Adolescents' perceptions of participation in group education using the Guided Self-Determination-Young method: a qualitative study.
Guided Self-Determination (GSD) is a person-centered communication and reflection method. Education in groups may have a greater impact than the content of the education, and constructive communication between parents and adolescents has been shown to be of importance. The purpose of this study was to describe adolescents' perceptions of participation in group education with the Guided Self-Determination-Young (GSD-Y) method, together with parents, in connection with the introduction of continuous subcutaneous insulin infusion. In the present qualitative interview study, 13 adolescents with type 1 diabetes were included after completing a GSD-Y group education program in connection with the introduction of continuous subcutaneous insulin infusion at three hospitals located in central Sweden. The adolescents were interviewed individually, and qualitative content analysis was applied to the interview transcripts. Two categories that emerged from the analysis were the importance of context and growing in power through the group process. An overarching theme that emerged from the interviews was the importance of expert and referent power in growing awareness of the importance of self-management as well as mitigating the loneliness of diabetes. GSD-Y has, in various ways, mitigated experiences of loneliness and contributed to conscious reflection about self-management in the group (referent power) together with the group leader (expert power). Overall, this highlights the benefits of group education, and the GSD method emphasizes the person-centered approach. ISRCTN22444034; Results.


Dilation of intraheptic bile ducts in choledochal cyst: case report with follow-up review of the literature.
Fifty-five cases of intrahepatic dilation of the bile ducts associated with choledochal cyst have been found in the literature, mostly reported over the past five years. Obstructive jaundice is often not present at an early stage in this group of patients, but dissociation of the serum bilirubin and alkaline phosphatase levels could be an early manifestation of this condition. Recent advances in diagnosis and new concepts of the cause and surgical management are reviewed. A case is reported where choledochocystojejunostomy was performed using automatic stapling instruments. Disappearance of symptoms, normalization of liver functions, and reduction in size of the cysts were observed during the two-year postoperative period.


Subjective and psychomotor effects of nitrous oxide in healthy volunteers.
The effects of nitrous oxide at subanesthetic doses (0%, 10%, 20%, and 40% in oxygen) on mood and psychomotor performance were determined in a group of 12 healthy volunteers (six males and six females). A randomized, placebo-controlled, double-blinded, crossover trial of five experimental sessions was used. Effects were measured before, during and after a 30-min inhalation period of the agent, using three subjective effects questionnaires (the Profile of Mood States, the Addiction Research Center Inventory, and the Visual Analogue Scale); and two psychomotor tests (auditory reaction time and Digit Symbol Substitution Test). In addition, an End-of-Session questionnaire, administered 60min after cessation of inhaling the agent, was used, which measured the subjects' reactions to the agent inhaled that day (i.e. peak concentration effect and concentration liking). The primary effects observed from nitrous oxide were confined to the inhalation of 20% and 40% concentrations. Subjects became more confused, sedated, high, dysphoric, and stimulated during inhalation of 40% nitrous oxide; fatigue, depression and anxiety increased after inhalation of 40% nitrous oxide had ceased. Significant or near-significant differences on several measures of subjective effects emerged between sexes. On the End-of-Session questionnaire, subjects' ratings of the peak effect of nitrous oxide were dose-related. There was individual variation in the degree to which subjects liked nitrous oxide: eight of the 12 subjects reported liking the 40% concentration, one was neutral, and three did not like it. Subjects' performance on the DSST was significantly impaired during inhalation of 40% nitrous oxide, but recovered soon after inhalation stopped. In summary, nitrous oxide had robust effects on mood, there appeared to be sex differences in the magnitude of subjective effects of nitrous oxide, and there was some variability in the extent to which subjects liked the anesthetic agent.


