, mitochondrial-targeted antioxidants (MTAs), a special class of compounds have emerged having high advantages over non-targeted antioxidants by virtue of efficient pharmacokinetics and better absorption rate with capability to localize many fold inside the mitochondrial matrix. Preclinical experimentations indicate that MTAs have the potential to act as better alternatives compared to conventional non-targeted antioxidants in treating PD; however, sufficient clinical trials have not been conducted to investigate the efficacies of MTAs in treating PD. Controversial clinical outcomes on the part of non-targeted antioxidants and lack of clinical trials involving MTAs have made it difficult to go ahead with a direct comparison and in turn have slowed down the progress of development of safer and better alternate strategies in treating PD. This review provides an insight on the roles MTAs and non-targeted antioxidants have played in the treatment of PD till date in preclinical and clinical settings and discusses about the limitations of mitochondria-targeted and non-targeted antioxidants that can be resolved for developing effective strategies in treating Parkinsonism.


Catalytic effect of (H2O) n (n = 1-3) on the HO2 + NH2 → NH3 + 3O2 reaction under tropospheric conditions.
The effects of (H2O) n (n = 1-3) clusters on the HO2 + NH2 → NH3 + 3O2 reaction have been investigated by employing high-level quantum chemical calculations with M06-2X and CCSD(T) theoretical methods, and canonical variational transition (CVT) state theory with small curvature tunneling (SCT) correction. The calculated results show that two kinds of reaction, HO2⋯(H2O) n (n = 1-3) + NH2 and H2N⋯(H2O) n (n = 1-3) + HO2, are involved in the (H2O) n (n = 1-3) catalyzed HO2 + NH2 → NH3 + 3O2 reaction. Due to the fact that HO2⋯(H2O) n (n = 1-3) complexes have much larger stabilization energies and much higher concentrations than the corresponding complexes of H2N⋯(H2O) n (n = 1-3), the atmospheric relevance of the former reaction is more obvious with its effective rate constant of about 1-11 orders of magnitude faster than the corresponding latter reaction at 298 K. Meanwhile, due to the effective rate constant of the H2O⋯HO2 + NH2 reaction being respectively larger by 5-6 and 6-7 orders of magnitude than the corresponding reactions of HO2⋯(H2O)2 + NH2 and HO2⋯(H2O)3 + NH2, the catalytic effect of (H2O) n (n = 1-3) is mainly taken from the contribution of the water monomer. In addition, the enhancement factor of the water monomer is 10.06-13.30% within the temperature range of 275-320 K, which shows that at whole calculated temperatures, a positive water effect is obvious under atmospheric conditions.


Visible-light-induced photocatalytic CO2 reduction over zirconium metal organic frameworks modified with different functional groups.
The reduction of CO2 into high value-added chemicals and fuels by a photocatalytic technology can relieve energy shortages and the environmental problems caused by greenhouse effects. In the current work, an amino-functionalized zirconium metal organic framework (Zr-MOF) was covalently modified with different functional groups via the condensation of Zr-MOF with 2-pyridinecarboxaldehyde (PA), salicylaldehyde (SA), benzaldehyde (BA), and trifluoroacetic acid (TA), named Zr-MOF-X (X = PA, SA, BA, and TA), respectively, through the post-synthesis modification. Compared with Zr-MOF and Zr-MOF-TA, the introduction of PA, SA, or BA into the framework of Zr-MOF can not only enhance the visible-light harvesting and CO2 capture, but also accelerate the photogenerated charge separation and transfer, thereby improving the photocatalytic ability of Zr-MOF for CO2 reduction. These results indicate that the modification of Zr-MOF with electron-donating groups can promote the photocatalytic CO2 reduction. Therefore, the current work provides an instructive approach to improve the photocatalytic efficiency of CO2 reduction through the covalent modification of MOFs.


Neonatal ethanol exposure triggers apoptosis in the murine retrosplenial cortex: Role of inhibition of NMDA receptor-driven action potential firing.
Exposure to ethanol during the last trimester equivalent of human pregnancy causes apoptotic neurodegeneration in the developing brain, an effect that is thought to be mediated, in part, by inhibition of NMDA receptors. However, NMDA receptors can rapidly adapt to the acute effects of ethanol and are ethanol resistant in some populations of developing neurons. Here, we characterized the effect of ethanol on NMDA and non-NMDA receptor-mediated synaptic transmission in the retrosplenial cortex (RSC), a brain region involved in the integration of different modalities of spatial information that is among the most sensitive regions to ethanol-induced neurodegeneration. A single 4-h exposure to ethanol vapor of 7-day-old transgenic mice that express the Venus fluorescent protein in interneurons triggered extensive apoptosis in the RSC. Slice electrophysiological recordings showed that bath-applied ethanol inhibits NMDA and non-NMDA receptor excitatory postsynaptic currents (EPSCs) in pyramidal neurons and interneurons; however, we found no evidence of acute tolerance development to this effect after the 4-h in-vivo ethanol vapor exposure. Acute bath application of ethanol reduced action potential firing evoked by synaptic stimulation to a greater extent in pyramidal neurons than interneurons. Submaximal inhibition of NMDA EPSCs, but not non-NMDA EPSCs, mimicked the acute effect of ethanol on synaptically-evoked action potential firing. These findings indicate that partial inhibition of NMDA receptors by ethanol has sizable effects on the excitability of glutamatergic and GABAergic neurons in the developing RSC, and suggest that positive allosteric modulators of these receptors could ameliorate ethanol intoxication-induced neurodegeneration during late stages of fetal development.


