Workplace bullying and suicidal ideation and behaviour: a systematic review and meta-analysis.
Suicidal ideation and behaviour are potential outcomes of workplace bullying. This review aimed to determine the extent of the association between workplace bullying and suicidal ideation and behaviour. The study incorporated a systematic review and meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed to conduct a comprehensive systematic review and meta-analysis. A combination of subject terms and free words was used to search nine electronic databases. Two reviewers independently screened articles and extracted information according to the inclusion criteria. A meta-analysis was performed with averaged weighted correlations across samples using the STATA software (version 16.0) from pooled estimates of the main results from all studies. In total, 25 articles of high or medium quality were included in the systematic review; 15 of these were included in the meta-analysis. The prevalence of suicidal ideation and behaviour was 18% and 4%, respectively. Individuals who experienced workplace bullying had 2.03-times and 2.67-times higher odds of reporting suicidal ideation and behaviour, respectively, after adjustment for confounding factors. Moderating and mediating factors may help reduce the risk of suicidal ideation and behaviour for individuals experiencing workplace bullying. This study indicated that exposure to workplace bullying significantly increased the risk of suicidal ideation and behaviour.


Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study.
The maximum tolerated dose (MTD) and overall safety of sunitinib plus pemetrexed and carboplatin was determined in patients with advanced solid malignancies. In this phase I dose-escalation study, patients received oral sunitinib on a continuous daily dosing (CDD) schedule (37.5 mg/day) or Schedule 2/1 (2 weeks on treatment, 1 week off treatment; 37.5 or 50 mg/day). Pemetrexed (400-500 mg/m(2) IV) and carboplatin (AUC = 5 mg·min/ml IV) were administered q3w. At the MTD for the chosen schedule, a cohort of patients with non-small cell lung cancer (NSCLC) or mesothelioma was further evaluated. Twenty-one patients were enrolled on Schedule 2/1 (expansion cohort included) and 3 patients on the CDD schedule. The MTD on Schedule 2/1 was sunitinib 37.5 mg/day with pemetrexed 500 mg/m(2) and carboplatin AUC = 5 mg·min/ml; MTD on the CDD schedule was not established. Dose-limiting toxicities included grade 3/4 neutropenia, grade 3 thrombocytopenia, and grade 3 hand-foot syndrome. The most common grade 3/4 drug-related non-hematologic adverse events at Schedule 2/1 MTD were fatigue/asthenia and diarrhea (both n = 4). Grade 3/4 hematologic abnormalities included neutropenia (83%) and leukopenia (83%). Pharmacokinetic data revealed no clinically significant drug-drug interactions. Best response at the Schedule 2/1 MTD was stable disease ≥8 weeks in 3/5 evaluable patients (60%). With this combination, in patients with advanced solid malignancies, sunitinib MTD on Schedule 2/1 was 37.5 mg/day. Sunitinib plus pemetrexed and carboplatin were tolerable at the MTD, although sunitinib dose delays and reductions were often required due to myelosuppression.


VDAC structure, selectivity, and dynamics.
VDAC channels exist in the mitochondrial outer membrane of all eukaryotic organisms. Of the different isoforms present in one organism, it seems that one of these is the canonical VDAC whose properties and 3D structure are highly conserved. The fundamental role of these channels is to control the flux of metabolites between the cytosol and mitochondrial spaces. Based on many functional studies, the fundamental structure of the pore wall consists of one α helix and 13 β strands tilted at a 46° angle. This results in a pore with an estimated internal diameter of 2.5nm. This structure has not yet been resolved. The published 3D structure consists of 19 β strands and is different from the functional structure that forms voltage-gated channels. The selectivity of the channel is exquisite, being able to select for ATP over molecules of the same size and charge. Voltage gating involves two separate gating processes. The mechanism involves the translocation of a positively charged portion of the wall of the channel to the membrane surface resulting in a reduction in pore diameter and volume and an inversion in ion selectivity. This mechanism is consistent with experiments probing changes in selectivity, voltage gating, kinetics and energetics. Other published mechanisms are in conflict with experimental results. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.


[Health reporting as part of public health surveillance: the example of diabetes].
The continuous collection and analysis of health data on relevant diseases (surveillance) is at the core of public health. The surveillance enables the implementation of measures to protect the populations' health. Therefore, relevant information needs to be provided in a timely and target-group-specific manner to the respective stakeholders.A dissemination strategy supports the effective communication of results and considers three key questions: (1) "What content is relevant to the surveillance?", (2) "Who requires which information?" and (3) "How are the results disseminated to the target audience?" In this context, digitalisation allows for novel possibilities in the design of publication formats.Since 2015, diabetes surveillance has been established at the Robert Koch Institute. Within a structured process of consensus, we defined four fields of action relevant for health policy including 40 indicators. Thereafter, we developed the first publication formats in collaboration with the scientific advisory board of the project that reflected novel possibilities offered by digitalisation. In addition to articles in scientific journals, the essential formats of the first project phase comprise the report "Diabetes in Germany" and a website including interactive visualisations of results. Additional posts on Twitter and YouTube are used to increase coverage.In addition to the further development of the indicator set, the focus of the next project phase is the advancement of the dissemination towards user- and action-oriented reporting. In close exchange with the scientific advisory board, we aim to explore the requirements of the target audience and reflect them in the design of further publication formats.


Trazodone and imipramine: comparative effects on canine cardiac conduction.
Lead II EKG and His bundle electrograms were recorded in closed-chest pentobarbital-anesthetized dogs. Trazodone, a structurally distinct, new antidepressant agent, had no effect on His--Purkinje (HV interval) or intraventricular (HS interval) conduction following intravenous injection at graded doses between 1 and 30 mg/kg. In contrast, the tricyclic psychotropic agent imipramine (0.5--5 mg/kg) significantly slowed impulse conduction as indicated by increases in both the HV and HS intervals. Imipramine (5 mg/kg) also slowed impulse transmission across the atrium (PA interval). These responses to imipramine were associated with a concurrent prolongation of both the PR interval and QRS duration. In the anesthetized dog, trazodone administration promoted no evidence of heart block or sign of rhythm disturbances other than slowing in normal sinus rhythm.


Enabling circular economy by N-recovery: Electrocatalytic reduction of nitrate with cobalt hydroxide nanocomposites on copper foam treating low conductivity groundwater effluents.
Fertilizers play a vital role in the food-energy-water nexus. The traditional method of artificial nitrogen fixation to produce ammonia is a high-energy intensive centralized process that has caused an imbalance of the N-cycle due to the release of N-species to water. Electrocatalytic nitrate reduction (ENR) to ammonia is a promising N-resource recovery alternative that can enable the circular reuse of ammonia in decentralized settings. However, the primary challenge is identifying selective and affordable electrocatalysts. Identifying electrodes that rely on something other than platinum-group metals is required to surpass barriers associated with using expensive and endangered elements. In this study, an earth-abundant bimetallic catalyst, Cu/Co(OH)x, prepared and optimized by electrodeposition, demonstrates superior ammonia production. Under environmentally relevant conditions of 30 mg NO3--N L-1, Cu/Co(OH)x showed higher ammonia production than pristine Cu foam with 0.7 and 0.3 mmol NH3 gcat-1 h-1, respectively. The experimental evaluation demonstrated direct reduction and catalytic hydrogenation mechanisms in Cu/Co(OH)x sites. Leaching analyses suggest that Cu/Co(OH)x has outstanding stability with negligible metal concentration below the maximum contaminant level for both Cu and Co. These results provide a framework for using earth-abundant materials in ENR with comparable efficiency and energy consumption to platinum-group materials.


Treatment of a large superficial basal cell carcinoma with 5% imiquimod: a case report and review of the literature.
Large superficial basal cell carcinomas (BCCs) may be difficult to treat surgically due to the potentially large resulting defect after removal. Imiquimod, an immune response modifier, when applied topically, has been demonstrated to be successful in treating superficial BCCs. There is no published experience on the treatment of larger superficial BCCs (greater than 2 cms2) with imiquimod at this time. To assess the clinical and histologic regression, as well as the short- and long-term effects of topical imiquimod on large superficial BCC. A 52-year-old white female with a 30 cm2 biopsy proven superficial BCC of 28 years duration on the right dorsal arm was treated with 5% imiquimod three times a week for 12 weeks. Clinical follow-up was conducted 1, 4, 6, and 10 months after treatment, as well as histologic assessment of recurrence at 4 months after treatment. Apparent clinical and histologic clearance was achieved. The treatment was well-tolerated and the patient completed the treatment schedule without a rest period, despite erosion of the lesion in the last week of treatment. This report describes the first case of a large superficial BCC (30 cm2) successfully treated with topical imiquimod and with a 10 month follow-up.


Shared spiritual beliefs between adolescents with cancer and their families.
FAmily CEntered (FACE) Advance Care Planning helps family decision makers to understand and honor patients' preferences for future health care, if patients cannot communicate. Spiritual well-being is a key domain of pediatric oncology care and an integral dimension of pediatric advance care planning. As part of four-site randomized controlled trial of FACE for teens with cancer, the functional assessment of chronic illness therapy-spiritual well-being- version 4 (FACIT-Sp-EX-4) was completed independently by 126 adolescents with cancer/family dyads. The prevalence-adjusted and bias-adjusted kappa (PABAK) measured congruence on FACIT-Sp-EX-4. Adolescents (126) had mean age of 16.9 years, were 57% female and 79% White. Religious/spiritual classifications were: Catholic (n = 18), Protestant (n = 76), Mormon (n = 3), none/atheist (n = 22), other (n = 5), and unknown (n = 2). Agreement at item level between spiritual well-being of adolescents and families was assessed. Three items had ≥90% agreement and Excellent PABAK: "I have a reason for living," "I feel loved," "I feel compassion for others in the difficulties they are facing." Three items had <61% agreement and Poor PABAK: "I feel a sense of harmony within myself," "My illness has strengthened my faith or spiritual beliefs," "I feel connected to a higher power (or God)." Dyadic congruence was compared by social-demographics using median one-way analysis. Male family members (median = 72%) were less likely to share spiritual beliefs with their adolescent than female family members (median = 83%), P = .0194. Family members may not share spiritual beliefs with adolescents and may be unaware of the importance of spiritual well-being for adolescents.


A bacteriology and treatment summary form for use in patients with tuberculosis.
A summary form for recording bacteriology results and treatment regimens is a concise method for recording essential information in patients with tuberculosis.


