Immunotoxins, ligand-toxin conjugates and molecular targeting.
Biotechnology provides tools for therapeutic exploitation following advances in the elucidation of protein-to-cell and cell-to-cell interactions. Molecular targeting of bacterial and plant toxins to the desired district of action can be achieved through effector molecules like monoclonal antibodies or protein ligands. Biochemical conjugation of these effectors to SO-6, a single-chain Ribosome Inactivating Protein from Saponaria officinalis, yielded powerful cytotoxic agents that are attractive candidates for therapeutic evaluation. Cloning of the gene for this plant toxin has been achieved. Technologies for expression of protein ligands, such as apolipoproteins or several growth factors, are available in recombinant microorganisms, providing adequate partners for the assembly of targeted chimaeras. Domain engineering of structural and functional regions in effector proteins is now possible and will be carried out with the available technologies to improve existing therapy.


Measuring longitudinal cognition: Individual tests versus composites.
Longitudinal cohort studies of cognitive aging must confront several sources of within-person variability in scores. In this article, we compare several neuropsychological measures in terms of longitudinal error variance and relationships with biomarker-assessed brain amyloidosis (Aβ). Analyses used data from the Wisconsin Registry for Alzheimer's Prevention. We quantified within-person longitudinal variability and age-related trajectories for several global and domain-specific composites and their constituent scores. For a subset with cerebrospinal fluid or amyloid positron emission tomography measures, we examined how Aβ modified cognitive trajectories. Global and theoretically derived composites exhibited lower intraindividual variability and stronger age × Aβ interactions than did empirically derived composites or raw scores from single tests. For example, the theoretical executive function outperformed other executive function scores on both metrics. These results reinforce the need for careful selection of cognitive outcomes in study design, and support the emerging consensus favoring composites over single-test measures.


Cathepsin B-sensitive dipeptide prodrugs. 2. Models of anticancer drugs paclitaxel (Taxol), mitomycin C and doxorubicin.
Substrates containing doxorubicin (DOX), paclitaxel (taxol), and mitomycin C (MMC) attached to the cathepsin B-sensitive dipeptide Phe-Lys via a self-immolative spacer were prepared as model compounds for internalizing anticancer immunoconjugates. Cathepsin B-mediated release rates of free drug, rat liver lysosomal susceptibility and human plasma stability were measured for each.


A Qualitative Study to Examine Feasibility and Design of an Online Social Networking Intervention to Increase Physical Activity in Teenage Girls.
Online social networks present wide-reaching and flexible platforms through which to deliver health interventions to targeted populations. This study used a social marketing approach to explore teenage girls' perceptions of physical activity and the potential use of online social networks to receive a physical activity intervention. Six focus groups were conducted with 19 Australian teenage girls (ages 13 to 18 years) with varying levels of physical activity and socioeconomic status. A semi-structured format was used, with groups discussion transcribed verbatim. Content analysis identified emergent themes, with triangulation and memos used to ensure accuracy. Physical activity was most appealing when it emphasised sport, exercise and fitness, along with opportunities for socialisation with friends and self-improvement. Participants were receptive to delivery of a physical activity intervention via online social networks, with Facebook the most widely reported site. Participants commonly accessed online social networks via mobile devices and particularly smartphones. Undesirable features included promotion of physical activity in terms of walking; use of cartoon imagery; use of humour; and promotion of the intervention via schools, each of which were considered "uncool". Participants noted that their parents were likely to be supportive of them using an online social networking physical activity intervention, particularly if not promoted as a weight loss intervention. This study identified key features likely to increase the feasibility and retention of an online social networking physical activity intervention for teenage girls. Guidelines for the design of interventions for teenage girls are provided for future applications.


Thrombotic risk of platinum combination chemotherapy with and without immune checkpoint inhibitors for advanced non-small cell lung cancer: a nationwide inpatient database study.
To determine the associated thromboembolism risk with adding immune checkpoint inhibitors (ICI) to platinum combination chemotherapy compared with platinum combination chemotherapy alone in patients with advanced non-small cell lung cancer. This study identified 75,807 patients with advanced non-small cell lung cancer from the Japanese Diagnosis Procedure Combination database who started platinum combination chemotherapy between July 2010 and March 2021. The incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and all-cause mortality within 6 months after commencing platinum combination chemotherapy was compared between patients receiving chemotherapy with ICI (ICI group, n = 7,177) and without ICI (non-ICI group, n = 37,903). Survival time analysis was performed using the overlap weighting method with propensity scores to adjust for background factors. The subdistribution hazard ratio for developing thromboembolism was calculated using the Fine-Gray model with death as a competing risk. The hazard ratio for all-cause mortality was also calculated using the Cox proportional hazards model. Overall, VTE and ATE occurred in 761 (1.0%) and 389 (0.51%) patients, respectively; mortality was 11.7%. Propensity score overlap weighting demonstrated that the subdistribution hazard ratio (95% confidence interval) for VTE and ATE in the ICI group was 1.27 (1.01-1.60) and 0.96 (0.67-1.36), respectively, compared with the non-ICI group. The mortality hazard ratio in the ICI group was 0.68 (0.62-0.74). The addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable.


Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical outcome of renal transplantation.
We retrospectively examined the association of polymorphisms in the CYP3A, CYP2J2, CYP2C8, and ABCB1 genes with pharmacokinetic (PKs) and pharmacodynamic (PDs) parameters of tacrolimus in 103 renal transplant recipients for a period of 1 year. CYP3A5 expressers had lower predose concentrations (C(0) )/dose and higher dose requirements than nonexpressers throughout the study. Among CYP3A5*1 carriers, those also carrying the CYP3A4*1B allele showed the lowest C(0) /dose, as compared with CYP3A4*1/CYP3A5*3 carriers (54.28±26.45, 59.12±24.00, 62.43±41.12, and 57.01±17.34 vs. 112.37± 76.60, 123.21±59.57, 163.34±76.23, and 183.07±107.82 at 1 week, 1 month, 5 months, and 1 year after transplantation). In addition, CYP3A4*1B/CYP3A5*1 carriers showed significantly lower dose-corrected exposure than CYP3A4*1/CYP3A5*1 carriers 1 year after transplantation (57.01±17.34 vs. 100.09±24.78; P=0.016). Only the ABCB1 TGC (3435-2677-1236) haplotype showed a consistent association with PDs (nephrotoxicity; OR=4.73; CI: 1.3-16.7; P=0.02). Our findings indicate that the CYP3A4*1B-CYP3A5*1 haplotype may have a more profound impact in tacrolimus PKs than the CYP3A5*1 allele. This study does not support a critical role of the CYP450 or ABCB1 single nucleotide polymorphisms in the occurrence of toxicity or acute rejection in renal transplant recipients treated with tacrolimus.


[Hypereosinophilic syndrome. Case report of the differential diagnosis of eosinophilic leukemia].
We report on a 48 years old patient with chronic eosinophilic leukemia. The diagnosis is based on changes of the blood picture with leukocytosis, deviation to the left to promyelocytes and sometimes normoblasts in the differential smear in with eosinophilia of up to 90%. A hepatosplenomegaly with an extensive extramedullary blood formation could be observed. Endocarditis parietalis fibroplastica was found on autopsy. The problem whether the organ changes observed are due to the eosinophilia existing for more than two years is discussed.


Patient-maintained propofol sedation for adult patients undergoing surgical or medical procedures: a scoping review of current evidence and technology.
Patient-maintained propofol sedation (PMPS) is the delivery of procedural propofol sedation by target-controlled infusion with the patient exerting an element of control over their target-site propofol concentration. This scoping review aims to establish the extent and nature of current knowledge regarding PMPS from both a clinical and technological perspective, thereby identifying knowledge gaps to guide future research. We searched MEDLINE, EMBASE, and OpenGrey databases, identifying 17 clinical studies for analysis. PMPS is described in the context of healthy volunteers and in orthopaedic, general surgical, dental, and endoscopic clinical settings. All studies used modifications to existing commercially-available infusion devices to achieve prototype systems capable of PMPS. The current literature precludes rigorous generalisable conclusions regarding the safety or comparative clinical effectiveness of PMPS, however cautious acknowledgement of efficacy in specific clinical settings is appropriate. Based on the existing literature, together with new standardised outcome reporting recommendations for sedation research and frameworks designed to assess novel health technologies research, we have made recommendations for future pharmacological, clinical, behavioural, and health economic research on PMPS. We conclude that high-quality experimental clinical trials with relevant comparator groups assessing the impact of PMPS on standardised patient-orientated outcome measures are urgently required.


Thermodynamic aspects of the adsorption of hexametaphosphate on kaolinite.
The adsorption of hexametaphosphate ion, an important deflocculant used in the ceramic industry, from aqueous solutions onto kaolinite has been studied at different temperatures. The adsorption isotherm follows the Langmuir model: the thermodynamic parameters DeltaG(ads)(0), DeltaH(ads)(0), and DeltaS(ads)(0) were calculated and found to be consistent with an interaction model involving the formation of an inner-sphere complex between HMP and aluminol groups. Also, the dependence of the adsorption behavior on the kaolinite volume fraction has been studied and discussed in term of association processes between the clay particles.


Risk factors for recurrent Pelvic Inflammatory Disease.
Pelvic inflammatory disease (PID) is a common infection which can result in severe long term morbidity, such as chronic pelvic pain and infertility. The morbidity increases in correlation to the number of PID events. Our study aim to assess the risk factors for recurrence of pelvic inflammatory disease. A retrospective case control study was conducted using data for all women who were admitted to a tertiary medical center for a recurrent PID over a duration of 15 years. Women who had a recurrent PID were compared to women admitted for PID treatment without further recurrence. Forward stepwise multivariate logistic regression analysis was subsequently carried out. The study included 133 women of whom 33 had recurrent PID. Women in the recurrent PID group had a higher rate of previous pelvic surgery (12 (36 %) vs. 20 (20 %), adjusted odds ratio [OR] 2.2 (95 % confidence interval CI 1.06-5.4, p = 0.05) and more had intrauterine devices (IUD) still in place if they had been previously present (5 (71.4 %) vs. 9(25.7 %), OR 7.2, (95 % CI 1.18-43.9), p = 0.02). The majority were treated with a combination of Ampicillin and Gentamycin, fewer received Augmentin or a cephalosporin base regimen (28 (84.8 %) vs 56 (56.0 %), OR 4.4, (95 % CI 1.5-12.3, p = 0.02), (1 (3.0 %) vs 27 (27.0 %), OR 0.08, (95 % CI 0.01-0.64), (4 (12.2 %) vs 17 (17.0 %)) respectively. In addition, invasive treatment had been required in more patients who later had a recurrent PID (6 (18.1 %) vs. 4(4.0 %), OR 5.3 (95 % CI 1.1.4-20.2), p = 0.007). Antibiotic regimens and invasive treatment were independently associated with recurrent PID (OR 2.69; 95 % CI 1.13-6.41, OR 2.10; 95 % CI 1.19-3.71, respectively). Among women with PID, special awareness should be given to women with previous pelvic surgery, who required an additional interventional treatment and have an IUD inserted. Efforts should be made to achieve treatment success and optimal prevention to prevent recurrent PID.


cAMP-regulated chloride currents in CHO cells.
We examined whether elevations in cAMP levels increase membrane chloride permeability in native CHO cells by measuring whole cell chloride currents and efflux of 125I and 36Cl. With 20 microM forskolin, no significant effect was seen on whole cell currents. However, 100 microM forskolin increased both whole cell chloride currents and the rate of 125I and 36Cl efflux. Forskolin-activated currents showed a linear current-voltage relationship in solutions with symmetrical chloride concentrations and reversal potential changed in the direction anticipated for a chloride-selective current when chloride was replaced with gluconate. These results indicate that native CHO cells exhibit cAMP-regulated chloride conductance pathways which become apparent only after large elevations in intracellular cAMP levels.