Kjellin's syndrome: Spastic paraplegia and multifocal pattern dystrophy simulating fundus flavimaculatus.
Kjellin's syndrome is a rare autosomal recessive hereditary neuro-ophthalmologic syndrome. The diagnosis of Kjellin's syndrome is based on the retinal appearance in a patient with spastic paraplegia, learning difficulties, amyotrophy and thin corpus callosum. We present the case of a 42-years-old man without visual symptoms, referred to study from the Neurology Service due to a degenerative condition. On ophthalmologic examination is found a multifocal pattern dystrophy simulating fundus flavimaculatus and a delay in the visual evoked potential responses. The performed tests are reviewed and a genetic analysis for subtypes 11 and 15 of hereditary spastic paraplegia are requested. These subtypes are associated with macular changes. A pathogenic variant in the SPG 11 gene is identified, which explains the patient's clinical manifestations. Ophthalmological findings were key in the diagnosis of this rare syndrome.


Amino group binding peptide aptamers with double disulphide-bridged loops selected by in vitro selection using cDNA display.
Peptide aptamers that specifically bind to the amino group on a solid-phase were screened by in vitro selection using the cDNA display method. The identified peptides have a unique structure containing two cyclic loops with disulphide bonds and a linkage region, which were indispensable for molecular recognition.


Prevalence of malignant or possibly malignant renal masses among homogeneous low-attenuation masses that are too small to characterize at computed tomography.
Homogeneous low-attenuation renal masses that are too small to characterize (tstc) are considered clinically insignificant; however, based primarily on expert opinion. To determine the prevalence of malignant or possibly malignant masses among homogeneous low-attenuation renal masses that are tstc. This retrospective cross-sectional study evaluated 75 patients with 104 tstc who underwent renal CT and MRI between Jan 2016 and Jul 2022. Low-attenuation renal masses measuring < 1 cm in size were identified and, independently evaluated by two blinded radiologists measuring attenuation (Hounsfield Units, HU) at non-contrast enhanced CT (NECT) and nephrographic phase contrast-enhanced (CE)-CT when possible. Reference standard for benign cyst was MRI and for other renal masses was pathology or MRI showing enhancement. Average tstc size was 6 ± 2 (range 2-10) mm. Considering only incidental tstc (CT performed for another reason), 100% (98/98, 95%CI 96-100%) tstc were benign. Overall, considering both incidental and tstc referred for further characterization, there were 94% (98/104; 95% Confidence Intervals [CIs] 88-98%) benign cysts and 6% (6/104; 95%CI 2-12%) other masses (1 Bosniak 2F cystic mass, 2 probable renal cell carcinoma (RCC), three metastases). Pseudoenhancement, attenuation change > 10 HU or > 20 HU, was present in 29% (15/59) and 12% (7/59) benign cysts. All six other masses enhanced by > 20 HU. CECT threshold of ≤ 30 HU correctly classified 62% of benign cysts (61/98). All six other masses measured > 30 HU at CECT. The prevalence of malignant or possibly malignant renal masses among homogeneous low-attenuation too small to characterize masses among incidental tstc masses is near zero. Attenuation measurements misclassify a substantial proportion of these cysts, likely due to their small size.


Hypophosphatasia: From Diagnosis to Treatment.
Hypophosphatasia (HPP) is a rare genetic disorder caused by mutations of the ALPL gene. ALPL encodes the tissue-non-specific isoenzyme of alkaline phosphatase (TNSALP). Consequently, bone mineralization is decreased leading to fractures, arthralgia, and extra-skeletal manifestations including tissue calcification, respiratory failure, and neurological complications. This review summarizes the most important clinical findings, diagnosis, and treatment options for HPP. Asfotase alfa is a recombinant human alkaline phosphatase, used as treatment for the underlying cause of HPP. Asfotase alfa enhances the survival in life-threatening HPP and improves bone mineralization, muscle strength, and pulmonary function. However, discontinuation of asfotase alfa leads to reappearance of bone hypomineralization. Due to its varied manifestations, HPP often mimics rheumatological and other bone diseases, thereby delaying its diagnosis. Asfotase alfa, a recombinant alkaline phosphatase, is available for the long-term enzyme replacement therapy in patients with pediatric-onset HPP to treat the bone manifestations of the disease.


