Reproductive biology and biotechnologies in wild felids.
Conservation strategies in natural habitats as well as in breeding centers are necessary for maintaining and reinforcing viable populations of wild felids. Among the fundamental knowledge that is required for conservation breeding, a solid understanding of reproductive biology is critical for improving natural breeding and enhance genetic diversity. Additionally, it offers the opportunity to develop assisted reproductive technologies (ARTs) in threatened and endangered species. Conservation breeding and reproductive biotechnologies of wild felids have advanced in the past decade. It has been clearly shown that female felids have species and individual patterns of reproductive cycles and respond differently to exogenous hormones. In males, several species still have poor semen quality often due to the loss of genetic diversity in small populations. To overcome the challenges of natural breeding (incompatibility between individuals or suboptimal environment) and mitigate inbreeding, artificial insemination, embryo production and embryo transfer have been further developed in 24 wild cat species. Major factors limiting ART success are inconsistent responses to ovarian stimulation, variable quality of gametes and embryos, and preparation of recipient females. Additional approaches including stem cell technologies have been explored for future medical applications. However, there still is a critical need for better knowledge of feline reproductive biology and improvement of ARTs efficiency to increase the genetic diversity and create sustainable populations of wild felids.


Mild Inflammatory Profile without Gliosis in the c-Rel Deficient Mouse Modeling a Late-Onset Parkinsonism.
The impact of neuroinflammation and microglial activation to Parkinson's disease (PD) progression is still debated. Post-mortem analysis of PD brains has shown that neuroinflammation and microgliosis are key features of end-stage disease. However, microglia neuroimaging studies and evaluation of cerebrospinal fluid (CSF) cytokines in PD patients at earlier stages do not support the occurrence of a pronounced neuroinflammatory process. PD animal models recapitulating the motor and non-motor features of the disease, and the slow and progressive neuropathology, can be of great advantage in understanding whether and how neuroinflammation associates with the onset of symptoms and neuronal loss. We recently described that 18-month-old NF-κB/c-Rel deficient mice (c-rel-/-) develop a spontaneous late-onset PD-like phenotype encompassing L-DOPA-responsive motor impairment, nigrostriatal neuron degeneration, α-synuclein and iron accumulation. To assess whether inflammation and microglial activation accompany the onset and the progression of PD-like pathology, we investigated the expression of cytokines (interleukin 1 beta (Il1b), interleukin 6 (Il6)) and microglial/macrophage activation markers (Fc gamma receptor III (Fcgr3), mannose receptor 1 (Mrc1), chitinase-like 3 (Ym1), arginase 1 (Arg 1), triggering receptor expressed on myeloid cells 2 (Trem2)), together with microglial ionized calcium binding adapter molecule 1 (Iba1) and astrocyte glial fibrillary acidic protein (GFAP) immunolabeling, in the substantia nigra (SN) of c-rel-/- mice, at premotor (4- and 13-month-old) and motor phases (18-month-old). By quantitative real-time RT-PCR we found increased M2c microglial/macrophage markers expression (Mrc1 and Arg1) in 4-month-old c-rel-/- mice. M2-type transcription dropped down in 13-month-old c-rel-/- mice. At this age, the pro-inflammatory Il1b, but not Il6 or the microglia-macrophage M1-polarization marker Fcgr3/CD16, increased when compared to wild-type (wt). Furthermore, no significant variation in the transcription of inflammatory and microglial/macrophage activation genes was present in 18-month-old c-rel-/- mice, that display motor dysfunctions and dopaminergic neuronal loss. Immunofluorescence analysis of Iba1-positive cells in the SN revealed no sign of overt microglial activation in c-rel-/- mice at all the time-points. MRC1-Iba1-positive cells were identified as non-parenchymal macrophages in 4-month-old c-rel-/- mice. Finally, no sign of astrogliosis was detected in the SN of the diverse animal groups. In conclusion, this study supports the presence of a mild inflammatory profile without evident signs of gliosis in c-rel-/- mice up to 18 months of age. It suggests that symptomatic PD-like phenotype can develop in the absence of concomitant severe inflammatory process.


Liquid chromatography-tandem mass spectrometry--application in the clinical laboratory.
This review provides a concise survey of liquid chromatography-tandem mass spectrometry (LC-TMS) as an emerging technology in clinical chemistry. The combination of two mass spectrometers with an interposed collision cell characterizes LC-TMS as an analytical technology on its own and not just as a more specific detector for HPLC compared with conventional techniques. In LC-TMS, liquid chromatography is rather used for sample preparation but not for complete resolution of compounds of interest. The instrument technology of LC-TMS is complex and comparatively expensive; however, in routine use, methods are far more rugged compared to conventional chromatographic techniques and enable high-throughput analyses with very limited manual handling steps. Moreover, compared to both gas chromatography-mass spectrometry (GC-MS) and conventional HPLC techniques, LC-TMS is substantially more versatile with respect to the spectrum of analyzable compounds. For these reasons it is likely that LC-TMS will gain far more widespread use in the clinical laboratory than HPLC and GC-MS ever did. In this article, the key features of LC-TMS are described, method development is explained, typical fields of application are discussed, and personal experiences are related.


Motor perseveration in geriatric medical patients.
Perseveration has long been considered as a pathognomonic sign of neurological disease, yet, surprisingly, little research exists regarding the accuracy of this assumption. This study matched 56 geriatric medical inpatients with 56 inpatients with recent cerebrovascular accidents. Participants were given one of two measures of general cognition and four Lurian tasks of motor coordination. The results suggest that both motor incoordination and across-tasks perseveration were associated with decreased cognitive status. After controlling for cognitive status, individuals with a neurological history evidenced greater dyscoordination and increased perseveration when compared to age-equivalent general medical patients. Perseveration in participants with recent strokes appeared more related to the amount of neural system disruption as opposed to specific lesion sites. Overall, the results suggest that motor incoordination and "stuck-in-set" perseveration are more indicative of global than localizable brain dysfunction. Possible nonneurologic factors associated with this behavior are also proposed as benchmarks for future research.


[Dizziness, tiredness and the risk of a stroke].
In a recent study, Bos et al. (JAMA 2007) showed that patients with nonfocal transient neurological attacks (TNA) have a higher risk of major vascular disease, comparable to patients with focal TNAs. This may prompt GPs to take a more active approach when dealing with patients experiencing short-lasting attacks of dizziness, paraesthesia and weakness. However, the category of nonfocal TNAs in the abovementioned study was very broad, and subgroup analysis for specific symptoms was not possible. Moreover, a third of nonfocal TNAs consisted of loss of consciousness or decreased consciousness, which might be responsible for the heightened risk of cerebrovascular accident. Also, a quarter of patients with nonfocal TNA had not presented their symptoms to a physician and reported the symptoms during a follow-up meeting, leaving room for recall bias. Since symptoms like dizziness are very frequent among elderly patients and nonfocal TNAs are difficult to recognize, both physicians and education campaigns should be careful not to arouse anxiety without good reason.


Plasmodium falciparum Kelch Propeller Polymorphisms in Clinical Isolates from Ghana from 2007 to 2016.
The continuous surveillance of polymorphisms in the kelch propeller domain of Plasmodium falciparum from Africa is important for the discovery of the actual markers of artemisinin resistance in the region. The information on the markers is crucial for control strategies involving chemotherapy and chemoprophylaxis for residents and nonimmune travelers to the country. Polymorphisms in the kelch propeller domain of Ghanaian malaria parasites from three different ecological zones at several time periods were assessed. A total of 854 archived samples (2007 to 2016) collected from uncomplicated malaria patients aged ≤9 years old from 10 sentinel sites were used. Eighty-four percent had wild-type sequences (PF3D7_1343700), while many of the mutants had mostly nonsynonymous mutations clustered around codons 404 to 650. Variants with different amino acid changes of the codons associated with artemisinin (ART) resistance validated markers were observed in Ghanaian isolates: frequencies for I543I, I543S, I543V, R561P, R561R, and C580V were 0.12% each and 0.6% for R539I. Mutations reported from African parasites, A578S (0.23%) and Q613L (0.23%), were also observed. Three persisting nonsynonymous (NS) mutations, N599Y (0.005%), K607E (0.004%), and V637G (0.004%), were observed in 3 of the 5 time periods nationally. The presence of variants of the validated markers of artemisinin resistance as well as persisting polymorphisms after 14 years of artemisinin-based combination therapy use argues for continuous surveillance of the markers. The molecular markers of artemisinin resistance and the observed variants will be monitored subsequently as part of ongoing surveillance of antimalarial drug efficacy/resistance studies in the country.


The effect of supervised exercise therapy for intermittent claudication on lower limb lean mass.
Supervised exercise is currently recommended for the first-line treatment of intermittent claudication based on improvement in walking capacity. However, the promotion of skeletal muscle atrophy by repetitive ischemia-reperfusion caused by treadmill-based programs remains a concern. Because preservation of skeletal muscle mass (SMM) and lean mass (LM) is integral to functional capacity and longevity, this study measured the effect of standard treadmill-based supervised exercise on SMM and regional lower limb LM in patients with intermittent claudication. Patients with calf claudication caused by infrainguinal peripheral artery disease underwent whole-body dual-energy X-ray absorptiometry scanning before and after completion of a 12-week supervised treadmill exercise program. Total body SMM and lower limb LM were measured according to anatomical regions of the lower limb (thigh vs calf) and side of symptoms. Walking performance was assessed using pain-free walking distance and 6-minute walking distance tests. Thirty-six patients with calf claudication completed exercise training and dual-energy X-ray absorptiometry scanning, allowing analysis of 55 symptomatic and 17 asymptomatic lower limbs. No difference in total body SMM (P = .41) or LM of symptomatic (P = .53) or asymptomatic calves (P = .59) was detected after the program. In contrast, a significant decrease in LM was observed in symptomatic (P = .04) and asymptomatic thighs (P = .005). Pain-free walking distance (P = .001) and the 6-minute walking distance both improved significantly (P = .004) but were not associated with changes in LM. Twelve weeks of standard treadmill-training for intermittent calf claudication did not result in loss of calf LM; however, a significant decrease in bilateral thigh LM was observed, even in patients with unilateral symptoms. Further research on optimum exercise modalities and end points are required to determine the pathophysiology and effects of these changes on function and survival.