Psychological factors influencing self-assessments of health: toward an understanding of the mechanisms underlying how people rate their own health.
Research in the past 20 years has shown that self-assessed health (SAH) is a consistent and reliable predictor of health outcomes. However, it is still unclear what factors are responsible for the association of SAH with mortality and other objective health indicators. This study examined the impact of trait positive affect, trait negative affect, and functional limitations (FL) on SAH cross-sectionally and longitudinally. We hypothesized that changes in SAH ratings would be mainly influenced by FL, whereas affective information would have a biasing effect on SAH ratings cross-sectionally. We analyzed longitudinal data obtained from five successive annual interviews conducted with over 800 elderly respondents (mean age = 73 years) using latent growth curve modeling. Results revealed that SAH judgments were related to FL and to trait affects in each of the five waves (cross-sectional data), but only changes in FL were related to changes in SAH over time. These data also showed that changes in SAH were predictive of mortality above and beyond its initial levels. The results suggest that the temporal trajectory of FL is a source of information that allows an individual's SAH to predict objective health measures of both morbidity and mortality.


Identification of a region of UDP-galactose:N-acetylglucosamine beta 4-galactosyltransferase involved in UDP-galactose binding by differential labeling.
The location of regions in the primary structure of UDP-galactose:N-acetylglucosamine beta 4-galactosyl-transferase (GT) that are involved in binding UDP-galactose has been investigated by differential chemical modification with two different reagents in the presence and absence of UDP-galactose. Treatment with periodate-cleaved UDP and NaCNBH3 resulted in a loss of 80% of GT activity, which was largely prevented by UDP-galactose. Stoichiometry of labeling and peptide maps of the modified enzyme samples indicated partial labeling at many sites. A major site of reaction in the absence of UDP-galactose that was essentially unmodified in its presence was found to correspond to Lys341 in the cDNA sequence of GT. As a second approach, the reactivities of the amino groups of GT were compared in the presence and absence of saturating levels of UDP-galactose by trace acetylation with [3H]acetic anhydride. UDP-galactose binding was found to perturb the reactivities of a number of lysines in the C-terminal region of GT, the most pronounced effect being a reduction in the reactivity of Lys351. The two procedures thus identified a region between residues 341 and 351 as being associated with UDP-galactose binding. This region overlaps a small section in the sequence of GT that was previously noted to be similar to part of bovine alpha-1,3-galactosyltransferase (Joziasse, D. H., Shaper, J. H., Van den Eijnden, D. H., Van Tunen, A. J., and Shaper, N. L. (1989) J. Biol. Chem. 264, 14290-14297). Sequence comparisons indicate that extended regions at the C terminus of each enzyme encompassing this area may represent homologous UDP-galactose-binding domains.


Executive functioning following surgery near the frontal aslant tract in low-grade glioma patients: A patient-specific tractography study.
The Frontal Aslant Tract (FAT) has been associated with executive functions (EF), but it remains unclear what role the FAT plays in EF, and whether preoperative dysfunction of the FAT is associated to long-lasting postsurgical executive impairments. In this study, we examined the course of EF from pre-surgery (n = 75) to 3 (n = 61) and 12 (n = 25) months after surgery in patients with frontal and parietal low-grade gliomas (LGGs), to establish the degree to which long-term EF deficits exist. Secondly, we used patient-specific tractography to investigate the extent to which overlap of the tumor with the FAT, as well as integrity of the FAT, presurgery were related to EF on the short and longer term after surgery. LGG patients performed worse than healthy controls on all EF tests before and 3 months postsurgery. Whereas performances on three out of the four tests had normalized 1 year postsurgery (n = 26), performance on the cognitive flexibility test remained significantly worse than in healthy controls. Patients in whom the tumor overlapped with the core of the right FAT performed worse presurgery on three of the EF tests compared to those in whom the tumor did not overlap with the right FAT. Presurgical right FAT integrity was not related to presurgical EF, but only to postsurgical EF (from pre-to 3 months postsurgery). Longitudinal analyses demonstrated that patients with right (but not left) FAT core overlap performed on average worse over the pre- and postsurgical timepoints on the cognitive flexibility test. We emphasized that LGG patients perform worse than healthy controls on the EF tests, which normalizes 1-year postsurgery except for cognitive flexibility. Importantly, in patients with right hemispheric tumors, tumor involvement of the FAT was associated with worse pre- and 3- months postsurgical performance, specifically concerning cognitive flexibility.


Mobile application as a prenatal education and engagement tool: A randomized controlled pilot.
Research has shown that mobile applications provide a powerful alternative to traditional paper diaries; however, little data exists in comparing apps to the traditional mode of paper as a patient education and engagement tool in the clinical setting. This study was designed to compare the effectiveness of a mobile app versus a spiral-notebook guide throughout prenatal care. This randomized (n=173) controlled pilot was conducted at an East Coast community hospital. Chi-square and repeated-measures analysis of variance was used to test intervention effects in the sample of 127 pregnant mothers who completed their prenatal care in the healthcare system. Patients who were distributed the mobile application used the tool to record information about pregnancy more frequently (p=.04) and developed greater patient activation (p=.02) than patients who were distributed notebooks. No difference was detected on interpersonal clinical communication. A mobile application successfully activated a patient population in which self-management is a critical factor. This study shows that mobile apps can prompt greater use and result in more activated patients. Findings may be translated to other patient populations who receive recurring care for chronic disease.


Pasteurella multocida infections in mice with reference to haemorrhagic septicaemia in cattle and buffalo.
Haemorrhagic septicaemia (HS) is an infectious disease of cattle and buffalo caused by particular serotypes of Pasteurella multocida and is one of the most economically important livestock diseases in South-East Asia. While HS has been recognized for many years, very little is understood about the disease, primarily because of the expense of cattle and a lack of suitable animal models. The suitability of using mice to study HS was assessed using parameters such as the critical pathogenic dose, kinetics of infection, pathology of disease and resistance to reinfection. Pasteurella multocida M1404, the type strain for Carter group B, the serotype responsible for Asian HS, was injected intraperitoneally into BALB/c mice. As few as 20 colony forming units produced an overwhelming septicaemia in mice in less than 30 h. The kinetics of infection demonstrated a very rapid in vivo multiplication rate. There was no evidence of inhibition of bacterial cell growth by natural host defence mechanisms, even with the very small inocula used. The gross pathology of the disease in mice was characterized by splenomegaly, lymphadenopathy and petechial haemorrhages similar to that observed in cattle and buffalo with HS. Mice were found to develop a short-lived resistance to reinfection following a primary infection which had been successfully treated with antibiotics. The mouse would seem to provide an ideal tool by which to study HS, but warrant further studies in order to be able to critically assess it as a model for this economically important disease.


A combination of experiment and theoretical methods to study the novel and low-cost corrosion inhibitor 1-hydroxy-7-azabenzotriazole for mild steel in 1 M sulfuric acid.
1-Hydroxy-7-azabenzotriazole (HOAT) was explored via experimental and theoretical computation methods as a corrosion inhibitor for mild steel in 1 M sulfuric acid. These data indicate that HOAT has good ability to suppress corrosion of the mild steel, with ideal agreement with between experimental and computational results. Besides, the electrochemical experiments show that HOAT is a mixed-type corrosion inhibitor for mild steel in 1 M H2SO4. Furthermore, HOAT adsorption on the surface of steel conforms to the Langmuir isotherm model. Finally, computational simulation was executed to deeply investigate the mechanism to HOAT inhibition corrosion of steel.


The role of aperiodic spectral slope in event-related potentials and cognition among children with and without attention deficit hyperactivity disorder.
Aperiodic spectral slope is a measure of spontaneous neural oscillatory activity that is believed to support regulation of brain responses to environmental stimuli. Compared to typically developing (TD) control participants, children with attention deficit hyperactivity disorder (ADHD) have been shown to have flatter aperiodic spectral slope at rest as well as attenuated event-related potential (ERP) amplitudes in response to environmental stimuli. A small body of research suggests that aperiodic slope may also explain differences in behavioral responses. In this study, we examine associations between prestimulus aperiodic slope, stimulus characteristics, environmental demands, and neural as well as behavioral responses to these stimuli. Furthermore, we evaluate whether ADHD diagnostic status moderates these associations. Seventy-nine children with ADHD and 27 TD school-age children completed two visual ERP experiments with predictable alternating presentations of task-relevant and task-irrelevant stimuli. Aperiodic slope was extracted from prestimulus time windows. Prestimulus aperiodic slope was steeper for the TD relative to ADHD group, driven by task-relevant rather than task-irrelevant stimuli. For both groups, the aperiodic slope was steeper during a task with lower cognitive demand and before trials in which they responded correctly. Aperiodic slope did not mediate the association between ADHD diagnosis and attenuated P300 amplitude. The aperiodic spectral slope is dynamic and changes in anticipation of varying stimulus categories to support performance. The aperiodic slope and P300 amplitude reflect distinct cognitive processes. Background neural oscillations, captured via aperiodic slope, support cognitive behavioral control and should be included in etiological models of ADHD.NEW & NOTEWORTHY This study constitutes the first investigation of associations between aperiodic spectral slope and three aspects of neurocognition: event-related potential (ERP) amplitudes, cognitive load, and task performance. We find that background oscillatory activity is dynamic, shifting in anticipation of varying levels of task relevance and in response to increasing cognitive load. Moreover, we report that aperiodic activity and ERPs constitute distinct neurophysiological processes. Children with attention deficit hyperactivity disorder (ADHD) show reduced aperiodic dynamics in addition to attenuated ERP amplitudes.


2-Hy-droxy-benzenaminium acetate.
In the title molecular salt, C6H8NO+·C2H3O2 -, the cations and anions are linked by O-H⋯O and N-H⋯O hydrogen bonds, generating a three-dimensional network.