[Endotoxins: a neglected environmental factor].
The effects of bacterial endotoxins are well known form an experimental and clinical point of view. Their presence in the environment in general and their possible role for the development of clinical symptoms at low exposure levels has been less studied. Experimental and epidemiological evidence for such effects are reviewed with reference to particular environments where this exposure might be present.


Functional analysis of novel RHD variants: splicing disruption is likely to be a common mechanism of variant D phenotype.
We previously showed that several variations in the RHD gene, including synonymous changes, can be classified as splice site variants and may play a direct role in D variant phenotype expression. We sought to extend our study to additional candidates, notably in the first and last exons of the gene, by engineering a novel universal splice reporting vector, i.e., minigene. Our previous plasmid construct was modified to allow subcloning of any exon(s) of interest for assessing effect of variations on splicing. Seventeen novel and/or uncharacterized variations of the RHD gene were selected for the study and tested in our novel model. We engineered and validated a novel universal minigene for assessing virtually any variations of interest for splicing defect. Of the 17 variants tested in the novel model, 11 were shown to alter splicing either totally or partially, including the silent c.1065C>T variation, which induces major skipping of exon 7, and may therefore be responsible for reducing D antigen expression. We also showed that while all three missense variations c.1154G>C, c.1154G>T, and c.1154G>A in exon 9 are splice site variants, splicing is differentially altered and D-negative phenotype observed in the presence of the latter substitution is likely due to a defect in RhD protein folding. Overall, we hypothesize that splicing alteration is likely to be a common mechanism of D phenotype variation that has been underestimated so far. Further large-scale studies are necessary to demonstrate this statement definitely.


Synthesis, Spectroscopic, and Antibacterial Characterizations of Cadmium-Based Nanoparticles.
In the current study, the co-precipitation technique was employed for the synthesis of Cadmium oxide (CdO) and Copper‒doped Cadmium oxide (Cu‒CdO) nanoparticles. The synthesized samples were subjected to powder X-Ray diffraction (P-XRD), Field emission scanning electron microscopy (FE-SEM), Energy-dispersive X-ray (EDX), Fourier transforms Infrared (FT-IR), UV-Vis spectroscopy, photoluminescence (PL), laser-induced fluorescence spectroscopy and antibacterial investigations. According to the P-XRD analysis, both the samples were simple cubic in structure and have average grain sizes of 54 and 28 nm, respectively. FE-SEM was deployed to explore the surface textures of the samples. EDX technique was used to look at the elemental compositions of the samples. The technique of FT-IR was employed to identify the vibrational modes. UV-Vis spectra in diffuse reflectance mode were obtained and the optical bandgaps of the CdO and Cu‒CdO samples were obtained as 4.52 eV and 2.83 eV, respectively. The photoluminescence studies were conducted at an excitation wavelength of 300 nm and emission peaks were red-shifted in both samples. Fluorescence spectroscopy was applied to explore the lifetimes of synthesized nanoparticles. The technique of Agar-well diffusion was applied to assess the antibacterial performance of the generated nanoparticles against Micrococcus Luteus (gram-positive) and Escherichia coli (gram-negative) bacterium at variable concentrations. Both samples in the current study are significantly effective against both bacterial strains.


Lifetime marijuana use in relation to cadmium body burden of US adults: results from the national health and nutrition examination surveys, 2009-2016.
Low-level cadmium exposure has been linked to chronic diseases, but the importance of marijuana use as a source of cadmium remains unknown. We aimed to determine the association of marijuana use with blood cadmium (BCd) and urinary cadmium (UCd) levels. We abstracted data from the National Health and Nutrition Examination Surveys, 2009-2016. We modeled lifetime marijuana exposure accounting for both duration and frequency of exposure. We used adjusted ratio of geometric means (ARM) and 95% confidence intervals (95% CIs) to compare outcomes among groups of marijuana exposure, relative to never users. The UCd level was adjusted for creatinine excretion. We included 163,250 adults (mean age, 38.7 years; 50% women). The ARM of BCd was 1.28 (95% CI = 1.04, 1.57), 1.40 (95% CI = 1.11, 1.76), and 1.77 (95% CI = 1.51, 2.09) in current users with <2 uses per week, 2-3 uses per week, and ≥4 uses per week, respectively. Marijuana use for ≥15 years was associated with both higher cadmium burden in adults with <2 uses per week (ARM of 1.30 (95% CI = 1.04-1.62) for BCd and 1.48 (95% CI: 1.05, 2.09) for UCd or ≥4 uses per week (ARM of 1.69 (95% CI = 1.40, 2.05) for BCd and 1.38 (95% CI = 1.11, 1.72) for UCd. In former users, marijuana use was significantly associated with higher UCd levels in those with ≥15 years of use [ARM of 1.39 (95% CI = 1.14, 1.69) for those with <2 uses/week and 1.51 (95% CI = 1.19, 1.92) for those with ≥4 uses/week]. The BCd level was higher in both current and former marijuana users than in never users. Marijuana use was also associated with higher UCd levels after a long-term use.