The impact of same-day antiretroviral therapy initiation on retention in care and clinical outcomes at four eThekwini clinics, KwaZulu-Natal, South Africa.
Same-day initiation (SDI) of antiretroviral therapy (ART) increases ART uptake, however retention in care after ART initiation remains a challenge. Public health behaviours, such as retention in HIV care and adherence to antiretroviral therapy (ART) pose major challenges to reducing new Human Immunodeficiency Virus (HIV) transmission and improving health outcomes among HIV patients. We evaluated 6-month retention in care, and clinical outcomes of an ART cohort comprising of SDI and delayed ART initiators. We conducted a 6 months' observational prospective cohort study of 403 patients who had been initiated on ART. A structured questionnaire was used to abstract data from patient record review which comprised the medical charts, laboratory databases, and Three Interlinked Electronic Registers.Net (TIER.Net). Treatment adherence was ascertained by patient visit constancy for the clinic scheduled visit dates. Retention in care was determined by status at 6 months after ART initiation. Among the 403 participants enrolled in the study and followed up, 286 (70.97%) and 267 (66.25%) complied with scheduled clinics visits at 3 months and 6 months, respectively. One hundred and thirteen (28.04%) had been loss to follow-up. 17/403 (4.22%) had died and had been out of care after 6 months. 6 (1.49%) had been transferred to other health facilities and 113 (28.04%) had been loss to follow-up. Among those that had been lost to follow-up, 30 (33.63%) deferred SDI while 75 (66.37%) initiated ART under SDI. One hundred and eighty-nine (70.79%) participants who had remained in care were SDI patients while 78 (29.21%) were SDI deferred patients. In the bivariate analysis; gender (OR: 1.672; 95% CI: 1.002-2.791), number of sexual partners (OR: 2.092; 95% CI: 1.07-4.061), age (OR: 0.941; 95% CI: 0.734-2.791), ART start date (OR: 0.078; 95% CI: 0.042-0.141), partner HIV status (OR: 0.621; 95% CI: 0.387-0.995) and the number of hospitalizations after HIV diagnosis (OR: 0.173; 95% CI: 0.092-0.326). were significantly associated with viral load detection. Furthermore, SDI patients who defaulted treatment were 2.4 (95% CI: 1.165-4.928) times more likely to have increased viral load than those who had been returned in care. Viral suppression under SDI proved higher but with poor retention in care. However, the results also emphasise a vital need, to not only streamline processes to increase immediate ART uptake further, but also to ensure retention in care.


Pick's disease: an immunocytochemical study of neuronal changes. Monoclonal antibodies show that Pick bodies share antigenic determinants with neurofibrillary tangles and neurofilaments.
We used rabbit antisera to the 210,000; 155,000; and 70,000 mol. wt. neurofilament - polypeptides and monoclonal antibodies (BF 10; RT97) known to react with human neurofilaments in an immunohistochemical study of neuronal changes in Pick's disease and in senile dementia of the Alzheimer type. Pick bodies as well as neurofibrillary tangles and neurites showed strong reactivity with the monoclonal antibodies but remained unlabeled when treated with the rabbit polyclonal antisera. Our results indicate that the stained material in Pick bodies share antigenic determinants with neurofibrillary tangles and neurofilaments.


Empyema necessitans mimicking mesothelioma; unusual presentation of active pulmonary TB in immuno-competent state.
•This case presented with very rare feature of active Pulmonary TB.•It denotes that Empyema Necessitans can mimick mesothelioma.•Unusual CT findings of Empyema Necessitans.•It states importance of induced sputum for TB diagnosis.•We recommend to test induced sputum for extrapulmonary tuberculosis to halt the spread of TB in the communities.


Behavioral robustness: an emergent phenomenon by means of distributed mechanisms and neurodynamic determinacy.
Theoretical discussions and computational models of bio-inspired embodied and situated agents are introduced in this article capturing in simplified form the dynamical essence of robust, yet adaptive behavior. This article analyzes the general problem of how the dynamical coupling between internal control (brain), body and environment is used in the generation of specific behaviors. Based on the Evolutionary Robotics (ER) paradigm, four computational models are described to support discussions including descriptions on performance after a series of structural, sensorimotor or mutational perturbations, or are developed in the absence of them. Experimental results suggest that 'dynamic determinacy' - i.e. the continuous presence of a unique dynamical attractor that must be chased during functional behaviors - is a common dynamic phenomenon in the analyzed robust and adaptive agents. These agents show dynamical states that are definitely and unequivocally characterized via transient dynamics toward a unique, yet moving attractor at neural level for coherent actions. This determinacy emerges as a control strategy rooted on behavioral couplings and relies on mechanisms that are distributed on brain, body and environment. Different ways to induce further distribution of behavioral mechanisms are also discussed in this paper from a bio-inspired ER perspective.


p-tert-Butylcalix[8]arene-bonded silica monoliths for liquid chromatography.
Monolithic silica columns have inspired considerable research interests in the separation science because of their unique properties in permeability, mass transfer, efficiency and throughput. In this paper, a chemically p-tert-butylcalix[8]arene-bonded silica monolith was prepared as the promising candidate for versatile LC separations. Micrometer-sized macropores and nanometer-sized mesopores in this derivatized silica monolith reduce the diffusion path length and provide both low backpressure and high column efficiencies, leading to high-speed and high-throughput separations. Since p-tert-butylcalix[8]arene possesses a pi-donors cavity composed of benzene rings while polycyclic aromatic hydrocarbons, anthraquinones, phenol regio isomers and fullerenes are pi-systems with appreciable electron affinity, they may have a chance to get involved in forming host-guest inclusion complexes through non-covalent interactions, e.g. hydrophobic and pi-pi interactions. Compared with RP-18e, the prepared calixarene-bonded monolith exhibited better selectivity to molecules which contains more pi-electrons and more condensed cyclic moieties. The column efficiency was about 22,000 plates/m. The calixarene-bonded monolith also showed its good performances in separation of fullerenes and dihydropyridines, indicating a promising approach for purification of fullerenes with high purity from the carbon soot.


Binding properties of a novel calcium channel activating dihydropyridine in monolayer cultures of beating myocytes.
Binding characteristics of [3H]BAY K 8644, a new class of pharmacologically potent compounds, the calcium channel activating dihydropyridines (DHP), were demonstrated in cultured myocardial cells. [3H]BAY K 8644 exhibited reversible and saturable binding to myocytes, and specific binding was Ca2+-dependent. The equilibrium dissociation constant, Kd, was 35.2 nM, and maximal binding capacity, Bmax, was 1.07 pmol/mg protein. Binding of the 3H-ligand was highly specific for various potently displacing DHP derivatives (either the calcium channel activating BAY K 8644, or the Ca2+ entry blockers of the nifedipine type) with inhibition constants (Ki values) in the nanomolar range. BAY K 8644, on the other hand, showed very low affinity to other receptors tested in brain and heart membranes. Displacement potency of BAY K 8644 correlated well with data of the functional pharmacology; e.g., the enhanced myocardial contractility. Results from competition studies using [3H]BAY K 8644 and [3H]nimodipine support the conclusion that both the channel activating and inhibiting DHP structures interact with the same specific receptor site that might be associated with the putative Ca2+-channel.


Operative and 5-year outcomes of combined carotid and coronary revascularization: review of a large contemporary experience.
Surgical treatment of concomitant coronary and carotid disease is controversial. Studies comparing staged versus combined coronary artery bypass grafting and carotid endarterectomy (CABG/CEA) report varying and often conflicting operative results. Also, few studies have investigated the long-term outcomes of combined surgery. We reviewed the operative outcome and 5-year survival results of 189 consecutive patients (69+/-9 years old, 66 [35%] female patients) who underwent combined CABG/CEA between 1994 and 1999. Survival follow-up was conducted in February 2001 and the incidence of late stroke, carotid surgery, and myocardial infarction was investigated in all surviving patients by mail survey. A phone interview was done by a surgeon of patients with late strokes or repeated CEA. Operative death occurred in 5 of 189 patients (2.65%) 4 of which were in-hospital deaths. A total of 5 (2 permanent, 3 transient [2.65%]) perioperative strokes were documented in these patients, and 1 of the perioperative strokes patients died in the hospital. In all, 156 of 189 patients (82.5%) were alive at the time of the study and completed surveys were collected from 153 of 156 patients (98%). Of these 153 patients, 4 reported a late stroke (2.6%), 5 suffered a myocardial infarction (3.3%), and 16 (10.5%) underwent subsequent CEA (7 ipsilateral to original CEA). Angioplasty (3 of 153, 2.0%) and redo surgery (1 of 153, 0.66%) occurred infrequently. Median survival follow-up was 51 months (range 12 to 84), and the corresponding 5-year Kaplan-Meier survival was 79.4%. This survival was similar to that of age-matched isolated CABG patients (n = 532) with documented history of cerebrovascular disease but no surgical carotid lesions. Our results suggest that combined CABG/ CEA is safe and may in fact reduce the risk of adverse outcomes in the intermediate term compared with age and risk-matched patients. We speculate the latter may be attributable to a cerebrovascular protective effect of CABG/CEA pending verification by randomized trials. An economic benefit of CABG/CEA may also be inferred from avoiding separate coronary and carotid operations and reduction in the high costs of perioperative stroke.


