Comparison between transport and degradation of leucine and glutamine by peripheral human lymphocytes exposed to concanavalin A.
Transport and pathways of leucine and glutamine degradation were evaluated in resting human peripheral lymphocytes and compared with the changes induced by concanavalin A (ConA). Cells were incubated with [1-14C]leucine (0.15 mM), [U-14C]leucine (0.15 mM), or [U-14C]glutamine (0.4 mM) after culture with or without 2, 5, 7, or 10 micrograms/ml ConA for 2, 18, or 24 hours, respectively. Initial rates of transport of leucine and glutamine were augmented 2.7-fold and threefold by the mitogen. Leucine transamination, irreversible oxidation, and catabolism beyond isovaleryl-CoA were increased by 90%, 20%, and 60%, respectively. Glutamine utilization increased threefold; accumulation of glutamate, aspartate, and ammonia increased by 700%, 50%, and 100%, respectively, and 14CO2 production by about 400% in response to ConA. The results indicate that ConA stimulates to about the same extent transport of leucine and glutamine into lymphocytes. Glutamine is mainly channeled into catabolic pathways, while leucine remains largely preserved. It is suggested that these metabolic changes provide more leucine for incorporation into protein and more N- and C-atoms required for the synthesis of macromolecules and energy from glutamine.


Changes of the bone structure after cap resurfacing arthroplasty of the humeral head.
Although humeral head resurfacing with a cap is relatively common in clinical practice, clinical studies about the changes of the bone are rare. The aim of this study was to analyse qualitative and quantitative changes of the bone after cup arthroplasty. Our hypothesis is that the implant leads to a new functional load with remarkable changes of the bone underneath the cap. Overall, 12 explanted caps with adherent bone tissues, retrieved at the revision surgery, were collected for histological examination. None of these implants were revised for loosening. Afterwards, there was a qualitative evaluation of the bone as well an assessment of established quantitative bone tissue parameters. Results were analyzed in correlation to the time to revision surgery, as well as to patient's age. A significant decrease of the bone volume and trabecular architecture underneath the cap was already observed after a relatively short lifetime. The quantitatively measured bone loss does not depend on the patient's age, but correlates significantly with the lifetime of the implants. In contrast to these findings within the central areas, an increased bone remodeling with bone densifications and microcallus formations was noticed at the edge of the cap in most cases. A significant reduction of the bone volume underneath the cap and remarkable changes of the trabecular architecture confirm our hypothesis. Even if these changes did not lead to a clinically relevant loosening in our series, they might influence revision surgeries. Thus, these findings might be of interest, especially when a non-stemmed reversed or anatomical revision arthroplasty with a central metaphyseal press-fit fixation is chosen. IV - retrospective or historical series.


Laryngeal adenosquamous carcinoma: A population-based perspective.
Adenosquamous carcinoma (ASC) is a rare entity, with fewer than 100 cases having been reported in the upper aerodigestive tract. Thus, no large samples characterizing its clinical behavior are available in the literature. Investigation of ASC has been further limited by difficulty in establishing histopathologic diagnosis. Our objective was to use a national population-based resource to evaluate patient demographics, clinical behavior, incidence, and survival for laryngeal adenosquamous carcinoma (LASC). Retrospective population-based analysis. The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to search for patients diagnosed with LASC between 1973 and 2012. Patient demographics, tumor characteristics, incidence, and survival trends were analyzed. Of the 68 identified LASC patients, 79.4% were male and 20.6% were female. The mean age at diagnosis was 66.0 ± 10.8 years. Whites represented 80.9% of patients, but no racial predominance was noted. LASC most commonly affected the glottis (47.1%), followed closely by the supraglottis (42.6%). Most cases were poorly differentiated (59.2%) and presented with stage IV disease (40.7%). Metastasis (M1) was noted in 10.7% of cases. The overall incidence was 0.003/100,000. The 5-year disease-specific survival rate was 36.6%, with a median observed survival of 33.6 months. This study notes that LASC has low overall incidence. It has a predilection for males, but does not demonstrate racial predominance. LASC tends to present with stage IV disease, with distant metastasis noted in approximately one in 10 cases. Overall prognosis is poor, with a median survival under 3 years. 4.


Extending the event calculus for tracking epidemic spread.
The email reporting system has been recognized as a key tool for early warning of disease outbreaks and surveillance of emerging diseases. The aim of the work reported here was to develop a formal language for building an event-centered representation of outbreak histories, described by outbreak reports, which could be used for tracking the spread of epidemics. The SpatioTemporal Extended Event Language (STEEL) we have built is an extension of the Event Calculus that is based on joint spatial and temporal location of event occurrences and structured conglomeration of events. This language allows us to represent and build aggregates of events, according to their spatiotemporal location. In a proof of concept study, this language was implemented in Prolog. A trial corpus of 35 outbreak reports from a PROMED-Mail diffusion list was hand coded in an experimental implementation of STEEL. The performances of this language were compared with three human experts during a question and answer task on this corpus. The experiment showed agreement between responses of the experts and the system. STEEL ensures the spatial and temporal location of event occurrence. The resulting representation is very close to the narrative. Further work must be made to develop a system capable of automatically modeling outbreak reports.


Interferon production potentials of various human lymphoblastoid cell lines.
A number of human lymphoblastoid cells were examined concerning their ability to produce spontaneously liberated and virus-induced interferon (IFN). It was found that, in addition to B cells, various T and nonT-nonB lymphoblastoid cells responded well to Sendai virus infection to form IFN, the characterization of which has been recently reported (20). One B lymphoblastoid cell line from an infectious mononucleosis (IM) patient produced a large amount of IFN-alpha and might become an alternative source of IFN production. Among 68 cell lines examined, 35 cell lines liberated 10 U/ml or more of IFN spontaneously in culture fluid. The presence of Epstein-Barr virus (EBV) genome or its activation appears to have no correlation with the spontaneous liberation of IFN. Spontaneously produced IFN from three cell lines was characterized as IFN-alpha. Comparatively higher amounts of IFN were produced in cells from IM patients than those from Burkitt's lymphoma cases or healthy adults. Spontaneously produced IFN was detected more easily in cells transformed by EBV alone than in those transformed by EBV and a tumor promoter, TPA.


Association between rheumatoid factor and metabolic syndrome in general population.
Rheumatoid arthritis, metabolic syndrome (MS) and cardiovascular disease (CVD) are mutually connected. We aim to investigate the association between rheumatoid factor (RF) and MS in general population, explore the potential value of RF for assessment of metabolic status, and further provide a reference to the establishment of CVD primary prevention for this population. We assessed the health check-up subjects, accordance with the inclusive criteria, from 1 January 2015 to 31 October 2021 in a large refereed general hospital, in this retrospective study. Subjects were categorized into four groups according to their levels of RF. Multivariate logistic regression models along with the Odds ratio (OR) and Confidence interval (CI) values were used to measure the association between RF and MS. A total of 13,690 subjects were analyzed. Prevalence of MS increased with RF level (P for trend < 0.001). Logistic regression analysis showed that, after adjusting for multiple covariates, RF level was significantly associated with MS prevalence (highest RF quartile: OR, 1.420; 95% CI 1.275,1.581, according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria; OR, 2.355; 95% CI 2.085,2.660, according to the International Diabetes Federation criteria) (both P for trends < 0.001). Among the MS components, there were evidence of increasing trends for overweight/obesity (highest RF quartile: OR, 3.165; 95% CI 2.827,3.543) and hypertension (highest RF quartile: OR, 1.722; 95% CI 1.549,1.914) (both P for trends < 0.001), but decreasing trend for low high-density lipoprotein-cholesterol (highest RF quartile: OR, 0.245; 95% CI 0.214,0.281) (P for trend < 0.001), with increasing RF quartiles. RF level is associated with MS prevalence in general population. RF might be a valuable biomarker for assessment of metabolic status in this population. We should be aware of the cardiovascular risk for the higher-RF subjects.


Expression, purification and characterization of recombinant mouse translation initiation factor eIF4E as a dihydrofolate reductase (DHFR) fusion protein.
One of the earliest steps in translation initiation is recognition of the mRNA cap structure (m7GpppX) by the initiation factor eIF4E. Studies of interactions between purified eIF4E and its binding partners provide important information for understanding mechanisms underlying translational control in normal and cancer cells. Numerous impediments of the available methods used for eIF4E purification led us to develop a novel methodology for obtaining fractions of eIF4E free from undesired by-products. Herein we report methods for bacterial expression of eIF4E tagged with mutant dihydrofolate reductase (DHFR) followed by isolation and purification of the DHFR-eIF4E protein by using affinity and anion exchange chromatography. Fluorescence quenching experiments indicated the cap-analog, 7MeGTP, bound to DHFR-eIF4E and eIF4E with a dissociation constant (K(d)) of 6+/-5 and 10+/-3 nM, respectively. Recombinant eIF4E and DHFR-eIF4E were both shown to significantly enhance in vitro translation in dose dependent manner by 75% at 0.5 microM. Nevertheless increased concentrations of eIF4E and DHFR-eIF4E significantly inhibited translation in a dose dependent manner by a maximum at 2 microM of 60% and 90%, respectively. Thus, we have demonstrated that we have developed an expression system for fully functional recombinant eIF4E. We have also shown that the fusion protein DHFR-eIF4E is functional and thus may be useful for cell based affinity tag studies with fluorescently labeled trimethoprim analogs.


Nuclear Notch3 expression is associated with tumor recurrence in patients with stage II and III colorectal cancer.
The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics. The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated. Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06-2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44-9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41-4.40; P = 0.0019). Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.