Transbronchial Cryobiopsy Is Superior to Forceps Biopsy for Diagnosing both Fibrotic and Non-Fibrotic Interstitial Lung Diseases.
Interstitial lung disease (ILD) evaluation often requires lung biopsy for definite diagnosis. In recent years, transbronchial cryobiopsy (TBCB) emerged as a procedure with higher diagnostic yield than transbronchial forceps biopsy (TBFB), especially for fibrotic ILDs. Nonetheless, studies comparing these modalities in non-fibrotic ILDs and for specific ILD diagnoses are scarce. The aim of this study was to evaluate the diagnostic yield and safety of TBCB and TBFB in patients with fibrotic and non-fibrotic ILDs. An observational retrospective multicenter study including patients with ILD diagnosis by multidisciplinary discussion that underwent TBCB or TBFB between 2017 and 2021. Chest CT scans were reviewed by a chest radiologist. Biopsy specimens were categorized as diagnostic (with specific histological pattern), nondiagnostic, or without lung parenchyma. Nondiagnostic samples were reassessed by a second lung pathologist. TBCB and TBFB diagnostic yields were analyzed by multivariate regression. Procedural complications were evaluated as well. 276 patients were included, 116 (42%) underwent TBCB and 160 (58%) TBFB. Fibrotic ILDs were present in 148 patients (54%). TBCB diagnostic yield was 78% and TBFB 48% (adjusted odds ratio [AOR] 4.2, 95% CI: 2.4-7.6, p < 0.01). The diagnostic yield of TBCB was higher than TBFB among patients with fibrotic ILD (AOR 3.8, p < 0.01), non-fibrotic ILD (AOR 5.8, p < 0.01), and across most ILD diagnoses. TBCB was associated with higher risk for significant bleeding (10% vs. 3%, p < 0.01), but similar risk for pneumothorax. Diagnostic yield of TBCB was superior to that of TBFB for both fibrotic and non-fibrotic ILDs, and across most diagnoses.


Dinitrophenyl (DNP) hapten sandwich staining (DHSS) procedure. A 10 year review of its principle reagents and applications.
Over the past 10 years an immunoperoxidase method using dinitrophenyl (DNP) hapten-labelled primary or secondary probes has been devised. Its widely successful application in research and diagnostic work has depended upon the development of certain key reagents. These include a novel non-deleterious DNP labelling compound, a unique multivalent monoclonal bridge antibody, and an efficient DNP hapten substituted or anti-DNP linked marker enzyme. In this article the development of these reagents and various modifications of the basic technique are reviewed in conjunction with the special applications accruing from their use.


Norcantharidin liposome emulsion hybrid delivery system enhances PD-1/PD-L1 immunotherapy by agonizing the non-canonical NF-κB pathway.
PD-1/L1 checkpoint blockade has gained approval in terms of treating patients suffering from hepatocellular carcinoma (HCC). It should be noted that the PD-1/L1 inhibitor (α-PD-1/L1) has a low overall response rate when used as a single agent. Accordingly, the combination of α-PD-1/L1 and a series of therapies to further increase the response rate has become a major research direction. In our previous study, we developed a novel norcantharidin (NCTD) liposome emulsion hybrid delivery system (NE) with enhanced anticancer activity and reduced toxicity. In this study, NE was combined with α-PD-1/L1 for treating HCC. The combination therapy exhibited an enhanced antitumor activity, which led to the up-regulated expression levels of white blood cells, interleukin 12 (IL-12), interferon γ (IFN-γ), PD-L1, as well as CD8. Furthermore, the combination of NE and α-PD-1 achieved the optimal efficiency. NCTD-based chemotherapy is capable of synergizing with α-PD-1/L1 while enhancing checkpoint immunotherapy. It follows a mechanism that NCTD agonizes the non-canonical NF-κB pathway of dendritic cells for better activating CD8+T cells. Furthermore, NCTD may enhance antitumor immunity due to the leukogenic effect. In brief, new therapeutic regimens were provided for anti-HCC treatment by integrating NE to PD-1/L1 immunotherapy.