Spontaneous physical functional recovery after hospitalization for COVID-19: insights from a 1 month follow-up and a model to predict poor trajectory.
Long COVID syndrome has emerged as a new global healthcare challenge, with impaired physical performance being a prominent debilitating factor. Cardiopulmonary rehabilitation is a mainstay of management of symptomatic post-COVID patients, and optimization of candidate selection might allow for more effective use of available resources. In order to study the natural dynamics and to identify predictors of physical functional recovery following hospitalization for COVID-19, 6 min walk test was performed pre-discharge in 176 patients (40% hypertensive, 53% female, mean age 53.2 ± 13.5 years) with re-evaluation at 1 month. Six min walk distance and the reached percent of predicted distance (6MWD%) were suboptimal at both visits-396 ± 71 m (68.7 ± 12.4%) pre-discharge and 466 ± 65 m (81.8 ± 13.6%) at 1 month. Associated changes included significant oxygen desaturation (2.9 ± 2.5 and 2.3 ± 2.2%, respectively) and insufficient increment of heart rate during the test (24.9 ± 17.5 and 28.2 ± 12.0 bpm) that resulted in low reached percent of individual maximum heart rate (61.1 ± 8.1 and 64.3 ± 8.2%). Automatic clusterization of the study cohort by the 6MWD% changes has allowed to identify the subgroup of patients with poor "low base-low increment" trajectory of spontaneous post-discharge recovery that were characterized by younger age (38.2 ± 11.0 vs. 54.9 ± 12.1, p < 0.001) but more extensive pulmonary involvement by CT (43.7 ± 8.8 vs. 29.6 ± 19.4%, p = 0.029) and higher peak ESR values (36.5 ± 9.7 vs. 25.6 ± 12.8, p < 0.001). Predictors of poor recovery in multivariate logistic regression analysis included age, peak ESR, eGFR, percentage of pulmonary involvement by CT, need for in-hospital oxygen supplementation, SpO2 and mMRC dyspnea score pre-discharge, and history of hypertension. COVID-19 survivors were characterized by decreased physical performance pre-discharge as assessed by the 6 min walk test and did not completely restore their functional status after 1 month of spontaneous recovery, with signs of altered blood oxygenation and dysautonomia contributing to the observed changes. Patients with poor "low base-low increment" trajectory of post-discharge recovery were characterized by younger age but more extensive pulmonary involvement and higher peak ESR values. Poor post-discharge recovery in the study cohort was predictable by the means of machine learning-based classification model that used age, history of hypertension, need for oxygen supplementation, and ESR as inputs.


Expanding disease spectrum associated with puerperal mastitis.
Staphylococcus aureus and the beta-hemolytic streptococci are the commonest causes of puerperal mastitis which tends to be a localized disease process. This report describes 2 cases attributable to these bacteria that resulted in extramammary involvement and augmented morbidity. Two cases of postpartum mastitis are described, one leading to necrotizing fasciitis caused by group A streptococci and the other leading to toxic shock syndrome (TSS) caused by S. aureus. The spectrum of disease commonly attributed to mastitis occurring in this setting should be expanded.


Transcriptome and protein networks to elucidate the mechanism underlying nitrite degradation by Lactiplantibacillus plantarum.
Excessive nitrite residue is one of the bottlenecks in the production of many fermented foods. Lactiplantibacillus plantarum PK25 obtained from traditional Chinese pickles exhibited excellent nitrite degradation ability. Here, transcriptome, protein-protein interaction networks, and phenotype were performed to evaluate systematically the mechanism of nitrite degradation of L. plantarum PK25. The results demonstrated that genes expression varied considerably at key time points for nitrite degradation. 553 (upregulated: 366, downregulated: 187) and 767 (upregulated: 425, downregulated: 342) differentially expressed genes were identified at 6 h and 24 h, respectively. The hub genes were mainly enriched in carbohydrate metabolism, energy metabolism, and nucleotide synthesis. PK25 expanded its carbon source utilizing profile and improved glycolysis to produce more ATP to counteract environmental stress. The related enzymes including glycoside hydrolase, sugar ABC transporter protein, and PTS sugar transporter were 5.714, 5.885, and 3.578-fold upregulated at the transcriptional level. For strain to sustain energy levels and acid generation, pyruvate metabolism was critical, with the result that phosphoenolpyruvate synthase and pyruvate oxidase were up-regulated to accelerate the pyruvate transition. To repair DNA lesions induced by nitrite, both base excision repair mechanism and recombinational DNA repair pathway were exploited, such as endodeoxyribonuclease upregulated 5.314 and 19.687-fold at the two moments. The results provided a theoretical reference and practical possibility to reduce nitrite residue and improve safety during food fermented products.


Influence of Timing Between Androgen Deprivation Therapy and External Beam Radiation Therapy in Patients With Localized, High-Risk Prostate Cancer.
Treatment with long-term androgen deprivation therapy (ADT) and radiation therapy (RT) is the nonsurgical standard-of-care for patients with high- or very high-risk prostate cancer (HR-PC), but the optimal timing between ADT and RT initiation is unknown. We evaluate the influence of timing between ADT and RT on outcomes in patients with HR-PC using a large national cancer database. Data for patients with clinical T1-T4 N0, M0, National Cancer Comprehensive Network HR-PC who were treated with definitive external RT (≥60 Gy) and ADT starting either before or within 14 days after RT start were extracted from the National Cancer Database (2004-2015). Patients were grouped on the basis of ADT initiation: (1) >11 weeks before RT, (2) 8 to 11weeks before RT, and (3) <8 weeks before RT. Kaplan-Meier, propensity score matching, and multivariable Cox proportional hazards were performed to evaluate overall survival (OS). With a median follow-up of 68.9 months, 37,606 patients with HR-PC were eligible for analysis: 13,346 (35.5%) with >11 weeks of neoadjuvant ADT, 11,456 (30.5%) with 8 to 11 weeks of neoadjuvant ADT; and 12,804 (34%) patients with <8 weeks of neoadjuvant ADT. The unadjusted 10-year OS rates for >11 weeks, 8 to 11 weeks, and <8 weeks neoadjuvant ADT groups were 49.9%, 51.2%, and 46.9%, respectively (P = .002). On multivariable and inverse probability of treatment weighting analyses, there was a significant OS advantage for patients in the 8 to 11 weeks neoadjuvant ADT group (adjusted hazard ratio 0.90; 95% confidence interval, 0.86-0.95; P < .001) but not the >11 weeks group. Neoadjuvant ADT initiation 8 to 11 weeks before RT is associated with significantly improved OS compared with shorter neoadjuvant ADT duration. Although prospective validation is warranted, this analysis is the largest retrospective study suggesting an influence of timing between ADT and RT initiation in HR-PC.


Defective intracellular killing of micro-organisms by murine alveolar macrophages.
Peritoneal and alveolar macrophages differ in phenotype, endocytic activities, and oxidative metabolism.


Synthesis of partially hydrolyzed graft copolymer (H-Ipomoea hederacea seed gum-g-polyacrylonitrile).
Polyacrylonitrile was grafted to Ipomoea hederacea (Ih) seed gum with 138.5% grafting yield and 43.55% grafting efficiency in a procedure that was performed under homogeneous microwave (MW) irradiation conditions for 70s in the absence of a radical initiator. Under similar conditions, a maximum grafting yield of 108% and 33.96% efficiency was achieved when the K2S2O8/ascorbic acid redox system was used as a radical initiator in a thermostatic water bath at 35 °C. The effects of reaction variables, such as monomer/Ih seed gum concentration, MW power, and exposure time on the graft copolymerization were studied. The partially hydrolyzed graft copolymer (H-Ih-g-PAN) formed a loose, porous surface and improved the water absorbency of Ih seed gum. The swelling behavior of H-Ih-g-PAN in various ionic salt (NaCl, MgCl2 and Na2SO4) solutions was also systematically investigated. The graft copolymer was further characterized using FTIR, TGA, XRD, and SEM.


The effects of short-term alcohol intake on clinic and ambulatory blood pressure in normotensive 'social' drinkers.
Office blood pressure (OBP), ambulatory blood pressure (ABP), and vascular reactivity were measured in 12 normotensive 'social' drinkers (mean alcohol consumption of 9.7 +/- 3.1 g/day) after 4 days of alcohol consumption (1 g/kg/day) and compared with the effects of an isocaloric substitute (sucrose, 1.75 g/kg/day) or no intervention. Alcohol consumption did not affect OBP or 24-mean ABP but appeared to decrease nocturnal systolic and diastolic blood pressure soon after consumption. Although vascular reactivity did not differ between the groups, the blood pressure rise in response to isometric exercise tended to be lower following alcohol. Thus, short-term alcohol ingestion by normotensive 'social' drinkers does not increase office or ambulatory blood pressure.


Naloxone Administration in US Emergency Departments, 2000-2011.
Rates of opioid overdose and opioid-related emergency department (ED) visits have increased dramatically. Naloxone is an effective antidote to potentially fatal opioid overdose, but little is known about naloxone administration in ED settings. We examined trends and correlates of naloxone administration in ED visits nationally from 2000 to 2011. Using data from the National Hospital Ambulatory Medical Care Survey, we examined ED visits involving (1) the administration of naloxone or (2) a diagnosis of opioid overdose, abuse, or dependence. We assessed patient characteristics in these visits, including concomitant administration of prescription opioid medications. We used logistic regression to identify correlates of naloxone administration. From 2000 to 2011, naloxone was administered in an estimated 1.7 million adult ED visits nationally; 19 % of these visits recorded a diagnosis of opioid overdose, abuse, or dependence. An estimated 2.9 million adult ED visits were related to opioid overdose, abuse, or dependence; 11 % of these visits involved naloxone administration. In multivariable logistic regression models, patient age, race, and insurance and non-rural facility location were independently associated with naloxone administration. An opioid medication was provided in 14 % of visits involving naloxone administration. Naloxone was administered in a minority of ED visits related to opioid overdose, abuse, or dependence. Among all ED visits involving naloxone administration, prescription opioids were also provided in one in seven visits. Further work should explore the provider decision-making in the management of opioid overdose in ED settings and examine patient outcomes following these visits.


Enhanced polysulphide redox reaction using a RuO2 nanoparticle-decorated mesoporous carbon as functional separator coating for advanced lithium-sulphur batteries.
A multi-functional RuO2 nanoparticle-embedded mesoporous carbon-coated separator is used as an electrocatalytic and adsorbing polysulphide-net to enhance the redox reaction of migrating polysulphides, to improve active material utilization and boost the electrochemical performance of lithium-sulphur batteries.