Statistical methods and resources for biomarker discovery using metabolomics.
Metabolomics is a dynamic tool for elucidating biochemical changes in human health and disease. Metabolic profiles provide a close insight into physiological states and are highly volatile to genetic and environmental perturbations. Variation in metabolic profiles can inform mechanisms of pathology, providing potential biomarkers for diagnosis and assessment of the risk of contracting a disease. With the advancement of high-throughput technologies, large-scale metabolomics data sources have become abundant. As such, careful statistical analysis of intricate metabolomics data is essential for deriving relevant and robust results that can be deployed in real-life clinical settings. Multiple tools have been developed for both data analysis and interpretations. In this review, we survey statistical approaches and corresponding statistical tools that are available for discovery of biomarkers using metabolomics.


Coping strategies moderate the relation of hypothalamus-pituitary-adrenal axis reactivity to self-injurious behavior.
An alarming proportion of adolescents engage in purposefully self-injurious behavior (SIB). SIB is a maladaptive strategy for coping with extreme tension generated in response to stress, particularly interpersonal stress. This study investigated the relation of older adolescents' SIB to the reactivity of the body's major physiological system for responding to stress, the hypothalamus-pituitary-adrenal (HPA) axis, after interpersonal stress. Adolescents' behavioral, cognitive, and emotional coping strategies were shown to alter the relation between SIB and HPA reactivity after conflict with a romantic partner.


Predictive Models for the Functional Recovery of Transplanted Kidney.
Renal transplantation is the gold standard treatment for end-stage renal disease, however, in 20% of cases, the graft develops a delayed graft function (DGF) that is associated with both early and late worsening of the outcome. The aim of this study was to examine and validate in a population of transplanted patients the appropriateness of the predictive score systems of DGF available to identify patients who might take advantage of a tailored immunosuppressive therapy. We conducted a systematic review of the literature to identify articles concerning scoring systems predicting DGF to identify those applicable to the study population and subsequently comparing their appropriateness for defining the most accurate one. From an analysis of the scientific literature, we found 7 scoring systems predicting DGF. Of these, 3 can be calculated for the study population. We enrolled 247 renal transplants in the study. DGF was recorded in 41 cases (15.95%). The Irish score recognized 25 of 41 cases (60.98%), the Jeldres score 41 of 41 cases (100%), and the Chapal score only 7 of 41 (17.07%). Although the Irish score did not identify all cases of DGF, the analysis of data revealed that it is the most accurate, with area under the receiver operating characteristic almost overlapping. The study resulted in some interesting and promising conclusions about the predictability of DGF, defining the Irish score as the most reliable. This result can be considered the fundamental requirement to develop a custom therapeutic algorithm to be applied to all recipients with higher probability of developing DGF.


Surgery or external beam radiation for solitary small hepatocellular carcinoma.
There is little evidence on the efficacy of external beam radiation (EBR) compared to liver resection (LR) for patients with solitary small (≤5 cm) hepatocellular carcinoma (HCC). We aimed to investigate this clinical question based on the Surveillance, Epidemiology, and End Results (SEER) database. SEER database was used to identify 416 patients with solitary small HCC who underwent LR or EBR. Survival analysis and Cox proportional hazards model were performed to evaluate overall survival (OS) and identify prognostic factors for OS. Propensity score matching (PSM) method was used to adjust the baseline characteristics of the two groups. Before PSM, the 1- and 2-year OS rates were 92.0% and 85.2% in the LR cohort and 76.0% and 60.3% in the EBR cohort, respectively (P < 0.001). After PSM, LR (n = 62) demonstrated improved OS compared to EBR (n = 62) (1-year OS rate: 96.5% vs. 76.0%; 2-year OS rate: 89.3% vs. 60.3%, P < 0.001), despite stratification on tumor size. Multivariate Cox regression analysis indicated that treatment type was the only factor associated with OS (hazard ratio: 5.297; 95% confidence interval: 1.952-14.371, P = 0.001). For patients with solitary small HCC, LR may offer better survival outcomes than EBR.


Central control of lactogenic receptors in liver membranes: effect of hypothalamic deafferentation.
The regulation by the central nervous system of a lactogenic receptor, present in the rat liver, was studied. The receptor, which is present in very low concentration or absent in the male rat, can be induced by anterior hypothalamic deafferentation, resulting in a typically female level of the receptor in lesioned male animals. Our observations indicate an important role of the brain in regulation of peripheral lactogenic receptors.


Organocatalytic enantioselective pyrazol-3-one addition to maleimides: reactivity and stereochemical course.
The enantioselective synthesis of pyrazol-3-ones has not been extensively studied in organic synthesis. Here in we report the first asymmetric addition of pyrazolones to maleimides catalyzed by bifunctional thiourea catalysts.


Soft and flexible: core-shell ionic liquid resistive memory for electronic synapses.
The human brain is the most efficient computational and intelligent system, and researchers are trying to mimic the human brain using solid-state materials. However, the use of solid-state materials has a limitation due to the movement of neurotransmitters. Hence, soft memory devices are receiving tremendous attention for smooth neurotransmission due to the ion concentration polarization mechanism. This paper proposes a core-shell soft ionic liquid (IL)-resistive memory device for electronic synapses using Cu/Ag@AgCl/Cu with multistate resistive behavior. The presence of the Ag@AgCl core shell in the liquid electrolyte significantly helps to control the movement of Cu2+ ions, which results in multistate resistive switching behavior. The core-shell IL soft memory device can open a gateway for electronic synapses.


Best (but often forgotten) Statistical Practices: Measuring Real-World Intervention Effectiveness using Electronic Health Data.
The evidence base supporting the use of most interventions consists primarily of data from randomized controlled trials (RCTs), but how and to whom interventions are delivered in clinical practice may differ substantially from these foundational RCTs. With the increasing availability of electronic health data, it is now feasible to study the "real-world" effectiveness of a wide range of interventions. However, real-world intervention effectiveness studies using electronic health data face many challenges including data quality, selection bias, confounding by indication, and lack of generalizability. In this article, we describe the key barriers to generating high-quality evidence from real-world intervention effectiveness studies and suggest statistical best practices for addressing them.


Strategies to improve DNA polyplexes for in vivo gene transfer: will "artificial viruses" be the answer?
For the purpose of introducing nucleic acids into cells, cationic polymers have been steadily improved as gene carriers. This has resulted in improved polymer-based gene transfer formulations, termed polyplexes, which efficiently transfect cell cultures and also have shown encouraging gene transfer potential in in vivo administration. Targeted delivery to liver, lung, tumor, or other tissues has been achieved in experimental animals by localized or systemic application. Therapeutic effect has been demonstrated, although efficiencies are still too low to justify clinical use. The limitations of first-generation polymeric carriers (modest activity and significant toxicity) have been addressed by developments of new biodegradable polycations, incorporation of targeting and intracellular transport functions, and polyplex formulations that avoid unspecific adverse interactions with the host. A key future step will be the development of polyplexes into artificial viruses, with virus-like entry functions presented by smart polymers and polymer conjugates. These polymers have to sense their biologic microenvironment, respond in a more dynamic manner to alterations in pH, ionic or redox environment, undergoing programmed structural changes compatible with the different gene delivery steps.


Metal-free anomalous [5+1] cycloaddition reactions of donor-acceptor aziridines for the synthesis of 2H-1,4-oxazines.
A new type of metal-free [5+1] cycloaddition reaction of donor-acceptor aziridines with 2-(2-isocyanoethyl)indoles is reported herein. This method exhibits broad substrate scope and atom-economy. A series of 2H-1,4-oxazines containing an indole heterocycle skeleton were obtained in up to 92% yield under mild reaction conditions. Control experiments revealed that free indole N-H is crucial for the above transformations. The theoretical calculation studies provided guidance on the in-depth insight into the reaction mechanism and the hydrogen-bond between the free indole N-H and carbonyl group was identified to lower the free energy barrier in the transition states.


Comparison of effects of aldosterone receptor antagonists spironolactone and eplerenone on cardiovascular outcomes and safety in patients with acute decompensated heart failure.
Differences in the clinical impacts of the aldosterone receptor antagonists spironolactone and eplerenone in patients with heart failure (HF) are unclear. Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with eplerenone were compared with 90 treated with spironolactone. The primary endpoint was a composite of cardiovascular death and hospitalization. A serial evaluation of the clinical parameters was performed 1 year after discharge. The mean dose of spironolactone was 27 ± 8 mg and of eplerenone was 34 ± 15 mg. During follow-up (mean 594 ± 317 days), primary endpoints occurred in 27 patients in the eplerenone group (30.0%) and 25 patients in the spironolactone group (27.8%). There were no significant intergroup differences in the primary endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated glomerular filtration rate did not differ significantly between groups. Although gynecomastia in men was common in the spironolactone group (p = 0.018), the discontinuation rates due to adverse events were similar in the two groups (p = 0.135). Subgroup analyses suggested that eplerenone was associated with a lower hazard rate of the primary endpoint in female patients (interaction, p = 0.076). Among patients with HF, eplerenone and spironolactone have similar impacts on cardiovascular outcomes and safety.


Chemical activation of divergent protein tyrosine phosphatase domains with cyanine-based biarsenicals.
Strategies for the direct chemical activation of specific signaling proteins could provide powerful tools for interrogating cellular signal transduction. However, targeted protein activation is chemically challenging, and few broadly applicable activation strategies for signaling enzymes have been developed. Here we report that classical protein tyrosine phosphatase (PTP) domains from multiple subfamilies can be systematically sensitized to target-specific activation by the cyanine-based biarsenical compounds AsCy3 and AsCy5. Engineering of the activatable PTPs (actPTPs) is achieved by the introduction of three cysteine residues within a conserved loop of the PTP domain, and the positions of the sensitizing mutations are readily identifiable from primary sequence alignments. In the current study we have generated and characterized actPTP domains from three different subfamilies of both receptor and non-receptor PTPs. Biarsenical-induced stimulation of the actPTPs is rapid and dose-dependent, and is operative with both purified enzymes and complex proteomic mixtures. Our results suggest that a substantial fraction of the classical PTP family will be compatible with the act-engineering approach, which provides a novel chemical-biological tool for the control of PTP activity and the study of PTP function.