Expression of MHC class I polypeptide-related sequence A (MICA) in colorectal cancer.
Background: The major histocompatibility complex class I polypeptide-related sequence A (MICA) is one of the ligands of the natural killer group 2D (NKG2D) activating receptor. MICA stimulates NKG2D, which further triggers activation of natural killer cells and leads to killing of infected target cells. To subvert the biological function of NKG2D, tumor cells utilize an escape strategy by shedding overexpressed MICA. In this study, we determined the levels of MICA in colorectal cancers (CRCs). Additionally, we established correlations between MICA expression and clinical characteristics. Publicly available data and bioinformatics tools were used for validation purposes. Methods: We determined the MICA RNA expression levels and assessed their correlation with clinicopathological parameters in CRC using the UALCAN web-portal. We performed immunohistochemical analysis on tissue microarrays having 192 samples, acquired from 96 CRC patients, to validate the expression of MICA in CRC and adjacent uninvolved tissue and investigated its prognostic significance by Kaplan-Meier and proportional hazards methods. Results: Bioinformatics and immunohistochemical analyses showed that MICA expression was significantly upregulated in CRCs as compared to uninvolved tissue, and the overexpression of MICA was independent of pathologic stage, histotype, nodal metastasis status, p53-status, as well as patient's race, age and gender. Moreover, PROGgeneV2 survival analysis of two cohorts showed a poor prognosis for CRC patients exhibiting high MICA expression. Conclusions: Overall, our findings for CRC patients demonstrate generally high expression of MICA, and suggest that a poor prognosis relates to high MICA expression. These results can be further explored due to their potential to provide clues to the contribution of the tumor microenvironment to the progression of CRC.


Fluorogenic Sydnone-Modified Coumarins Switched-On by Copper-Free Click Chemistry.
The synthesis, photophysical characterization, and biochemical application of sydnone-modified coumarins, a novel class of fluorogenic clickable reagents, are reported. The sydnone moiety, a stable aromatic 1,3-dipole, efficiently quenched the fluorescence of coumarin, which could be restored, with a 132-fold enhancement, upon cycloadditions with cyclooctynes, thereby expanding the fluorogenic click toolbox. TD-DFT calculations suggest that the fluorescence quenching of the sydnone-modified coumarins is likely due to the presence of an energetically low-lying nonemissive charge-separated state.


Cutaneous Sarcoidosis.
Sarcoidosis is a chronic, multisystem, inflammatory disorder of unknown etiology that is characterized by noncaseating granulomas that impair normal organ functioning. Sarcoidosis predominantly affects the lungs, but the skin is often cited as the second most frequently involved organ. Cutaneous manifestations of sarcoidosis are highly variable and ongoing research seeks to better understand the relationship between clinical morphology and disease prognosis. Skin findings in patients with sarcoidosis can be "specific," in which sarcoidal granulomas infiltrate the skin, or they can represent a "nonspecific" reactive inflammatory process, as is seen in calcinosis cutis and erythema nodosum. Cutaneous sarcoidosis can be the initial presenting sign or develop later in the course of the disease. In some patients, the skin will be the most involved and impactful organ system and will drive therapy. In other cases, the skin will be an incidental or minor finding, but may be easily accessible for biopsy to confirm the diagnosis. There are many potential therapies for sarcoidosis, though no one therapy is universally effective.


Multidisciplinary and Multisociety Practice Guideline on Reprocessing Flexible Gastrointestinal Endoscopes and Endoscopic Accessories.
The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.


Inhibition of the sodium-dependent HCO3- transporter SLC4A4, produces a cystic fibrosis-like airway disease phenotype.
Bicarbonate secretion is a fundamental process involved in maintaining acid-base homeostasis. Disruption of bicarbonate entry into airway lumen, as has been observed in cystic fibrosis, produces several defects in lung function due to thick mucus accumulation. Bicarbonate is critical for correct mucin deployment and there is increasing interest in understanding its role in airway physiology, particularly in the initiation of lung disease in children affected by cystic fibrosis, in the absence of detectable bacterial infection. The current model of anion secretion in mammalian airways consists of CFTR and TMEM16A as apical anion exit channels, with limited capacity for bicarbonate transport compared to chloride. However, both channels can couple to SLC26A4 anion exchanger to maximise bicarbonate secretion. Nevertheless, current models lack any details about the identity of the basolateral protein(s) responsible for bicarbonate uptake into airway epithelial cells. We report herein that the electrogenic, sodium-dependent, bicarbonate cotransporter, SLC4A4, is expressed in the basolateral membrane of human and mouse airways, and that it's pharmacological inhibition or genetic silencing reduces bicarbonate secretion. In fully differentiated primary human airway cells cultures, SLC4A4 inhibition induced an acidification of the airways surface liquid and markedly reduced the capacity of cells to recover from an acid load. Studies in the Slc4a4-null mice revealed a previously unreported lung phenotype, characterized by mucus accumulation and reduced mucociliary clearance. Collectively, our results demonstrate that the reduction of SLC4A4 function induced a CF-like phenotype, even when chloride secretion remained intact, highlighting the important role SLC4A4 plays in bicarbonate secretion and mammalian airway function.