A latent class analysis of life stress among female East Asian college students: A multi-country study.
This study aimed to identify subgroups of East Asian female college students experiencing life stress frequencies, and examine whether a difference in general characteristics existed between the extracted classes. This used a cross-sectional design. Female college students from South Korea (n = 220) and Hong Kong (n = 300) participated in the study. Life stress frequencies using the Life Stress Scale were measured. Latent class analysis as well as binary and multinomial logistic regression analyses were performed to identify the factors associated with extracted classes, and ascertain whether a difference in general characteristics existed between the extracted classes. South Korean participants were classified into two latent groups: "life stress - high" (18.6%) or "life stress - low" (81.4%). Within the Korean latent groups, subjective health status was significantly associated with group classification. In Hong Kong, participants were classified into three latent groups: "life stress - high" (13.7%), "life stress - moderate" (43.9%), and "life stress - low" (42.4%), and the classified groups were significantly associated with the financial status of participants' parents, subjective health status, and body mass index. It is difficult to generalize the results to college females in the whole of South Korea and Hong Kong due to the convenience sampling method. Furthermore, further studies using a longitudinal design will be needed to confirm the variables' causal relationship. For alleviating the experienced stress frequency, it is important for female college students to have interventions at the family, societal, and national levels, in addition to their individual efforts.


Oliguric acute kidney injury after microwave ablation of large liver tumors: incidence and preventive measures.
Acute kidney injury (AKI), especially oliguric AKI, is a recognized complication following microwave ablation (MWA) of large liver tumors. This study evaluated the clinical features, mechanisms, risk factors and prevention strategies for oliguric AKI after MWA of large liver tumors. From March 2011 to May 2015, 441 patients with liver tumors ≧5 cm received MWA in our hospital. The clinical features, prevention strategies, further mechanisms and possible risk factors for oliguric AKI after MWA were analyzed. One hundred four (23.6%) patients had AKI after MWA; 11 (10.6%) patients had oliguric AKI, and 93 (89.4%) patients had nonoliguric AKI. All patients with nonoliguric AKI recovered without any special treatments. The eleven patients with oliguric AKI received appropriate treatments and had completely normal renal function three months later. Using double needles for ablation was a risk factor for nonoliguric AKI, while high preoperative levels of red blood cells (RBC), hemoglobin (HGB) and albumin (Alb) were risk factors for oliguric AKI. The decrease levels of hemoglobin were significantly high in oliguric AKI patients (p < .05). Patients with oliguric AKI had abnormally high postoperative transaminase and renal function indicators. Compared to postoperative prevention, intraoperative prevention significantly lowered the occurrence of oliguric AKI (0% vs. 3.7%, p = .018) and shortened the hospital stay. Patients who underwent MWA for large liver tumors are prone to develop oliguric AKI. Implementation of intraoperative strategies during MWA can effectively prevent the occurrence of this severe complication.


Characterization and functional analysis of liver-expressed antimicrobial peptide-2 (LEAP-2) from golden pompano Trachinotus ovatus (Linnaeus 1758).
The liver-expressed antimicrobial peptide-2 (LEAP-2) is an important component of the innate immune defense system and plays an important role in resisting the invasion of pathogenic microorganisms. In this study, LEAP-2 from golden pompano (Trachinotus ovatus) was characterized and its expression in response to Photobacterium damselae was investigated. The full-length LEAP-2 cDNA was 1758 bp, which comprised a 5'-UTR of 250 bp, an ORF of 321 bp, and a 3'-UTR of 1187 bp, encoding 106 amino acids. LEAP-2 consisted of a conserved saposin B domain and four conserved cysteines that formed two pairs of disulphide bonds. The genomic organization of LEAP-2 was also determined and shown to consisted of three introns and two exons. The predicted promoter region of ToLEAP-2 contained several putative transcription factor binding sites. Quantitative real-time (qRT-PCR) analysis indicated that LEAP-2 was ubiquitously expressed in all examined tissues, with higher mRNA levels observed in the muscle, liver, spleen, and kidney. After P. damselae stimulation, the expression level of LEAP-2 mRNA was significantly upregulated in various tissues of golden pompano. In addition, SDS-PAGE showed that the molecular mass of recombinant LEAP-2 expressed in pET-32a was approximately 23 kDa. The purified recombinant protein showed antibacterial activity against Gram-positive and Gram-negative bacteria. Luciferase reporters were constructed for five deletion fragments of different lengths from the promoter region (-1575 bp to +251 bp), and the results showed that L3 (-659 bp to +251 bp) presented the highest activity, and it was therefore defined as the core region of the LEAP-2 promoter. The seven predicted transcription factor binding sites were deleted by using PCR technology, and the results showed that the mutation of the USF transcription factor binding site caused the activity to significantly decrease. The results indicate that golden pompano LEAP-2 potentially exhibits antimicrobial effects in fish innate immunity.


Impact of queen infection on kitten susceptibility to different strains of Bartonella henselae.
Domestic cats are the natural reservoir of Bartonella henselae, the agent of cat scratch disease in humans. In kittens, maternal IgG antibodies are detectable within two weeks postpartum, weaning in six to ten weeks postpartum and kittens as young as six to eight weeks old can become bacteremic in a natural environment. The study's objective was to evaluate if maternal antibodies against a specific B. henselae strain protect kittens from infection with the same strain or a different strain from the same genotype. Three seronegative and Bartonella-free pregnant queens were infected with the same strain of B. henselae genotype II during pregnancy. Kittens from queens #1 and #2 were challenged with the same strain used to infect the queens while kittens from queen #3 were challenged with a different genotype II strain. All queens gave birth to non-bacteremic kittens. After challenge, all kittens from queens infected with the same strain seroconverted, with six out of the seven kittens presenting no to very low levels of transitory bacteremia. Conversely, all four kittens challenged with a different strain developed high bacteremia (average 47,900 CFU/mL by blood culture and 146,893 bacteria/mL by quantitative PCR). Overall, qPCR and bacterial culture were in good agreement for all kittens (Kappa Cohen's agreement of 0.78). This study demonstrated that young kittens can easily be infected with a different strain of B. henselae at a very young age, even in the presence of maternal antibodies, underlining the importance of flea control in pregnant queens and young kittens.


Intracellular increases of cAMP induce opposite effects in glutamic acid decarboxylase (GAD67) and glial fibrillary acidic protein immunoreactivities in C6 cells.
C6 is a cell line that expresses glial and neuronal markers. Treatments that increase intracellular cAMP levels induce the differentiation of these cells. We had previously demonstrated that forskolin, an agent that activates adenylate cyclase, produced changes in gene expression in C6 cells. As a consequence of this treatment, glutamic acid decarboxylase (GAD) activity and the mRNA for GAD67, one of the isoforms of the enzyme, decreased. In contrast, this treatment increased the transcription of the glial fibrillary acidic protein (GFAP) gene. We now show, by immunocytochemistry, that the changes in gene expression are phenotypically reflected by corresponding changes in the levels of the proteins encoded by the GAD67 and GFAP genes. Computer-assisted image analysis demonstrated that both the increase in GFAP immunofluorescence, and the decrease in GAD67 immunofluorescence are statistically significant. The changes in gene expression and in protein immunoreactivity are part of the differentiation process of the C6 cells towards a more mature glial phenotype.


Fatigue mediates the relationship between emotional and cognitive functioning in children post-cancer treatment.
Children treated for cancer are at risk to develop cognitive problems. Insight in underlying associations with emotional functioning and fatigue can be used to optimize interventions. We therefore aim to study emotional functioning, fatigue, and cognitive functioning in children postcancer treatment and investigate whether fatigue mediates the relationship between emotional and cognitive functioning. Emotional functioning, fatigue, and cognitive functioning were assessed in children post-cancer treatment using subscales of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales, Multidimensional Fatigue Scale and Cognitive Functioning Scale. A one sample t-test was used to compare outcomes with general population peers and mediation analysis was used to address the effect of fatigue on the relationship between emotional and cognitive functioning. A total of 137 children (mean age: 13.6, SD ± 3.3 years; mean time since end of treatment: 7.1 months, SD ± 5.9) participated. Lower scores on emotional functioning (Cohen's d [D]: 0.4), fatigue (D: 0.8) and cognitive functioning (D: 0.6) were found (p < .001) in children post-cancer treatment than in peers. A medium association was found between emotional and cognitive functioning (standardized regression coefficient [β]: 0.27, p < .001), which was mediated by fatigue (β = 0.16). Outcomes on emotional and cognitive functioning are decreased and fatigue is increased in children postcancer treatment. Fatigue mediates the relationship between emotional and cognitive functioning. Our results show the importance to focus on fatigue amongst stress as a target for intervention to improve cognitive functioning.


Hemophagocytic lymphohistiocytosis syndrome in Dengue hemorrhagic fever.
Hemophagocytic lymphohistiocytosis (HLH) is a life threatening florid activation of macrophages of the lymphoreticular system. It is reported to be associated with dengue in children in India and carries a high mortality. Patients present with high fever, worsening blood cell counts, splenomegaly, abnormal liver enzymes with features of liver failure, coagulopathy and neurological complications. The diagnosis is according to "Diagnostic Guidelines for HLH 2004", based on a triad of clinical, blood parameters and bone marrow cytology. In the present study, data of 212 children admitted with dengue were analyzed. Of 212 children, 31 children were classified as suspect HLH and advised bone marrow evaluation; of whom 23 children had marrow evidence of HLH. Worsening of blood cell counts were recorded in all children with a mean platelet count of 58,303.03 cells/cumm, low hematocrit in 95.65 %, low mean hemoglobin level of 8.37 g/dL, high erythrocyte sedimentation rate (ESR) and prolonged pro-thrombin time/international normalization ratio (PT/INR). Serum triglycerides, ferritin and transaminases were high. Of the 23 children, 19 patients received intravenous immunoglobulin (IVIG) and all of these children recovered. Dengue with multi-organ dysfunction is commonly concurrent to HLH in the marrow and hence, an early diagnosis based on clinical, laboratory and bone marrow evaluation is significant. A bone marrow evaluation confirms the diagnosis of HLH.


Psychophysical evidence for a purely binocular color system.
Two adaptation experiments were conducted to examine a hypothesis for a purely binocular color system that responds only to simultaneous inputs from the two eyes and that inhibits the activities of a pair of monocular color systems with each receiving input from their respective eye. In the first experiment, after a red or green stimulus was presented to both eyes to adapt the hypothesized binocular system, its compensatory color was presented alternately to each eye to nullify the adaptation effect of the hypothesized monocular systems. Results showed that after adaptation, the color appearance of a test stimulus shifted more to that of the compensatory color in binocular viewing than in monocular viewing. In the second experiment, a red or green stimulus was presented either to both eyes or to the left eye, and then its compensatory color was presented only to the left eye. Comparison was made to the adaptation effect between the binocular presentation of the color stimulus and its monocular presentation. Results showed that the color appearance viewed with the left eye shifted toward the compensatory color for the binocular adaptation and was constant for the monocular adaptation. These results are consistent with the idea of a "purely" binocular color system inhibiting the activity of a pair of monocular systems.


Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma.
Malignant pleural mesothelioma (MPM) is a lethal and rare cancer, even if its incidence has continuously increased all over the world. Asbestos exposure leads to the development of mesothelioma through multiple mechanisms, including chronic inflammation, oxidative stress with reactive oxygen species (ROS) generation, and persistent aberrant signaling. Together, these processes, over the years, force normal mesothelial cells' transformation. Chronic inflammation supported by "frustrated" macrophages exposed to asbestos fibers is also boosted by the release of pro-inflammatory cytokines, chemokines, growth factors, damage-associated molecular proteins (DAMPs), and the generation of ROS. In addition, the hypoxic microenvironment influences MPM and immune cells' features, leading to a significant rewiring of metabolism and phenotypic plasticity, thereby supporting tumor aggressiveness and modulating infiltrating immune cell responses. This review provides an overview of the complex tumor-host interactions within the MPM tumor microenvironment at different levels, i.e., soluble factors, metabolic crosstalk, and oxidative stress, and explains how these players supporting tumor transformation and progression may become potential and novel therapeutic targets in MPM.


Indole prevents Escherichia coli cell division by modulating membrane potential.
Indole is a bacterial signalling molecule that blocks E. coli cell division at concentrations of 3-5 mM. We have shown that indole is a proton ionophore and that this activity is key to the inhibition of division. By reducing the electrochemical potential across the cytoplasmic membrane of E. coli, indole deactivates MinCD oscillation and prevents formation of the FtsZ ring that is a prerequisite for division. This is the first example of a natural ionophore regulating a key biological process. Our findings have implications for our understanding of membrane biology, bacterial cell cycle control and potentially for the design of antibiotics that target the cell membrane.


Ovulation and successful pregnancy in a woman with ovarian failure after hypophysectomy and gonadotropin therapy.
A 38-year-old woman ovulated and conceived after administration of human menopausal gonadotropins despite a previous diagnosis of ovarian failure at age 18. Possible explanations include restoration of down-regulated gonadotropin receptors by development of a prolactinoma, spontaneous remission of autoimmune oophoritis, or prior tumor secretion of biologically inert gonadotropins.


CXCL12 derived from CD248-expressing cancer-associated fibroblasts mediates M2-polarized macrophages to promote nonsmall cell lung cancer progression.
Nonsmall cell lung cancer (NSCLC) is among the most prevalent malignant tumours threatening human health. In the tumour microenvironment (TME), cancer-associated fibroblasts (CAFs) induce M2-polarized macrophages, which strongly regulate tumour progression. However, little is known about the association between CAFs and M2 macrophages. CD248 is a transmembrane glycoprotein found in several cancer cells, tumour stromal cells, and pericytes. Here, we isolated CAFs from tumour tissues of NSCLC patients to detect the relationship between CD248 expression and patient prognosis. We knocked down the expression of CD248 on CAFs to detect CXCL12 secretion and macrophage polarization. We then examined the effects of CD248-expressing CAF-induced M2 macrophage polarization to promote NSCLC progression in vitro and in vivo. We found that CD248 is expressed mainly in NSCLC-derived CAFs and that the expression of CD248 correlates with poor patient prognosis. Blocking CXCL12 receptor (CXCR4) drastically decreased M2 macrophage chemotaxis. CD248 promotes CAFs secreting CXCL12 to mediate M2-polarized macrophages to promote NSCLC progression both in vitro and in vivo. Collectively, our data suggest that CD248-positive CAFs induce NSCLC progression by mediating M2-polarized macrophages.


Cancer prevention with semi-allogeneic ES cell-derived dendritic cells.
Dendritic cells (DC) genetically modified to present tumor-associated antigen are a promising means for anti-cancer immunotherapy. By introducing expression vectors into ES cells and subsequently inducing differentiation to DC (ES-DC), we can generate transfectant DC expressing the transgenes. In the future clinical application of this technology, the unavailability of human ES cells genetically identical to the patients will be a problem. However, in most cases, semi-allogeneic ES cells sharing some of HLA alleles with recipients are expected to be available. In the present study, we observed that model tumor antigen (OVA)-expressing mouse ES-DC transferred into semi-allogeneic mice potently primed OVA-reactive CTL and elicited a significant protection against challenge with OVA-expressing tumor. Genetic modification of ES-DC to overexpress SPI-6, the specific inhibitor of granzyme B, further enhanced their capacity to prime antigen-specific CTL in semi-allogeneic recipient mice. These results suggest the potential of ES-DC as a novel means for anti-cancer immunotherapy.


A potential antioxidant enzyme belonging to the atypical 2-Cys peroxiredoxin subfamily characterized from rock bream, Oplegnathus fasciatus.
Peroxiredoxins (Prxs), a diverse family of antioxidant enzymes, exert their antioxidant function through which different peroxide species are detoxified. This study describes both structural and functional characterization of a mitochondrial Prx identified in rock bream, Oplegnathus fasciatus (RbPrx5). The ORF (573 bp) of RbPrx5 encoded a protein of 190 amino acids (20 kDa) containing a putative mitochondrial targeting sequence (residues 1-20) and a thioredoxin-2 motif (residues 31-190) and three conserved Cys residues. Homology assessment and phylogenetic analysis clearly disclosed relatively higher amino acid sequence similarities and a closer evolutionary position of RbPrx5 with those of other teleost homologs. The ORF of RbPrx5 was distributed among six exons as found in other vertebrates, but it possessed an additional exon in its 5'-UTR. In silico examination of RbPrx5 gene's putative promoter region revealed the presence of several cis-elements which may be important in its transcriptional regulation. Constitutive expression of RbPrx5 was detected in eleven tissues with the highest level in the heart. Modulation of RbPrx5 transcription was evidenced from varying mRNA levels in head kidney post in vivo LPS-, poly I:C-, Edwardsiella tarda bacterial- and rock bream iridoviral-challenges. The antioxidant function of RbPrx5 was investigated using recombinant RbPrx5 protein. Results of an in vitro mixed-function oxidase assay demonstrated a dose-dependent inhibition of DNA damage by rRbPrx5. A H2O2 tolerance assay showed that in vivo overexpression of rRbPrx5 increased the bacterial survival under H2O2-mediated oxidative stress condition. These findings provide an overall insight into the structural, expressional and functional aspects of RbPrx5.


Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis.
We have identified an inhibitor of the protein C anticoagulant pathway in the plasma of a patient with systemic lupus erythematosus and a history of recurrent deep vein thrombosis, fetal wastage, and seizures. The patient's plasma contained anticardiolipin antibodies as well as a weak lupus anticoagulant. Examination of this patient's plasma revealed normal levels of protein C and protein S antigen, normal levels of functional protein C, as well as essentially normal levels of every blood coagulation factor. In a modified prothrombin time assay, the activated protein C-mediated prolongation of the clotting time observed in normal plasma was not observed in this patient's plasma. Gel permeation chromatography of the patient's plasma revealed that the inhibitory material was a high molecular weight protein that coeluted with the IgM peak. The inhibitor did not appear to circulate as a complex with protein C, since the inhibitor could easily be separated from protein C during fractionation procedures, and did not interfere with the activation of protein C in plasma as assessed by a functional amidolytic assay. Our findings suggest that the recurrent thrombotic episodes observed in this patient may have occurred as a result of the patient's antiphospholipid antibody neutralizing specific phospholipids essential for the full expression of the anticoagulant activity of activated protein C.


Functional ProTracer identifies patterns of cell proliferation in tissues and underlying regulatory mechanisms.
A genetic system, ProTracer, has been recently developed to record cell proliferation in vivo. However, the ProTracer is initiated by an infrequently used recombinase Dre, which limits its broad application for functional studies employing floxed gene alleles. Here we generated Cre-activated functional ProTracer (fProTracer) mice, which enable simultaneous recording of cell proliferation and tissue-specific gene deletion, facilitating broad functional analysis of cell proliferation by any Cre driver.


Chromatographic separation of conformers of substituted asymmetric nitrosamines.
The syn and anti conformers of N-nitrosoproline, N-nitrososarcosine and N-nitroso-2-(ethylamino)-ethanol, have been separated by liquid chromatography. These conformers result from hindered rotation about the N-N bond. Separation was achieved using adsorption, reversed-phase, and ion-exchange modes. For the nitroso-amino acids, a shift in the equilibrium conformer concentration was observed with changes in pH.


The role of cross-sectional echocardiography in the diagnosis of flail mitral leaflet.
Cross-sectional echocardiography was performed on two patients with mitral regurgitation in whom M-mode echocardiographic findings were not specific for the etiology of mitral regurgitation. In one patient, flail motion of the free edge of the anterior mitral leaflet into the left atrium was demonstrated only by cross-sectional echocardiograms. In the second patient, the flail posterior mitral leaflet was suggested to be a result of bacterial endocarditis. Cross-sectional echocardiograms clearly identified a flail motion of a mass of vegetation attached to the posterior mitral leaflet. Thus, cross-sectional echocardiography can provide critical information in recognizing patients with a flail mitral leaflet.


[Whole-gut irrigation for large bowel preparation in colorectal surgery (author's transl)].
In a controlled trial with 32 patients, whole-gut irrigation (wgi) was compared with elemental diet as a method of large-bowel preparation. Cleansing effect, caloric intake (bad taste of diet), and preparation time were significantly better in the first group (wgi). Since 1976, 203 patients have undergone wgi. Investigations concerning the effect of addition of antibiotics to the irrigant revealed optimum reduction of fecal flora with neomycin--bacitracin--clindamycin.


Ca2+ sparks and cellular distribution of ryanodine receptors in developing cardiomyocytes from rat.
Although abundant ryanodine receptors (RyRs) exist in cardiomyocytes from newborn (NB) rat and despite the maturity of their single-channel properties, the RyR contribution to excitation-contraction (E-C) coupling is minimal. Immature arrangement of RyRs in the Ca(2+) release site of the sarcoplasmic reticulum and/or distant RyRs location from the sarcolemmal Ca(2+) signal could explain this quiescence. Consequently, Ca(2+) sparks and their cellular distribution were studied in NB myocytes and correlated with the formation of dyads and transverse (T) tubules. Ca(2+) sparks were recorded in fluo-4-loaded intact ventricular myocytes acutely dissociated from adult and NB rats (0-9 days old). Sparks were defined/compared in the center and periphery of the cell. Co-immunolocalization of RyRs with dihydropyridine receptors (DHPR) was used to estimate dyad formation, while the development of T tubules was studied using di-8-ANEPPS and diIC12. Our results indicate that in NB cells, Ca(2+) sparks exhibited lower amplitude (1.7+/-0.5 vs. 3.6+/-1.7 F/F(0)), shorter duration (47+/-3.2 vs. 54.1+/-3 ms), and larger width (1.7+/-0.8 vs. 1.2+/-0.4 microm) than in adult. Although no significant changes were observed in the overall frequency, central sparks increased from approximately 60% at 0-1 day to 82% at 7-9 days. While immunolocalization revealed many central release sites at 7-8 days, fluorescence labeling of the plasma membrane showed less abundant internal T tubules. This could imply that although during the first week, release sites emerge forming dyads with DHPR-containing T tubules; some of these T tubules may not be connected to the surface, explaining the RyR quiescence during E-C coupling in NB.