Correction to: Neuroendocrine characteristics of induced pluripotent stem cells from polycystic ovary syndrome women.
In the original publication the Fig. 2 and the Supplementary Material 1 was incorrect. The correct version of Fig. 2 and the Supplementary Material are provided in this correction article. NESTIN should be corrected to PAX6 in Fig. 2C legend and at page 528 and Supplementary Material 1. NANOG should be corrected to PAX6 in Fig. 2C picture. Fig. 2. Differentiation and identification of NSCs from PCOS-derived iPSCs. (A) Schematic procedure of NSCs differentiation from iPSCs. NSC: Neural stem cell; EB: embryoid body. (B) The phenotype of specific differentiated NSCs. Scale bars = 100 µm. (C) Immunofluorescence images of the NSC markers SOX2 and PAX6. Scale bars = 50 µm. ZOOM, scale bars = 25 μm. (D) The mitochondrial respiration function of PCOS- and non-PCOS-derived iPSCs and NSCs. (E) Quantitative analysis of basal oxygen consumption, ATP production, maximal respiration, and proton leak. (F) Proposed neuroendocrine state in normal and PCOS patients. In normal patients, the GnRH pulsatile frequency is critical for steroidogenesis and follicular development. Low frequency pulses prefer FSH, and high frequency pulses favour LH. In PCOS, the increased GnRH release led to a high level of LH pulsatility, impairing the preferential release of FSH and follicular maturation, thus leading to polycystic ovaries. Red: increased; Blue: decreased. Solid arrow: up regulated; Dotted arrow: down regulated.


Computerized tomographic diagnosis of aneurysms of the thoracic aorta.
Accurate diagnosis of aneurysms of the thoracic aorta and its major branches can easily be performed by CT scanning of the mediastinum. The use of contrast enhancement aids in the diagnosis and allows distinction between flowing and clotted blood within the aneurysm. CT scanning of these lesions seen on chest radiographs may obviate the need for arteriography for diagnosis.


Knowledge of current abortion law and views on abortion law reform: a community survey of NSW residents.
To report results of a community survey of NSW residents' knowledge of current abortion law and views on abortion law reform. A total of 1,015 men and women participated. Recruitment and questionnaires were completed anonymously online using survey panel sampling. Seventy-six per cent of respondents were unaware that abortion remains a criminal offence in the Crimes Act 1900 (NSW) and 73% thought it should be decriminalised and regulated as a healthcare service. Support for decriminalisation was consistent across genders, age groups, residents of metropolitan/regional and rural areas and levels of education. Support was strong for women seeking abortion to be protected from harassment (89%) and for protester exclusion zones around clinics (81%), with support for these measures significantly stronger among regional/rural residents than Sydney-based respondents. Abortion law in NSW is out of step with contemporary community views. Residents are largely unaware that it remains a criminal offence and, when informed, support decriminalisation. There is strong support for legal changes to protect women from harassment and to provide protester exclusion zones around abortion clinics. Implications for public health: Abortion law reform would reduce current inequities of access, be democratic and support women's autonomy and reproductive rights.


[Myositis as a post-acute sequela of COVID-19 disease? : Even in times of the pandemic, muscle biopsies can only be assessed in the context of accurate clinical information].
A case of a patient suffering from COVID-19 with suspected associated myositis is reported, in which the initially limited information about the history and disease course led to difficulties in establishing a reasonable diagnosis. Through inquiry, further data could be collected, so that the diagnosis of an infection-associated thrombotic microangiopathy in the context of a Morganella morganii myositis could be made. This patient study shows that even in times of the omnipresent pandemic and despite the context of a positive COVID-19 test result, differential diagnoses and the integrative clinicopathologic approach in interpreting muscle biopsy findings should not be neglected.


Impact of COVID-19 on health risk behaviors in northern California: A cross-sectional survey.
The COVID-19 pandemic has been disruptive, unevenly impacting health behaviors in different geographical regions and population groups. We examined how COVID-19 affected perceived changes in physical activity, sleep, and diet and the impact of socio-demographic variables on a calculated health risk behavior score. In this cross-sectional study, 505 residents of northern California completed a web-based survey from August to November of 2020. Chi-square and multivariable linear regression analyses examined the association between socio-demographic variables and the health risk behavior score. Approximately 84 % of respondents experienced at least one unfavorable behavior change after the pandemic, with 49.5 % indicating a reduction in physical activity, 29.7 % a decrease in sleep, 33.1 % an increase in sugary snack consumption, and 29.3 % a decrease in fruit and vegetable intake. Multivariate analyses indicated a higher health risk behavior score (less favorable) for females compared to males (male beta = -0.815, p < 0.0001) and Hispanics compared to Whites (Hispanics beta = 0.396, p = 0.033). The negative changes in health behavior observed in females could be attributed to a higher reduction in fruit and vegetable consumption, and a larger increase in sugary and salty snacks when compared to males. A higher reduction in exercise, sleep, and fruit and vegetable intake were the main drivers of the unfavorable results seen for Hispanics when compared to Whites. Findings highlight the detrimental behavioral changes during the COVID-19 pandemic and the disproportionate impact on Hispanics and women. These results are valuable to policymakers to identify ways to support those most affected by the pandemic and its potential long-term effects.


Nodding syndrome in Uganda is a tauopathy.
Nodding syndrome is an epidemic neurologic disorder of unknown cause that affects children in the subsistence-farming communities of East Africa. We report the neuropathologic findings in five fatal cases (13-18 years of age at death) of nodding syndrome from the Acholi people in northern Uganda. Neuropathologic examination revealed tau-immunoreactive neuronal neurofibrillary tangles, pre-tangles, neuropil threads, and dot-like lesions involving the cerebral cortex, subcortical nuclei and brainstem. There was preferential involvement of the frontal and temporal lobes in a patchy distribution, mostly involving the crests of gyri and the superficial cortical lamina. The mesencephalopontine tegmental nuclei, substantia nigra, and locus coeruleus revealed globose neurofibrillary tangles and threads. We conclude that nodding syndrome is a tauopathy and may represent a newly recognized neurodegenerative disease.


The Development and Validation of a Mobile Application for Guidance for Management of Severe Diabetic Ketoacidosis.
To develop and validate a mobile application-based tool for the management guidance of children and adolescents with diabetic ketoacidosis (DKA). The study involved the development of a mobile application-based tool for DKA management in accordance with the International Society of Pediatric and Adolescent Diabetes (ISAPD) guidelines, 2018. The impact of the mobile application in preventing protocol deviation and resultant complications was assessed. Case records of 70 children and adolescents [39 boys, 8.9 (4.1) y of age] with severe DKA managed in the authors' intensive care unit were examined. The application guidance and real-time management were compared to the standard protocol. Protocol deviations were observed in 58 (82.9%), with two or more errors in 28 (40%). These included lack of initial fluid bolus (4, 5.7%), excessive fluid supplementation (8, 11.4%), inadequate initial fluid (25, 35.7%) and potassium supplementation (13, 18.6%), delayed response to fall in potassium (15, 21.4%) and glucose levels (24, 34.3%), and erroneous insulin administration (19, 27.1%). These errors contributed to 42.1% of severe hypokalemia and 56% of significant hypoglycemia episodes. The mobile application guidance was in accordance with the protocol in all the case scenario. Deviation from the management protocol is common in DKA and associated with adverse outcomes. Mobile application guidance is expected to reduce the protocol deviation with a potential of improving outcomes.


Impact of the affordable care act dependent coverage provision on young adult cancer patient insurance coverage by sociodemographic and economic characteristics.
To evaluate the impact of the Affordable Care Act Dependent Care Provision by sociodemographic and economic characteristics in young adult cancer patients. The National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) 18 database were queried for young adult cancer cases diagnosed during 2007-2014. Using a difference-in-differences approach, we examined insurance coverage in different subgroups of policy-eligible 19-25 year-olds versus policy-ineligible 27-29 year-olds from the pre- (2007-2009) to post- (2011-2014) Dependent Care Provision period. Across subgroups and study populations, insurance coverage increased significantly following the Provision enactment in the policy-eligible versus policy-ineligible group across most subgroups (range in NCDB: 1.83 to 6.38% for low and mid-low education areas, respectively; range in SEER: 1.43 to 6.18 for Non-Hispanic Others and Hispanics, respectively). Heterogenous impacts were observed by sex with a larger impact in males (NCDB: 5.14%, 95% CI 3.59-6.69; SEER: 4.46, 2.12-6.8) than females (NCDB: 2.51%, 95% CI 1.39-3.62; SEER: 2.50, 0.82-4.18). We observed no other statistical evidence for Dependent Care Provision subgroup heterogeneity except for a smaller impact in individuals from low education areas in NCDB. Our results indicate a positive Dependent Care Provision impact on insurance coverage in young adults with cancer across subgroups, with evidence for a smaller impact in females relative to males and in low relative to high education areas.


Osteochondral Fractures of the Knee in Skeletally Immature Patients: Short-Term Results of Operative Fixation using Omnitech Screws.
Retrospective case series looking at the use of Omnitech compression screws for the management of osteochondral fractures in skeletally immature patients. Nine patients with a mean age of 14 were included in the study with a mean follow up of 26 months. The average KOOS, IKDC and Tegner Lysholm Scores were 86.7, 90.34 and 96.1 respectively. The use of Omnitech screws in the acute setting for skeletally immature patients shows excellent short-term outcomes.