Prevalence and predictors of cervical cancer screening among HIV-positive women in rural western Uganda: insights from the health-belief model.
Women living with HIV are at increased risk of developing cervical cancer (CC). Screening for cancer is an important preventive strategy for the early detection of precancerous lesions and its management. There has been inadequate evidence on cervical cancer screening (CCS) practices among HIV-positive women in rural western Uganda. This study aimed to assess the prevalence and predictors of CCS among HIV-positive women, as well as knowledge and practices regarding cervical cancer screening. A cross-sectional, analytical study was conducted among HIV-positive women attending HIV care facilities located in rural settings of western Uganda. A validated and interview-based data collection form was used to capture statistics regarding demographics, HIV care, obstetric profile, health belief constructs, and knowledge and history of CCS from the participants. Bivariate and multivariate logistic regression analyses were used to correlate women's characteristics and health beliefs toward CCS practices. The prevalence of CCS among HIV-positive women was found to be 39.1% (95%CI: 14.0-71.7). A multivariate logistic regression analysis showed that post-secondary education attainment (AOR = 3.21; 95%CI = 2.12-7.28), four years or more lapsing after being diagnosed as HIV-positive (AOR = 2.87; 95%CI = 1.34-6.13), having more than one child (AOR = 1.87; 95%CI = 1.04-3.35), antenatal care attendance (AOR = 1.74; 95%CI = 1.02-3.43), post-natal care attendance (AOR = 3.75; 95%CI = 1.68-5.89), and having good knowledge regarding CC (AOR = 1.26; 95%CI = 1.98-3.02) were positively associated with adherence to CCS among HIV-positive women in western Uganda. Health Belief Model (HBM) constructs like the perceived risk of developing CC (AOR = 1.82; 95%CI = 1.16-2.01), worries about developing CC (AOR = 5.01; 95%CI = 4.26-8.32), believing that CC leads to death (AOR = 2.56; 95%CI = 1.64-3.56), that screening assists in early identification (AOR = 2.12; 95%CI = 1.84-3.74) and treatment (AOR = 4.63; 95%CI = 2.78-6.43) of precancerous lesions, reducing the risk of mortality (AOR = 1.84; 95%CI = 1.12-2.75), and the reassurance provided by negative test results (AOR = 2.08; 95%CI = 1.33-4.22) were positively associated with adhering to CCS. A female doctor performing the screening (AOR = 2.02; 95%CI = 1.57-3.98) as well as offering a free screening service (AOR = 3.23; 95%CI = 1.99-4.38) were significantly associated with CCS. Meanwhile, screening being painful (AOR = 0.28; 95%CI = 0.12-0.45), expensive (AOR = 0.36; 95%CI = 0.24-0.53), time-consuming (AOR = 0.30; 95%CI = 0.19-0.41), embarrassing (AOR = 0.02; 95%CI = 0.01-0.06), and the fear of positive results (AOR = 0.04; 95%CI = 0.02-0.10) were found to have a significant negative association with adhering to CCS. Only one-third of HIV-positive women had undergone CCS. Variables including secondary education attainment, four years or more lapsing after being diagnosed as HIV-positive, having more than one child, antenatal care attendance, post-natal care attendance, and knowledge about CC were positively associated with CCS adherence. Educational programs should be geared towards the risk of CC, severity of cases, benefits of screening, and reducing barriers associated with screening, which can significantly improve cervical CCS among HIV-positive women. The study proposes the incorporation of free screening services and the inclusion of trained female staff in CC prevention policies to improve CCS.


Reactive transport of iomeprol during stream-groundwater interactions.
The transport and biochemical transformations of the iodinated X-ray contrast medium (ICM) iomeprol were studied at the stream/groundwater interface. During a one-month field experiment piezometric pressure heads, temperatures, and concentrations of redox-sensitive species, iomeprol and 15 of its transformation products (TPs) were collected in stream- and groundwater. The data set was analyzed and transformation processes and rates identified by comparing conservative and reactive transport simulations. ICM and TP transformations were simulated as a cometabolic process during organic carbon degradation. Using iomeprol/TPs ratios as calibration constrain mitigated the uncertainties associated with the high variability of the ICM wastewater discharge into the investigated stream. The study provides evidence that biodegradation of ICM occurs at the field-scale also for predominantly denitrifying conditions. Under these anaerobically dominated field conditions shortest simulated half-life (21 days) was in the same range as previously reported laboratory-determined half-lives for aerobic conditions.


Population structure and demographic history of Sicyopterus japonicus (Perciformes; Gobiidae) in Taiwan inferred from mitochondrial control region sequences.
The amphidromous goby Sicyopterus japonicus is distributed throughout southern Taiwan and Japan. Larvae of this freshwater fish go through a long marine stage. This migratory mode influences population genetic structure. We examined the genetic diversity, population differentiation, and demographic history of S. japonicus based on the mitochondrial DNA control region. We identified 102 haplotypes from 107 S. japonicus individuals from 22 populations collected from Taiwan and Islet Lanyu. High mean haplotype diversity (h = 0.999) versus low nucleotide diversity (θπ = 0.008) was detected across populations. There was low correspondence between clusters identified in the neighbor-joining tree and geographical region, as also indicated by AMOVA and pairwise F(ST) estimates. Both mismatch distribution analysis and Tajima's D test indicated that S. japonicus likely experienced a demographic expansion. Using a Bayesian skyline plot approach, we estimated the time of onset of the expansion of S. japonicus at 135 kyr (during the Pleistocene) and the time of stable effective population size at approximately 2.5 kyr (last glacial maximum). Based on these results, we suggest 1) a panmictic population at the oceanic planktonic larval stage, mediated by the Kuroshio current; 2) a long planktonic marine stage and long period of dispersal, which may have permitted efficient tracking of environmental shifts during the Pleistocene; and 3) a stable, constant population size ever since the last glacial maximum.


Thrombopoietic cytokine and P-selectin levels in patients with multiple myeloma undergoing autologous stem cell transplantation: decrease in posttransplantation P-selectin levels might predict the degree of maximum response.
This study was designed to determine the pretransplantation levels of thrombopoietic cytokines, which have a fundamental role in both megakaryopoiesis and myeloma pathogenesis and P-selectin in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (AHSCT) and to correlate the cytokine levels with time to platelet recovery. The effect of AHSCT on the levels of the cytokines and its correlation with maximum disease response was also investigated. The levels of thrombopoietin, interleukin (IL)-6, IL-11, IL-1beta, and P-selectin was measured before and 30 days after AHSCT in 32 patients with a median age of 55 years. The median time to platelet recovery was day +11 (range, 0-14 days) without any significant correlation with pretransplantation cytokine levels. No significant change was observed in thrombopoietic cytokines after AHSCT, whereas serum P-selectin levels showed a significant decrease after AHSCT (P = .001). The decrease in P-selectin was found to be significant in patients who achieved complete remission (P1 = .008) and partial remission (P2 = .018) early after AHSCT. Our data suggest that the level of thrombopoietic cytokines does not have a role in time to platelet recovery. The change in P-selectin levels early after transplantation could be a surrogate marker in determining the maximum posttransplantation response.


Reinforcement learning application in diabetes blood glucose control: A systematic review.
Reinforcement learning (RL) is a computational approach to understanding and automating goal-directed learning and decision-making. It is designed for problems which include a learning agent interacting with its environment to achieve a goal. For example, blood glucose (BG) control in diabetes mellitus (DM), where the learning agent and its environment are the controller and the body of the patient respectively. RL algorithms could be used to design a fully closed-loop controller, providing a truly personalized insulin dosage regimen based exclusively on the patient's own data. In this review we aim to evaluate state-of-the-art RL approaches to designing BG control algorithms in DM patients, reporting successfully implemented RL algorithms in closed-loop, insulin infusion, decision support and personalized feedback in the context of DM. An exhaustive literature search was performed using different online databases, analyzing the literature from 1990 to 2019. In a first stage, a set of selection criteria were established in order to select the most relevant papers according to the title, keywords and abstract. Research questions were established and answered in a second stage, using the information extracted from the articles selected during the preliminary selection. The initial search using title, keywords, and abstracts resulted in a total of 404 articles. After removal of duplicates from the record, 347 articles remained. An independent analysis and screening of the records against our inclusion and exclusion criteria defined in Methods section resulted in removal of 296 articles, leaving 51 relevant articles. A full-text assessment was conducted on the remaining relevant articles, which resulted in 29 relevant articles that were critically analyzed. The inter-rater agreement was measured using Cohen Kappa test, and disagreements were resolved through discussion. The advances in health technologies and mobile devices have facilitated the implementation of RL algorithms for optimal glycemic regulation in diabetes. However, there exists few articles in the literature focused on the application of these algorithms to the BG regulation problem. Moreover, such algorithms are designed for control tasks as BG adjustment and their use have increased recently in the diabetes research area, therefore we foresee RL algorithms will be used more frequently for BG control in the coming years. Furthermore, in the literature there is a lack of focus on aspects that influence BG level such as meal intakes and physical activity (PA), which should be included in the control problem. Finally, there exists a need to perform clinical validation of the algorithms.