Electrophoretic elution of nucleic acids from acrylamide and agarose gels.
A simple method for electrophoretic elution of nucleic acids from gel slices is described. The procedure utilizes a standard tube gel system and can be completed in as little as one hour. Nucleic acids are recovered in a small volume with almost 100% efficiency. The procedure is applicable equally to acrylamide and agarose gels, and small as well as large RNA and DNA molecules. The eluted nucleic acids are essentially undegraded and are suitable for a variety of structural and biological analyses.


Ocular complications of severe vernal keratoconjunctivitis (VKC) in Yemen.
The objective of this study was to assess the ocular complications and visual loss among patients with severe vernal keratoconjunctivitis (VKC). Four hundred and thirty-one patients with VKC seen at Ibn Al-Haitham Eye Center were the study group. This is a retrospective non-comparative observational study between 01 January 2002 and 31 December 2002. Visual acuity was measured with the standard Snellen visual acuity chart and for children under 5 years of age Kay pictures were used. Visual impairment was assessed by means of the World Health Organization criteria for visual disabilities. Cases with severe VKC that developed ocular complications leading to blindness and severe visual impairment were analyzed. The majority of VKC patients were males (75.9%) with a male:female ratio of 3.1:1. A total of 68 (15.7%) patients (54 boys and 14 girls) had severe VKC. The ocular findings among 20 patients with severe VKC that led to blindness and severe visual impairment included keratoconus (7); steroid-induced cataract (5), central corneal scars (5) and steroid-induced glaucoma (3). Two of the keratoconus cases developed acute hydrops. Severe VKC in developing countries including Yemen is a potentially blinding disease. Visual loss may be due to keratoconus and corneal scars, as well as complications of the unsupervised use of topically administered corticosteroids.


Personalizing oral delivery of nanoformed piroxicam by semi-solid extrusion 3D printing.
Semi-solid extrusion (SSE) 3D printing enables flexible designs and dose sizes to be printed on demand and is a suitable tool for fabricating personalized dosage forms. Controlled Expansion of Supercritical Solution (CESS®) is a particle size reduction technology, and it produces particles of a pure active pharmaceutical ingredient (API) in a dry state, suspendable in the printing ink. In the current study, as a model API of poorly water-soluble drug, nanoformed piroxicam (nanoPRX) prepared by CESS® was accommodated in hydroxypropyl methylcellulose- or hydroxypropyl cellulose-based ink formulations to warrant the printability in SSE 3D printing. Importantly, care must be taken when developing nanoPRX formulations to avoid changes in their polymorphic form or particle size. Printing inks suitable for SSE 3D printing that successfully stabilized the nanoPRX were developed. The inks were printed into films with escalating doses with exceptional accuracy. The original polymorphic form of nanoPRX in the prepared dosage forms was not affected by the manufacturing process. In addition, the conducted stability study showed that the nanoPRX in the prepared dosage form remained stable for at least three months from printing. Overall, the study rationalizes that with nanoparticle-based printing inks, superior dose control for the production of personalized dosage forms of poorly water-soluble drugs at the point-of-care can be achieved.


Effect of systematic empiric treatment with imipenem on the bacterial ecology in a burns unit.
This study took place over 18 months and was divided into three 6 month periods. During the first and third periods, the bacterial ecology of the unit was reviewed, including the observation of bacteria which were isolated and led us to prescribe general antimicrobial therapy, and record the subsequent antibiograms that became available. During the second 6 month period, any patient developing an infection due (or possibly due) to a "Gram negative" strain received imipenem (as beta lactam antimicrobial agent), usually combined with tobramycin. The comparison between bacteria and antibiograms isolated during the first and the third periods did not show any increase in multiple resistant bacteria or imipenem resistant strains, including methicillin resistant Staphylococcus aureus (MRSA). During the third period, in comparison with the first, the number of Pseudomonas aeruginosa and Acinetobacter strains was lower; however, the number of Enterobacter and Klebsiella had increased. There was an increase of overall resistance to ticarcillin, but there was no increase in resistance to the other antimicrobials concerned in the study. Therefore, we concluded that wide use of imipenem did not impair the bacterial ecology of the unit, if used with precautions such as high dose regimen, de-escalation, and both pharmacokinetics and ecology monitoring.


Relationship between antipyrine absorption and blood flow rate in rat jejunum, ileum, and colon.
The appearance rate of antipyrine in intestinal venous blood was measured in anesthetized rats during perfusion (0.2 ml/min) of a buffered solution with 1 mmol/l labeled antipyrine through a jejunal, ileal, or colonic segment (length: 2-5 cm). When the blood flow rate was increased from 0.9-1.2 to 1.6-2.0 ml min-1 g-1 by raising the systemic blood pressure from 80 to 130 mm Hg, the absorption of antipyrine increased only in the colon. Stepwise reduction of the blood flow rate from 1.4-1.7 to 0.2-0.3 or stepwise raise from 0.2-0.3 to 1.4 ml min-1 g-1 by constriction or release of the mesenteric artery decreased or increased the absorption rate of antipyrine. The relation between absorption and flow rate can be described by curves which ascend at low and level off into a horizontal section at high flow rates. At the same blood flow rate the regional absorption rate decreased in the order jejunum, ileum, and colon with the largest step between ileum and colon. Model analysis yielded the following results for jejunum, ileum, and colon, respectively: permeability-surface area product 0.083, 0.074, and 0.037 ml min-1 g-1; fraction of absorptive site blood flow rate 0.24, 0.19, 0.08. The differences can be attributed mainly to the change of the surface area from jejunum to ileum and colon.


Evidence that the Gh protein is a signal mediator from alpha 1-adrenoceptor to a phospholipase C. II. Purification and characterization of a Gh-coupled 69-kDa phospholipase C and reconstitution of alpha 1-adrenoceptor, Gh family, and phospholipase C.
Our studies on the alpha 1-adrenoceptor signaling have demonstrated that the Gh family is a signal mediator. We report here that a 69-kDa phospholipase C (PLC) is the effector in this signal pathway. The enzyme was isolated by dissociating a Gh7-PLC complex which was induced in the bovine liver membranes incubating with (-)-epinephrine and GTP. The enzyme displayed a marked preference hydrolysis for phosphatidylinositol 4,5-bisphosphate over other phosphatidylinositides at micromolar calcium. Reconstitution of PLC with the alpha 1-adrenoceptor and Gh (Gh7) into phospholipid vesicles resulted in a lowered Ca2+ requirement for the substrate hydrolysis in the presence of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) when the receptor was activated with the alpha 1-agonist. The formation of inositol phosphate was hormone concentration dependent and reached maximal within 3 min which was faster than the formation in the presence of the alpha 1-antagonist. An Gh7 alpha antibody co-immunoprecipitated 80-85% of phospholipase C activity in the presence of GTP gamma S, but not in the presence of GDP or buffer, showing the association of PLC with the alpha-subunit of Gh family. Thus, our novel approaches to identify the effector involved in the alpha 1-adrenoceptor signaling, as well as the reconstitution studies, substantially demonstrate that the alpha 1-adrenoceptor-mediated transmembrane signaling involves the Gh family and a 69-kDa PLC.


Using radiomic features of lumbar spine CT images to differentiate osteoporosis from normal bone density.
This study aimed to develop a predictive model to detect osteoporosis using radiomic features from lumbar spine computed tomography (CT) images. A total of 133 patients were included in this retrospective study, 41 men and 92 women, with a mean age of 65.45 ± 9.82 years (range: 31-94 years); 53 had normal bone mineral density, 32 osteopenia, and 48 osteoporosis. For each patient, the L1-L4 vertebrae on the CT images were automatically segmented using SenseCare and defined as regions of interest (ROIs). In total, 1,197 radiomic features were extracted from these ROIs using PyRadiomics. The most significant features were selected using logistic regression and Pearson correlation coefficient matrices. Using these features, we constructed three linear classification models based on the random forest (RF), support vector machine (SVM), and K-nearest neighbor (KNN) algorithms, respectively. The training and test sets were repeatedly selected using fivefold cross-validation. The model performance was evaluated using the area under the receiver operator characteristic curve (AUC) and confusion matrix. The classification model based on RF had the highest performance, with an AUC of 0.994 (95% confidence interval [CI]: 0.979-1.00) for differentiating normal BMD and osteoporosis, 0.866 (95% CI: 0.779-0.954) for osteopenia versus osteoporosis, and 0.940 (95% CI: 0.891-0.989) for normal BMD versus osteopenia. The excellent performance of this radiomic model indicates that lumbar spine CT images can effectively be used to identify osteoporosis and as a tool for opportunistic osteoporosis screening.


Oestrogen and cyclical progestogen in postmenopausal hormone replacement therapy.
To ascertain the effectiveness, safety and incidence of side effects of a postmenopausal hormone replacement regimen consisting of continuous conjugated equine oestrogens and cyclical medroxyprogesterone acetate given for the first 14 days of each calendar month. A six month, prospective, open label, two centre, outpatient study of continuous Premarin (0.625 mg; Wyeth-Ayerst) and cyclical Provera (10 mg; Upjohn). Dosage adjustment was allowed in one centre. Seventy-six postmenopausal women in Adelaide and Brisbane. Menopausal symptom score, serum lipid levels, routine biochemical and haematological indices, endometrial histology and clinical bleeding pattern, blood pressure, weight changes, side effects, withdrawal from the study, compliance and necessary dose adjustment. Eight women withdrew from the study and nearly 50% experienced some minor side effect. Where dosage adjustment was allowed, almost all side effects were eliminated. Most patients had acceptable regular withdrawal bleeds although some were deemed heavy. There was a statistically highly significant 54% reduction in the menopausal symptoms score at three months and a 62% reduction at six months. Endometrial biopsy at six months showed atrophic or secretory endometrium with no inappropriate proliferation or hyperplasia. Total cholesterol and low density lipoprotein (LDL) cholesterol levels were significantly decreased. The high density lipoprotein (HDL) cholesterol level remained unchanged and triglyceride levels were raised within the normal range. There were no other clinically relevant biochemical, haematological or clinical changes. Continuous conjugated equine oestrogens (0.625 mg) and cyclical medroxyprogesterone acetate (10 mg) for the first 14 days of each calendar month proved to be a safe and effective postmenopausal therapy regimen. Initial minor side effects were common but could be readily ameliorated with early follow-up and dose titration.