Health-related quality of life of children and adolescents prior to hematopoietic progenitor cell transplantation: diagnosis and age effects.
The health-related quality of life (HRQOL) may vary among children before undergoing hematopoietic progenitor cell transplantation (HPCT). This study examined the HRQOL of children scheduled for HPCT, the effects of diagnosis and age on HRQOL, and the convergent validity of one generic and two disease-specific measures of HRQOL. The sample consisted of 111 children (mean age = 10.4 years) diagnosed with acute lymphoblastic leukemia (ALL; 22%), other leukemias (26%), neuroblastoma (19%), other solid tumors (18%), and hematologic disorders (15%). Convergence validity was tested with 67 children (mean age = 10.3 years) who had an equivalent distribution of diagnoses except for neuroblastoma (12%). The Child Health Questionnaire (CHQ), a generic measure, and the Pediatric Oncology Quality of Life Scale (POQOL) and the Play Performance Scale (PPS), disease-specific measures, were completed by one parent prior to HPCT. Compared to the norms for healthy children, the CHQ Physical summary scores for every diagnostic subgroup and the CHQ Psychosocial summary scores for ALL were poorer. Compared to the cancer norms for Total POQOL and PPS scores, scores for ALL and neuroblastoma were the poorest. These measures also revealed that adolescents' HRQOL was perceived to be worse than children's. Total POQOL scores showed strong convergent validity with CHQ Physical and Psychosocial scores and moderate convergent validity with the PPS scores. Based on parental reports, children treated for ALL and neuroblastoma appear to be at the greatest risk for poor HRQOL before undergoing HPCT, and adolescents seem to be more compromised than younger children, based on parental reports. The POQOL measure seems to be the best predictor of HRQOL. These results have clinical implications for the care of children undergoing HPCT.


PTPN22 C1858T and the risk of psoriasis: a meta-analysis.
Psoriasis is a chronic autoimmune skin disease with both environmental and genetic risk factors. Previous studies of the association between psoriasis and PTPN22 C1858T (rs2476601), a gain of function variant associated with a stronger inhibitory effect of T-lymphocytes, have produced inconsistent results. The purpose of the current study is to evaluate the association between PTPN22 C1858T and psoriasis using meta-analysis to: (1) have a sufficient sample size for detecting a weak association; and (2) to explore the heterogeneity between studies. A meta-analysis based on random-effects model was performed with ten studies (3,334 psoriasis cases and 5,753 controls) identified from a literature search. A non-significantly positive association between psoriasis and the PTPN22 T1858 was observed [summary allelic odds ratio (OR) = 1.15, 95 % confidence interval (CI): 1.00-1.33] and the association appears stronger among subjects with psoriatic arthritis (summary allelic OR = 1.23, 95 % CI: 1.00-1.52). A null association between PTPN22 T1858 and early-onset psoriasis was observed (summary allelic OR = 1.08, 95 % CI: 0.92-1.28). The current analysis showed a non-significantly positive association between psoriasis and the PTPN22 T1858 allele, and the association appeared stronger among subjects with psoriatic arthritis. Future studies of psoriasis should incorporate gene-environment interaction in the analysis and pay attention to the heterogeneity of psoriasis cases and bias associated with population stratification.


Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions.
The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feeding studies-the DASH and DASH-Sodium trials. Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions: DASH (n=219) and DASH-Sodium (n=395). Using multivariable linear regression models, associations were examined between metabolites and change in systolic BP and DBP. Tested for interactions between diet interventions and metabolites were the following comparisons: (1) DASH versus control diets in the DASH trial (serum), (2) DASH high-sodium versus control high-sodium diets in the DASH-Sodium trial (urine), and (3) DASH low-sodium versus control high-sodium diets in the DASH-Sodium trial (urine). Sixty-five significant interactions were identified (DASH trial [serum], 12; DASH high sodium [urine], 35; DASH low sodium [urine], 18) between metabolites and systolic BP or DBP. In the DASH trial, serum tryptophan betaine was associated with reductions in DBP in participants consuming the DASH diets but not control diets (P interaction, 0.023). In the DASH-Sodium trial, urine levels of N-methylglutamate and proline derivatives (eg, stachydrine, 3-hydroxystachydrine, N-methylproline, and N-methylhydroxyproline) were associated with reductions in systolic BP or DBP in participants consuming the DASH diets but not control diets (P interaction, <0.05 for all tests). We identified metabolites that were associated with BP lowering in response to dietary interventions. URL: https://www. gov/ct2/show/NCT03403166; Unique identifier: NCT03403166 (DASH trial). URL: https://www. gov/ct2/show/NCT00000608; Unique identifier: NCT00000608 (DASH-Sodium trial).


Enhanced bioactivity of Si3N4 through trench-patterning and back-filling with Bioglass®.
Using a simple and innovative sandblasting process, disks of monolithic biomedical silicon nitride (β-Si3N4) were texturized with a matrix of regular, discrete square trenches with a total depth in the range of hundreds of microns. The process consisted of sandblasting Si3N4 substrates through a stainless-steel wire-mesh (150 or 200 μm) using abrasive silicon carbide powders (α-SiC, ∼40 μm) under 1,034 kPa (150 psi) of gas pressure. The depth of the porosities could be controlled varying both the treatment time and the distance from the surface. Part of the samples were then filled with 45S5 Bioglass® powders to improve the osteointegration and stimulate the production of bone tissue. Due to the increased macroscopic and microscopic roughness, biological testing using human osteosarcoma cells (SaOS-2) showed improved cell proliferation and greater production of both mineral (hydroxyapatite) and organic (collagen) phases on the patterned surfaces compared to untreated β-Si3N4 or to the biomedical titanium control samples. Both of these effects were further enhanced when the porosities were filled with Bioglass®.


Grassroots research: how to have a stab at your first project and succeed.
Current initiatives are aimed at building the capacity within Australian primary care to undertake high quality research and evaluation, including clinicians who are not primarily researchers. To provide a simple guide to encourage practice based research projects. TIPS AND ADVICE: Be parsimonious with the amount of data collected, ensure the literature is searched first, keep the project as simple as possible, invest time in planning and managing the project, readily ask for help and advice, and make every effort to publish the results. A modest, carefully supported and systematic approach is recommended for increasing the chance of success and quality of the research.


The association between diet quality, plant-based diets, systemic inflammation, and mortality risk: findings from NHANES.
To our knowledge, no studies have examined the association of diet quality and plant-based diets (PBD) with inflammatory-related mortality in obesity. Therefore, this study aimed to determine the joint associations of Healthy Eating Index-2015 (HEI-2015), plant-based dietary index (PDI), healthy PDI (hPDI), unhealthy PDI (uPDI), pro-vegetarian dietary index (PVD), and systemic inflammation with all-cause, cardiovascular disease (CVD), and cancer mortality risks by obesity status. Participants from NHANES were included in cross-sectional (N = 27,915, cycle 1999-2010, 2015-2018) and longitudinal analysis (N = 11,939, cycle 1999-2008). HEI-2015, PDI, hPDI, uPDI, and PVD were constructed based on the 24-h recall dietary interview. The grade of inflammation (low, moderate, and high) was determined based on C-reactive protein (CRP) values and multivariable ordinal logistic regression was used to determine the association. Cox proportional hazard models were used to determine the joint associations of diet and inflammation with mortality. In the fully adjusted model, HEI-2015 (ORT3vsT1 = 0.76, 95% CI 0.69-0.84; p-trend = < 0.001), PDI (ORT3vsT1 = 0.83, 95% CI 0.75-0.91; p trend = < 0.001), hPDI (ORT3vsT1 = 0.79, 95% CI 0.71-0.88; p trend = < 0.001), and PVD (ORT3vsT1 = 0.85, 95% CI 0.75-0.97; p trend = 0.02) were associated with lower systemic inflammation. In contrast, uPDI was associated with higher systemic inflammation (ORT3vsT1 = 1.18, 95% CI 1.06-1.31; p-trend = 0.03). Severe inflammation was associated with a 25% increase in all-cause mortality (ORT3vsT1 = 1.25, 95% CI 1.03-1.53, p trend = 0.02). No association was found between PDI, hPDI, uPDI, and PVD with mortality. The joint association, between HEI-2015, levels of systemic inflammation, and all-cause, CVD and cancer mortality, was not significant. However, a greater reduction in mortality risk with an increase in HEI-2015 scores was observed in individuals with low and moderate inflammation, especially those with obesity. Higher scores of HEI-2015 and increased intake of a healthy plant-based diet were associated with lower inflammation, while an unhealthy plant-based diet was associated with higher inflammation. A greater adherence to the 2015 dietary guidelines may reduce the risk of mortality associated with inflammation and may also benefit individuals with obesity who had low and moderate inflammation.


Breast Cancer Subtype is Associated With Axillary Lymph Node Metastasis: A Retrospective Cohort Study.
The purpose of this study was to assess whether breast cancer subtype (BCS) as determined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 can predict the axillary lymph node metastasis in breast cancer. Patients who received breast conserving surgery or mastectomy and axillary lymph node dissection were identified from 2 cancer centers. The associations between clinicopathological variables and axillary lymph node involvement were evaluated in univariate and multivariate regression analyses. A total of 3471 patients met the inclusion criteria, and 53.0% had axillary lymph node metastases at diagnosis. Patients with hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)- subtype had a higher grade disease and the lowest rate of lymphovascular invasion. Univariate and multivariable logistic regression analyses showed that BCS was significantly associated with lymph node involvement. Patients with the HR-/HER2- subtype had the lowest odds of having nodal positivity than those with other BCSs. HR+/HER2- (odds ratio [OR] 1.651, 95% confidence interval [CI]: 1.349-2.021, P < 0.001), HR+/HER2+ (OR 1.958, 95%CI 1.542-2.486, P < 0.001), and HR-/HER2+ (OR 1.525, 95%CI 1.181-1.970, P < 0.001) tumors had higher risk of nodal positivity than the HR-/HER2- subtype. The other independent predictors of nodal metastases included tumor size, tumor grade, and lymphovascular invasion. Breast cancer subtype can predict the presence of axillary lymph node metastasis in breast cancer. HR-/HER2- is associated with a reduced risk of axillary lymph node metastasis compared to other BCSs. Our findings may play an important role in guiding axillary treatment considerations if further confirmed in larger sample size studies.