Risk of adverse events after covid-19 in Danish children and adolescents and effectiveness of BNT162b2 in adolescents: cohort study.
To assess the risk of acute and post-acute adverse events after SARS-CoV-2 infection in children and adolescents in Denmark and to evaluate the real world effectiveness of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) among adolescents. Cohort study. Nationwide Danish healthcare registers. All Danish people younger than 18 years who were either tested for SARS-CoV-2 using reverse transcriptase polymerase chain reaction (RT-PCR) or vaccinated with BNT162b2 to 1 October 2021. Risk of hospital admissions (any hospital contact of ≥12 hours); intensive care unit (ICU) admissions; serious complications, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and neuroimmune disorders; and initiating drug treatment and health service use up to six months after being tested. Vaccine effectiveness in vaccine recipients compared with unvaccinated peers was evaluated as one minus the risk ratio at 20 days after the first dose and 60 days after the second dose. Of 991 682 children and adolescents tested for SARS-CoV-2 using RT-PCR in Denmark, 74 611 (7.5%) were positive. The risk of hospital admission with any variant for ≥12 hours was 0.49% (95% confidence interval 0.44% to 0.54%; 361/74 350), and 0.01% (0.01% to 0.03%; 10/73 187) of participants were admitted to an ICU within 30 days of testing positive. The risk of MIS-C within two months of SARS-CoV-2 infection was 0.05% (0.03% to 0.06%; 32/70 666), whereas no participants had myocarditis outside of MIS-C or encephalitis and fewer than five had Guillain-Barré syndrome. In the post-acute phase (1-6 months after infection), participants who tested positive for SARS-CoV-2 showed a 1.08-fold (95% confidence interval 1.06-fold to 1.10-fold) increase in rate of contacts with general practitioners compared with a reference cohort sampled among all children tested for SARS-CoV-2 during the study period. Overall, 278 649 adolescents received BNT162b2. Compared with unvaccinated adolescents, the estimated vaccine effectiveness among 229 799 adolescents vaccinated with one dose was 62% (95% confidence interval 59% to 65%) after 20 days, and among 175 176 vaccinated with two doses was 93% (92% to 94%) after 60 days during a period when delta was the dominant variant. The absolute risks of adverse events after SARS-CoV-2 infection were generally low in Danish children and adolescents, although MIS-C occurred in 0.05% (32/70 666) of participants with RT-PCR confirmed SARS-CoV-2 infection. In adjusted analyses, rates of general practitioner visits were slightly increased in SARS-CoV-2 positive children and adolescents, which could indicate persisting symptoms. BNT162b2 appeared to be effective in reducing the risk of SARS-CoV-2 infection with the delta variant in adolescents.


T cell recognition of weak ligands: roles of signaling, receptor number, and affinity.
T cell recognition of antigen is a crucial aspect of the adaptive immune response. One of the most common means of pathogen immune evasion is mutation of T cell epitopes. T cell recognition of such ligands can result in a variety of outcomes including activation, apoptosis and anergy. The ability of a given T cell to respond to a specific peptide-MHC ligand is regulated by a number of factors, including the affinity, on- and off-rates and half-life of the TCR-peptide-MHC interaction. Interaction of T cells with low-potency ligands results in unique signaling patterns and requires engagement with a larger number of T cell receptors than agonist ligands. This review will address these aspects of T cell interaction with weak ligands and the ways in which these ligands have been utilized therapeutically.


Hyper-parameter tuning and feature extraction for asynchronous action detection from sub-thalamic nucleus local field potentials.
Decoding brain states from subcortical local field potentials (LFPs) indicative of activities such as voluntary movement, tremor, or sleep stages, holds significant potential in treating neurodegenerative disorders and offers new paradigms in brain-computer interface (BCI). Identified states can serve as control signals in coupled human-machine systems, e.g., to regulate deep brain stimulation (DBS) therapy or control prosthetic limbs. However, the behavior, performance, and efficiency of LFP decoders depend on an array of design and calibration settings encapsulated into a single set of hyper-parameters. Although methods exist to tune hyper-parameters automatically, decoders are typically found through exhaustive trial-and-error, manual search, and intuitive experience. This study introduces a Bayesian optimization (BO) approach to hyper-parameter tuning, applicable through feature extraction, channel selection, classification, and stage transition stages of the entire decoding pipeline. The optimization method is compared with five real-time feature extraction methods paired with four classifiers to decode voluntary movement asynchronously based on LFPs recorded with DBS electrodes implanted in the subthalamic nucleus of Parkinson's disease patients. Detection performance, measured as the geometric mean between classifier specificity and sensitivity, is automatically optimized. BO demonstrates improved decoding performance from initial parameter setting across all methods. The best decoders achieve a maximum performance of 0.74 ± 0.06 (mean ± SD across all participants) sensitivity-specificity geometric mean. In addition, parameter relevance is determined using the BO surrogate models. Hyper-parameters tend to be sub-optimally fixed across different users rather than individually adjusted or even specifically set for a decoding task. The relevance of each parameter to the optimization problem and comparisons between algorithms can also be difficult to track with the evolution of the decoding problem. We believe that the proposed decoding pipeline and BO approach is a promising solution to such challenges surrounding hyper-parameter tuning and that the study's findings can inform future design iterations of neural decoders for adaptive DBS and BCI.


Behavioural analysis and control of psychosomatic symptoms of patients receiving intensive cancer treatment.
During the course of cancer treatment behavioural symptoms such as gagging, coughing and vomiting often develop in the absence of apparent tissue damage. Moreover, symptoms whose onsets are clearly related to disease processes often continue after the disease has been eliminated. The reported research incorporated time-series analyses of patients' behavioural symptoms and assessments of behavioural interventions involving the modification of nurse--patient and family--patient interactions. Results showed that: (1) inadvertent social reinforcement by hospital staff and family members fosters the development of behavioural symptoms; (2) personnel associated with treatment can become discriminative stimuli for social attention and thereby evoke symptom behaviours; and (3) by modifying the social reinforcement contingencies associated with treatment protocols, the frequency of psychosomatic symptoms can be reduced without changing the quality of medical/nursing care and social interaction.


Chronic pain: a difficult problem.
The author discusses the general problem of the small but significant population of people in whom pain persists for months or years after a precipitating event, such as a hand injury. The nature of pain, the perception of pain, and characteristics of chronic pain patients are discussed, as well as evaluation and treatment of chronic pain.


Development of an environmental contextual factor item set relevant to global functioning and health in patients with axial spondyloarthritis.
To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health.


Prognostic Implications of Mitral Valve Inflow Pattern Overlap during Ivabradine Therapy.
The prognostic impact of mitral inflow wave overlap during ivabradine therapy in patients with heart failure with reduced ejection fraction (HFrEF) remains to be unknown. Thus, in this study, we have retrospectively examined consecutive inpatients with HFrEF admitted with decompensated heart failure who continued ivabradine following the index discharge. Ideal heart rate (HR), at which echocardiographic mitral inflow wave overlap is theoretically 0, was retrospectively calculated as follows: 96 - 0.13 × (deceleration time [msec]). HR difference was then calculated as follows: actual HR - ideal HR. The association between the HR difference at index discharge and a composite outcome of cardiovascular death and heart failure readmissions was investigated. In total, 16 patients (68 [47, 75] years old, 11 men, median left ventricular ejection fraction 28% [22%, 35%]) were included in this study for analysis. Baseline actual HR was determined to be 88 (81, 93) bpm, whereas the ideal HR was calculated as 75 (73, 76) bpm. Following the initiation of ivabradine, actual HR at index discharge was 75 (64, 84) bpm. Patients with optimal HR (actual HR - ideal HR < ± 10 bpm; n = 9) were found to have experienced a lower incidence of the composite endpoint (40% versus 100%, P = 0.013) compared with those with sub-optimal HR (n = 7) with a hazard ratio of 0.10 (95% confidence interval 0.01-0.91) adjusted for actual HR at index discharge. In conclusion, HR modulation therapy using ivabradine may improve outcomes in patients with HFrEF if individualized ideal HR was achieved.


Prevention of early postoperative deep vein thrombosis by passive exercise of leg during surgery.
A clinical trial assessed the effect of passive exercise of the lower limb during surgery on the incidence of early postoperative deep vein thrombosis. Thrombosis was diagnosed by means of the (125)I-fibrinogen uptake test. Passive exercise of the lower limb during the operation was achieved by using a motorized foot mover designed for use on supine subjects, and by pedalling only one leg each patient acted as his own control.In a sequential statistical analysis, 47 patients were required to reach the 5% level of significance. Thrombosis was detected in 11 control (unpedalled) legs alone, and in only one pedalled leg alone. Two patients developed thrombosis bilaterally. The investigation shows that the incidence of early thrombosis in legs which were exercised during surgery was reduced by 77%.