Plasma membrane steroidogenic cholesterol: the relative importance of membrane internalization rate and cholesterol extraction rate of internalized membrane.
Most cholesterol destined to become steroid hormone passes through the plasma membrane. Using MA-10 Leydig tumor cells as a model system, we determined that plasma membrane cholesterol disappeared 2.5-fold faster in cAMP-stimulated cells. Stimulation of MA-10 cells increased internalization so that 1.4-fold more membrane cycled through the cell per unit time. Increased internalization accounted for 26% of the cholesterol actually lost from cycling membrane. The remaining 74% was accounted for by increasing the extraction of cholesterol from internalized membrane.


Axial Spondyloarthritis in Japan.
The differences in the epidemiology and management of patients with axial spondyloarthritis (axSpA) among regions and countries largely depend on the positivity of human leukocyte antigen (HLA)-B27 and the health care system. This review article focused on axSpA in Japan, where the prevalence of HLA-B27 is extremely low (0.3%) and the universal health insurance system typically provides a 70% or more copayment by the government. A nationwide survey was conducted in Japan in 2018, which estimated that there were 3200 patients (95% confidence interval [CI]: 2400-3900) with ankylosing spondylitis (AS), a term interchangeable with radiographic axSpA (r-axSpA), and 800 patients (95% CI: 530-1100) had non-radiographic (nr)-axSpA. These data indicate a prevalence of 2.6/100,000 or 0.0026% for AS and 0.6/100,000 or 0.0006% for nr-axSpA. Patients with AS, but not those with nr-axSpA, are designated as suffering from intractable diseases in Japan; thus, their medical expenses are reduced by grant under the Act on Medical Care for Patients with Intractable Diseases. As of February 2022, infliximab, adalimumab, secukinumab, ixekizumab, and brodalumab have been approved for AS, and secukinumab, ixekizumab, and brodalumab have been approved for nr-axSpA. An algorithm for nr-axSpA in Japan has been developed for the proper diagnosis and use of these therapeutic agents. A low prevalence of axSpA, especially that of nr-axSpA, was found in Japan. Early referral and the resultant diagnosis and appropriate treatment of these patients by rheumatologists are crucial issues in Japan, as in other countries.


The significance of neuronal lateralisation in Parkinson's disease.
The destruction of the dopaminergic neurons in the substantia nigra (SN) and consequent depletion of striatal dopamine elicits the main movement deficits related to Parkinson's disease (PD). In the early stages of the illness, the motor symptoms are often exhibited asymmetrically. Thus, the onset of PD features starts on either the right or left side. The side of onset appears to determine the prognosis of the disorder and other features, such as right-side tremor dominance has a better prognosis in contrast to left-side dominant bradykinesia-rigidity. In addition, left-side onset of motor features is associated with cognitive decline. Therefore, an intricate relation appears to exist between the side of disease onset and progression/severity and other non-motor symptoms. Unilateral PD in turn corresponds to neuronal nigrostriatal degeneration in the contralateral hemisphere. Indeed positron emission tomography has demonstrated a positive correlation between symptom asymmetry and brain function (Hoorn et al. Parkinsonism Relat Disord 17:58-60, 2011), which corresponds to a unilateral pattern of degeneration. This phenomenon appears to be exclusive to PD. Additionally, the variation in motor symptom(s) dominance exhibited in the disorder conforms to the notion that PD is a spectrum disease with many sub-groups. Thus, clinical and post mortem studies on "lateralisation" may serve as a vital tool in understanding the mechanism(s) eliciting the characteristic destruction of the SN neurons. Additionally, it may be employed as a predictive indicator for the symptomology and prognosis of the illness thus allowing selective treatment strategies targeted at the pronounced hemispheric degeneration.


Distribution characteristics and noncarcinogenic risk assessment of culturable airborne bacteria and fungi during winter in Xinxiang, China.
Bioaerosols are an important component of particulate matter in the atmosphere and are harmful to human health. In this study, the concentration, size distribution, and factors influencing culturable airborne bacteria and fungi in the atmosphere were investigated using a six-stage impactor device in the city of Xinxiang, China, during the winter season. The results revealed that the concentration of culturable airborne bacteria and fungi varied significantly during the sampling period: 4595 ± 3410 and 6358 ± 5032 CFU/m3, respectively. The particle sizes of the bioaerosols were mainly within stage V (1.1-2.1 μm), and fine particulate matter accounted for 45.9% ± 18.9% of airborne bacteria and 52.0% ± 18.5% of airborne fungi, respectively. With the deterioration of air quality, the concentration of airborne fungi gradually increased, and that of airborne bacteria increased when the air quality index was lower than 200 and decreased when it was higher than 200. With respect to the diurnal variation pattern of bioaerosol concentration, the highest and lowest concentrations were registered at night and noon, respectively, probably because of changes in ultraviolet radiation intensity. Bioaerosol concentration positively correlated with humidity, concentration of PM2.5, PM10, SO2, and NO2 and negatively correlated with O3 concentration. The risk of exposure of humans to the airborne bacteria was primarily associated with the respiratory inhalation pathway, and the risk of skin exposure was negligible. These results should improve our understanding of the threat of bioaerosols to public health.


A two-scale model for simultaneous sintering and crystallization of glass-ceramic scaffolds for tissue engineering.
Bioglass-based glass-ceramic foams have been developed recently as highly porous, mechanically competent, bioactive and degradable scaffolds for bone tissue engineering. However, the development of the material so far has been based on a trial-and-error approach, and the existing materials are far from being optimized. In this paper, a mechanism-based model is presented for sintering deformation of Bioglass foams. The porous foams consist of struts which, in turn, consist of Bioglass particles. A corresponding two-scale model is developed based on existing viscous sintering models. Crystallization plays a key role in the sintering deformation of Bioglass foams and is taken into account in the model. Qualitative comparison between the model predictions and experimental observations is presented, showing that the model is able to capture the complicated interplay between crystallization and viscous flow during the sintering process.


Chemical and biological sensors based on organic thin-film transistors.
The application of organic thin-film transistors (OTFTs) to chemical and biological sensing is reviewed. This review covers transistors that are based on the modulation of current through thin organic semiconducting films, and includes both field-effect and electrochemical transistors. The advantages of using OTFTs as sensors (including high sensitivity and selectivity) are described, and results are presented for sensing analytes in both gaseous and aqueous environments. The primary emphasis is on the major developments in the field of OTFT sensing over the last 5-10 years, but some earlier work is discussed briefly to provide a foundation.


Erratum: Autophagy Maintains the Function of Bone Marrow Mesenchymal Stem Cells to Prevent Estrogen Deficiency-Induced Osteoporosis: Erratum.
[This corrects the article DOI: 10.7150/thno.17949.].


Longitudinal flow of endolymph measured by distribution of tetraethylammonium and choline in scala media.
Longitudinal endolymph flow rate in the guinea pig cochlea was measured by determining the rate of migration of extrinsic ions, tetraethylammonium chloride (TEA) or choline, with a potassium sensitive ion-selective microelectrode (ISM). Low concentrations of iontophoretically injected TEA were detected with the ISM at various distances from the injection electrode. The results were variable when the ISM was used to record spread of TEA from turn II to turn I and vice versa. However, consistent data were obtained when the TEA spread was measured at different electrode separations (0.2, 0.5, 0.7 mm) within turn II. Electrode locations were systematically exchanged without changing their distance, i.e. the ISM electrode was placed basally or apically with respect to the TEA electrode. Comparison of data with a model, which combines the bulk diffusion of TEA and the flow of endolymph, is consistent with a rate of endolymph flow in turn II of about 0.2 mm/min, apex to base. A similar value was also obtained with the iontophoretic injection of choline. The endolymph flow rate may be different in turn I as indicated by measurements of compound action potential (CAP) changes. However, the results of experiments when TEA spread is measured at large distances must be interpreted cautiously because TEA may enter cellular walls of the cochlear duct and alternative routes of transport may be involved.


Polydopamine-based Implantable Multifunctional Nanocarpet for Highly Efficient Photothermal-chemo Therapy.
We report a design and fabricate multifunctional localized platform for cancer therapy. Multiple stimuli-responsive polydopamine (PDA) was used for surface modification of electrospun doxorubicin hydrochloride (DOX) loaded polycaprolactone (PCL) fibers to make a designated platform. Photothermal properties such as photothermal performance and stability of the resulting composite mats were studied under the irradiation of the near-infrared (NIR) laser of 808 nm. With the incorporation of PDA into the fiber, a remarkable increase of local temperature was recorded under NIR illumination in a concentration-dependent manner with excellent stability. Drug released assay results revealed PDA coated PCL-DOX mats showed pH and NIR dual responsive behavior thereby exhibiting improved drug release in an acidic medium compared to physiological pH condition (pH 7.4) which is further increased by NIR exposure. The cancer activity in vitro of the mats was evaluated using cell counting (CCK) and live and dead cell assays. The combined effect of NIR mediated hyperthermia and chemo release resulting improved cells death has been reported. In summary, this study presents a major step forward towards a therapeutic model to cancer treatment utilizing pH and NIR dual responsive property from PDA alone in a fibrous mat.


Global burden and trends of transport injuries from 1990 to 2019: an observational trend study.
Transport injuries (TIs) are a major cause of global disability-adjusted life-years (DALYs) and mortality. In this study, we aimed to assess the global burden and trends of TIs from 1990 to 2019. We assessed the annual age-standardised incidence rate (ASIR) and age-standardised DALYs rate of TIs by sex, age, Social Development Index (SDI) and geographical region from 1990 to 2019 from the Global Burden of Disease Study 2019. The changing trends were described by estimated annual percentage changes (EAPCs). Globally, in 2019, the ASIR and age-standardised DALYs rates of TIs were 134 6.06/100 000 (95% UI 11 42.6/100 000-157 5.57/100 000) and 97 7.91/100 000 (86 8.91/100 000-107 6.81/100 000), respectively. From 1990 to 2019, the global ASIR of TIs presented significant upwards trends with the EAPC (0.25%, 95% CI 0.19% to 0.31%), and it was significantly increased in the age groups of 15-49 (0.37%, 95% CI 0.29% to 0.45%), 50-69 (0.40%, 95% CI 0.36% to 0.44%) and 70+ (0.22%, 95% CI 0.17% to 0.28%). Prominent increases in ASIR were detected in middle-SDI areas (0.72%, 95% CI 0.57% to 0.87%), low-middle SDI areas (0.66%, 95% CI 0.59% to 0.72%) and low-SDI areas (0.21%, 95% CI 0.17% to 0.26%). The global age-standardised DALYs rate presented downwards trends with the EAPC (-1.27%, 95% CI -1.35% to -1.2%), and it was significantly decreased in all age groups and SDI areas. Globally, TIs still cause a serious burden, and the incidence has significantly increased, especially in people above the age of 14 and in middle-SDI and low-SDI areas, thus necessitating more attention and health interventions.