Measuring the chi 1 torsion angle in protein by CH-CH cross-correlated relaxation: a new resolution-optimised experiment.
Here we introduce an experiment with high sensitivity and resolution for the measurement of CH-CH dipolar-dipolar cross-correlated relaxation rates (CCRR) in protein side-chains. The new methodology aims to the determination of structural and dynamical parameters around the torsion angle chi(1) by measuring C(alpha)H(alpha)-C(beta)H(beta) cross-correlated relaxation rates. The method is validated on the protein ubiquitin: the chi(1) angles determined from the CCRR data are compared with the chi(1) angles of a previously determined NMR structure. The agreement between the two data sets is excellent for most residues. The few discrepancies that were found between the CCR-derived chi(1) angles and the angles of the previously determined NMR structure could be explained by taking internal motion into account. The new methodology represents a very powerful tool to determine both structure and dynamics of protein side-chains in only one experiment.


Messaging inclusion with consequence: U.S. sanctuary cities and immigrant wellbeing.
In the United States (U.S.), sanctuary cities have increasingly garnered public attention as places dedicated to increasing immigrant safety, inclusion, and health. These cities primarily rely on limiting local police cooperation with federal immigration enforcement to deter immigrant detention and deportation. However, sanctuary policies' inability to extend immigrants' legal rights and their reliance on police as ushers of sanctuary may complicate how these spaces attend to their stated goals. In this paper, we examine how organizational workers conceptualize sanctuary, safety, and immigrant health and wellbeing within sanctuary cities. We draw on interviews with organizational workers in two sanctuary cities: Boston, Massachusetts and Seattle, Washington collected between February and August 2018. Our findings reveal that immigrants continue to face structural barriers to housing, safe employment, education, and healthcare within sanctuary cities with consequences to wellbeing. Workers' definitions of safety draw on interconnected structural exclusion that prevent immigrants from accessing basic needs and fail to account for historically rooted forms of racism and nativism. Organizational workers identified tensions between messages of sanctuary and what local sanctuary policies offer in practice, providing insight into consequences of institutionalizing a grassroots social movement. As organizational workers negotiate these tensions, they must develop everyday sanctuary practices to extend immigrant inclusion, safety, health, and wellbeing.


The amygdala: a potential player in timing CS-US intervals.
Pavlovian conditioning is the reference paradigm for the study of associative learning based on the programmed relation of two stimuli, the conditioned stimulus (CS) and the unconditioned stimulus (US). Some authors believe that learning the CS-US interval is a co-requisite of or a pre-requisite to learning the CS-US association. There is a substantial literature showing that the amygdala is a critical player in Pavlovian conditioning, with both aversive and appetitive USs. We review a sparse but growing body of literature suggesting that the amygdala may also participate in processing the timing of the CS-US interval. We discuss whether the amygdala, in particular its central, basal and lateral nuclei, in concert with the network it belongs to, may play a role in learning the CS-US interval. We also suggest new and dedicated strategies that would result in better knowledge of the neural mechanisms underlying the learning of the CS-US time interval in isolation from the CS-US association.


Complications of cerebral angiography.
All types of complications, both minor and major, are tabulated and analyzed in 5531 consecutive cerebral angiographies performed on 3730 patients during a period of 5 years.


Analysis of electrocautery generated smoke by chromatographic-mass spectrometry.
to analyze the chemical components of the smoke from electrocautery from coagulating muscle and liver tissues of pigs. we collected smoke produced by electrocautery applied to porcine tissue in previously evacuated bottles, with qualitative and quantitative analysis of the compounds present through the hyphenated technique gas chromatography / mass spectrometry. there was a majority of decanal aldehyde in the fumes from the subcutaneous, muscle and liver tissues. Fumes of subcutaneous and muscular tissues also showed the presence of hexanal and phenol. In the fumes of subcutaneous and liver tissues we also found toluene and limonene and, finally, nonanal smoke was present in the muscle and liver tissues. there is increasing evidence showing that smoke from electrocautery used in subcutaneous, muscle and liver tissue is harmful to human health. Thus, there is need to reduce exposure to it or wear masks with filters capable of retaining these particles. analisar quimicamente os componentes da fumaça do eletrocautério, provenientes da coagulação de tecidos, muscular e hepático de suino. coleta de fumaça produzida por eletrocauterização de tecido porcino em frascos previamente evacuados com análise qualitativa e quantitativa dos compostos presentes, através de técnica hifenada, cromatografia a gás/espectrometria de massas. houve presença majoritária do aldeído decanal nas fumaças provenientes dos tecidos subcutâneo, muscular e hepático. Fumaças dos tecidos subcutâneo e muscular mostraram também a presença de hexanal e fenol. Nas fumaças dos tecidos subcutâneo e hepático foram encontrados ainda tolueno e limoneno e, por fim, nonanal estava presente nas fumaças dos tecidos muscular e hepático. há número crescente de evidências mostrando que fumaça proveniente de eletrocauterização de tecidos subcutâneo, muscular e hepático é nociva à saúde de seres humanos. Portanto, há necessidade de reduzir a exposição a ela ou usar máscara com filtro capaz de reter essas partículas.


SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance.
Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin. Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity. Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.


The brain's calendar: neural mechanisms of seasonal timing.
The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal component of the mammalian biological clock, the neural timing system that generates and coordinates a broad spectrum of physiological, endocrine and behavioural circadian rhythms. The pacemaker of the SCN oscillates with a near 24 h period and is entrained to the diurnal light-dark cycle. Consistent with its role in circadian timing, investigations in rodents and non-human primates furthermore suggest that the SCN is the locus of the brain's endogenous calendar, enabling organisms to anticipate seasonal environmental changes. The present review focuses on the neuronal organization and dynamic properties of the biological clock and the means by which it is synchronized with the environmental lighting conditions. It is shown that the functional activity of the biological clock is entrained to the seasonal photic cycle and that photoperiod (day length) may act as an effective zeitgeber. Furthermore, new insights are presented, based on electrophysiological and molecular studies, that the mammalian circadian timing system consists of coupled oscillators and that the clock genes of these oscillators may also function as calendar genes. In summary, there are now strong indications that the neuronal changes and adaptations in mammals that occur in response to a seasonally changing environment are driven by an endogenous circadian clock located in the SCN, and that this neural calendar is reset by the seasonal fluctuations in photoperiod.


Cortical contribution to visuomotor coordination in locomotion and reaching.
One of the hallmarks of mammals is their ability to make precise visually guided limb movements to attain objects. This is best exemplified by the reach and grasp movements of primates, although it is not unique to this mammalian order. Precise, coordinated, visually guided movements are equally as important during locomotion in many mammalian species, especially in predators. In this context, vision is used to guide paw trajectory and placement. In this review we examine the contribution of the fronto-parietal network in the control of such movements. We suggest that this network is responsible for visuomotor coordination across behaviours and species. We further argue for analogies between cytoarchitectonically similar cortical areas in primates and cats.


[Interference of reticulocyte metabolism with enzyme activity analyses in haemolytic anaemias (author's transl)].
This paper outlines the procedure for the preparation of leucocyte-free reticulocytes and normocytes and details the activities of the key enzymes in reticulocytes, normocytes and leucocytes. An assesment of the error in normocyte enzyme analyses due to contamination with reticulocytes and leucocytes is enabled by these means.


Structural-functional connectivity bandwidth predicts processing speed in mild traumatic brain Injury: A multiplex network analysis.
An emerging body of work has revealed alterations in structural (SC) and functional (FC) brain connectivity following mild TBI (mTBI), with mixed findings. However, these studies seldom integrate complimentary neuroimaging modalities within a unified framework. Multilayer network analysis is an emerging technique to uncover how white matter organization enables functional communication. Using our novel graph metric (SC-FC Bandwidth), we quantified the information capacity of synchronous brain regions in 53 mild TBI patients (46 females; age mean = 40.2 years (y), σ = 16.7 (y), range: 18-79 (y). Diffusion MRI and resting state fMRI were administered at the acute and chronic post-injury intervals. Moreover, participants completed a cognitive task to measure processing speed (30 Seconds and Counting Task; 30-SACT). Processing speed was significantly increased at the chronic, relative to the acute post-injury intervals (p = <0.001). Nonlinear principal components of direct (t = -1.84, p = 0.06) and indirect SC-FC Bandwidth (t = 3.86, p = <0.001) predicted processing speed with a moderate effect size (R2 = 0.43, p < 0.001), while controlling for age. A subnetwork of interhemispheric edges with increased SC-FC Bandwidth was identified at the chronic, relative to the acute mTBI post-injury interval (pFDR = 0.05). Increased interhemispheric SC-FC Bandwidth of this network corresponded with improved processing speed at the chronic post-injury interval (partial r = 0.32, p = 0.02). Our findings revealed that mild TBI results in complex reorganization of brain connectivity optimized for maximum information flow, supporting improved cognitive performance as a compensatory mechanism. Moving forward, this measurement may complement clinical assessment as an objective marker of mTBI recovery.


Occurrence and distribution of per-and polyfluoroalkyl substances (PFAS) in surface and groundwaters in an urbanized and agricultural area, Southern Brazil.
Per- and polyfluoroalkyl substances, known as PFAS, are emerging contaminants detected in surface water, groundwater, drinking water, air, and food. Due to its chemical stability and high hydrophobicity, these compounds are used as surfactants, surface protectors, flame retardants, textile impregnation, fire-fighting foam, and pesticides and may be a risk for human health in the long-term exposure. Currently, a little research has been carried out for these compounds in Brazil. In this study, the concentration and distribution of 23 PFAS were analyzed in groundwater samples collected from water wells in urbanized areas and in surface water samples from Porto Alegre, one of the biggest cities in Brazil. The total concentrations of PFAS (ΣPFAS) in a groundwater sample varied between 22 and 718 ng L-1. Eleven PFAS species were detected in groundwater, including PFOA, PFHxA, PFPeA, PFBA, PFDA, PFNA, and PFOS. Most of PFAS were quantified in samples located in the aquifer formed by medium to coarse sands intercalated with silty-sandy lenses and low organic matter content that could facilitate the percolation of these compounds. The total concentrations of PFAS (ΣPFAS) in a surface water sample varied between 11 and 17 ng L-1. Ten species were founded in surface water being PFOA, PFOS, and PFHpA the most dominant. Considering all the samples, PFOA was the predominant species in the study. In addition, tributary water bodies had higher concentrations of PFAS than the main water body (Guaiba Lake) probably due dilution process.