Gender and sexual maturation-dependent contrasts in the neuroregulation of growth hormone secretion in prepubertal and late adolescent males and females--a general clinical research center-based study.
Although numerous studies have delineated an impact of gender on the neuroendocrine control of GH secretion in the adult, few investigations have defined the nature and extent of sex differences before puberty. This deficit reflects jointly the sensitivity limitations of earlier GH assays and the paucity of intensive sampling protocols in healthy children. Here we have applied a chemiluminescence-based GH assay (sensitivity, 0.005 microg/L) to study GH release in blood sampled every 10 min for 12 h from 1800-0600 h in 58 healthy children. Males and females were evaluated in prepuberty (n = 17 boys; n = 11 girls) and late adolescence (n = 13 males; n = 17 females). We quantitated the principal regulated facets of GH release by 1) deconvolution analysis to assess basal vs. pulsatile GH secretion, 2) approximate entropy to compute the regularity of GH release patterns, and 3) cosine regression analysis to evaluate the overnight rhythmic release of GH. Gender by maturation analysis of variance revealed a mean 2.3-fold increase in the integrated serum GH concentration between prepuberty and late adolescence (P < 10(-6)). Deconvolution analysis disclosed that 91-97% of total GH secretion was pulsatile. Pulsatile, but not basal, GH release showed marked sexual maturation dependence (P < 10(-5)). Pulsatile GH release rose in adolescents due to a 2.25-fold greater GH secretory burst mass (P = 0.00011), which reflected joint 1.5-fold increases in GH secretory pulse amplitude and duration (P < 0.01). Pulse-mass enhancement across puberty was gender independent, but mechanistically specific, as GH pulse frequency, intersecretory burst interval, and half-life were invariant of pubertal status. The approximate entropy statistic identified more disorderly GH secretion patterns in adolescent females compared with prepubertal children and adolescent males (P = 0.00074). Cosinor analysis unmasked elevated overnight rhythms in GH secretory burst mass and interburst intervals in late adolescents of both genders compared with prepubertal boys (for burst mass) or girls (for interburst intervals). Linear regression analysis disclosed strong correlations among 1) the plasma insulin-like growth factor I concentration and GH secretory burst mass (P < 10(-3)), 2) the GH pulse mass and the serum testosterone concentration (P = 10(-3)), 3) the irregularity (entropy) of GH secretory patterns and the serum estradiol concentration (P < 10(-4)), and 4) the basal GH secretion rate and the serum estradiol concentration (P = 10(-2)). In summary, healthy prepubertal children and late adolescent boys and girls manifest distinctive mechanisms controlling GH release, as appraised for all three of the pulsatile, entropic, and 12-h rhythmic modes of GH neuroregulation. The major maturational contrast in the pulsatile mode of GH secretion is amplified secretory burst mass in adolescents due to jointly heightened GH pulse amplitude and duration. The dominant gender distinction lies in the reduced orderliness of GH release patterns in late adolescent girls. Overnight rhythms in GH secretory burst mass and interburst intervals enlarge in both sexes at adolescence, thus signaling enhanced coupling between the rhythmic and pulsatile control of GH release at this time. At the extrema of pubertal development, sex steroid hormones are associated differentially with specific facets of GH release, e.g. an elevated basal GH secretion rate (estrogen), greater irregularity of GH release patterns (estrogen), and amplified GH secretory burst mass and higher plasma insulin-like growth factor I concentrations (testosterone). Accordingly, we postulate that sex steroids supervise selectively each of the dominant facets of GH neurosecretory control across human puberty.


A new CT reconstruction technique using adaptive deformation recovery and intensity correction (ADRIC).
Sequential same-patient CT images may involve deformation-induced and non-deformation-induced voxel intensity changes. An adaptive deformation recovery and intensity correction (ADRIC) technique was developed to improve the CT reconstruction accuracy, and to separate deformation from non-deformation-induced voxel intensity changes between sequential CT images. ADRIC views the new CT volume as a deformation of a prior high-quality CT volume, but with additional non-deformation-induced voxel intensity changes. ADRIC first applies the 2D-3D deformation technique to recover the deformation field between the prior CT volume and the new, to-be-reconstructed CT volume. Using the deformation-recovered new CT volume, ADRIC further corrects the non-deformation-induced voxel intensity changes with an updated algebraic reconstruction technique ("ART-dTV"). The resulting intensity-corrected new CT volume is subsequently fed back into the 2D-3D deformation process to further correct the residual deformation errors, which forms an iterative loop. By ADRIC, the deformation field and the non-deformation voxel intensity corrections are optimized separately and alternately to reconstruct the final CT. CT myocardial perfusion imaging scenarios were employed to evaluate the efficacy of ADRIC, using both simulated data of the extended-cardiac-torso (XCAT) digital phantom and experimentally acquired porcine data. The reconstruction accuracy of the ADRIC technique was compared to the technique using ART-dTV alone, and to the technique using 2D-3D deformation alone. The relative error metric and the universal quality index metric are calculated between the images for quantitative analysis. The relative error is defined as the square root of the sum of squared voxel intensity differences between the reconstructed volume and the "ground-truth" volume, normalized by the square root of the sum of squared "ground-truth" voxel intensities. In addition to the XCAT and porcine studies, a physical lung phantom measurement study was also conducted. Water-filled balloons with various shapes/volumes and concentrations of iodinated contrasts were put inside the phantom to simulate both deformations and non-deformation-induced intensity changes for ADRIC reconstruction. The ADRIC-solved deformations and intensity changes from limited-view projections were compared to those of the "gold-standard" volumes reconstructed from fully sampled projections. For the XCAT simulation study, the relative errors of the reconstructed CT volume by the 2D-3D deformation technique, the ART-dTV technique, and the ADRIC technique were 14.64%, 19.21%, and 11.90% respectively, by using 20 projections for reconstruction. Using 60 projections for reconstruction reduced the relative errors to 12.33%, 11.04%, and 7.92% for the three techniques, respectively. For the porcine study, the corresponding results were 13.61%, 8.78%, and 6.80% by using 20 projections; and 12.14%, 6.91%, and 5.29% by using 60 projections. The ADRIC technique also demonstrated robustness to varying projection exposure levels. For the physical phantom study, the average DICE coefficient between the initial prior balloon volume and the new "gold-standard" balloon volumes was 0.460. ADRIC reconstruction by 21 projections increased the average DICE coefficient to 0.954. The ADRIC technique outperformed both the 2D-3D deformation technique and the ART-dTV technique in reconstruction accuracy. The alternately solved deformation field and non-deformation voxel intensity corrections can benefit multiple clinical applications, including tumor tracking, radiotherapy dose accumulation, and treatment outcome analysis.


Auricular point acupressure to manage chronic low back pain in older adults: a randomized controlled pilot study.
This prospective, randomized clinical trial (RCT) pilot study was designed to (1) assess the feasibility and tolerability of an easily administered, auricular point acupressure (APA) intervention and (2) provide an initial assessment of effect size as compared to a sham treatment. Thirty-seven subjects were randomized to receive either the real or sham APA treatment. All participants were treated once a week for 4 weeks. Self-report measures were obtained at baseline, weekly during treatment, at end-of-intervention (EOI), and at a 1-month follow-up. A dropout rate of 26% in the real APA group and 50% in the sham group was observed. The reduction in worst pain from baseline to EOI was 41% for the real and 5% for the sham group with a Cohen's effect size of 1.22 (P < 0.00). Disability scores on the Roland Morris Disability Questionnaire (RMDQ) decreased in the real group by 29% and were unchanged in the sham group (+3%) (P < 0.00). Given the high dropout rate, results must be interpreted with caution; nevertheless, our results suggest that APA may provide an inexpensive and effective complementary approach for the management of back pain in older adults, and further study is warranted.


Unusual Fusion Proteins of HIV-1.
Despite its small genome size, the Human Immunodeficiency Virus 1 (HIV-1) is one of the most successful pathogens and has infected more than 70 million people worldwide within the last decades. In total, HIV-1 expresses 16 canonical proteins from only nine genes within its 10 kb genome. Expression of the structural genes gag, pol, and env, the regulatory genes rev and tat and the accessory genes vpu, nef, vpr, and vif enables assembly of the viral particle, regulates viral gene transcription, and equips the virus to evade or counteract host immune responses. In addition to the canonically expressed proteins, a growing number of publications describe the existence of non-canonical fusion proteins in HIV-1 infected cells. Most of them are encoded by the tat-env-rev locus. While the majority of these fusion proteins (e.g., TNV/p28 tev , p186Drev, Tat1-Rev2, Tat^8c, p17tev, or Ref) are the result of alternative splicing events, Tat-T/Vpt is produced upon programmed ribosomal frameshifting, and a Rev1-Vpu fusion protein is expressed due to a nucleotide polymorphism that is unique to certain HIV-1 clade A and C strains. A better understanding of the expression and activity of these non-canonical viral proteins will help to dissect their potential role in viral replication and reveal how HIV-1 optimized the coding potential of its genes. The goal of this review is to provide an overview of previously described HIV-1 fusion proteins and to summarize our current knowledge of their expression patterns and putative functions.


Elevated temporal QT variability index in patients with chronic renal failure.
Patients with CRF (chronic renal failure) are at increased risk of cardiovascular diseases, and 60% of cardiovascular mortality in CRF is attributed to sudden death. Various abnormalities in myocardial repolarization are associated with the risk of ventricular arrhythmia. The aim of this study was to evaluate an index of temporal myocardial repolarization lability, the temporal QTVI (QT variability index), in patients with CRF. ECGs were recorded in 153 patients with CRF on haemodialysis (n=67), continuous ambulatory peritoneal dialysis (n=43) or conservative treatment (n=43) during 30 min of rest. QTVI was calculated as the logarithm of the ratio between the variances of the normalized QT and RR intervals. Age-matched healthy subjects (n=39) were examined for comparison. QTVI was increased by 47% in CRF patients compared with healthy subjects (-0.82+/-0.56 compared with -1.54+/-0.27 respectively; P<0.01). QTVI did not differ among patients on dialysis or conservative treatment, whereas QTVI was elevated further in patients with diabetes compared with non-diabetic CRF patients (-0.56+/-0.54 compared with -0.94+/-0.52 respectively; P<0.01). In a multiple linear regression analysis, diabetes and a history of coronary artery disease were the only independent predictors of QTVI in the CRF population. The present study demonstrates that elevated QTVI in patients with CRF is associated with diabetes and coronary disease. The present findings are important given that repolarization instability may predispose to ventricular arrhythmia and sudden death, events that occur frequently in CRF patients.


The role of ventral striatal cAMP signaling in stress-induced behaviors.
The cAMP and cAMP-dependent protein kinase A (PKA) signaling cascade is a ubiquitous pathway acting downstream of multiple neuromodulators. We found that the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facilitated cAMP degradation and homeostasis of cAMP/PKA signaling. In mice, loss of Cdk5 throughout the forebrain elevated cAMP levels and increased PKA activity in striatal neurons, and altered behavioral responses to acute or chronic stressors. Ventral striatum- or D1 dopamine receptor-specific conditional knockout of Cdk5, or ventral striatum infusion of a small interfering peptide that selectively targeted the regulation of PDE4 by Cdk5, produced analogous effects on stress-induced behavioral responses. Together, our results demonstrate that altering cAMP signaling in medium spiny neurons of the ventral striatum can effectively modulate stress-induced behavioral states. We propose that targeting the Cdk5 regulation of PDE4 could be a new therapeutic approach for clinical conditions associated with stress, such as depression.