Contribution of acquired carbapenem-hydrolyzing oxacillinases to carbapenem resistance in Acinetobacter baumannii.
Carbapenem-hydrolyzing oxacillinases are reported increasingly in Acinetobacter baumannii. Since they hydrolyze carbapenems at low levels, the roles of carbapenem-hydrolyzing oxacillinases OXA-23, OXA-40, and OXA-58 in A. baumannii were determined. The bla(OXA-23), bla(OXA-40), and bla(OXA-58) genes were inserted in broad-host-range plasmid pAT801 and transformed in Escherichia coli DH10B and in A. baumannii CIP 70.10 and its point mutant derivative A. baumannii BM4547, which overexpresses the efflux pump AdeABC. Natural plasmids harboring the bla(OXA-23) and bla(OXA-58) genes were also transformed in A. baumannii CIP 70.10. In addition, the bla(OXA-40) gene was inactivated at its chromosome location in A. baumannii CLA-1. Intermediate levels of resistance or reduced susceptibilities to carbapenems were observed for A. baumannii transformants expressing OXA-23, OXA-40, and OXA-58. The inactivation of bla(OXA-40) in A. baumannii CLA-1 yielded reduced susceptibilities to carbapenems. Carbapenem-hydrolyzing oxacillinases OXA-23, OXA-40, and to a lesser extent OXA-58 play a role in carbapenem resistance in A. baumannii, and overexpression of efflux pump AdeABC may also contribute to higher levels of resistance to beta-lactams, including carbapenems.


Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy.
This study evaluated the ability of dexmedetomidine to provide analgesia and sedation for outpatient colonoscopy, examining outcomes including cardiorespiratory variables, side effects, and discharge readiness. Sixty-four patients were randomly assigned to one of three treatment regimens. In group D, patients received 1 microg/kg dexmedetomidine over 15 min followed by an infusion of 0.2 microg x kg x h. Group P received meperidine (1 mg/kg) with midazolam (0.05 mg/kg), and group F received fentanyl (0.1-0.2 mg intravenous) on demand. The assessment included measurements of heart rate, blood pressure, oxygen saturation, respiratory rate, quality of sedation/analgesia, and an evaluation of the recovery time. The study was terminated before the planned 90 patients had been recruited because of adverse events in group D. In all groups, negligible hemoglobin oxygen saturation and respiratory rate variations were observed. In group D, there was a significantly larger decrease in heart rate (to approximately 40 beats/min in 2 of 19 cases) and blood pressure (to less than 50% of the initial value in 4 of 19 patients). Supplemental fentanyl was required in 47% of patients receiving dexmedetomidine to achieve a satisfactory level of analgesia (vs. 42.8% of patients in group P and 79.2% of patients in group F). Vertigo (5 patients), nausea/vomiting (5 patients), and ventricular bigeminy (1 patient) were observed only in group D. Time to home readiness was longest in group D (85 +/- 74, 39 +/- 21, and 32 +/- 13 min in groups D, P and F, respectively; P = 0.007). The use of dexmedetomidine to provide analgesia/sedation for colonoscopy is limited by distressing side effects, pronounced hemodynamic instability, prolonged recovery, and a complicated administration regimen.


The alphabeta T cell repertoire comes into focus.
The size of the lymphocyte repertoire is of great interest, but direct information has been elusive. Moon et al. (2007) report the enumeration and isolation of naive CD4(+) T cells and show their numbers could predict the size and diversity of the primary immune response.


Three-dimensional NMR spectroscopy of a protein in solution.
The geometric information used to solve three-dimensional (3D) structures of proteins by NMR spectroscopy resides in short (less than 5 A) interproton-distance data. To obtain these distances, the 1H-NMR spectrum must first be assigned using correlation and nuclear Overhauser effect (NOE) experiments to demonstrate through-bond (scalar) and through-space connectivities, respectively. Because the NOE is proportional to r-6, distance information can then be derived. The increased resolution afforded by extending NMR experiments into a second dimension enables one to detect and interpret effects that would not be possible in one dimension owing to extensive spectral overlap and much reduced information. A number of small protein structures have previously been solved in this way. Extending this methodology to larger proteins, however, requires yet an additional improvement in resolution as overlap of cross-peaks in the two-dimensional (2D) NMR spectra present a major barrier to their unambiguous identification. One way of increasing the resolution is to extend the 2D-NMR experiments into a third dimension. We report here the applicability of three-dimensional NMR to macromolecules using the 46-residue protein alpha 1-purothionin as an example.


Post radical hysterectomy urinary incontinence: a prospective study of transurethral bulking agents injection.
The aim of the present study is to prospectively investigate the efficacy and complications of macroplastique transurethral implantation in cervical cancer patients affected by stress urinary incontinence (SUI) after radical hysterectomy (RH). Patients affected by de novo SUI post type 3 RH were considered for eligibility in this study. Preoperative and postoperative assessment included a standardized urogynecological history, urogynecological and neurological physical examination, evaluation of severity of SUI symptoms, a 3-day voiding diary, urine culture and urodynamic assessment. All patients underwent transurethral implantation using Macroplastique Implantation System (MIS). Patient follow-up was performed 6 and 12 months after surgery. A total of 24 consecutive patients were enrolled. At the 12 month follow up SUI cure rate was 42% (10 of 24 patients), the improvement rate was 42% (10 of 24) and the failure rate was 16% (4 of 24). The overall success rate was 84% (10 patients cured and 10 improved). No intraoperative or postoperative early complications were found. The 4 patients in whom treatment was not a success had preoperative urethral hypermobility. Subjective patient perception of SUI symptom severity showed significant improvement (mean severity of urinary loss perception 6.6+/-1.8 vs 2.3+/-3.3, p<0.05). The frequency of incontinence on the 3-day voiding diary was significantly reduced at the follow up (14.5+/-5.8 vs 4.3+/-7.9 episodes per 3 days, p<0.05). Bulking agents urethral injection could be a valid option having no surgical complications. This therapeutic strategy is able to treat SUI and improve well being of cervical cancer patients after radical surgery.