Continuous-wave diode laser thermokeratoplasty: first clinical experience in blind human eyes.
To evaluate the safety and stability of laser thermokeratoplasty (LTK) with a continuous-wave diode laser in blind human eyes and to optimize parameters for a study in sighted eyes. Department of Ophthalmology, Medical University Lübeck, Germany. A continuous-wave diode laser was set to emit radiation with a wavelength of 1.854 microns (Group 1, n = 4) or 1.870 microns (Group 2, n = 4) and 100 to 150 mW power for 10 seconds. A focusing handpiece was coupled with an application mask and fixed by partial vacuum to the conjunctiva or cornea. The radiation was focused into the corneal stroma between 400 and 600 microns in Group 1 and set to 1000 microns in Group 2. Eight (Group 1, single ring) or 16 (Group 2, double ring) coagulations were applied. The refractive change increased with higher laser power and smaller ring diameters. Two rings of coagulations provided higher and more stable refractive changes of up to 5.66 diopters (D) than a single ring. The refractive effect stabilized between 3 and 6 months postoperatively. At 1 year, mean refractive change was +0.99 D +/- 0.39 (SD) in Group 1 and +2.32 +/- 2.24 D in Group 2. Extensive endothelial damage occurred in Group 1 but was minimal in Group 2. Diode LTK was used to treat hyperopia safely and effectively. Regression occurred mainly in the first 3 postoperative months. With a wavelength of 1.870 microns, corneal endothelial damage was limited.


Apple Vision Pro for Ophthalmology and Medicine.
The emergence of new technologies continues to break barriers and transform the way we perceive and interact with the world. In this scientific article, we explore the potential impact of the new Apple XR headset on revolutionizing accessibility for individuals with visual deficits. With its rumored exceptional 4-K displays per eye and 5000 nits of brightness, this headset has the potential to enhance the visual experience and provide a new level of accessibility for users with visual impairments. We delve into the technical specifications, discuss the implications for accessibility, and envision how this groundbreaking technology could open up new possibilities for individuals with visual deficits.


Oral Mucosal Infections: Insights into Specimen Collection and Medication Management.
Oral mucosal infections appear as localized or generalized lesions. Symptoms range from almost unnoticeable lesions to severe pain. Systemic disease, age, immunocompromised condition, and medication use are common causes. Local causes include dentures, poor oral hygiene, traumatized epithelium, ulcerations, dentures, implants, oral piercing, and reduced salivary secretion. Oral mucosal infections are underdiagnosed and microbiological diagnosis should be more frequently used. Candidiasis is most frequently diagnosed. Clinical appearances are not always clear and are varied, creating a diagnostic challenge. Thorough understanding of clinical appearance and updated information on diagnostic and therapeutic management are essential for successful patient outcome.


BCR and co-receptor crosstalk facilitate the positive selection of self-reactive transitional B cells.
The establishment of a diverse B cell repertoire requires fine-tuning of antigen receptor selection during development in order to permit sufficient diversity while reducing the potential for autoimmunity. In this review, we highlight recent studies demonstrating the central role of the B cell antigen receptor (BCR), in coordination with other key pro-survival signals mediated by CD40, BAFF-R, TACI and/or TLRs, in regulating both negative and positive selection of autoreactive B cells. In particular, we show how altered antigen or co-stimulatory signaling can facilitate positive selection of transitional B cells with self-reactive BCRs, ultimately leading to their entry into the mature, naive B cell compartment. We propose a model wherein altered receptor signals (due to inherited genetic changes) leads: first, to enhanced positive selection of autoreactive cells into the naïve B cell repertoire; subsequently, to an increased probability of pathogenic germinal center responses in individuals with a broad range of autoimmune disorders.


Airway occlusion pressure at 0.1 s (P0.1) after extubation: an early indicator of postextubation hypercapnic respiratory insufficiency.
To examine variables associated with postextubation respiratory distress in chronic obstructive pulmonary disease (COPD) patients. Prospective, clinical investigation. Intensive care unit of a university hospital. Forty COPD patients, considered ready for extubation. We recorded, from the digital display of a standard ventilator, breathing frequency (f), tidal volume (VT) and f/VT for the respiratory pattern, airway occlusion pressure at 0.1 s (P0.1) for the respiratory drive and measured blood gases: i) before extubation, following 30 min of a 6 cm H2O pressure support (PS) ventilation trial, ii) 1 h after extubation, at the 30th min of a face mask 4 cm H2O PS ventilation trial. According to the weaning outcome, the patients were divided into two groups: respiratory distress, and non-respiratory distress within 72 h of the discontinuation of mechanical ventilation. The respiratory distress was defined as the combination of f more than 25 breaths/min, an increase in PaCO2 of at least 20% compared with the value measured after extubation, and pH lower than 7.35. We determined whether those patients who developed respiratory distress after extubation differed from those who did not. Respiratory pattern data and arterial blood gases recorded, either before or after extubation, and P0.1 recorded before extubation, were inadequate to differentiate the two groups. Only P0.1 recorded 1 h after the discontinuation of mechanical ventilation differentiated the patients who developed respiratory distress from those who did not (4.2+/-0.9 vs 1.8+/-0.8, p < 0.01). P0.1 recorded after extubation may be a good indicator of postextubation respiratory distress. Measuring P0.1 and/or the analysis of the evolution of this parameter could facilitate decisions during the period following extubation.


Dizziness.
Dizziness is a common but difficult symptom to evaluate because, due to its subjective nature, it is virtually impossible to measure objectively. In essence, dizziness means different things to different people. The most useful historical information is the patient's own description of the dizziness, its characterization, and the effects of position on the patient's symptoms. After taking a detailed history, the clinician should perform a thorough physical examination with emphasis on determining whether the dizziness is vestibular or nonvestibular in origin. Patient disposition is determined by the prognosis of the underlying cause and the presence of support mechanisms.


Primary adenoid cystic carcinoma of the esophagus: report of a case.
A case of primary adenoid cystic carcinoma of the esophagus is reported. A 51-year-old male patient had a tumor in the lower third of the esophagus which was incidentally found during an examination for cholelithiasis, and resected successfully. The tumor exhibited a polypoid appearance covered by normal esophageal epithelium, localized entirely in the submucosal layer, and morphologically identical to adenoid cystic carcinoma in the salivary glands. The patient is still alive and well three and one-half years after surgery. This seems to be a typical case of adenoid cystic carcinoma of the esophagus arising from the submucosal esophageal gland.


Proteolysis, proteasomes and antigen presentation.
Proteins presented to the immune system must first be cleaved to small peptides by intracellular proteinases. Proteasomes are proteolytic complexes that degrade cytosolic and nuclear proteins. These particles have been implicated in ATP-ubiquitin-dependent proteolysis and in the processing of intracellular antigens for cytolytic immune responses.


Epidemiology of Heart Failure in Asia.
Epidemiologic study is essential to improve management and outcomes in patients hospitalized for heart failure (HF). The academic and socioeconomic status can be clarified by epidemiologic study, and the unsolved issues can be realized. Based on results from epidemiologic studies, strategies to improve the present status could be considered. This article describes several key issues to conduct and interpret an epidemiologic study, for example, definition of HF, time frame, ethnicity, and site selection. Furthermore, assessments and evaluations that are based on comparisons with Western or other Asian data can give a clue to solve the present issues regarding HF management.


The chloride shift may facilitate oxygen loading and unloading to/from the hemoglobin from the brown bear (Ursus arctos L.).
1. The oxygen binding properties of hemolyzed bear blood were studied in 0.1 M Tris and 0.1 M Hepes buffer with respect to the possible effects of temperature, pH, pCO2, 2,3-DPG, and chloride ions. 2. There was a significant Bohr shift with a Bohr factor (delta log P50/delta pH) of the magnitude of -0.5. The temperature sensitivity expressed by the apparent heat of oxygenation minus the heat of oxygen in solution was about -8.1 kcal/mol at pH 7.4. 3. Chloride ions decreased the oxygen affinity in the concentration range 50-200 mM, and there was a marked increase in the co-operativity of oxygenation up to a chloride concentration of about 200 mM. 4. There were no effects of pCO2 and 2,3-DPG in the presence of 200 mM Cl-, while in the absence of Cl-, 2,3-DPG had the same effect as 200 mM Cl- at 37 degrees C and pH 7.4. 5. Our results suggests at least two different binding sites for the chloride ion, one high affinity site which may also bind 2,3-DPG in the absence of chloride, and one or more low affinity sites, which only binds chloride. 6. The results further show, that a chloride shift of about 33 mM may account for as much as a 40% increase in O2 unloading, without taking into account the additional effect of the Bohr shift.


Stem Cell Therapy, Artificial Heart or Xenotransplantation: What will be New "Regenerative" Strategies in Heart Failure during the Next Decade?
The main limitation of allotransplantation and in particular heart transplantation is the insufficient supply of donor organs. As alternative strategies to heart transplantation, stem cells opened the way of regenerative medicine in early 2000. While new biotechnologies tried to minimize side effects due to hemocompatibility in artificial hearts, progress in xenotransplantation allowed in 2022 to realize the first pig-to-human heart transplant on a compassionate use basis. This xenotransplantation has been successful thanks to genetically modified pigs using the CRISPR-Cas9 technology. Indeed, gene editing allowed modifications of immune responses and thrombotic potential to modulate graft and systemic reaction. Academic research and preclinical studies of xenogeneic tissues already used in clinic such as bioprosthesis valve and of new xenotransplantation options will be necessary to evaluate immune-thrombosis and organ/vascular damages more deeply to make this hope of xenotransplantation a clinical reality. Stem cells, artificial heart and xenotransplantation are all in line to overcome the lack of donor hearts. Combination of stem cell approaches and/or xenogeneic tissue and/or artificial organs are probably part of the research objectives to make these projects real in the short term.