Text mining in livestock animal science: introducing the potential of text mining to animal sciences.
In biological research, establishing the prior art by searching and collecting information already present in the domain has equal importance as the experiments done. To obtain a complete overview about the relevant knowledge, researchers mainly rely on 2 major information sources: i) various biological databases and ii) scientific publications in the field. The major difference between the 2 information sources is that information from databases is available, typically well structured and condensed. The information content in scientific literature is vastly unstructured; that is, dispersed among the many different sections of scientific text. The traditional method of information extraction from scientific literature occurs by generating a list of relevant publications in the field of interest and manually scanning these texts for relevant information, which is very time consuming. It is more than likely that in using this "classical" approach the researcher misses some relevant information mentioned in the literature or has to go through biological databases to extract further information. Text mining and named entity recognition methods have already been used in human genomics and related fields as a solution to this problem. These methods can process and extract information from large volumes of scientific text. Text mining is defined as the automatic extraction of previously unknown and potentially useful information from text. Named entity recognition (NER) is defined as the method of identifying named entities (names of real world objects; for example, gene/protein names, drugs, enzymes) in text. In animal sciences, text mining and related methods have been briefly used in murine genomics and associated fields, leaving behind other fields of animal sciences, such as livestock genomics. The aim of this work was to develop an information retrieval platform in the livestock domain focusing on livestock publications and the recognition of relevant data from cattle and pigs. For this purpose, the rather noncomprehensive resources of pig and cattle gene and protein terminologies were enriched with orthologue synonyms, integrated in the NER platform, ProMiner, which is successfully used in human genomics domain. Based on the performance tests done, the present system achieved a fair performance with precision 0.64, recall 0.74, and F(1) measure of 0.69 in a test scenario based on cattle literature.


[Robotic kidney transplantation.]
Renal transplant surgery has not undergone any major changes until a few years ago, probably due to the technical difficulty involved in performing a laparoscopic transplant. With the introduction of robotic technology, the difficulties derived from laparoscopic surgery in certain procedures have been reduced, so we can now offer a minimally invasive approach to kidney recipients. Review of published literature on robotic kidney transplantation. Since the first robot-assisted renal transplantation in 2009, several hundred cases have been performed. The different series of published cases, although with different surgical techniques, show initial functional results comparable to conventional open surgery. Despite this evidence, there are no comparative quality studies that confirm this hypothesis. Robotic renal transplantation is a feasible surgical technique with interesting functional results. As a minimally invasive route, it is a promising option to reduce the surgical morbidity inherent to the renal transplant.


Direct instrumental conditioning of neural activity using functional magnetic resonance imaging-derived reward feedback.
Successful learning is often contingent on feedback. In instrumental conditioning, an animal or human learns to perform specific responses to obtain reward. Instrumental conditioning is often used by behavioral psychologists to train an animal (or human) to produce a desired behavior. Shaping involves reinforcing those behaviors, which in a stepwise manner are successively closer to the desired behavior until the desired behavior is reached. Here, we aimed to extend this traditional approach to directly shape neural activity instead of overt behavior. To achieve this, we scanned 22 human subjects with functional magnetic resonance imaging and performed image processing in parallel with acquisition. We delineated regions of interest (ROIs) in finger and toe motor/somatosensory regions and used an instrumental shaping procedure to induce a regionally specific increase in activity by providing an explicit monetary reward to reinforce neural activity in the target areas. After training, we found a significant and regionally specific increase in activity in the ROI being rewarded (finger or toe) and a decrease in activity in the nonrewarded region. This demonstrates that instrumental conditioning procedures can be used to directly shape neural activity, even without the production of an overt behavioral response. This procedure offers an important alternative to traditional biofeedback-based approaches and may be useful in the development of future therapies for stroke and other brain disorders.


Postoperative Complications of Impacted Mandibular Third Molar Extraction Related to Patient's Age and Surgical Difficulty Level: A Cross-Sectional Retrospective Study.
Mandibular third molar surgical extraction, either partially erupted or fully impacted, is the most common surgical procedure in oral and maxillofacial surgery (OMFS). However, this procedure can be associated with many postoperative complications including persistent pain, swelling, trismus, and paresthesia due to nerve injury. This study aimed to identify the correlation of postoperative complications with patient's age, sex, and surgical difficulty level. This study was a cross-sectional retrospective and single-center research conducted on patients with a history of mandibular third molar surgical extraction in the period between 2017 and 2019 at Dental and Oral Hospital Universitas Airlangga, Surabaya, Indonesia. The researchers assessed the factors of age, sex, and surgical difficulty level regarding postoperative complications on the first day of the surgery and after one week on the 7th day of it. Among 916 respondents, the majority of the sample was females (59%) and the dominant age group (60.9%) was the age group of 21-30 years while the dominant surgical difficulty level was shown by the advanced cases group (77%). The statistical analysis showed that there was a significant correlation between surgical difficulty level and postoperative complications including pain, trismus, and paresthesia on the first-day assessment. On the other hand, age was significantly related to complications like pain, swelling, and trismus on the first-week assessment. Age and surgical difficulty level were the most common risk factors of the mandibular third molar extraction postoperative complications. Dentists should take into consideration that older patients (≥51 years) and patients with complex surgical level are more vulnerable to severe postoperative complications.


The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex.
Circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about their role in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC. Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with particular enrichment in patients with TP53 mutations. circPVT1 up- and down-regulation determine, respectively, an increase and a reduction of the malignant phenotype in HNSCC cell lines. We show that circPVT1 expression is transcriptionally enhanced by the mut-p53/YAP/TEAD complex. circPVT1 acts as an oncogene modulating the expression of miR-497-5p and genes involved in the control of cell proliferation. This study shows the oncogenic role of circPVT1 in HNSCC, extending current knowledge about the role of circular RNAs in cancer.


Correlation of PD-1 and PD-L1 expression in oral leukoplakia and oral squamous cell carcinoma: an immunohistochemical study.
The programmed cell death protein (PD-1)/programmed cell death protein ligand (PD-L1) pathway and cytotoxic T lymphocyte antigen are the most important co-stimulatory molecules that play a key role in the negative regulation of T cells during carcinogenesis. We aimed to evaluate the immunohistochemical expression of PD-1 and PD-L1 in oral leukoplakia and squamous cell carcinoma compared with normal oral mucosa. Twenty-five cases of oral squamous cell carcinoma, oral leukoplakia and normal oral mucosa tissue specimens were immunohistochemically stained to assess PD-1 and PD-L1 expression. The PD-L1 positivity of subepithelial TAFs (p < 0.001) increased with increasing grades of oral leukoplakia. Pearson's correlation indicated a high positive correlation between the PD-L1 labelling index of epithelial tumour cells and the PD-1 labelling index of tumour infiltrating lymphocytes (p value: 0.005) in OSCC. A high positive correlation was noted between the H-score of PD-L1 positive tumour epithelial cells and the H-score of PD-1 positive tumour infiltrating lymphocytes in OSCC (p value: 0.001). PD-L1 positivity increased in dysplastic epithelial cells from premalignant lesions to malignancy. The sub-epithelial PD-L1 positive TAFs were higher in oral leukoplakia compared to OSCC inferring that PD-L1 positivity in TAFs decreased with malignant transformation. The PD-1 positivity in TILs was higher in oral leukoplakia than in OSCC.


The relative meaning of absolute numbers: the case of pain intensity scores as decision support systems for pain management of patients with dementia.
Assessment and management of pain in patients with dementia is known to be challenging, due to patients' cognitive and/or communication difficulties. In the UK, pain in hospital is managed through regular assessments, with the use of pain intensity scores as triggers for action. The aim of this study was to understand current pain assessment practices, in order to later inform the development of a decision support tool designed to improve the management of pain for people with dementia in hospital. An exploratory study was conducted in four hospitals in the UK (11 wards), with observations of patients with dementia (n = 31), interviews of staff (n = 52) and patients' family members (n = 4) and documentary analysis. A thematic analysis was carried out, structured along dimensions of decision making. This paper focuses on the emergent themes related to the use of assessment tools and pain intensity scores. A variety of tools were used to record pain intensity, usually with numerical scales. None of the tools in actual use had been specifically designed for patients with cognitive impairment. With patients with more severe dementia, the patient's body language and other cues were studied to infer pain intensity and then a score entered on behalf of the patient. Information regarding the temporality of pain and changes in pain experience (rather than a score at a single point in time) seemed to be most useful to the assessment of pain. Given the inherent uncertainty of the meaning of pain scores for patients with dementia, numerical scales were used with caution. Numerical scores triggered action but their meaning was relative - to the patient, to the clinician, to the time of recording and to the purpose of documenting. There are implications for use of data and computerized decision support systems design. Decision support interventions should include personalized alerting cut-off scores for individual patients, display pain scores over time and integrate professional narratives, mitigating uncertainties around single pain scores for patients with dementia.


Characterization of a novel light-cured star-shape poly(acrylic acid)-composed glass-ionomer cement: fluoride release, water sorption, shrinkage, and hygroscopic expansion.
This study evaluated the fluoride release, water sorption, curing shrinkage, and hygroscopic expansion of a novel experimental light-cured glass-ionomer cement. The effects of glycidyl methacrylate (GM) grafting, polymer : water (P : W) and powder : liquid (P : L) ratios were investigated. Commercial Fuji II and Fuji II LC cements were used as controls for comparison. All the specimens were conditioned in deionized water at 37 degrees C before testing. The results demonstrated that the experimental cement showed lower burst and slower bulk fluoride release than Fuji II and Fuji II LC. The experimental cement absorbed more water than Fuji II and Fuji II LC as a result of its hydroxyl and carboxyl functional group content. The lower water-diffusion rate and reduced hygroscopic expansion of the experimental cement suggest that it had a highly crosslinked network. Both Fuji II and Fuji II LC exhibited much higher shrinkage values (2.8% and 4.7%) than the experimental cement (0.8%). It appears that this novel cement will be a clinically attractive dental restorative because not only has it shown superior mechanical strength, it has also demonstrated satisfactory physical properties.


Lecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease.
To review current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of lecanemab in patients with Alzheimer disease. A literature search of PubMed (April 1, 2016-November 15, 2023) and ClinicalTrials.gov search were conducted using the following search terms: lecanemab and BAN2401. Additional articles were identified by hand from references. We included English-language clinical trials, randomized controlled trials, reviews, and systematic reviews evaluating lecanemab pharmacology, efficacy, or safety in humans for the management of Alzheimer disease. In the Clarity AD phase III trial, lecanemab led to a decrease in brain amyloid levels and showed moderate improvement in clinical measures of cognition and function. At 18 months, lecanemab 10 mg/kg biweekly exhibited a lower least squares mean change from baseline (1.21) compared to placebo (1.66) of Clinical Dementia Rating-Sum of Boxes score, signifying a significant difference of -0.45 (95% CI, -0.67 to -0.23; P < 0.001). In a subset of 698 participants, lecanemab reduced brain amyloid burden by -59.1 Centiloids (95% CI, -62.6 to -55.6). Lecanemab demonstrated favorable differences in Alzheimer Disease Assessment Scale-cognitive subscale 14, Alzheimer Disease Composite Score, and Alzheimer Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living scores. Adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%). Lecanemab reduces cognitive decline but raises concerns about intravenous administration, cost, and magnetic resonance imaging needs. Ongoing trials exploring subcutaneous dosing and positron emission tomography scans may offer solutions. Lecanemab is a humanized monoclonal antibody that is selective for soluble amyloid-beta (Aβ) aggregates. Lecanemab has exhibited a decrease in brain Aβ plaques and moderately less decline on clinical measures of cognitive function.


The Role of Direct and Visual Force Feedback in Suturing Using a 7-DOF Dual-Arm Teleoperated System.
The lack of haptic feedback in robotics-assisted surgery can result in tissue damage or accidental tool-tissue hits. This paper focuses on exploring the effect of haptic feedback via direct force reflection and visual presentation of force magnitudes on performance during suturing in robotics-assisted minimally invasive surgery (RAMIS). For this purpose, a haptics-enabled dual-arm master-slave teleoperation system capable of measuring tool-tissue interaction forces in all seven Degrees-of-Freedom (DOFs) was used. Two suturing tasks, tissue puncturing and knot-tightening, were chosen to assess user skills when suturing on phantom tissue. Sixteen subjects participated in the trials and their performance was evaluated from various points of view: force consistency, number of accidental hits with tissue, amount of tissue damage, quality of the suture knot, and the time required to accomplish the task. According to the results, visual force feedback was not very useful during the tissue puncturing task as different users needed different amounts of force depending on the penetration of the needle into the tissue. Direct force feedback, however, was more useful for this task to apply less force and to minimize the amount of damage to the tissue. Statistical results also reveal that both visual and direct force feedback were required for effective knot tightening: direct force feedback could reduce the number of accidental hits with the tissue and also the amount of tissue damage, while visual force feedback could help to securely tighten the suture knots and maintain force consistency among different trials/users. These results provide evidence of the importance of 7-DOF force reflection when performing complex tasks in a RAMIS setting.


Benign and tumor parenchyma metabolomic profiles affect compensatory renal growth in renal cell carcinoma surgical patients.
Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG. Contra-lateral kidney volume fold-change within a 3.3 +/- 2.1 years follow-up interval was used as a surrogate for long-term CRG. Using a multivariable statistical model, we identified metabolites whose abundances significantly associate with CRG. Our analysis found 13 metabolites in the benign (e.g. L-urobilin, Variable Influence in Projection, VIP, score = 3.02, adjusted p = 0.017) and 163 metabolites in the malignant (e.g. 3-indoxyl-sulfate, VIP score = 1.3, adjusted p = 0.044) tissues that significantly associate with CRG. Benign/tumor fold change in metabolite abundances revealed three additional metabolites with that significantly positively associate with CRG (e.g. p-cresol sulfate, VIP score = 2.945, adjusted p = 0.033). At the pathway level, we show that fatty-acid oxidation is highly enriched with metabolites whose benign tissue abundances strongly positively associate with CRG, both pre-operatively and long term, whereas in the tumor tissue significant enrichment of dipeptides and benzoate (positive association), glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways, were observed. These data suggest that specific biological processes in the benign as well as in the tumor parenchyma strongly influence compensatory renal growth.


Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells.
Human dental mesenchymal stem cells (MSCs) are considered as highly accessible and attractive MSCs for use in regenerative medicine, yet some of their features are not as well characterized as other MSCs. Hypoxia-preconditioning and hypoxia-inducible factor 1 (HIF-1) alpha overexpression significantly improves MSC therapeutics, but the mechanisms involved are not fully understood. In the present study, we characterize immunomodulatory properties of dental MSCs and determine changes in their ability to modulate adaptive and innate immune populations after HIF-1 alpha overexpression. Human dental MSCs were stably transduced with green fluorescent protein (GFP-MSCs) or GFP-HIF-1 alpha lentivirus vectors (HIF-MSCs). A hypoxic-like metabolic profile was confirmed by mitochondrial and glycolysis stress test. Capacity of HIF-MSCs to modulate T-cell activation, dendritic cell differentiation, monocyte migration, and polarizations towards macrophages and natural killer (NK) cell lytic activity was assessed by a number of functional assays in co-cultures. The expression of relevant factors were determined by polymerase chain reaction (PCR) analysis and enzyme-linked immunosorbent assay (ELISA). While HIF-1 alpha overexpression did not modify the inhibition of T-cell activation by MSCs, HIF-MSCs impaired dendritic cell differentiation more efficiently. In addition, HIF-MSCs showed a tendency to induce higher attraction of monocytes, which differentiate into suppressor macrophages, and exhibited enhanced resistance to NK cell-mediated lysis, which supports the improved therapeutic capacity of HIF-MSCs. HIF-MSCs also displayed a pro-angiogenic profile characterized by increased expression of CXCL12/SDF1 and CCL5/RANTES and complete loss of CXCL10/IP10 transcription. Immunomodulation and expression of trophic factors by dental MSCs make them perfect candidates for cell therapy. Overexpression of HIF-1 alpha enhances these features and increases their resistance to allogenic NK cell lysis and, hence, their potential in vivo lifespan. Our results further support the use of HIF-1 alpha-expressing dental MSCs for cell therapy in tissue injury and immune disorders.


Surface morphology in the ofactory epithelium of normal male and female rhesus monkeys.
Olfactory epithelium of male and female rhesus monkeys has been studied by transmission electron microscopy. It is shown that the epithelial surface differs greatly between male and female monkeys. Differences are most prominent between male and preovulatory females. During the ovulatory phase of the ovarian cycle remarkable histological alterations occur especially in the sustentacular cells. These alterations are correlated with physiological and behavioral phenomena demonstrating a possible structural basis for the changes in olfactory threshold in relation to sex hormones.


Assessing the asymptomatic reservoir and dihydroartemisinin-piperaquine effectiveness in a low transmission setting threatened by artemisinin resistant Plasmodium falciparum.
In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented. A cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014. Plasmodium spp. was assessed with high volume quantitative real-time polymerase chain reaction (qPCR). Plasmodium falciparum-positive samples were screened for mutations in the k13-propeller domain gene. Treatment effectiveness was established after 28 days (D28) using the same qPCR technique. Data from the provincial surveillance system targeting symptomatic cases, supported by Médecins Sans Frontières (MSF), were used to assess incidence. District P. falciparum prevalence was of 0.74 % [0.41; 1.21]; village prevalence ranged from 0 to 4.6 % [1.4; 10.5]. The annual incidence of P. falciparum was 16.8 cases per 1000 inhabitants in the district; village incidence ranged from 1.3 to 54.9 for 1000 inhabitants. Two geographical clusters with high number of cases were identified by both approaches. The marker for artemisinin resistance was found in six samples out of the 11 tested (55 %). 34.9 % of qPCR blood analysis of symptomatic patients were still positive at D28. The overall low prevalence of P. falciparum was confirmed in Chey Saen district in Cambodia, while there were important variations between villages. Symptomatic cases had a different pattern and were likely acquired outside the villages. It illustrates the importance of prevalence surveys in targeting interventions for elimination. Mutations in the k13-propeller domain gene (C580Y), conferring artemisinin resistance, were highly prevalent in both symptomatic and asymptomatic cases (realizing the absolute figures remain low). Asymptomatic individuals could be an additional reservoir for artemisinin resistance. The low effectiveness of dihydroartemisinin-piperaquine (DHA-PPQ) for symptomatic cases indicates that PPQ is no longer able to complement the reduced potency of DHA to treat falciparum malaria and highlights the need for an alternative first-line treatment.