Genome Analysis and Physiology of Pseudomonas sp. Strain OVF7 Degrading Naphthalene and n-Dodecane.
The complete genome of the naphthalene- and n-alkane-degrading strain Pseudomonas sp. strain OVF7 was collected and analyzed. Clusters of genes encoding enzymes for the degradation of naphthalene and n-alkanes are localized on the chromosome. Based on the Average Nucleotide Identity and digital DNA-DNA Hybridization compared with type strains of the group of fluorescent pseudomonads, the bacterium studied probably belongs to a new species. Using light, fluorescent, and scanning electron microscopy, the ability of the studied bacterium to form biofilms of different architectures when cultured in liquid mineral medium with different carbon sources, including naphthalene and n-dodecane, was demonstrated. When grown on a mixture of naphthalene and n-dodecane, the strain first consumed naphthalene and then n-dodecane. Cultivation of the strain on n-dodecane was characterized by a long adaptation phase, in contrast to cultivation on naphthalene and a mixture of naphthalene and n-dodecane.


Performance indicators of photovoltaic heat-pumps.
In the last few decades, the demand for reversible heating and cooling systems has increased significantly, together with the need to generate energy in a more efficient and sustainable way. Consequently, the concept of solar photovoltaic (PV) powered heat pumps (HP) has become very attractive in order to match the heating/cooling demand with a renewable and environmentally-friendly energy source. This paper presents a review of the different solutions for PV-HP systems that have been studied theoretically and/or experimentally tested, and of the Key Performance Indicators (KPIs) that were mainly used. An analysis of these traditional KPIs has been performed and their boundaries were identified. As a result, new KPIs (PR25, PRref,25, SPFPV-HP and SPFPV-HP,ref,25) were proposed for trying to mitigate such limitations, as well as for evaluating not only the quality of the HP and the PV system, but also the quality of their integration and the renewable character of the whole PV-HP system. This paper is aimed to be framed in the common effort of the PV-HP research community to reach a set of KPIs that allow comparing the different future works and, therefore, a set of recommendations and future research lines are also proposed.


The electric potential field around cytochrome c and the effect of ionic strength on reaction rates of horse cytochrome c.
1. The electric potential fields around tuna ferri- and ferrocytochrome c were calculated assuming that (i) all of the lysines and arginines are protonated, (ii) all of the glutamic and aspartic acids and the terminal carboxylic acid are dissociated, and (iii) the haem has a net charge of +1e in the oxidized form. 2. Near the haem crevice high values for the potential (greater than +2.5 kT/e) are found. Consequently, electron transfer via the haem edge is favored if the oxidant or reductant is negatively charged. 3. The inhomogeneous distribution of charges leads to a dipole moment of 244 and 238 debye for oxidized and reduced tuna cytochrome c, respectively. Horse cytochrome c has dipole moments of 303 (oxidized) and 286 (reduced) debye. 4. A line through the positive and negative charge centres, the dipole axis, crosses the tuna cytochrome c surface at Ala 83 (positive part) and Lys 99 (negative part). The direction of the dipole axis of horse cytochrome c is very similar. Since the centre of the domain on the cytochrome c surface, which is involved in the binding to cytochrome c oxidase, is found at the beta-carbon of the Phe 82 in horse cytochrome c (Ferguson-Miller, S., Brautigan, D.L. and Margoliash, E. (1978) J. Biol. Chem. 253, 149--159) it is suggested that the direction of the dipole is of physiological importance. 5. The activity coefficients of horse ferri- and ferrocytochrome c were calculated as a function of ionic strength using a formula derived by Kirkwood (Kirkwood, J.G. (1934) J. Chem. Phys. 2, 351--361). 6. Due to the high net charge at pH 7.5 the influence of the dipole moments of horse ferri- and ferrocytochrome c on the respective activity coefficients can be neglected at I less than or equal to 50 mM. 7. Using the Brønsted relation the effect of ionic strength on reaction rates of horse cytochrome c was calculated. Good agreement is found between theory and experimental results reported in the literature.