Ketamine reduces the need for intubation in patients with acute severe mental illness and agitation requiring transport to definitive care: An observational study.
The aim of this study was to review mental health patients transported by a dedicated statewide critical care retrieval team before and after the implementation of a ketamine sedation guideline. This is a a retrospective cohort study of mental health patients with acute behavioural disturbance, transported between January 2010 and December 2015. A total of 78 patients were transported in the study period, 50 before and 28 after implementation of the ketamine guideline in June 2013. The introduction of the ketamine guideline was associated with a significant reduction in intubation for transport (36.00 vs 7.14%) (odds ratio 0.14, 95% confidence interval 0.02-0.71, P < 0.01). The likelihood of utilising ketamine for non-intubated patients (n = 58) was higher in the period after implementation (37.50 vs 84.62%, odds ratio 9.17, 95% confidence interval 2.54-33.08, P < 0.005). The incidence of complications in our series was low. The implementation of a ketamine clinical practice guideline for agitated mental health patients was associated with an increase in the number of patients receiving ketamine as part of their sedation regime and a reduction in the number of patients requiring intubation for transport. Appropriately trained critical care retrieval teams should consider ketamine as part of the sedation regime for agitated mental health patients.


Differential efficacy of ablation therapy versus partial nephrectomy between clinical T1a and T1b renal tumors: A systematic review and meta-analysis.
To assess the differential clinical outcomes of patients treated with partial nephrectomy (PN) vs. those treated with ablation therapy (AT) such as radiofrequency ablation, cryoablation and microwave ablation for cT1b compared to cT1a renal tumors. Multiple databases were searched for articles published before August 2021. Studies were deemed eligible if they compared clinical outcomes in patients who underwent PN with those who underwent AT for cT1a and/or cT1b renal tumors. Overall, 27 studies comprising 13,996 patients were eligible for this meta-analysis. In both cT1a and cT1b renal tumors, there was no significant difference in the percent decline of estimated glomerular filtration rates or in the overall/severe complication rates between PN and AT. Compared to AT, PN was associated with a lower risk of local recurrence in both patients with cT1a and cT1b tumors (cT1a: pooled risk ratio [RR]; 0.43, 95% confidence intervals [CI]; 0.28-0.66, cT1b: pooled RR; 0.41, 95%CI; 0.23-0.75). Subgroup analyses regarding the technical approach revealed no statistical difference in local recurrence rates between percutaneous AT and PN in patients with cT1a tumors (pooled RR; 0.61, 95%CI; 0.32-1.15). In cT1b, however, PN was associated with a lower risk of local recurrence (pooled RR; 0.45, 95%CI; 0.23-0.88). There was no difference in distant metastasis or cancer mortality rates between PN and AT in patients with cT1a, or cT1b tumors. AT has a substantially relevant disadvantage with regards to local recurrence compared to PN, particularly in cT1b renal tumors. Despite the limitations inherent to the nature of retrospective and unmatched primary cohorts, percutaneous AT could be used as a reasonable alternative treatment for well-selected patients with cT1a renal tumors.


Inhibition of γ-glutamyltransferase ameliorates ischaemia-reoxygenation tissue damage in rats with hepatic steatosis.
Hepatic steatosis may be associated with an increased γ-glutamyltransferase (γ-GT) levels. Ischaemia-reoxygenation (IR) injury causes several deleterious effects. We evaluated the protective effects of a selective inhibitor of γ-GT in experimentally induced IR injury in rats with obesity and steatosis. Otsuka Long-Evans Tokushima Fatty (OLETF) rats with hepatic steatosis were used in the current study. The portal vein and hepatic artery of left lateral and median lobes were clamped to induce ischaemia. Before clamping, 1 ml of saline (IR group) or 1-ml saline containing 1 mg·kg-1 body weight of GGsTop (γ-GT inhibitor; IR-GGsTop group) was injected into the liver via the inferior vena cava. Blood flow was restored after at 30 min of the start of ischaemia. Blood was collected before, at 30 min after ischaemia and at 2 h and 6 h after reoxygenation. All the animals were killed at 6 h and the livers were collected. Treatment with GGsTop resulted in significant reduction of serum ALT, AST and γ-GT levels and hepatic γ-GT, malondialdehyde, 4-hydroxy-2-nonenal and HMGB1 at 6 h after reoxygenation. Inhibition of γ-GT retained normal hepatic glutathione levels. There was prominent hepatic necrosis in IR group, which is significantly reduced in IR-GGsTop group. Treatment with GGsTop significantly increased hepatic glutathione content, reduced hepatic MDA, 4-HNE and HMGB1 levels and, remarkably, ameliorated hepatic necrosis after ischaemia-reoxygenation. The results indicated that GGsTop could be an appropriate therapeutic agent to reduce IR-induced liver injury in obesity and steatosis.


Multimodal assessment of nervous and immune system responses following sciatic nerve injury.
Subsequent to peripheral nerve compression and irritation, pathophysiological processes take place within nervous and immune systems. Here, we utilized a multimodal approach to comprehend peripheral and central soft tissue changes as well as alterations occurring in systemic analytes following unilateral chronic constriction injury (CCI) of the sciatic nerve in rodents. Using magnetic resonance imaging and [18F]-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography, we demonstrated robust structural abnormalities and enhanced FDG uptake within the injured nerve and surrounding muscle, respectively. To assess whether central morphological changes were induced by nerve injury, diffusion tenor imaging was performed. A decrease in fractional anisotropy in primary motor cortex contralateral to the injury site was observed. Evaluation of a panel of circulating cytokines, chemokines, and growth factors showed decreased levels of interleukin-1β and Fractalkine in CCI animals. Area under the receiver operating curve (ROC) calculations of analyte levels, imaging, and behavioral end points ranged from 0.786 to 1, where behavioral and peripheral imaging end points (eg, FDG uptake in muscle) were observed to have the highest discriminatory capabilities (maximum area under ROC = 1) between nerve injury and sham conditions. Lastly, performance of correlation analysis involving all analyte, behavioral, and imaging data provided an understanding of the overall association amongst these end points, and importantly, a distinction in correlation patterns was observed between CCI and sham conditions. These findings demonstrate the multidimensional pathophysiology of sciatic nerve injury and how a combined analyte, behavioral, and imaging assessment can be implemented to probe this complexity.


New plasmid-mediated phosphorylation of gentamicin C in Staphylococcus aureus.
A clinical isolate of Staphylococcus aureus resistant to gentamicin, kanamycin and 3',4'-dideoxykanamycin B contained two enzymes capable of inactivating gentamicin, i.e., an aminoglycoside 2''-phosphotransferase and aminoglycoside acetyltransferase.


Renal Function Alters Antihypertensive Regimens in Type 2 Diabetic Patients.
To determine the prevalence of multidrug antihypertensive therapy (MDAT), records were evaluated for patients with both type 2 diabetes and hypertension during a 5-year period at Joslin Diabetes Center. Hypertension control was defined as requiring multiple drugs if three or more antihypertensive drugs were used, one of which must be a diuretic (unless patient is receiving dialysis), or use of four or more antihypertensive drugs, one of which a diuretic (unless patient is receiving dialysis) was established. The objective was to determine the prevalence of multidrug requirement for hypertensive therapy in relationship to four levels of renal function estimated by the Modification of Diet in Renal Disease formula for glomerular filtration rate (GFR). Among 10,151 patients, mean estimated GFR was 80 mL/min. Using standard (ASN) classification for renal function, we noted the following breakdown of MDAT use: Estimated GFR Drugs, Mean No. ≥3 Drugs, No. (%) ≥4 Drugs, No. (%) <30 3.1 379 (67) 214 (38) 30-60 2.7 1233 (55) 538 (24) 60-90 2.0 1279 (33) 458 (12) >90 1.5 600 (17) 185 (5) Prevalence of multidrug antihypertensive therapy is markedly increased in the presence of reduced renal function.


Psychosocial factors influence control of moderate and severe hypertension.
Factors affecting the degree of blood pressure control achieved by antihypertensive drug treatment in 150 patients with moderate and severe essential hypertension were analyzed. Patients were under continuing treatment for 1-23 years. Most patients were referred for hypertension which was difficult to control. All were managed by the senior author. They received multiple drug regimens and extensive efforts were made to encourage their adherence to the regimens. In spite of these efforts, 16 (11%) had poor blood pressure control. Satisfactory control was achieved in 52 (35%) patients and excellent control in 82 (55%) patients. As a group, their ideal body weight (IBW) was 125 +/- 22% (mean +/- SD) of normal. The mean number of antihypertensive tablets per day was significantly greater (P = 0.0009) in those with poor control as compared to those with satisfactory and excellent control. As % IBW increased, the number of antihypertensive tablets increased (P = 0.0021). We examined the relationship of blood pressure control with an index of compliance, with psychosocial factors (life events score, martial status) and with socioeconomic factors (work status, income). Poor blood pressure control was associated with a lower compliance index (P less than 0.0001) and a higher life events score (P less than 0.006). Poorly controlled patients were more likely to have poor health in general (P = 0.0002), to have kept fewer medical appointments during the preceding year (P less than 0.0001), to be unmarried (P less than 0.0001), to be unemployed (P less than 0.0028) and have a lower income (P less than 0.009). As % IBW increased, compliance index decreased, (P = 0.0045). Therefore, psychosocial and socioeconomic factors, as well as physical factors, influence blood pressure control in moderate and severe essential hypertension.


Prevention and Treatment of Cancer-Associated Venous Thromboembolism: a Review.
Patients with cancer have an increased risk of venous thromboembolism (VTE). Cancer-associated VTE is associated with an increased risk of morbidity and mortality. Treatment of VTE in cancer is associated with higher rates of recurrent thrombosis as well as major bleeding compared with the general population. The goal of this review is to provide a summary of current evidence for the prevention and treatment of cancer-associated VTE. Validated risk prediction models are available to aide clinicians in identifying patients with cancer with the highest risk of VTE. Those patients with intermediate to high risk of VTE may benefit from primary prophylaxis with apixaban or rivaroxaban. Low-molecular-weight heparin is superior to vitamin K antagonists for the treatment of cancer-associated VTE. There is mounting evidence to support use of the direct oral anticoagulants for VTE in patients with cancer. Decisions on type and duration of anticoagulation in patients with cancer, either for primary or secondary prevention, should be made on a case-by-case basis with taking into account the individual patient bleeding and thrombotic risk.