Trauma care construction under the guidance of county-level trauma centers.
Severe trauma has the characteristics of complicated condition, multiple organs involved, limited auxiliary examinations, and difficulty in treatment. Most of the trauma patients were sent to primary hospitals to receive treatments. But the traditional mode of separate discipline management can easily lead to delayed treatment, missed or wrong diagnosis and high disability, which causes a high mortality in severe trauma patients. Therefore, if the primary hospitals, especially county-level hospitals (usually the top general hospital within the administrative region of a county), can establish a scientific and comprehensive trauma care system, the success rate of trauma rescue in this region can be greatly improved. On March 1st, 2013, Tiantai People's Hospital of Zhejiang Province, China set up a trauma care center, which integrated the pre-hospital and in-hospital trauma treatment procedures, and has achieved good economic and social benefits. Till March 1st, 2017, 1265 severe trauma patients (injury severity score >16) have been treated in this trauma center. The rescue success rate reached 95% and the delayed and/or missed diagnosis rate was less than 5%. Totally 86 severe cases of pelvic fractures with unstable hemodynamics were treated, and the success rate was 92%. The in-hospital emergency rescue response time is less than 3 min, and the time from definite diagnosis to surgery is within 35 min.


A comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on superovulation in Asian women with normal ovulatory cycles.
To compare the effect of the aromatase inhibitor letrozole and clomiphene citrate (CC) on superovulation in women with normal ovulation. A cross-over randomized study of 22 women with normal ovulation, divided randomly into two equal cohorts, was carried out. Each group of 11 women was randomly allocated to take letrozole or CC for one cycle. After washing out for one cycle, the alternative drug was administered in the subsequent cycle. The number and size of mature follicles, endometrial thickness, and estradiol and progesterone levels were monitored. The number of mature follicles and estradiol levels on ovulation day were significantly lower in the letrozole group than the CC group (p < 0.05 for both). However, no differences between the two groups in endometrial thickness and pattern were observed. Progesterone levels showed ovulation in all cycles. The administration of 50 mg CC on days 3-5 was superior to 2.5 mg letrozole for superovulation induction in women with normal ovulation.


[Association of retractile mesenteritis and ischemic enteritis].
A case of retractile mesenteritis associated with ischaemic enteritis in a 77-year old woman is described. The clinicopathological features of retractile mesenteritis are briefly reviewed.


Effect of polystyrene microplastics on the degradation of sulfamethazine: The role of persistent free radicals.
Microplastic (MPs) pollution is increasingly becoming a global environmental problem. MPs entering the environment are subjected to various aging processes, among which photoaging is the most important process leading to MPs oxidation. Persistent free radicals (EPFRs) are formed on the surface of MPs during photoaging, but it is not clear whether EPFRs on the surface of MPs can produce reactive oxygen species (ROS) and thus degrade organic pollutants. In this study, with polystyrene (PS) as the representative plastic and sulfamethazine (SMT) degradation as the target pollutant, the effect and mechanism of light-induced PS on SMT degradation were investigated by experiment and theoretical calculation. It was found that PS can stimulate the production of ROS under sunlight, which can significantly improve the degradation rate of SMT. Through quenching experiment and free radical trapping experiment, it was found that the mechanism of PS promoting the degradation of SMT was mainly due to the production of hydroxyl radical (·OH) in the system, and ·OH was the main ROS species affecting the oxidative degradation of SMT. The characterization results show that the high reactive oxygen generation ability of PS under solar irradiation was due to the abundant photoactive oxidation functional groups on its surface. In addition, the key reaction sites of SMT were predicted by density functional theory (DFT) calculation. The results of different calculations consistently showed that the sulfonamide group of SMT, the pyrimidine heterocycle and the amino group of aniline are the reaction sites of ·OH priority attack. The main intermediates were determined by UHPLC-HRMS/MS. Combined with theoretical calculation, it was proposed that the oxidative degradation pathway of SMT mainly includes SN bond cleavage, SMILES rearrangement and SO2 group removal. This study clarified the effect of PS on the degradation of organic pollutants under light, and provided theoretical guidance for the degradation mechanism.


The impact of food intake on the luminal environment and performance of oral drug products with a view to in vitro and in silico simulations: a PEARRL review.
Using the type of meal and dosing conditions suggested by regulatory agencies as a basis, this review has two specific objectives: first, to summarize our understanding on the impact of food intake on luminal environment and drug product performance and second, to summarize the usefulness and limitations of available in vitro and in silico methodologies for the evaluation of drug product performance after food intake. Characterization of the luminal environment and studies evaluating product performance in the lumen, under conditions suggested by regulatory agencies for simulating the fed state, are limited. Various in vitro methodologies have been proposed for evaluating drug product performance in the fed state, but systematic validation is lacking. Physiologically based pharmacokinetic (PBPK) modelling approaches require the use of in vitro biorelevant data and, to date, have been used primarily for investigating the mechanisms via which an already observed food effect is mediated. Better understanding of the impact of changes induced by the meal administration conditions suggested by regulatory agencies on the luminal fate of the drug product is needed. Relevant information will be useful for optimizing the in vitro test methods and increasing the usefulness of PBPK modelling methodologies.


Characterization of pretentorial periaqueductal gray matter neurons mediating intraspecific defensive behaviors in the rat by microinjections of kainic acid.
Unilateral microinjections of 40 pmol of kainic acid (KA; in 0.2 microliter) within the periaqueductal gray matter (PAG) evoked intraspecific defensive postures (defensive uprights, defensive alterting, defensive sideways, backing) in rats confronted with a conspecific. These reactions, which lasted for up to 30 min, were seemingly identical to the rat's natural defensive reaction to attacks by a conspecific although they were evoked by the investigatory approach, rather than the attack, of another rat. Histological analysis revealed that the strongest defensive reactions were evoked from sites within a restricted part of the pretentorial periaqueductal gray matter. Lower doses of KA induced fewer (20 pmol) or non-significant increases (4 pmol) in defensive reactions. Higher doses (100 and 200 pmol) increased the percentage of defensive behavior and also induced oriented jumps out of the test cage. In tests with a conspecific, defensive reactions were elicited most frequently when investigation by the partner was localized to the side of the body contralateral to the injection site. This was confirmed in a sensory reactivity test in which tactile stimulation by the experimenter elicited most defensive reactions when applied on the side of the body contralateral to the injection side. This test also revealed a somatotopic gradient in the animal's reaction: tactile stimulation of the contralateral head and the forelimb evoked the strongest reactions, whereas no responses were observed upon tactile stimulation of the contralateral flank or hindlimb. Measurement of electroencephalographic activity at the cortical, hippocampal, amygdala and PAG levels indicated that the evoked defensive reactions were not secondary to epileptogenic effects. Finally, quantitative analysis of an autoradiographic study found that [3H]KA diffused within a diameter of 1.0-1.2 mm around the cannula tip. Taken together, these results indicate the existence of a population of neurons within a restricted part of the pretentorial PAG of the rat, the excitation of which produces defensive responses and demonstrate that these defensive reactions have a socially adaptive value.


The distribution of vascular endothelial growth factor in human meniscus and a meniscal injury model.
The meniscus plays an important role in controlling the complex biomechanics of the knee. Meniscus injury is common in the knee joint. The perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Angiogenesis factors, such as vascular endothelial growth factor (VEGF), have important roles in promoting vascularization of various tissues. VEGF-mediated neovascularization is beneficial to the healing of injured tissues. However, the distribution and angiogenic role of VEGF remains unclear in the meniscus and injured meniscus. We hypothesized that VEGF could affect meniscus cells and modulate the meniscus healing process. Menisci were obtained from total knee arthroplasty patients. Meniscal injury was created ex vivo by a microsurgical blade. VEGF mRNA and protein expression were detected by the polymerase chain reaction and immunohistochemical analyses, respectively. In native meniscal tissue, the expression of VEGF and HIF-1α mRNAs could not be detected. However, VEGF and HIF-1α mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1α: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1α, with the increase being greatest in the outer area. Immunohistochemical analyses revealed that VEGF protein was detected mainly in the outer region and around injured areas of the meniscus. However, VEGF concentrations were similar between inner and outer menisci-derived media. This study demonstrated that both the inner and outer regions of the meniscus contained VEGF. HIF-1α expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1α and VEGF that may be preserved in the extracellular matrix as the healing stimulator of damaged meniscus, especially in the outer meniscus.


ADHD in Children and Adults: Diagnosis and Prognosis.
Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neuropsychiatric disorder associated with significant impairment and distress throughout the lifespan. Recent investigations have shed light on different aspects regarding the trajectory of ADHD, including reports on risk factors in childhood, that are associated with remission or persistence in adulthood. Despite significant advances in our understanding of the pathophysiology of the disorder, the diagnosis of ADHD remains strictly clinical and is based on behavioral symptoms of inattention, impulsivity, and hyperactivity. In this chapter we review the diagnostic process of ADHD, discuss the clinical presentation of the disorder across the lifespan, and examine patterns of comorbidity and longitudinal predictor of outcomes.


A single dose of sulfametopyrazine versus 7 days of ampicillin in acute on chronic bronchitis.
Forty-two patients with acute on chronic bronchitis received in double-blind fashion either a single dose of 2 g of sulfametopyrazine or ampicillin 250 mg thrice daily for 7 days. There were no significant differences between treatments in the number of patients achieving white sputum, the time to do so, or the incidence of pathogens at the end of treatment. Blood levels of sulfametopyrazine between 8 and 24 hours and on the seventh day were likely to result in sputum concentration adequate to kill Haemophilus influenzae.