Significance of the RBD mutations in the SARS-CoV-2 omicron: from spike opening to antibody escape and cell attachment.
We computationally investigated the role of the omicron RBD mutations on its structure and interactions with the surrounding domains in the spike trimer as well as with ACE2. Our results suggest that, compared to WT and delta, the mutations in the omicron RBD facilitate a more efficient RBD "down" to "up" conformation as well as ACE2 attachment. These effects, combined with antibody evasion, may have contributed to its dominance over delta.


Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.
The lack of functional evidence for the majority of missense variants limits their clinical interpretability and poses a key barrier to the broad utility of carrier screening. In Lynch syndrome (LS), one of the most highly prevalent cancer syndromes, nearly 90% of clinically observed missense variants are deemed "variants of uncertain significance" (VUS). To systematically resolve their functional status, we performed a massively parallel screen in human cells to identify loss-of-function missense variants in the key DNA mismatch repair factor MSH2. The resulting functional effect map is substantially complete, covering 94% of the 17,746 possible variants, and is highly concordant (96%) with existing functional data and expert clinicians' interpretations. The large majority (89%) of missense variants were functionally neutral, perhaps unexpectedly in light of its evolutionary conservation. These data provide ready-to-use functional evidence to resolve the ∼1,300 extant missense VUSs in MSH2 and may facilitate the prospective classification of newly discovered variants in the clinic.


Transurethral urethrotomy under vision.
Transurethral urethrotomy under vision with the Sachse urethrotome is a new surgical procedure for the treatment of urethral strictures. The chief advantage of the urethrotome is the fact that the surgeon can cut strictures selectively and accurately under clear vision. The procedure is less painful than blind internal urethrotomy and less extensive cases can be done in the office with the patient under local anesthesia. We report on 36 cases with at least 6 months of followup. In 20 cases the strictures were distal to the prostate and the results were considered good in 16, improved in 3 and a failure in 1. The other 16 cases involved vesical neck contractures and all patients had good results. The technique for urethral strictures distal to the prostate and for vesical neck contractures is described and postoperative treatment is emphasized and discussed.


Carbonic Anhydrase Inhibitors. Part 55 Metal Complexes of 1,3,4-Thiadiazole-2-Sulfonamide Derivatives: In Vitro Inhibition Studies With Carbonic Anhydrase Isozymes I, II and IV.
Coordination compounds of 5-chloroacetamido-1,3,4-thiadiazole-2-sulfonamide (Hcaz) with V(IV), Cr(lll), Fe(ll), Co(ll), Ni(ll) and Cu(ll) have been prepared and characterized by standard procedures (spectroscopic, magnetic, EPR, thermogravimetric and conductimetric measurements). Some of these compounds showed very good in vitro inhibitory properties against three physiologically relevant carbonic anhydrase (CA)isozymes, i.e., CA I, II, and IV. The differences between these isozymes in susceptibility to inhibition by these metal complexes is discussed in relationship to the characteristic features of their active sites, and is rationalized in terms useful for developing isozyme-specific CA inhibitors.


Diagnosis and management of tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder with a high spontaneous mutation rate. Understanding of this disorder has greatly increased in recent years. Two chromosomal loci can produce the TSC phenotype: 9q34 and 16p13. These appear to code for proteins that have a tumor suppressor function. TSC results in hamartomas that affect various organ systems, most commonly brain, skin, heart, and kidney. Previously thought to consist of intractable seizures, facial angiofibromas, and dementia, increasing numbers of persons with less severe involvement have been identified. Diagnostic criteria, various types of lesions, and medical management are reviewed.


Identification of circular RNAs hsa_circ_0140271 in peripheral blood mononuclear cells as a novel diagnostic biomarker for female rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic autoimmune disease, which commonly affects women. Accumulating evidence shows that differentially expressed circular RNAs (circRNAs) play crucial roles in the progress of RA. However, the roles of circRNAs in female RA remains unclear. This study explores potential role and diagnostic value of hsa_circ_0140271 from peripheral blood mononuclear cells (PBMC) in female RA. Differential expression of circRNAs was determined by RNA-sequencing in PBMC from 4 healthy controls (HC) and 4 RA patients, and we further measured the level of hsa_circ_0140271 in a validation cohort consisting of 47 RA and 47 HC via RT-qPCR. Besides, correlation studies with clinical variables were also examined. What's more, we performed bioinformatics analysis to predict the potential role of hsa_circ_0140271. PBMC expression of hsa_circ_0140271 of female RA was significantly higher than that of female HC, and it was positively correlated with antistreptolysin (ASO). Furthermore, the receiver operating characteristic (ROC) curve indicated that hsa_circ_0140271 could distinguish female RA from female HC and female patients with ankylosing spondylitis (AS) or osteoarthritis (OA). Besides, the combined diagnosis anti-cyclic citrullinated peptide (Anti-CCP) + hsa_circ_0140271 could improve diagnostic accuracy with an area under the curve (AUC) of 0.818 to compared with Anti-CCP. Furthermore, KEGG pathway enrichment analysis indicated hsa_circ_0140271 may act as microRNA sponge and participate in fatty acid metabolism pathways. Hsa_circ_0140271 was likely to be used as a promising diagnostic biomarker for female RA; it may act as microRNA sponge to regulate fatty acid metabolism pathways in RA.