Ex vivo method to visualize and quantify vascular networks in native and tissue engineered skin.
Neovascularization plays a pivotal role in tissue engineering and tissue regeneration. However, reliable technologies to visualize and quantify blood vessel networks in target tissue areas are still pending. In this work, we introduce a new method which allows comparing vascularization levels in normal and tissue-engineered skin. Normal skin was isolated, and vascular dermal regeneration was analyzed based on tissue transillumination and computerized digital segmentation. For tissue-engineered skin, a bilateral full skin defect was created in a nude mouse model and then covered with a commercially available scaffold for dermal regeneration. After 3 weeks, the whole skin (including scaffold for dermal regeneration) was harvested, and vascularization levels were analyzed. The blood vessel network in the skin was better visualized by transillumination than by radio-angiographic studies, the gold standard for angiographies. After visualization, the whole vascular network was digitally segmented showing an excellent overlapping with the original pictures. Quantification over the digitally segmented picture was performed, and an index of vascularization area (VAI) and length (VLI) of the vessel network was obtained in target tissues. VAI/VLI ratio was calculated to obtain the vessel size index. We present a new technique which has several advantages compared to others, as animals do not require intravascular perfusions, total areas of interest can be quantitatively analyzed at once, and the same target tissue can be processed for further experimental analysis.


An Italian research project to study the play of children with motor disabilities: the first year of activity.
The paper presents the main outline of a new research project carried out by the SIVA research team concerning the development of methodologies to select and use assistive technology to allow children with motor disabilities to play with toys. Giving them the same opportunities to play as their peers without disabilities can best enhance their cognitive and social development. A review of the literature in the field is also included.


Perceptions of intelligence & sentience shape children's interactions with robot reading companions.
The potential for robots to support education is being increasingly studied and rapidly realised. However, most research evaluating education robots has neglected to examine the fundamental features that make them more or less effective, given the needs and expectations of learners. This study explored how children's perceptions, expectations and experiences are shaped by aesthetic and functional features during interactions with different robot 'reading buddies'. We collected a range of quantitative and qualitative measures of subjective experience before and after children read a book with one of three different robots. An inductive thematic analysis revealed that robots have the potential offer children an engaging and non-judgemental social context to promote reading engagement. This was supported by children's perceptions of robots as being intelligent enough to read, listen and comprehend the story, particularly when they had the capacity to talk. A key challenge in the use of robots for this purpose was the unpredictable nature of robot behaviour, which remains difficult to perfectly control and time using either human operators or autonomous algorithms. Consequently, some children found the robots' responses distracting. We provide recommendations for future research seeking to position seemingly sentient and intelligent robots as an assistive tool within and beyond education settings.


HIV infection of mononuclear cells is calcium-dependent.
Strategies that prevent initial HIV infection of cells are greatly needed. In this study, we determined the requirement of divalent cations for HIV infection of and attachment to peripheral blood mononuclear cells (PBMC), which contain several types of HIV-infectable cells-CD4(+) T cells, monocytes and dendritic cells. EDTA, added only during PBMC exposure to HIV, reduced infection by an average of 92%. The reduction of infection by EDTA was accompanied by a reduction in HIV binding to PBMC; R5, X4 and dual-tropic HIV binding to PBMC were inhibited by >85%. EGTA similarly reduced HIV binding to PBMC, while addition of Ca(2+) or Mn(2+), but not Mg(2+), fully restored binding. Virus attachment was inhibited in a dose-dependent manner by trypsin treatment of PBMC, indicating protein involvement in HIV binding. In contrast, mannan or soluble ICAM-1 did not inhibit HIV binding to PBMC. These data indicate that a Ca(2+)-dependent cell-surface protein(s) is responsible for the majority of HIV attachment to and infection of PBMC. Further studies of this are likely to reveal novel strategies to prevent infection of PBMC.


[Computerized tomographic evaluation of latero-cervical lymphatic metastasis of carcinoma of the larynx. Personal experience in 170 cases].
CT can be considered the most reliable technique in detecting nodal metastases of the cervical district. The Authors have studied 170 patients with laryngeal cancer (104 N0, 21 N1, 21 N2 and 24 N3 clinically) with CT of the cervical region during infusion of contrast material. All patients underwent radical neck dissection with pathological examination of the nodes. CT diagnosis and pathological findings were correlated. Our findings show that CT has an overall accuracy of 91.8% (100% in groups N2 and N3) and fed false positives and false negatives.


Electron paramagnetic resonance spectroscopy in structural-dynamic studies of large protein complexes.
Macromolecular protein assemblies are of fundamental importance for many processes inside the cell, as they perform complex functions and constitute central hubs where reactions occur. Generally, these assemblies undergo large conformational changes and cycle through different states that ultimately are connected to specific functions further regulated by additional small ligands or proteins. Unveiling the 3D structural details of these assemblies at atomic resolution, identifying the flexible parts of the complexes, and monitoring with high temporal resolution the dynamic interplay between different protein regions under physiological conditions is key to fully understanding their properties and to fostering biomedical applications. In the last decade, we have seen remarkable advances in cryo-electron microscopy (EM) techniques, which deeply transformed our vision of structural biology, especially in the field of macromolecular assemblies. With cryo-EM, detailed 3D models of large macromolecular complexes in different conformational states became readily available at atomic resolution. Concomitantly, nuclear magnetic resonance (NMR) and electron paramagnetic resonance spectroscopy (EPR) have benefited from methodological innovations which also improved the quality of the information that can be achieved. Such enhanced sensitivity widened their applicability to macromolecular complexes in environments close to physiological conditions and opened a path towards in-cell applications. In this review we will focus on the advantages and challenges of EPR techniques with an integrative approach towards a complete understanding of macromolecular structures and functions.


Nitrogen budget of a subarctic stream altered by beaver (Castor canadensis).
Beaver (Castor canadensis) influence stream ecosystems through their wood cutting and dam building activities. To quantify this influence we have used measured rates of nitrogen dynamics to construct a nitrogen budget for a section of a second order stream in eastern Québec and a beaver dam in that stream. The budget demonstrates the importance of sediment accumulations and an expanded wetted area to the annual nitrogen economy and to pathways of nitrogen cycling. Major changes after impoundment (per unit area) include a reduction in allochthonous nitrogen and an increase in nitrogen fixation by sediment microbes. Overall, the beaver-modified section accumulated ∼103 times more nitrogen than before alteration. The ecosystem implications of beaver activity suggest that current concepts of patterns and processes in running waters require modification.


Health-related quality of life data collected in chimeric antigen receptor T-cell (CAR-T) therapy clinical trials.
Chimeric antigen receptor T-cell (CAR-T) therapy represents a novel approach to cancer treatment, particularly advanced cancer. Much of the current evidence for the effectiveness of these therapies is associated with considerable uncertainty. This uncertainty poses a challenge for decision-makers and health systems responsible for granting patients access to these therapies. While the stage of development of the technology is a component of this uncertainty, it can be reduced with relevant data collection alongside clinical trials that is meaningful to patients and decision-makers. The objective of this research was to investigate the frequency with which HRQoL data is collected in currently registered clinical trials investigating CAR-T cancer treatment. We searched for current CAR-T clinical trials at a registry compiled at United States National Institutes of Health National Library of Medicine (NLM) database. Trials were required to be active, recruiting, or completed. Trials were required to be phase I-IV, listed as 'interventional', and specific to cancer treatment. There were 424 clinical trials that were included in our analysis. The majority of these trials (76 %) were investigating CAR-T therapy in haematological malignancies. Of the included studies, only 29 (6.8 %) included HRQoL as a primary or secondary outcome measure. Only 25 (5.9 %) trials reported collecting data on overall survival. This investigation into clinical trials for CAR-T therapies has shown a failure to collect valuable HRQoL data. Sponsors of clinical trials need to appreciate that clinical trials for novel therapies need to collect relevant data that is paramount to informing decision-making and providing access to patients. The effectiveness of innovative cancer therapies, such as CAR-T, remains associated with considerable uncertainty. This uncertainty can be reduced for decision-makers via the collection of critical HRQoL data. Sponsors of clinical trials should be incentivized to collect these data, particularly where the intention is to use that trial for a reimbursement submission and decision..


3D localized lactate detection in muscle tissue using double-quantum filtered 1 H MRS with adiabatic refocusing pulses at 7 T.
Lactate is a key metabolite in skeletal muscle and whole-body physiology. Its MR visibility in muscle is affected by overlapping lipid signals and fiber orientation. Double-quantum filtered (DQF) 1 H MRS selectively detects lactate at 1.3 ppm, but at ultra-high field the efficiency of slice-selective 3D-localization with conventional RF pulses is limited by bandwidth. This novel 3D-localized 1 H DQF MRS sequence uses adiabatic refocusing pulses to unambiguously detect lactate in skeletal muscle at 7 T. Lactate double-quantum coherences were 3D-localized using slice-selective Shinnar-Le Roux optimized excitation and adiabatic refocusing pulses (similar to semi-LASER). DQF MR spectra were acquired at 7 T from lactate phantoms, meat specimens with injected lactate (exploring multiple TEs and fiber orientations), and human gastrocnemius in vivo during and after exercise (without cuff ischemia). Lactate was readily detected, achieving the full potential of 50% signal with a DQF, in solution. The effects of fiber orientation and TE on the lactate doublet (peak splitting, amplitude, and phase) were in good agreement with theory and literature. Exercise-induced lactate accumulation was detected with 30 s time resolution. This novel 3D-localized 1 H DQF MRS sequence can dynamically detect glycolytically generated lactate in muscle during exercise and recovery at 7 T.


Mycotoxins in maize products of the 1994/95 marketing season.
The levels of mycotoxins found were generally lower the more refined the maize products were. The highest levels of deoxynivalenol, nivalenol and fumonisins were found in maize bran and maize screenings. Ochratoxin A was found in a defatted germ meal sample at 50 μg/kg. Zearalenone was found randomly in samples at low levels (50 - 100 μg/kg). All other mycotoxins tested for, except in maize bran and maize screenings, were absent above the detection limits.


SFI, a sex hormone binding globulin based nomogram for predicting non-alcoholic fatty liver disease in the Chinese population.
The purpose of this study is to establish a novel nomogram model for accurate detection of non-alcoholic fatty liver disease (NAFLD) in the Chinese population based on sex hormone binding globulin (SHBG) and other routine laboratory tests. A total of 1417 participants (1003 testing and 414 validations) were enrolled into the study. Risk factors independently associated with NAFLD were identified and incorporated in the new nomogram, SFI. The performance of nomogram was assessed by analysis of receiver operating characteristic (ROC) curve, calibration curve, and decision curve. We formulated a new nomogram incorporating four independent factors: SHBG, body mass index (BMI), ALT/AST, and triglycerides (TG). The nomogram achieved good indexes of area under ROC 0.898 (95% confidence interval 0.865-0.926) in predicting NAFLD, which was significantly superior to previously reported models of FLI, HSI, LFS, and LAP. The calibration curve and decision curve demonstrated high performance and clinical utility of the nomogram in predicting NAFLD. The nomogram SFI has high performance in predicting NAFLD in Chinese population and may be used as a cost-effective screening model to assess NAFLD in the general population.