Ureteric obstruction by the gravid uterus.
This paper reports the only 6 cases of ureteric obstruction apparently caused by the gravid uterus diagnosed at the Mercy Maternity Hospital in the past 17 years, during which time there were 82,836 confinements. In 3 of the 6 cases there was clear radiographic evidence that the level of obstruction was at the pelvic brim. The rapid resolution of the ureteric obstruction shortly after delivery strongly suggested that the gravid uterus was the cause of the obstruction. Cases 1-3 were the only patients of 793 with polyhydramnios who developed bilateral ureteric obstruction and acute renal failure. In Cases 4 and 5 there was unilateral ureteric obstruction and pyelonephritis; in Case 4 a ureteric catheter was inserted from below, and in Case 5 a ureteric stent was inserted via a nephrostomy tube. In Case 6 a percutaneous nephrostomy tube was inserted.


The predictive effect of different machine learning algorithms for pressure injuries in hospitalized patients: A network meta-analyses.
Pressure injury has always been a focus and difficulty of nursing. With the development of nursing informatization, a large amount of structured and unstructured data has been generated, and it is difficult for traditional methods to utilize these data. With the intersection of artificial intelligence and nursing, it has become a new trend to apply machine learning algorithms to build pressure injury prediction models to manage pressure injuries. However, there is no evidence on the effectiveness of the method and which of a large number of algorithms for machine learning is more applicable to pressure injuries. This review aims to systematically synthesize existing evidence to determine the effectiveness of applying machine learning algorithms for pressure injury management, to further evaluate and compare pressure injury prediction models constructed by numerous machine learning algorithms, and to derive evidence for the best algorithms for predicting and managing pressure injuries. Systematic review and network meta-analysis. A systematic electronic search was conducted in the EBSCO, Embase, PubMed, and Web of Science databases. We included all retrospective diagnostic accuracy trials and prospective diagnostic accuracy trials constructing a predictive model by machine learning for pressure injuries up to December 2021. Two review authors independently selected relevant studies and extracted data using the Cochrane handbook for systematic reviews of diagnostic test accuracy. The network meta-analysis was conducted using statistical software R and STATA. The certainty of the evidence was rated using the QUADAS-2 tool. Twenty-five clinical diagnostic trials with a total of 237397 participants were identified in this review. The results of our study revealed that pressure injury machine learning models can effectively predict these injuries. Combining the algorithms separately yields the main results: decision trees (sensitivity: 0.66, 95% CI: 0.42 to 0.84, specificity: 0.90, 95% CI: 0.78 to 0.96, diagnostic odds ratio [DOR]: 18, 95% CI: 7 to 49, AUC: 0.88, 95% CI: 0.85 to 0.91), logistic regression (sensitivity: 0.71, 95% CI: 0.60 to 0.80, specificity: 0.83, 95% CI: 0.75 to 0.89, DOR: 12, 95% CI: 9 to 17, AUC: 0.84, 95% CI: 0.81 to 0.87), neural networks (sensitivity: 0.73, 95% CI: 0.55 to 0.86, specificity: 0.78, 95% CI: 0.65 to 0.87, DOR: 9, 95% CI: 5 to 19, AUC: 0.82, 95% CI: 0.79 to 0.85), random forests (sensitivity: 0.72, 95% CI: 0.26 to 0.95, specificity: 0.96, 95% CI: 0.80 to 0.99, DOR: 56, 95% CI: 3 to 1258, AUC: 0.95, 95% CI: 0.93 to 0.97), support vector machines (sensitivity: 0.81, 95% CI: 0.69 to 0.90, specificity: 0.81, 95% CI: 0.59 to 0.93, DOR: 19, 95% CI: 6 to 54, AUC: 0.88, 95% CI: 0.85 to 0.90). According to the analysis of ROC and AUC values, random forest is the best algorithm for the prediction model of pressure injury. This review revealed that machine learning algorithms are generally effective in predicting pressure injuries, and after data merging, the random forest algorithm is the best algorithm for pressure injury prediction. Further well-designed diagnostic controlled trials are recommended to strengthen the current evidence. CRD42021276993.


Interleukin-8 production in primary cultures of human gastric epithelial cells induced by Helicobacter pylori.
Interleukin-8 (IL-8) production by the gastric mucosa is increased in Helicobacter pylori infection. Previous studies indicated that H. pylori induces IL-8 synthesis in cancer cell lines, and the ability of H. pylori to stimulate IL-8 production is supposed to be associated with cagA and other cag pathogenicity island genes, including picB gene. In the present study, we investigated the induction of IL-8 in primary cultures of normal human gastric epithelial cells to elucidate the IL-8 induction by wild type strains and by the picB knockout strain. Human gastric epithelial cells were obtained from surgically resected specimens from four patients. Three H. pylori strains (TN2F4; type 1 clinical isolate, TN2F4m1; isogenic picB mutant of TN2F4, Tx30a; type 2 strain) were cocultured with the normal gastric epithelial cells or the transformed MKN-28. IL-8 levels in culture medium were determined by enzyme immunoassay. Human gastric epithelial cells produced IL-8 at a 10-50 times higher level than MKN-28 did when cocultured with TN2F4. The mutant TN2F4m1 induced IL-8 at significantly lower levels than the parent strain. Cells from four patients behaved similarly on IL-8 production. The results of the present study demonstrated the induction of IL-8 in normal gastric epithelial cells, suggesting that picB gene product may play an essential role in vivo.


Three-quarter prone approach to the pineal-tentorial region.
A three-quarter prone, operative approach to the pineal region is described: the three-quarter prone, operated-side-down position. This approach avoids the disadvantages of the approaches from other directions to this region and provides a comfortable position for the surgeon and assistant, minimal retraction of the parietal-occipital lobe, and access to the third ventricle, pineal region, midbrain, and superior vermis.


Loss of indicator in the thermodilution technique.
The use of a second thermistor for detecting the injectate temperature in the extravascular segment of a standard right heart thermodilution catheter is described. Experiments with chilled (0 degrees C) indicator show that the temperature of the injectate as it enters the catheter is always greater than zero and that it depends on time and the gradient between indicator and surroundings; that serial injections made 30 to 60 seconds apart are successively cooler and do not plateau until the third injection. These variables amount to an overestimation in the cardiac output of 3 to 12%.


Pulmonary vein varix: diagnosis with multi-slice helical CT.
The diagnosis of a pulmonary vein varix with a recently introduced new CT technology, multi-slice helical CT, is discussed. The advantage of multi-slice helical CT lies in increased thin-slice coverage during a single breath hold, which is the predominant factor limiting scan time. This CT technique facilitates the diagnosis of vascular pulmonary pathology.


The existence of distinct classes of prostaglandin E2 receptors mediating adenylate cyclase and phospholipase C pathways in osteoblastic clone MC3T3-E1.
We have reported previously that PGE2 evoked an increase in intracellular calcium level ([Ca2+]i) in mouse osteoblastic cells (1). Here, we investigated the effects of PGE1 and PGF2 alpha on cAMP production and [Ca2+]i in comparison with those of PGE2. In osteoblastic clone, MC3T3-E1 cells, PGE1 stimulated cAMP production, but had no effect on [Ca2+]i, whereas PGF2 alpha evoked only [Ca2+]i increase. In contrast, PGE2 not only stimulated cAMP production, but also increased [Ca2+]i. From the Scatchard plot analysis of PGE2 it was confirmed that there were two classes of PGE2 binding sites (Kd value, 9.2 nM; binding site, 29 fmole/mg protein, and Kd value, 134 nM; binding site, 148 fmole/mg protein). As the increase in [Ca2+]i was caused by PGF2 alpha and PGE2, but not by PGE1, we investigated the displacement of [3H]-PGF2 alpha binding. The displacement capacity of unlabeled PGE2 was about 110 of that of PGF2 alpha, while that of PGE1 was very low even at 500-fold excess. These data indicate the possibility that the dual action of PGE2 is mediated by distinct receptor systems.


N6-methyladenosine methylation regulator RBM15 promotes the progression of diabetic nephropathy by regulating cell proliferation, inflammation, oxidative stress, and pyroptosis through activating the AGE-RAGE pathway.
Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world, and m6A modification plays a critical role in the progression of DN. We aimed to find m6A-related genes and their regulatory mechanisms in DN. The expression levels of four important m6A-related genes (METTL16, RBM15, IGF2BP1, and ALKBH5) were detected by quantitative real-time PCR (RT-qPCR). RBM15 was chosen and its function was explored. The downstream pathway of RBM15 was screened by transcriptome sequencing. The levels of AGE, inflammation, and oxidative stress were determined with enzyme-linked immunosorbent assay, and the expression of AGE-RAGE pathway-related proteins were detected by Western blot (WB). Cell proliferation was assessed by Cell counting Kit-8 (CCK-8). The levels of pyroptosis-related proteins were evaluated by RT-qPCR or WB. METTL16 and RBM15 were up regulated in the mouse model of DN, in which RBM15 was more significant. Silencing RBM15 recovered cell proliferation, reduced the levels of inflammation factors, and inhibited cell pyroptosis in high glucose-induced HK-2 cells. Transcriptome sequencing suggested that the AGE-RAGE pathway might be downstream of RBM15. RBM15 knockdown reduced AGE level and the expression of AGE-RAGE pathway-related proteins. After silencing RBM15, we found that activating the AGE-RAGE pathway inhibited cell proliferation, increased the levels of inflammation factors, promoted oxidative stress, and induced cell pyroptosis in HK-2 cell model of DN. The m6A-related gene RBM15 inhibited cell proliferation, promoted inflammation, oxidative stress, and cell pyroptosis, thereby facilitating the progression of DN through the activation of the AGE-RAGE pathway.


[Secretory antibodies in saliva against group G streptococci (author's transl)].
Saliva of 310 persons were examined for their ability to agglutinate 33 streptococcal strains of the groups A-T. It was found that the saliva of persons with blood group O agglutinated significantly more often streptococci of strain G9 than the saliva of persons with blood group A (33.3%, and 18.75% resp., p less than 0.01). A statistical significant difference between persons of blood group B and O, or A and B did not exist. The agglutination reactions were caused probably by unspecific immunoglobulins because this strain G9 binds unspecifically human IgG. It is known, that some streptococcal strains of the groups A, B, C, D, and G contain receptors for the Fc-fragment of IgG and/or IgA. The results demonstrate that persons of the blood group O secrete more often immunoglobulin than those with blood group A.