Effect of m-health-based core stability exercise combined with self-compassion training for patients with non-specific chronic low back pain: study protocol for a randomized controlled trial.
Non-specific chronic low back pain (NCLBP) has a high incidence, which has a significant impact on a patient's body and mind and is a common condition affecting people's quality of life. Core stability exercise (CSE) is a modestly effective treatment for NCLBP; however, CSE has only been shown to be a useful treatment option in the short term. Many clinical practice guidelines recommend the use of a biopsychosocial framework to guide the management of NCLBP. Self-compassion training (SCT) is a promising psychotherapy treatment option for NCLBP; however, there is still a lack of research on CSE combined with SCT. In this study, we will seek to determine whether CSE combined with SCT is an effective treatment option for patients with NCLBP compared to CSE alone. In this study, we will randomize 166 adults with NCLBP to a combined SCT and CSE arm or a CSE alone arm (83 participants per group). Both interventions will consist of four weekly 1.5-h group sessions of CSE supplemented by home practice. The combined group protocol also includes 2 h of SCT before CSE. Interviewers masked to the treatment assignments will assess the outcomes at 4 and 16 weeks post-randomization. The primary outcomes are back pain disability (based on the Roland-Morris Disability Questionnaire) and pain intensity (NRS; average pain, worst pain, average pain) at 16 weeks. If SCT is found to enhance the effectiveness of CSE for patients with chronic back pain, the results of the study may promote the development of mind-body therapies for chronic low back pain. Chinese Clinical Trial Registry ChiCTR2100042810 . Registered on 21 January 2021.


Pretreatment Fasting Plasma Glucose Modifies Dietary Weight Loss Maintenance Success: Results from a Stratified RCT.
Levels of fasting plasma glucose (FPG) and fasting insulin (FI) were studied as diet-specific prognostic markers for successful weight loss maintenance in participants with overweight. After losing ≥ 8% of body weight, participants received one of three ad libitum diets for 6 months: (1) a moderate-fat diet high in monounsaturated fatty acids (MUFA); a low-fat, high-fiber diet (Nordic Nutrition Recommendations [NNR]); and the Average Danish Diet (ADD). Participants were categorized as having low (< 90 mg/dL) or high (90-105 mg/dL) FPG based on preintervention values. Median FI among those having high FPG was used as a cutoff for FI (FI ≤ 50 pmol/L; FI > 50 pmol/L). Participants with low FPG and randomized to MUFA, NNR, and ADD regained similarly 2.1 to 2.5 kg after 6 months. By contrast, participants with high FPG and randomized to MUFA, NNR, and ADD regained 2.73 kg (95% CI 1.33 to 4.13; P < 0.001), -0.05 kg (95% CI -1.95 to 1.86; P = 0.96), and 4.16 kg (95% CI 2.27 to 6.06; P < 0.001) after 6 months, respectively, resulting in lower weight regain on NNR compared to ADD (-4.21 kg [95% CI -6.83 to -1.59]; P = 0.002) and MUFA (95% CI -2.77 kg [-5.12 to -0.43]; P = 0.020). The addition of FI strengthened these associations. Slightly elevated pretreatment FPG determined success in dietary weight loss maintenance among overweight patients on ad libitum diets differing in macronutrient and fiber content.


Paired indirect immunoenzyme staining with primary antibodies from the same species. Application of horseradish peroxidase and alkaline phosphatase as sequential labels.
Paired indirect immunoenzyme staining based on primary antisera from the same species was performed sequentially without intermediate antibody elution. The first antigen was labelled brown by an immunoperoxidase procedure (either the two-stage indirect method, the unlabelled antibody peroxidase-antiperoxidase method, or the avidin-biotin bridge method using diaminobenzidine (DAB) and hydrogen peroxide as the substrates. The second antigen was labelled blue by applying a two-stage indirect immuno-alkaline phosphatase procedure using naphthol AS phosphate and Fast Blue BB salt as the substrate. In this way, polyclonal mucosal immunocytes were revealed in distinctly contrasting colours when stained for kappa and lambda light chains. Glucagon and somatostatin (D) cells in human pancreatic islets, and gastrin and D cells in human gastric antral glands, were likewise clearly differentiated. Conversely, a mixed colour appeared in some immunocytes after staining for alpha and kappa chains. However, unbalanced colour mixing was sometimes difficult to interpret, and additional experiments demonstrated that unwanted interactions could take place between the two sequences of reagents if the density of the DAB deposits was insufficient. These pitfalls were incompatible with unequivocal double staining in the same cell. Nevertheless, paired staining could be conveniently applied with the described procedures when prior knowledge had established that the antigens in question were located in separate cells.