Sol and gel states in peptide hydrogels visualized by Gd(III)-enhanced magnetic resonance imaging.
The hydrogels assembled from a pair of self-repulsive but mutually attractive decapeptides are visualized by magnetic resonance imaging (MRI). It is found that in the absence of Gd(III)-chelate, gelation has little effect on MRI signal intensity. In the presence of Gd(III)-chelate, gelation leads to significant changes in water relaxation and MR signal intensity. The sol to gel transition is best visualized by T2-weighted imaging using large echo time with the sol producing a bright spot and the gel producing a dark spot. MRI studies point to high local Gd(III)-chelate concentration. Small-angle X-ray scattering study indicates that this local enrichment of Gd(III)-chelate has two contributing processes: first, the aggregation of peptides into fibers; second, within peptide fibers, Gd(III)-chelate further aggregate into clusters. This work demonstrates that the status of peptide-based hydrogels can be visualized by MRI with the aid of covalently linked Gd(III)-chelates. This result has implications for monitoring peptide scaffolds in vivo.


A Dynamic Model for Predicting Survival up to 1 Year After Ischemic Stroke.
This study developed and validated a dynamic prediction model for survival after ischaemic stroke up to 1 year. Patients with stroke (n = 425) who participated in a sub-study (2002-2004) from the South London Stroke Register (SLSR) were selected for model derivation. The model was developed using the extended Cox model with time-dependent covariates. The two temporal validation cohorts from SLSR included 1735 (1995-2002) and 2155 patients (2004-2016). The discrimination, calibration and clinical utility of the model were assessed. Six strong predictors were used in the model, namely, age, sex, stroke subtype, stroke severity and pre-stroke and post-stroke disabilities. The c-statistics was 0.822 at 1 year in the derivation cohort. The model had a fair performance with prognostic accuracies of 77%-83% in the validation 1 cohort and 70%-75% in the validation 2 cohort. A good calibration was observed in the derivation cohort. The proposed model can accurately predict survival up to 1 year after ischaemic stroke.


Exciplexes and conical intersections lead to fluorescence quenching in π-stacked dimers of 2-aminopurine with natural purine nucleobases.
Fluorescent analogues of the natural DNA bases are useful in the study of nucleic acids' structure and dynamics. 2-Aminopurine (2AP) is a widely used analogue with environmentally sensitive fluorescence behavior. The quantum yield of 2AP has been found to be significantly decreased when engaged in π-stacking interactions with the native bases. We present a theoretical study on fluorescence quenching mechanisms in dimers of 2AP π-stacked with adenine or guanine as in natural DNA. Relaxation pathways on the potential energy surfaces of the first excited states have been computed and reveal the importance of exciplexes and conical intersections in the fluorescence quenching process.


Comparative analysis of epigenetic inhibitors reveals different degrees of interference with transcriptional gene silencing and induction of DNA damage.
Repetitive DNA sequences and some genes are epigenetically repressed by transcriptional gene silencing (TGS). When genetic mutants are not available or problematic to use, TGS can be suppressed by chemical inhibitors. However, informed use of epigenetic inhibitors is partially hampered by the absence of any systematic comparison. In addition, there is emerging evidence that epigenetic inhibitors cause genomic instability, but the nature of this damage and its repair remain unclear. To bridge these gaps, we compared the effects of 5-azacytidine (AC), 2'-deoxy-5-azacytidine (DAC), zebularine and 3-deazaneplanocin A (DZNep) on TGS and DNA damage repair. The most effective inhibitor of TGS was DAC, followed by DZNep, zebularine and AC. We confirmed that all inhibitors induce DNA damage and suggest that this damage is repaired by multiple pathways with a critical role of homologous recombination and of the SMC5/6 complex. A strong positive link between the degree of cytidine analog-induced DNA demethylation and the amount of DNA damage suggests that DNA damage is an integral part of cytidine analog-induced DNA demethylation. This helps us to understand the function of DNA methylation in plants and opens the possibility of using epigenetic inhibitors in biotechnology.


Natural variation of Arabidopsis root architecture reveals complementing adaptive strategies to potassium starvation.
Root architecture is a highly plastic and environmentally responsive trait that enables plants to counteract nutrient scarcities with different foraging strategies. In potassium (K) deficiency (low K), seedlings of the Arabidopsis (Arabidopsis thaliana) reference accession Columbia (Col-0) show a strong reduction of lateral root elongation. To date, it is not clear whether this is a direct consequence of the lack of K as an osmoticum or a triggered response to maintain the growth of other organs under limiting conditions. In this study, we made use of natural variation within Arabidopsis to look for novel root architectural responses to low K. A comprehensive set of 14 differentially responding root parameters were quantified in K-starved and K-replete plants. We identified a phenotypic gradient that links two extreme strategies of morphological adaptation to low K arising from a major tradeoff between main root (MR) and lateral root elongation. Accessions adopting strategy I (e.g. Col-0) maintained MR growth but compromised lateral root elongation, whereas strategy II genotypes (e.g. Catania-1) arrested MR elongation in favor of lateral branching. K resupply and histochemical staining resolved the temporal and spatial patterns of these responses. Quantitative trait locus analysis of K-dependent root architectures within a Col-0 × Catania-1 recombinant inbred line population identified several loci each of which determined a particular subset of root architectural parameters. Our results indicate the existence of genomic hubs in the coordinated control of root growth in stress conditions and provide resources to facilitate the identification of the underlying genes.


Calphostin C induces expression of amphiregulin mRNA via reactive oxygen species in IEC-6 cells.
Calphostin C, a secondary metabolite of the fungus Cladosporium cladosporioides, is generally used as a specific inhibitor of protein kinase C. It is known that 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, induces expression of mRNA for amphiregulin (AR), a member of EGF-related polypeptides, in mammalian epithelial cells. In this work, we determined the effect of calphostin C on AR mRNA expression in IEC-6 cells, a rat intestinal epithelial cell line, and unexpectedly found that this compound enhanced the TPA-induced expression of AR mRNA. Moreover, calphostin C alone induced expression of AR mRNA in a light-dependent manner, and this effect was abrogated by pretreatment with N-acetylcysteine. These results suggest that calphostin C can upregulate expression of AR mRNA via reactive oxygen species.


[Cognitive rehabilitation in Alzheimer's disease patients: multidisciplinary team report].
This study aims to show preliminary results of the 'combined treatment' (acetylcholinesterase inhibitor + cognitive training) on a group of mild Alzheimer's disease (AD) patients, followed-up for 7 months. Six mild AD patients, diagnosed according to ICD-10 and NINCDS-ADRDA criteria, were included on a open trial with Rivastigmine, 6-12 mg/day, for 2 months, followed by a weekly cognitive rehabilitation group, for 5 months. Caregivers were submitted to a weekly group of counseling and support for 5 months. Stabilization or mild improvement of patients' cognitive and activities of daily living deficits were found, besides reduction of patients and caregivers' depressive and anxiety levels. The 'combined treatment' can help on the stabilization or result on a mild improvement of AD patients' cognitive and functional deficits. Support and counseling interventions can reduce the levels of caregivers' psychiatric symptoms.


Selection of lactic acid bacteria as biopreservation agents and optimization of their mode of application for the control of Listeria monocytogenes in ready-to-eat cooked meat products.
In order to meet consumers´ demands for more natural foods and to find new methods to control foodborne pathogens in them, research is currently being focused on alternative preservation approaches, such as biopreservation with lactic acid bacteria (LAB). Here, a collection of lactic acid bacteria (LAB) isolates was characterized to identify potential biopreservative agents. Six isolates (one Lactococcus lactis, one Lacticaseibacillus paracasei and four Lactiplantibacillus plantarum) were selected based on their antimicrobial activity in in vitro assays. Whole genome sequencing showed that none of the six LAB isolates carried known virulence factors or acquired antimicrobial resistance genes, and that the L. lactis isolate was potentially a nisin Z producer. Growth of L. monocytogenes was successfully limited by L. lactis ULE383, L. paracasei ULE721 and L. plantarum ULE1599 throughout the shelf-life of cooked ham, meatloaf and roasted pork shoulder. These LAB isolates were also applied individually or as a cocktail at different inoculum concentrations (4, 6 and 8 log10 CFU/g) in challenge test studies involving cooked ham, showing a stronger anti-Listerial activity when a cocktail was used at 8 log10 CFU/g. Thus, a reduction of up to ~5.0 log10 CFU/g in L. monocytogenes growth potential was attained in cooked ham packaged under vacuum, modified atmosphere packaging or vacuum followed by high pressure processing (HPP). Only minor changes in color and texture were induced, although there was a significant acidification of the product when the LAB cultures were applied. Remarkably, this acidification was delayed when HPP was applied to the LAB inoculated batches. Metataxonomic analyses showed that the LAB cocktail was able to grow in the cooked ham and outcompete the indigenous microbiota, including spoilage microorganisms such as Brochothrix. Moreover, none of the batches were considered unacceptable in a sensory evaluation. Overall, this study shows the favourable antilisterial activity of the cocktail of LAB employed, with the combination of HPP and LAB achieving a complete inhibition of the pathogen with no detrimental effects in physico-chemical or sensorial evaluations, highlighting the usefulness of biopreservation approaches involving LAB for enhancing the safety of cooked meat products.


A randomised trial of two cisplatin-containing chemotherapy regimens in patients with stage III-B and IV non-small cell lung cancer.
Seventy-four newly diagnosed patients with histologically proven Stage III-B and IV non-small cell lung cancer were randomized to receive either cisplatin: 20 mg/m2 x day x 5, ifosfamide: 1.8 g/m2 x day x 5, mesna: 1.2 g/m2 x day x 5, etoposide: 100 mg/m2 x day x 5 (ICE) or cisplatin: 20 g/m2 x day x 5 and etoposide: 100 mg/m2 x day x 5. Response rates were 59% in the ICE and 40% in the CE arm with a significant advantage in response duration and overall survival in the ICE receiving patients (P = 0.03, P = 0.0008). As we used granulocyte colony stimulating factor (G-CSF) very frequently, myelotoxicity remained substantial but acceptable.