Hydrothermal treatment for TiN as abrasion resistant dental implant coating and its fibroblast response.
Dental implant made of pure titanium (Ti) is prone to scratch and abrasion during routine oral hygiene procedures. This results an increase in surface roughness and therefore, facilitates the adhesion of bacteria. In severe cases, this could lead to peri-implantitis. To overcome this problem, surface modification of Ti is necessary to improve its abrasion resistance. Besides, a strong implant-gingiva interface should also be guaranteed to prevent the adhesion of bacteria. In this study, titanium nitride (TiN) coating was first prepared with gas nitriding to increase surface hardness of pure the substrate. Then, the TiN was hydrothermally treated in CaCl2 solution in order to improve its soft tissue biocompatibility. The effect of hydrothermal treatment temperature on surface properties of TiN was investigated and its biocompatibility was assessed in vitro using NIH3T3 fibroblast cell. It was determined that 120°C was the critical temperature for the hydrothermal treatment condition. Treatment below 120°C could incorporate Ca into TiN surface, oxidize TiN surface partially and then improve the wettability while preserving its morphology and hardness. Fibroblast cell attachment and proliferation were improved and cell spreading was enhanced on hydrothermally treated specimens compared with untreated ones. Improved wettability, Ca incorporation and negative surface due to interstitial N were believed to be the main reasons. Hydrothermal treatment is expected to make TiN a promising dental implant coating with excellent abrasion resistance and good soft tissue affinity.


Key Parameters for the Rational Design, Synthesis, and Functionalization of Biocompatible Mesoporous Silica Nanoparticles.
Over the last few years, research on silica nanoparticles has rapidly increased. Particularly on mesoporous silica nanoparticles (MSNs), as nanocarriers for the treatment of various diseases because of their physicochemical properties and biocompatibility. The use of MSNs combined with therapeutic agents can provide better encapsulation and effective delivery. MSNs as nanocarriers might also be a promising tool to lower the therapeutic dosage levels and thereby to reduce undesired side effects. Researchers have explored several routes to conjugate both imaging and therapeutic agents onto MSNs, thus expanding their potential as theranostic platforms, in order to allow for the early diagnosis and treatment of diseases. This review introduces a general overview of recent advances in the field of silica nanoparticles. In particular, the review tackles the fundamental aspects of silicate materials, including a historical presentation to new silicates and then focusing on the key parameters that govern the tailored synthesis of functional MSNs. Finally, the biomedical applications of MSNs are briefly revised, along with their biocompatibility, biodistribution and degradation. This review aims to provide the reader with the tools for a rational design of biocompatible MSNs for their application in the biomedical field. Particular attention is paid to the role that the synthesis conditions have on the physicochemical properties of the resulting MSNs, which, in turn, will determine their pharmacological behavior. Several recent examples are highlighted to stress the potential that MSNs hold as drug delivery systems, for biomedical imaging, as vaccine adjuvants and as theragnostic agents.


Association of Baseline Viral Serology and Sirolimus Regimens With Kidney Transplant Outcomes: A 14-Year Registry-Based Cohort Study in the United States.
The risks for transplant outcomes associated with baseline viral serostatus in kidney transplant recipients (KTR) on sirolimus have not been widely studied. We performed a cohort-study of 61 590 adult KTR in 2000 to 2013. We used Cox regression models to determine the adjusted hazard ratio (aHR) of patient death, death-censored graft loss and posttransplant malignancy associated with the baseline serostatus (+ or -: hepatitis B core [HBc], hepatitis C virus [HCV], Epstein-Barr virus [EBV], or cytomegalovirus [CMV]) in KTR on sirolimus (SRL) + mycophenolate (MPA) or SRL + tacrolimus (Tac), relative to the control-regimen: Tac + MPA. Compared with Tac + MPA, SRL + MPA, and SRL + Tac were associated with higher risks of 5-year mortality (aHR, 1.41; 95% CI, 1.23-1.60 and aHR, 1.59; 95% CI, 1.38-1.83, respectively) and death-censored graft loss (aHR, 1.41; 95% CI, 1.24-1.60 and aHR, 1.38; 95% CI, 1.21-1.57, respectively). In KTR with negative pretransplant EBV, CMV, HBc, or HCV serostatus, SRL + MPA not SRL + Tac was associated with a lower risk of posttransplant malignancy compared with control (aHR, 0.27; 95% CI, 0.10-0.72; aHR, 0.61; 95% CI, 0.43-0.88; aHR, 0.79; 95% CI, 0.64-0.97; and aHR, 0.80; 95% CI, 0.65-0.98, respectively, for SRL + MPA and aHR, 0.98: 95% CI, 0.52-1.80; aHR, 0.69; 95% CI, 0.46-1.06; aHR, 0.83; 95% CI, 0.66-1.06 and aHR, 0.85; 95% CI, 0.67-1.07, respectively, for SRL + Tac). In KTR with positive serostatus to any of the above viruses, SRL + MPA or SRL + Tac was not associated with a different malignancy risk compared with control. Compared with Tac + MPA, SRL regimens were associated with higher risks for patient death and graft loss, although SRL + MPA was associated with a lower risk for posttransplant malignancy in kidney allograft recipients with negative pretransplant HBc, HCV, EBV, or CMV serology.


Interleukin 4 improved adipose-derived stem cells engraftment via interacting with fibro/adipogenic progenitors in dystrophic mice.
Adipose-derived stem cells (ADSC) therapy shows promise as an effective treatment for dystrophinopathy. Fibro-/adipogenic progenitors (FAPs) play an essential role in the myogenesis of muscle satellite cells and contribute to muscle fibrosis and adipocyte infiltration. The interleukin 4 (IL-4) pathway acts as a switch that regulates the functions of FAPs. The interaction between FAPs and engrafted cells remains unclear. In this study, we used a co-culture system to investigate possible crosstalk between the FAPs of dystrophic mice and ADSC overexpressing IL4 (IL4-ADSC) and control ADSC. Systemic transplantation of IL4-ADSC and control ADSC in dystrophic mice was conducted for 16 weeks, after which motor function and molecular improvements were evaluated. Overexpression of IL4 in ADSC significantly promoted myogenesis in vitro, increasing the expression of Pax7, Myogenin, and MyHC. Co-culture indicated that although myoblasts derived from control ADSC promoted adipogenic and fibrogenic differentiation of FAPs, FAPs did not significantly affect myogenesis of ADSC-derived myoblasts. However, overexpression of IL4 in ADSC inhibited their myotube-dependent promotion of FAPs differentiation on the one hand and promoted FAPs to enhance myogenesis on the other. Dystrophic mice administered with IL4-ADSC-derived myoblasts displayed significantly better motor ability, more engrafted cells showing dystrophin expression, and less muscle fibrosis, intramuscular adipocytes, and macrophage infiltration than mice administered control-ADSC-derived myoblasts. In conclusion, IL4 activation enhanced the therapeutic potential of ADSC transplantation in dystrophic mice, possibly by improving the myogenesis of IL4-ADSC and altering the crosstalk between engrafted stem cells and resident FAPs.


A peer-based substance abuse intervention for HIV+ rural women: a pilot study.
Alcohol and other drug (AOD) use plays a major role in the acquisition and spread of HIV, and the majority of women living with HIV are either active or recovering drug users. Forty-six percent of women's cases of HIV infection have been attributed to injection-drug use and 18% to women's heterosexual contacts with injection-drug users. Substance abuse often contributes to noncompliance with HIV treatment. Individuals with multiple diagnoses, such as those with HIV and substance abuse, may not be able to withstand the burden of integrating the different clinical approaches used to treat their substance abuse and other comorbid disorders such as HIV. This article reports the results of an intervention pilot study testing a peer counseling intervention for substance abuse in rural women with HIV. Thirteen women completed the intervention. Although limited by sample size, results suggest that this intervention was effective in helping women to acknowledge problems with their alcohol and drug abuse and to begin taking steps to achieve sobriety.


Sending people to care homes in lower-income countries: A qualified defence.
In recent years, a proportion of older Germans has been sent to relatively high-end care homes within lower-income countries where the care tends to be cheaper and more extensive than that in German care homes. Destination countries are found predominantly within Eastern Europe (e.g. Poland, Hungary, Czech Republic), but to a lesser extent also within South-East Asia (e.g. Thailand). At the same time, these expatriations have caused much controversy, with some German commentators calling them 'inhumane' and 'shameful'. In this article, I argue that such criticisms are overdrawn. Although sending an older individual to a care home within a lower-income country can be morally impermissible, I find that there are at least three sets of conditions under which it is not.


Meta-Analysis for Social Support Degree of Kidney Transplant Recipients: Evidence from China.
Social support refers to the subjective and (or) objective influence of various social relationships on individuals, which has a certain influence on the negative emotions of the kidney transplant patients. But there are still significant differences among various studies, so we performed a meta-analysis to analyze the social support degree of kidney transplant recipients. This article searched and selected the relevant cross-sectional surveys from PubMed, Embase, VIP, CNKI, Wanfang, and CBM databases according to the inclusion and exclusion criteria and used the STROBE list combined with the observational research quality evaluation tools of Sanderson to conduct the quality appraisal. The "meta" and "metaphor" packages of the R software version 3.5.1 were used for the meta-analysis. A total of 17 studies with 2697 patients were included. The total scores of the social support and objective support of the renal transplant patients were abundant after the operation, indicating that the economic, physical, and emotional supports from the family, society, and the official organization are accepted. But the subjective support and support utilization degree were general. The support utilization was different among different genders, and female patients were lower than the males. In particular, the female patients relatively presented autism and the social support utilization degree was low. Medical staffs are needed to join the family, hospital, and society to create favorable conditions and improve the social support system and the utilization degree of the social support, thereby promoting the physical and mental health development of the patients.