Feature blindness: A challenge for understanding and modelling visual object recognition.
Humans rely heavily on the shape of objects to recognise them. Recently, it has been argued that Convolutional Neural Networks (CNNs) can also show a shape-bias, provided their learning environment contains this bias. This has led to the proposal that CNNs provide good mechanistic models of shape-bias and, more generally, human visual processing. However, it is also possible that humans and CNNs show a shape-bias for very different reasons, namely, shape-bias in humans may be a consequence of architectural and cognitive constraints whereas CNNs show a shape-bias as a consequence of learning the statistics of the environment. We investigated this question by exploring shape-bias in humans and CNNs when they learn in a novel environment. We observed that, in this new environment, humans (i) focused on shape and overlooked many non-shape features, even when non-shape features were more diagnostic, (ii) learned based on only one out of multiple predictive features, and (iii) failed to learn when global features, such as shape, were absent. This behaviour contrasted with the predictions of a statistical inference model with no priors, showing the strong role that shape-bias plays in human feature selection. It also contrasted with CNNs that (i) preferred to categorise objects based on non-shape features, and (ii) increased reliance on these non-shape features as they became more predictive. This was the case even when the CNN was pre-trained to have a shape-bias and the convolutional backbone was frozen. These results suggest that shape-bias has a different source in humans and CNNs: while learning in CNNs is driven by the statistical properties of the environment, humans are highly constrained by their previous biases, which suggests that cognitive constraints play a key role in how humans learn to recognise novel objects.


Role of Lactobacillus biofilms in Listeria monocytogenes adhesion to glass surfaces.
Listeria monocytogenes can form long-lasting biofilms on food-contact surfaces. Lactic acid bacteria (LAB) have shown promise in antagonizing this microorganism in liquid media. However, the ecological relationships differ when cells are forming biofilms. In this work, we propose the use of Lactobacillus biofilms as surface "conditioners" to modulate the adhesion of L. monocytogenes. For this, the biofilm formation ability of Lactobacillus fermentum MP26 and Lactobacillus salivarius MP14 (human milk origin), fluorescently labeled by transfer of the mCherry-encoding pRCR12 plasmid, was first evaluated. Then, mature biofilms of these strains transformed with pRCR12 for expressing the fluorescent protein mCherry were used as adhesion substrate for GFP-tagged L. monocytogenes Scott A. The resulting biofilms were studied in terms of cellular population and attached biomass (cells plus matrix). Species distribution inside the biofilm structure was revealed by confocal laser scanning microscopy (CLSM). Although none of the Lactobacillus spp. strains reduced the adhesion of L. monocytogenes Scott A, species interactions seem to interfere with the synthesis of extracellular polymeric substances and species distribution inside the biofilms. In dual-species biofilms, CLSM images revealed that Lactobacillus cells were trapping those of L. monocytogenes Scott A. When surfaces were conditioned with Lactobacillus biofilms, the spatial distribution of L. monocytogenes Scott A cells was species-specific, suggesting these interactions are governing the ultimate biofilm structure. The results here obtained open new possibilities for controlling L. monocytogenes dispersal using these Lactobacillus spp. biofilms as a "natural" immobilization way. Whether species interactions could modify the virulence of L. monocytogenes still remains unclear.


[Thrombotic microangiopathy and cancer].
Thrombotic microangiopathy (TMA) is a group of disorders characterized by mechanical hemolytic anemia with thrombocytopenia and an ischemic organic lesion of variable and potentially fatal importance affecting mostly the kidneys and the brain with histologically a disseminated and occlusive microvasculopathy. The incidence of TMA represents 15% of acute kidney failure in oncological setting, largely due to the introduction of anti-angiogenic agents over the past decade. It may be more rarely related to cancer itself. The iatrogenic TMA can be classified into 2 types: The type I, secondary to chemotherapy (mitomycinC, gemcitabine), exposes to a chronic dose-dependent renal injury as well as an increase in morbidity and mortality; iatrogenic type II, secondary to anti-angiogenic agents', results in a dose-independent renal involvement and renal functional recovery is usual when the drug is discontinued. There is no randomized controlled trial to establish EBM-type management in TMA support. However, complement activation pathways and regulatory factors analyses allowed us to understand the mechanisms of endothelial lesions. As a result, the current trend includes the use of immunosuppressive agents in recurrent or plasmapheresis-refractory MAT.


The interplay between NSAIDs and Candida albicans on the gastrointestinal tract of guinea pigs.
Recent studies suggest that Candida albicans colonization is associated with several gastrointestinal inflammatory disorders and is also responsible for the delay in ulcer healing. No data are reported about the effects of C. albicans on the nonsteroidal anti-inflammatory drugs (NSAIDs)-induced necroinflammatory lesions. On the other hand, beneficial effects of NSAIDs regarding the colonization potential with C. albicans have been reported. Our aim was to investigate whether the association between NSAIDs and C. albicans could potentially induce necroinflammatory lesions in the guinea pigs gastric and enteral mucosa. Three interventional groups of 11 guinea pigs each were investigated after 5 days of receiving indomethacin, C. albicans or the association of both. C. albicans and necroinflammatory lesions were graded based on histological examinations. Statistical analysis used Mann-Whitney nonparametric test. NSAIDs did not significantly decrease C. albicans colonization grades on gastrointestinal mucosa. Administration of indomethacin subsequent to C. albicans determined significantly more severe necroinflammatory lesions compared to group that only received C. albicans. The association of NSAIDs and C. albicans did not cause significantly more severe degenerative or inflammatory lesions compared to the administration of only NSAIDs in this experimental model. Associations between NSAIDs and C. albicans caused significantly more severe necroinflammatory injuries than the lesions produced by C. albicans, without enhancing the mucosal injury or inflammation caused by NSAIDs.


Protecting the airway during swallowing: what is the role for afferent surveillance?
Mechanoreceptors are ubiquitous throughout the upper aerodigestive tract and provide spatiotemporal information on movement and stretch of muscles and connective tissues involved in feeding. Experimental studies in humans suggest that upper airway sensory signals provide important tonic and kinesthetic feedback to central neural circuits underlying upper airway perception and laryngeal closure during swallowing. These circuits include brainstem and cortical feedforward loops that facilitate swallowing function. A clinical implication of this organization is the potential to harness the sensory system for enhancing laryngeal closure during swallowing. Therapeutic sensory stimulation is a promising method for treating dysphagia and preventing aspiration pneumonia in patients with cortical lesions.


Selection of antibodies from synthetic antibody libraries.
More than 2 dozen years had passed since the field of antibody engineering was established, with the first reports of bacterial [1-3] and mammalian cells [4] expression of recombinant antibody fragments, and in that time a lot of effort was dedicated to the development of efficient technological means, intended to assist in the creation of therapeutic monoclonal antibodies (mAbs). Research focus was given to two intertwined technological aspects: the selection platform and the recombinant antibody repertoires. In accordance with these areas of interest, it is the goal of this chapter to describe the various selection tools and antibody libraries existing, with emphasis on the later, and their applications. This chapter gives a far from exhaustive, subjective "historic account" of the field, describing the selection platforms, the different formats of antibody repertoires and the applications of both for selecting recombinant antibodies. Several excellent books provide detailed protocols for constructing antibody libraries and selecting antibodies from those libraries [5-13]. Such books may guide a newcomer to the field in the fine details of antibody engineering. We would like to offer advice to the novice: although seemingly simple, effective library construction and antibody isolation provide best benefits in the hands of professionals. It is an art as much as it is science.


The molecular basis of autosomal recessive diseases among the Arabs and Druze in Israel.
The Israeli population mainly includes Jews, Muslim and Christian Arabs, and Druze In the last decade, data on genetic diseases present in the population have been systematically collected and are available online in the Israeli national genetic database ( http://www.goldenhelix.org/server/israeli ). In the non-Jewish population, up to 1 July 2010, the database included molecular data on six diseases relatively frequent in the whole population: thalassemia, familial Mediterranean fever (FMF), cystic fibrosis, deafness, phenylketonuria and congenital adrenal hyperplasia, as well as data on 195 autosomal recessive diseases among Muslim Israeli Arabs, 11 among the Christian Arabs and 31 among Druze. A single mutation was characterized in 149 out of the 238 rare disorders for which the molecular basis was known. In many diseases, mutation had never been observed in any other population and was present in one family only suggesting that it occurred as a de novo event. In other diseases, the mutation was present in more than one community or even in other populations such as Bedouins from the Arab peninsula or Christians from Lebanon. In the 89 other disorders, more than one mutation was characterized either in the same gene or in more than one gene. While it is probable that most of these cases represent random events in some cases such as Bardet Biedl among the Bedouins, the reason may be a selective advantage to the heterozygotes.


Metabolic disorders in severe abdominal sepsis: glutamine deficiency in skeletal muscle.
The metabolic profiles of 14 patients with prolonged abdominal sepsis were analysed on the second day after laparotomy. The profiles of survivors were compared with those of non-survivors who died one to five days after the time of evaluation due to uncontrollable multiple organ failure. In the non-surviving patients plasma glucose and glucagon levels were significantly higher than in surviving patients. The plasma concentrations of phosphoserine, cysteine, valine, phenylalanine, and 3-methylhistidine were found to be significantly increased in non-survivors and their muscle tissue showed significantly decreased concentrations of glutamine, proline and lysine with increases in valine and leucine. A correct classification of non-survivors and survivors could be obtained from the plasma and muscle amino acid concentrations, the highest discriminant power being from muscle glutamine. In severe sepsis metabolic changes correlate with the outcome of the patients, and amino acid metabolism seems to be characterised by low concentrations of muscle glutamine and high levels of the branched chain amino acids possibly indicating an inhibited intracellular glutamine formation in muscle tissue.


Primary biliary cirrhosis: the future.
Primary biliary cirrhosis is a progressive cholestatic liver disease of presumed autoimmune etiology. Patterns of disease are changing with earlier recognition and better access to investigation and treatment. With the convergence of animal, genetic, and clinical studies over the coming years, it is hoped that a greater understanding in the pathophysiology of the disease will translate into improved clinical endpoints for patients.