FR discrimination training effects in SHR and microencephalic rats.
Fixed-ratio (FR) discrimination learning in adult male spontaneously hypertensive rats (SHR), methylazoxymethanol-induced microencephalic Sprague-Dawley (MAM), and Sprague-Dawley control rats was examined. SHR and MAM rats had little problem learning incrementally more difficult FR discriminations (FR1 vs. FR16, FR4 vs. FR16, and FR8 vs. FR16) that resulted in parallel increases in errors in all animals, and displayed only modest learning deficits during a subsequent FR4 vs. FR16 position reversal. When training involved nonincremental changes in difficulty (FR8 vs. FR16, FR4 vs. FR16, FR8 vs. FR16, FR12 vs. FR16, and FR14 vs. FR16), SHR and MAM rats evidenced relatively large learning deficits during the initial FR8 vs. FR16 discrimination but had no difficulty with the last two discriminations. Furthermore, training selectively and significantly elevated hippocampal weight in MAM rats. These findings: a) question prior suggestions that MAM and SHR model separate human developmental disabilities; b) indicate that manifestation of learning deficits in even markedly brain-damaged organisms depends on initial task difficulty and can be overcome by experience; and c) are the first indicating that training-induced antagonism of prenatally induced hippocampal hypoplasia and its consequences is possible.


Synthesis and structure-activity relationship of novel 6-aryl-1,4-dihydrobenzo[d][1,3]oxazine-2-thiones as progesterone receptor modulators leading to the potent and selective nonsteroidal progesterone receptor agonist tanaproget.
Tanaproget represents a potential first-in-class nonsteroidal PR agonist for contraception with improved safety and side effect profiles versus currently available steroidal oral contraceptives. Additional SAR, biological activity, and structural information from a tanaproget/hPR-LBD (hPR-LBD = human progesterone receptor ligand binding domain) cocrystal structure will also be presented.


Trans-synaptic regulation of gene expression.
Neurotransmitters regulate gene expression through second messenger cascades that transmit the signal from the plasma membrane to the nucleus of the postsynaptic cell. Ca2+ and cAMP are two of the second messengers that regulate gene expression in response to neurotransmitters. The Ca2+ and cAMP signals induce expression of a class of genes, termed immediate early genes, within minutes of neurotransmitter receptor activation. Many of these genes encode transcription factors that regulate the expression of late response genes. The results of recent experiments have elucidated mechanisms by which neurotransmitter-induced Ca2+ and cAMP signals regulate immediate early gene expression.


Optimizing the geometry of aerodynamic lens injectors for single-particle coherent diffractive imaging of gold nanoparticles.
Single-particle X-ray diffractive imaging (SPI) of small (bio-)nanoparticles (NPs) requires optimized injectors to collect sufficient diffraction patterns to allow for the reconstruction of the NP structure with high resolution. Typically, aerodynamic lens-stack injectors are used for NP injection. However, current injectors were developed for larger NPs (>100 nm), and their ability to generate high-density NP beams suffers with decreasing NP size. Here, an aerodynamic lens-stack injector with variable geometry and a geometry-optimization procedure are presented. The optimization for 50 nm gold-NP (AuNP) injection using a numerical-simulation infrastructure capable of calculating the carrier-gas flow and the particle trajectories through the injector is also introduced. The simulations were experimentally validated using spherical AuNPs and sucrose NPs. In addition, the optimized injector was compared with the standard-installation 'Uppsala injector' for AuNPs. Results for these heavy particles showed a shift in the particle-beam focus position rather than a change in beam size, which results in a lower gas background for the optimized injector. Optimized aerodynamic lens-stack injectors will allow one to increase NP beam density, reduce the gas background, discover the limits of current injectors and contribute to structure determination of small NPs using SPI.


Double-barrel entanglement of intracranial Enterprise stents resulting from undetected incomplete stent apposition.
Although intracranial stents have expanded the spectrum of aneurysms amenable to coiling, closed cell design variants can be prone to incomplete stent apposition around tightly curved arterial bends. A case is presented illustrating the technical ramifications of this phenomenon during subsequent treatment. A 49-year-old woman who had previously undergone Enterprise (closed cell design) stent mediated coiling of a wide necked ophthalmic carotid artery aneurysm was noted to harbor residual central filling on follow-up imaging, and was scheduled for additional embolization. During retreatment, performed with a second concentrically placed Enterprise and further coil packing using the jailing technique, the proximal portion of the second Enterprise stent failed to expand as expected. C-arm cone beam CT (CBCT) revealed the second stent to have been navigated into and out of the orphaned lumen created by the incompletely apposed first Enterprise stent at the carotid siphon. This stent entanglement resulted in the formation of a trapped proximal double-barrel lumen in the curved segment and resolution to a single barrel lumen in the distal straight segment of the parent vessel facing the aneurysm neck. Caution is urged when navigating around curved vessel segments through previously deployed intracranial stents, which may be incompletely apposed to the vessel wall, to avoid deleterious and potentially catastrophic entanglement. CBCT imaging may be helpful in delineating the spatial relationship of previously deployed intracranial stents during subsequent endovascular navigation.


Prognostic value of preoperative prognostic nutritional index in patients with renal cell carcinoma after nephrectomy.
The present study was performed to explore the prognostic value of prognostic nutritional index (PNI) in renal cell carcinoma (RCC) patients following nephrectomy. A total of 660 patients were included. PNI was calculated based on the following formula: serum albumin level (g/L) + 0.005 × total lymphocyte count (per mm3). Kaplan-Meier survival curve and the log-rank test were conducted. Univariate analysis and multivariate Cox regression analysis were performed to explore the prognostic factors. The patients in low PNI group were more likely to be older (P < 0.001), have a larger tumor (P < 0.001), higher pathological T stage (P < 0.001), positive lymph node (P = 0.038), distant metastasis (P = 0.005), higher tumor grade (P < 0.001) and tumor necrosis (P < 0.001). Multivariable analysis revealed low preoperative PNI was an independent predictor of overall survival (OS) (P = 0.034) and progression-free survival (PFS) (P = 0.004) for all patients. Besides, low preoperative PNI was also significantly associated with poor OS (P = 0.008), cancer-specific survival (CSS) (P = 0.032) and PFS (P = 0.003) for non-metastatic RCC patients. The patients with lower preoperative PNI were associated with adverse factors. Furthermore, the low preoperative PNI was also associated with inferior oncological outcomes in RCC patients who underwent nephrectomy.


Identification of the HECT E3 ligase UBR5 as a regulator of MYC degradation using a CRISPR/Cas9 screen.
MYC oncoprotein is a multifunctional transcription factor that regulates the expression of a large number of genes involved in cellular growth, proliferation and metabolism. Altered MYC protein level lead to cellular transformation and tumorigenesis. MYC is deregulated in > 50% of human cancers, rendering it an attractive drug target. However, direct inhibition of this class of proteins using conventional small molecules is challenging due to their intrinsically disordered state. To discover novel posttranslational regulators of MYC protein stability and turnover, we established a genetic screen in mammalian cells by combining a fluorescent protein-based MYC abundance sensor, CRISPR/Cas9-based gene knockouts and next-generation sequencing. Our screen identifies UBR5, an E3 ligase of the HECT-type family, as a novel regulator of MYC degradation. Even in the presence of the well-described and functional MYC ligase, FBXW7, UBR5 depletion leads to accumulation of MYC in cells. We demonstrate interaction of UBR5 with MYC and reduced K48-linked ubiquitination of MYC upon loss of UBR5 in cells. Interestingly, in cancer cell lines with amplified MYC expression, depletion of UBR5 resulted in reduced cell survival, as a consequence of MYC stabilization. Finally, we show that MYC and UBR5 are co-amplified in more than 40% of cancer cells and that MYC copy number amplification correlates with enhanced transcriptional output of UBR5. This suggests that UBR5 acts as a buffer in MYC amplified settings and protects these cells from apoptosis.


Cryoablation of Hepatocellular Carcinoma with High-Risk for Percutaneous Ablation: Safety and Efficacy.
The aim of this study was to evaluate the safety and effectiveness of cryoablation in the treatment of subcapsular hepatocellular carcinoma (HCC) adjacent to various organs. Twenty-eight patients with subcapsular HCC were treated with cryoablation in our institution. The degree of peri-procedural pain was measured using the visual analog scale (VAS). Technical success, local tumor progression, and overall disease progression rates were calculated. Procedure-related complications were identified by reviewing electronic medical records. Biochemical data, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels before and after the procedure were collected. Subcapsular HCC tumors were located near the gallbladder, colon, stomach, kidney, diaphragm, or abdominal wall. The technical success rate of cryoablation was 96.4 % (27/28). Local recurrence- and progression-free survival rates were 96 and 84 % at 6 months, and 82 and 43 % at 1 year, respectively. All patients survived during the follow-up period. The VAS pain score ranged from 0 to 3 (mean, 1.57). A major complication occurred in one patient (3.6 %) and minor complications occurred at a rate of 17.9 %. Transient elevations of serum AST, ALT, and bilirubin levels were observed. Cryoablation is a safe and an effective procedure for the treatment of subcapsular HCC adjacent to various major organs.


An immuno-electronmicroscopical study comparing vasopressin, oxytocin, substance P and enkephalin containing nerve terminals in the nucleus of the solitary tract of the rat.
Vasopressin, oxytocin, substance P and enkephalin fibers were demonstrated to terminate synaptically in the nucleus of the solitary tract. The detergent Triton X-100 proved to be indispensable for the demonstration of vasopressin and oxytocin while enkephalin and substance P could be visualized very well without it. The differences with respect to morphology between these 4 peptides disappeared when Triton X-100 was used in both groups.


Effects of the breeder age on the egg yield and egg quality traits of Landes geese (Anser anser).
This study aimed to determine the effects of the breeder age on the egg yield and egg quality traits of Landes geese in the first egg production cycle. One hundred ninety-four Landes geese aged 48 weeks were kept in the yard area throughout the egg production period. Egg number, egg weight, egg mass production, and goose-day egg production were significantly affected by the breeder age (p < 0.001). Breeder age affected the albumen index, yolk index, Haugh unit, albumen pH, yolk pH, and yolk color values. The albumen index, yolk index, and yolk color values were significantly higher at 55 weeks of age compared to the other breeder ages (62 and 64 weeks of age) (p < 0.05; p < 0.001). The shape index, albumen ratio, and yolk ratio were not significantly affected by the breeder age. There was a decrease in the shell thickness, albumen index, and yolk index as the egg production period progressed. Since the shell thickness, albumen index, and yolk index decreased with age, it is concluded that the egg quality of Landes geese may deteriorate with age.