Isoforms of Acyl-CoA:Diacylglycerol Acyltransferase2 Differ Substantially in Their Specificities toward Erucic Acid.
In most oilseeds, two evolutionarily unrelated acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes, DGAT1 and DGAT2, are the main contributors to the acylation of diacylglycerols in the synthesis of triacylglycerol. DGAT1 and DGAT2 are both present in the important crop oilseed rape (Brassica napus), with each type having four isoforms. We studied the activities of DGAT isoforms during seed development in microsomal fractions from two oilseed rape cultivars: edible, low-erucic acid (22:1) MONOLIT and nonedible high-erucic acid MAPLUS. Whereas the specific activities of DGATs were similar with most of the tested acyl-CoA substrates in both cultivars, MAPLUS had 6- to 14-fold higher activity with 22:1-CoA than did MONOLIT. Thus, DGAT isoforms with different acyl-CoA specificities are differentially active in the two cultivars. We characterized the acyl-CoA specificities of all DGAT isoforms in oilseed rape in the microsomal fractions of yeast cells heterologously expressing these enzymes. All four DGAT1 isoforms showed similar and broad acyl-CoA specificities. However, DGAT2 isoforms had much narrower acyl-CoA specificities: two DGAT2 isoforms were highly active with 22:1-CoA, while the ability of the other two isoforms to use this substrate was impaired. These findings elucidate the importance, which a DGAT isoform with suitable acyl-CoA specificity may have, when aiming for high content of a particular fatty acid in plant triacylglycerol reservoirs.


Ultrastructure and distribution of the taste buds in the buccal cavity in relation to the food and feeding habit of a herbivorous fish: Oreochromis niloticus.
The buccal cavity of an herbivorous fish Oreochromis niloticus was investigated by means of scanning electron microscopy. The buccal cavity distinguished into the roof and the floor. Three different types of taste buds (type I, II and III) are distributed in the buccal cavity. The proximal part of the buccal cavity bears relatively high epidermal papillae in which type I TBs was found. The middle region of the buccal cavity is mostly occupied by low epidermal papillae containing type II TBs. Type III TBs which are present within the metabranchial buccal cavity; never rise above the normal level of the epithelium. The different types of TBs are useful for ensuring full utilization of the gustatory ability of the fish. It is postulated that the TBs serve different functions: TBs type I and II may act as chemoreceptors and mechanoreceptors. TBs type III acts predominantly as a chemoreceptors. TBs of each type show two kinds of receptor villi within their receptor areas: tall villi and small villi. The surface of the lining epithelial cells shows a delicate microridge system. These structures protect against physical abrasion potentially caused during food maneuvering and swallowing. Furthermore, protection of the epithelium from abrasion is enhanced with goblet cells secretion.


Ghost Ileostomy in Anterior Resection for Bowel Endometriosis: Technical Description.
To demonstrate our application of the ghost ileostomy in the setting of laparoscopic segmental bowel resection for symptomatic bowel endometriosis nodule. Technical step-by-step surgical video description (educative video) SETTING: University Tertiary Hospital. Institutional Review Board ruled that approval was not required for this study. Endometriosis affects the bowel in 3% to 37% of all cases, and in 90% of these cases, the rectum or sigmoid colon is also involved. Infiltration up to the rectal mucosa and invasion of >50% of the circumference have been suggested as an indication for bowel resection [1]. Apart from general risks (bleeding, infection, direct organ injuries) and bowel and bladder dysfunctions, anastomotic leakage is one of the most severe complications. In women with bowel and vaginal mucosa endometriosis involvement, there is a risk of rectovaginal fistula after concomitant rectum and vagina resections. Hence, for lower colorectal anastomosis, the use of temporary protective ileostomy is usually recommended to prevent these complications but carries on stoma-related risks, such as hernia, retraction, dehydration, prolapse, and necrosis. Ghost ileostomy is a specific technique, first described in 2010, that gives an easy and safe option to prevent anastomotic leakage with maximum preservation of the patient's quality of life [2]. In case of anastomotic leakage, the ghost (or virtual) ileostomy is converted, under local anesthesia, into a loop (real) ileostomy by extracting the isolated loop through an adequate abdominal wall opening. In principle, avoiding readmission for performing the closure of the ileostomy, with all the costs related, means a considerable saving for the hospital management. Also, applying a protective rectal tube in intestinal anastomosis may have a beneficial effect [3]. These options are performed by general surgeons in oncological scenarios, but their use in endometriosis has never been described. In a 32-year-old woman with intense dysmenorrhea, deep dyspareunia, dyschesia, and cyclic rectal bleeding, a complete laparoscopic approach was performed using blunt and sharp dissection with cold scissors, bipolar dissector and a 5-mm LigaSure Advance (Covidien, Valley lab, Norwalk, Connecticut). An extensive adhesiolysis restoring the pelvic anatomy and endometriosis excision was done. Afterward, the segmental bowel resection was performed using linear and circular endo-anal stapler technique with immediate end-to-end bowel anastomosis and transit reconstitution. Once anastomosis was done, the terminal ileal loop was identified, and a window was made in the adjacent mesentery. Then, an elastic tape (vessel loop) was passed around the ileal loop, brought out of the abdomen through the right iliac fossa 5-mm port site incision and, fixed to the abdominal wall using nonabsorbable stitches. Finally, a trans-anal tube was placed for 5 days. The patient was discharged on the fifth day postoperatively without any complications. The tape was removed 10 days after surgery, and the loop dropped back. Two months after the intervention, the patient remains asymptomatic. Ghost ileostomy is a simple, safe, and feasible technique available in the setting of lower colorectal anastomosis following bowel endometriosis resection.


Genetic polymorphism of tetrazolium oxidase in dogs.
Two alleles, To(A) and To(B), determine a genetic polymorphism of tetrazolium oxidase in canine erythrocytes. The approximate gene frequencies for most dog breeds are 0.94 for To(A) and 0.06 for To(B). The gene frequencies' of the German shepherd, 0.8 for To(A) and 0.2 for To(B), differ significantly from those of other breeds. The electrophoretic tetrazolium oxidase isozyme pattern of Canis latrans closely resembles the tetrazolium oxidase A pattern of Canis familiaris.


The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes.
Lipid peroxidation in rat liver microsomes induced by asbestos fibres, crocidolite and chrysotile, is greatly increased in the presence of NADPH, leading to malondialdehyde levels comparable with those induced by CCl4, a very strong inducer of lipid peroxidation. This synergic effect only occurs during the first minutes and could be explained by an increase or a regeneration of the ferrous active sites of asbestos by NADPH, which in turn could rapidly be prevented by the adsorption of microsomal proteins on the surface of the fibres. It is not inhibited by superoxide dismutase, catalase and mannitol, indicating that oxygen radicals are not involved in the reaction. It is also not inhibited by desferrioxamine, indicating that it is not due to a release of free iron ions in solution from the fibres. Lipid peroxidation in NADPH-supplemented microsomes is also greatly increased upon addition of magnetite. This could be linked to the presence of ferrous ions in this solid iron oxide, since the ferric oxides haematite and goethite are completely inactive.


An acute care surgery rotation contributes significant general surgical operative volume to residency training compared with other rotations.
Surgical resident rotations on trauma services are criticized for little operative experience and heavy workloads. This has resulted in diminished interest in trauma surgery among surgical residents. Acute care surgery (ACS) combines trauma and emergency/elective general surgery, enhancing operative volume and balancing operative and nonoperative effort. We hypothesize that a mature ACS service provides significant operative experience. A retrospective review was performed of ACGME case logs of 14 graduates from a major, academic, Level I trauma center program during a 3-year period. Residency Review Committee index case volumes during the fourth and fifth years of postgraduate training (PGY-4 and PGY-5) ACS rotations were compared with other service rotations: in total and per resident week on service. Ten thousand six hundred fifty-four cases were analyzed for 14 graduates. Mean cases per resident was 432 ± 57 in PGY-4, 330 ± 40 in PGY-5, and 761 ± 67 for both years combined. Mean case volume on ACS for both years was 273 ± 44, which represented 35.8% (273 of 761) of the total experience and exceeded all other services. Residents averaged 8.9 cases per week on the ACS service, which exceeded all other services except private general surgery, gastrointestinal/minimally invasive surgery, and pediatric surgery rotations. Disproportionately more head/neck, small and large intestine, gastric, spleen, laparotomy, and hernia cases occurred on ACS than on other services. Residents gain a large operative experience on ACS. An ACS model is viable in training, provides valuable operative experience, and should not be considered a drain on resident effort. Valuable ACS rotation experiences as a resident may encourage graduates to pursue ACS as a career.


Effect of COVID-19-related lockdown on ophthalmic practice in Italy: A report from 39 institutional centers.
To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value <0.05 was considered significant. A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65-0.80 and 0.61-0.75, respectively, p < 0.001 for both). This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.


The effects in vitro of hypoglycaemia and recovery from anoxia on synaptosomal metabolism.
Synaptosomes from several regions of the rat brain were found to exhibit half-maximal rates of 14CO2 output and [14C]acetylcholine synthesis from D-[U-14C]glucose at glucose concentrations approx. 50-fold lower than those required by the brain in situ. However, synaptosomal acetylcholine synthesis was found not to be directly proportional to substrate oxidation as measured by 14CO2 output. When synaptosomes had been exposed to anoxia in vitro, their metabolic indices (14CO2 and [14C]acetylcholine synthesis, and adenine nucleotide levels) were found not to be significantly different from control aerobic values, unless they had been subjected to veratridine depolarization. This is in accord with previous findings that neither the absolute metabolic rates nor the vulnerability to hypoxic damage exhibited by brain in situ is reflected by brain slices in vitro, unless these are stimulated by depolarization. The use of synaptosomes as a model for synaptic damage in vivo is discussed.


Salvage of acetabular insufficiency with cementless components.
In conclusion, it appears that large outside-diameter bipolar devices or threaded, cement-free acetabular components (with or without porous surfaces) provide excellent hip stability when used to salvage hips with acetabular insufficiency. The bipolar or threaded devices can maintain or restore normal or nearly normal hip mechanics, minimize pain by preventing motion between the cup and the bone, and permit fill-in of bony defects and healing of nonunited fractures. Both grafting should be used whenever possible, since it may prevent medial migration and allow for replacement with a cemented or cementless porous-surfaced cup in the future should pain occur. A cane or crutch should be used to minimize stress across the joint and thereby prolong the life of the reconstruction. All patients must realize that these are salvage procedures.