En Bloc removal of soft tumors within the brain parenchyma using spoon retractors: traction-dissection method. Technical note.
En bloc removal of soft tumors within the brain parenchyma has rarely been performed. We describe a safe technique for en bloc removal of the tumors using a spoon retractor, which enables retraction while holding the soft mass upward. Dissection of a tumor mass is performed under traction of the surrounding brain tissue by retracting the mass using a spoon retractor. A dissection plane is first established in a relatively safe area, not opposite the critical area, after a corticotomy. The dissection plane is then extended toward the critical side. After circumferential dissection of the tumor mass, the dissection is continued spirally into deeper regions by retracting and holding the mass upward using a spoon retractor. In this way, the tumor is removed en bloc. The traction-dissection method using spoon retractors is useful in performing en bloc removal of soft tumors within the brain parenchyma less invasively and provides an appropriate operating field even at depth, reducing intraoperative bleeding, and in vascular rich tumors, possibly preventing tumor seeding in cases of malignant tumors.


Glucocorticoids modulate the induction of BLTE/granzyme A activity in the murine T cell hybridoma PC60.
The cytolytic granule-associated serine esterase granzyme A cleaves the synthetic substrate benzyloxycarbonyl-L-lysinate-thiobenzylester (BLT) and has been described as a marker for cytotoxic T lymphocyte (CTL) activation. We recently showed that BLT-esterase activity (BLTE activity) can be induced in the murine CTL-hybridoma PC60 by exogenous interleukin-1 (IL-1) and/or a rise of the intracellular cAMP level, although cAMP does not act as a second messenger for IL-1 in this system. The present study demonstrates that glucocorticoids (GC) such as dexamethasone and hydrocortisone efficiently inhibit the induction of BLTE activity by IL-1 and/or cAMP and downregulate the basal BLTE levels in PC60 cells; these results could be reproduced in part with progesterone and were steroid class-specific, since estrogen did not affect the induction of BLTE activity. The GC-induced effects on the production of BLTE activity required the activation of specific GC receptors, since induction of the activity could be restored upon addition of the contragestative drug RU 38486; they further could not be related to any alteration of the cellular metabolism of arachidonic acid and did not appear to be mediated by secreted macromolecules such as lipocortins.


Two-state dynamics of the SH3-SH2 tandem of Abl kinase and the allosteric role of the N-cap.
The regulation and localization of signaling enzymes is often mediated by accessory modular domains, which frequently function in tandems. The ability of these tandems to adopt multiple conformations is as important for proper regulation as the individual domain specificity. A paradigmatic example is Abl, a ubiquitous tyrosine kinase of significant pharmacological interest. SH3 and SH2 domains inhibit Abl by assembling onto the catalytic domain, allosterically clamping it in an inactive state. We investigate the dynamics of this SH3-SH2 tandem, using microsecond all-atom simulations and differential scanning calorimetry. Our results indicate that the Abl tandem is a two-state switch, alternating between the conformation observed in the structure of the autoinhibited enzyme and another configuration that is consistent with existing scattering data for an activated form. Intriguingly, we find that the latter is the most probable when the tandem is disengaged from the catalytic domain. Nevertheless, an amino acid stretch preceding the SH3 domain, the so-called N-cap, reshapes the free-energy landscape of the tandem and favors the interaction of this domain with the SH2-kinase linker, an intermediate step necessary for assembly of the autoinhibited complex. This allosteric effect arises from interactions between N-cap and the SH2 domain and SH3-SH2 connector, which involve a phosphorylation site. We also show that the SH3-SH2 connector plays a determinant role in the assembly equilibrium of Abl, because mutations thereof hinder the engagement of the SH2-kinase linker. These results provide a thermodynamic rationale for the involvement of N-cap and SH3-SH2 connector in Abl regulation and expand our understanding of the principles of modular domain organization.


Biomarker Panels in Critical Care.
Biomarker panels have the potential to advance the field of critical care medicine by stratifying patients according to prognosis and/or underlying pathophysiology. This article discusses the discovery and validation of biomarker panels, along with their translation to the clinical setting. The current literature on the use of biomarker panels in sepsis, acute respiratory distress syndrome, and acute kidney injury is reviewed.


Decitabine induces G2/M cell cycle arrest by suppressing p38/NF-κB signaling in human renal clear cell carcinoma.
The anti-neoplastic effects of decitabine, an inhibitor of DNA promoter methylation, are beneficial for the treatment of renal cell carcinoma (RCC); however, the mechanism of action of decitabine is unclear. We analyzed gene expression profiling and identified specific pathways altered by decitabine in RCC cells. Four human RCC cell lines (ACHN, Caki-1, Caki-1, and A498) were used in this study; growth suppression of RCC cells by decitabine was analyzed using the WST-1 assay. Apoptosis and cell cycle arrest were examined using flow cytometric analysis. Gene expression of RCC cells induced by decitabine was evaluated with cDNA microarray, and potential biological pathways were selected using Ingenuity Pathway Analysis. The activity of the p38-NF-κB pathway regulated by decitabine was confirmed by Western blotting. Decitabine suppresses the proliferation of RCC cells in vitro. Although decitabine did not significantly induce apoptosis, decitabine caused cell cycle arrest at G2/M in a dose-dependent manner. Gene expression regulated by decitabine in RCC cells was investigated using microarray analysis. Ubiquitin carboxyl terminal hydrolase 1 (UCHL1), interferon inducible protein 27 (IFI27), and cell division cycle-associated 2 (CDCA2) may be involved in growth suppression of RCC cells by decitabine. The phosphorylation of p38-NF-κB pathway was suppressed by decitabine in RCC cells. We investigated gene expression profiling and pathways modulated by decitabine in RCC cells. Decitabine was shown to suppress the growth of RCC cells via G2/M cell cycle arrest and the p38-NF-κB signaling pathway may play a role in the anti-neoplastic effect of decitabine in RCC cells.


Ethylene, the natural regulator of leaf abscission.
Natural leaf fall is triggered by increased ethylene production in senescing cells close to abscission zones.


Initial experience with a modified "candy-plug" technique for false lumen embolization in chronic type B aortic dissection.
Persistent distal false lumen (FL) perfusion after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) can lead to aneurysmal degeneration and an increased risk of rupture. We have presented our initial experience using a modified "candy-plug" (CP) technique for FL embolization. From February 2021 to July 2022, we treated six patients using the modified CP technique. All the patients had undergone prior or simultaneous TEVAR for chronic TBAD with persistent FL perfusion and aneurysm expansion. Bilateral common femoral artery access was obtained, and intravascular ultrasound was used to confirm wire access in the true lumen (TL) and FL. A conformable TAG device (W.L. Gore & Associates, Flagstaff, AZ) was used in four cases and an Excluder aortic cuff (W.L. Gore & Associates) in two cases. The device was modified by placing a constraining "napkin-ring" suture through the middle segment of the device. Femoral sheaths were placed in the TL and FL. A standard TL TEVAR extension was performed at the level of the celiac artery (zone 5). Next, the CP device was advanced and deployed in the FL, distally aligning it with the TL device. An appropriately sized Amplatzer II plug (Abbot Vascular, Santa Clara, CA) was then deployed in the constrained segment of the modified stent graft. Completion angiography was performed to confirm successful FL embolization. Technical success was defined as successful deployment of the CP device in the FL. The technical success rate was 100% (six of six patients). Clinical success was defined as the cessation of aneurysm growth on follow-up computed tomography angiography. No 30-day mortality, myocardial infarction, stroke, spinal cord ischemia, access site complications, or aortic-related reinterventions occurred. Surveillance imaging at a mean follow-up of 10 months confirmed clinical success (stable aneurysm size or shrinkage) for all five patients with follow-up data available. The modified CP embolization technique is a promising solution for persistent distal FL perfusion after TEVAR for TBAD. Further investigation is required to determine the long-term durability of this technique as an adjunct to TEVAR to promote aortic remodeling.


A controlled trial of aseptic enteral diet preparation--significant effects on bacterial contamination and nitrogen balance.
This study was performed to evaluate the clinical effectiveness of the 'standard' and aseptic enteral diet preparation techniques and to investigate the relationship between bacterial contamination of diets and symptoms during enteral nutrition. In this controlled study patients were prescribed isonitrogenous polymeric diets prepared using either 'standard' or aseptic techniques, administered by 24 nasogastric infusion. 'Standard' diet preparation resulted in significant bacterial contamination (p<0.01), but this did not increase incidence of diet related symptoms. Use of sterile techniques permitted safe use of large volumes (1.5-2 litre) containers, and this resulted in significantly better nitrogen intake (p<0.05) and balance (p<0.05).


[Organization and prerequisites for the delegation of dosimetry tasks].
The planning of irradiation treatments is a task of medical physics, based on the appropriate calculations of a dose distribution from radiation beams, virtually set up on a simulation software. This task is at the centre of the chain of treatment preparation: between the contouring phase and the objective definition, which are specialties of the radiation oncologist, and the joint validation of the treatment plan by the physician and the physicist. Historically, this task has been performed by the medical physicist, but can be delegated to other professionals, especially radiation technologists. The evolution of the techniques and procedures tends to a specialization of the skilled workers toward this new work of dosimetry specialist or treatment planning technician. In this paper, the training, relational and organizational aspects will be described to explain how the delegation of the tasks, in the context of treatment plan preparation between professionals can be set up with the highest level of quality and security for the patient treatment and with the respect of legal obligations and requirements of each profession.


[Traumatic dissection of the internal carotid artery following whiplash injury. Diagnostic workup and therapy of an often overlooked but potentially dangerous additional vascular lesion].
We report on the case of a 33-year-old male patient who was brought to the emergency room of our hospital after suffering a high-energy trauma due to an automobile accident. Besides a scaphoid fracture there were no signs of any neurological deficits. After several hours without clinical symptoms the patient developed dysarthria as the first manifestation of local cerebral ischemia based on a traumatic dissection of the internal carotid artery. Under systemic high-dose heparin therapy, fast and complete remission of all neurological disorders could be achieved. In the course of time a dissecting aneurysm developed. Temporary anticoagulation with phenprocoumon was started in the meantime and no further complications have appeared up to now. Besides presenting this absorbing case, this article highlights the diagnostic and therapeutic regime in cases of a traumatic dissection of supra-aortal arteries for rapid and adequate management of this rare but potentially dangerous complication.


COVID-19 and pneumonia: a role for the uPA/uPAR system.
Here, we highlight recent findings on the urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system that suggest its potential role as a main orchestrator of fatal progression to pulmonary, kidney, and heart failure in patients with coronavirus. Patients with prolonged background inflammation can present aberrant inflammatory reactions, well recognized as the main factors that can result in death and probably sustained by a dysregulated uPA/uPAR system. SuPAR, the soluble form of uPAR, represents a biomarker of disease progression, and its levels correlate well with comorbidities associated with the death of patients with coronavirus. New drugs that regulate the uPA/uPAR system could help treat the severe complications of highly pathogenic human coronaviruses (hCoVs), including pandemic coronavirus 2019 (COVID-19).


It took two decades for private payor contracts to erode the bottom line: plan on a 2+ year comeback--here's how, part I.
This article will help you understand the payor side of the industry and create the foundation for strategically tackling contract negotiations. It will summarize significant industry events and factors over the past two decades, briefly describe the importance of understanding ERISA or self-insured health plans, and provide the first steps to getting your payor contracts in order.


Accuracy of pneumonia hospital admissions in a primary care electronic medical record database.
When using electronic medical record data to study drug use, hospitalizations are markers of severe outcomes. To identify events within a specified time window, it is important to validate hospitalization diagnoses and dates. Our objective was to validate pneumonia hospitalizations and their dates identified using hospitalization codes in The Health Improvement Network (THIN), a UK primary care electronic medical record. This cross-sectional study used a cohort of THIN adult visits for acute nonspecific respiratory infections from June 1985 to August 2006. Pneumonia hospitalizations within 30 days after the visit were identified using THIN diagnosis and hospitalization codes; 60 participants were randomly selected for validation. Patients' general practitioners (GPs) returned de-identified hospital summaries and consultants' letters regarding overnight hospitalizations within a 180-day window around the THIN hospitalization. Positive predictive value (PPV) was the number of GP-validated hospitalizations divided by THIN documented hospitalizations. GPs returned 59 of 60 patient records; 52 had confirmed hospitalizations. PPV of THIN hospitalization documentation was 88% (95%CI = 77-95). One admission was not for pneumonia; PPV of THIN-documented pneumonia admission was 86% (95%CI = 75-94). Of 52 valid THIN hospitalizations, 50 were actually admitted within 14 days of the documented THIN date (range = -2 to +18). The absolute median difference between THIN and validated admission dates was +0.5 days, and the absolute mean difference was +3.1 days. In 16 of 52 admitted patients, the THIN admission date was the actual discharge date. THIN hospitalization codes performed well in identifying acute pneumonia hospitalizations and their timing. Admission date validity might be better for conditions associated with shorter versus longer hospitalizations.


An Optimization Procedure for Preparing Aqueous CAR/HP-CD Aggregate Dispersions.
β-Carotene is a very important molecule for human health. It finds a large application in the food industry, especially for the development of functional foods and dietary supplements. However, β-carotene is an unstable compound and is sensitive to light, temperature, and oxygen. To overcome those limitations, various delivery systems were developed. The inclusion of β-carotene by cyclodextrin aggregates is attractive due to non-toxicity, low hygroscopicity, stability, and the inexpensiveness of cyclodextrins. In this study, β-carotene/2-hydroxypropyl-β-cyclodextrin aggregates were prepared based on the procedure of the addition of β-carotene in an organic solvent to the hot water dispersion of 2-hydroxypropyl-β-cyclodextrin and the following instant evaporation of the organic solvent. The best conditions for the aggregate preparation were found to be as follows: 25% concentration of 2-hydroxypropyl-β-cyclodextrin in water, 65 °C temperature, and acetone for β-carotene dissolution. The efficiency of entrapping was equal to 88%. The procedure is attractive due to the short time of the aggregate preparation.


Correlation of cytotoxic activity of betulinines and their hydroxy analogues.
This research is based on intention to prepare and test 3beta-hydroxy and 3beta,28-dihydroxy analogues of new pro-apoptotic derivatives (betulinines) using selective hydrolysis procedure and strategic protective groups. The evaluation of cytotoxicity of prepared compounds on several tumor cell lines using an MTT test was our interest. It was found that hydrolysis of acetates in betulinines afforded compounds with higher cytotoxicity in case of 18-lupene-21-ones (e.g., ethyl 3beta-hydroxy-21-oxolup-18-en-28-oate), whereas hydrolysis of the 18-lupene-21,22-diones gave less active derivatives.


Advanced imaging findings in a cat with left ventricular apical aneurysm.
An eight-year-old, male neutered, domestic shorthair cat presented with severe anemia. Two-dimensional echocardiography identified severe left ventricular apical dilation with wall thinning and akinesia. The basal portion of the left ventricle showed equivocal hypertrophy and subjective hyperkinesis. Speckle tracking echocardiography showed marked abnormalities in all deformation planes (longitudinal, circumferential, radial strain) and twist. Three-dimensional Bull's eye plot reconstruction was also performed. Post-mortem evaluation showed a pale and paper-thin left ventricular apex and histopathology confirmed full-thickness cardiomyocytes loss with fibrous replacement. Left ventricular acquired apical aneurysms are the result of chronic damage of the myocardium and are associated with many disease conditions in people, including coronary artery disease and cardiomyopathy. The exact pathophysiological mechanism could not be determined with certainty in the cat of the present report, but advanced echocardiographic evaluation added some fine details into the characterization of this infrequently reported abnormality.


Lesions of the parapharyngeal space. Role of MR imaging.
Because the parapharyngeal space is one of the deep spaces of the upper neck, it is a difficult region to examine clinically. On each side of the head, this space is located lateral to the pharynx and medial to the ramus of the mandible, the pterygoid muscles, and the parotid gland. It is only with bimanual palpation that any small fullness within this space may be clinically appreciated. When a parapharyngeal mass is sufficiently large, it displaces the lateral pharyngeal wall and pharyngeal tonsil toward the midline and may cause lateral displacement of the parotid gland. Only when a lesion is very large does it manifest as a fullness near the angle of the mandible. Thus, clinical evaluation of the space is quite limited.


Estimated incidence and case fatality rate of traumatic brain injury among children (0-18 years) in Sub-Saharan Africa. A systematic review and meta-analysis.
Studies from Sub-Saharan Africa (SSA) countries have reported on the incidence and case fatality rate of children with Traumatic Brain Injury (TBI). However, there is lack of a general epidemiologic description of the phenomenon in this sub-region underpinning the need for an accurate and reliable estimate of incidence and outcome of children (0-18 years) with TBI. This study therefore, extensively reviewed data to reliably estimate incidence, case fatality rate of children with TBI and its mechanism of injury in SSA. Electronic databases were systematically searched in English via Medline (PubMed), Google Scholar, and Africa Journal Online (AJOL). Two independent authors performed an initial screening of studies based on the details found in their titles and abstracts. Studies were assessed for quality/risk of bias using the modified Newcastle-Ottawa Scale (NOS). The pooled case fatality rate and incidence were estimated using DerSimonian and Laird random-effects model (REM). A sub-group and sensitivity analyses were performed. Publication bias was checked by the funnel plot and Egger's test. Furthermore, trim and fill analysis was used to adjust for publication bias using Duval and Tweedie's method. Thirteen (13) hospital-based articles involving a total of 40685 participants met the inclusion criteria. The pooled case fatality rate for all the included studies in SSA was 8.0%; [95% CI: 3.0%-13.0%], and the approximate case fatality rate was adjusted to 8.2%, [95% CI:3.4%-13.0%], after the trim-and-fill analysis was used to correct for publication bias. A sub-group analysis of sub-region revealed that case fatality rate was 8% [95% CI: 2.0%-13.0%] in East Africa, 1.0% [95% CI: 0.1% -3.0%] in Southern Africa and 18.0% [95% CI: 6.0%-29.0%] in west Africa. The pooled incidence proportion of TBI was 18% [95% CI: 2.0%-33.0%]. The current review showed that Road Traffic Accident (RTA) was the predominant cause of children's TBI in SSA. It ranged from 19.1% in South Africa to 79.1% in Togo. TBI affects 18% of children aged 0 to 18 years, with almost one-tenth dying in SSA. The most common causes of TBI among this population in SSA were RTA and falls. TBI incidence and case fatality rate of people aged 0-18 years could be significantly reduced if novel policies focusing on reducing RTA and falls are introduced and implemented in SSA.


A novel mechanism of methylglyoxal cytotoxicity in prostate cancer cells.
Methylglyoxal is one of the most powerful glycating agents of proteins and other important cellular components and has been shown to be toxic to cultured cells. Methylglyoxal cytotoxicity appears to occur through cell-cycle arrest but, more often, through induction of apoptosis. In this study we examined whether, and through which molecular mechanism, methylglyoxal affects the growth of poorly aggressive LNCaP and invasive PC3 human prostate cancer cells, where its role has not been exhaustively investigated yet. We demonstrated that methylglyoxal is cytotoxic on LNCaP and PC3 and that such cytotoxicity occurs not via cell proliferation but apoptosis control. Moreover, we demonstrated that methylglyoxal cytotoxicity, potentiated by the silencing of its major scavenging enzyme Glyoxalase I, occurred via different apoptotic responses in LNCaP and PC3 cells that also showed a different susceptibility to this metabolite. Finally, we showed that the observed methylglyoxal apoptogenic role involved different molecular pathways, specifically mediated by methylglyoxal or methylglyoxal-derived argpyrimidine intracellular accumulation and NF-kB signaling-pathway. In particular, in LNCaP cells, methylglyoxal, through the accumulation of argpyrimidine, desensitized the key cell survival NF-kB signaling pathway, which was consistent with the modulation of NF-kB-regulated genes, triggering a mitochondrial apoptotic pathway. The results suggest that this physiological compound merits investigation as a potential chemo-preventive/-therapeutic agent, in differently aggressive prostate cancers.