Cognitive Impairment in Older Adults With Concurrent Hearing and Vision Impairment: A Systematic Scoping Review Protocol.
Introduction: As the prevalence of age-related sensory impairment increases, more evidence emerges on the association between uni-sensory and cognitive impairment (CI) in older adults. However, the link between CI and concurrent hearing and vision impairment (referred to as dual sensory impairment/DSI) is not well-understood, and this combined effect may be additive or multiplicative. Moreover, the existing evidence on CI in older adults with DSI is scattered and limited. Through this systematic scoping review, we aim to map existing evidence on CI in older adults with DSI, and to summarize what is known about the prevalence, incidence and risk factors of CI, and tools used to screen or assess CI in older adults with DSI. Methods and Analysis: We will use the Joanna Briggs Institute framework to perform the review. Eleven databases [MEDLINE, CINAHL/EBSCO, EMBASE, Mednar, WorldWideScience, PsycEXTRA, OAIster, OpenGrey (SIGLE), Global Health, PsycINFO, and Web of Science] and clinical trial registries (ISRCTN Registry, WHO ICTRP, and ClinicalTrials.gov) will be searched. Study selection will be completed using Covidence, and data will be extracted using an a priori data extraction tool. To be included, studies had to be peer-reviewed, had older adults with DSI as the focal population, and are related to CI. Data will be presented using a narrative summary with emphasis on implications for future research and practice. Discussion: Reliable cognitive screening is of the utmost importance for prevention and treatment of CI within DSI population. The study findings will have significant implications for health services delivery and policy research. The summarized findings on the prevalence, incidence, associated risk factors, and CI screening and assessment tools will inform geriatric care. The review will also document knowledge gaps on CI in the DSI population and identify areas of interest for future studies. Ethics and Dissemination: The scoping study, being a review of existing documents, does not require ethics approval. The findings will be disseminated with relevant stakeholders using knowledge translation activities such as scientific presentations and publications. We intend to use the findings to conduct a Delphi study to evaluate which CI tools are suitable for older population with DSI.


Clinical outcomes according to symptom presentation in patients with acute myocardial infarction: Results from the FAST-MI 2010 registry.
Atypical clinical presentation in acute myocardial infarction (AMI) patients is not uncommon; most studies suggest that it is associated with unfavorable prognosis. Long-term clinical impact differs according to predominant symptom presentation (typical chest pain, atypical chest pain, syncope, cardiac arrest, or dyspnea) in AMI patients. FAST-MI 2010, a nationwide French registry, included 4169 patients with AMI in 213 centers at the end of 2010 (76% of active centers). Demographics, medical history, hospital management, and outcomes were compared according to predominant symptom presentation. Typical chest pain with no other symptom was reported in 3020 patients (68% in STEMI patients, 76% in NSTEMI patients). Atypical chest pain, dyspnea, syncope, and cardiac arrest were reported in 11%, 11%, 5%, and 1%, respectively. Patients with atypical clinical presentation had a higher cardiovascular risk profile and received fewer medications and a less invasive strategy. Using Cox multivariate analysis, atypical chest pain was not associated with higher death rate at 3 years (HR: 0.96, 95% CI: 0.69-1.33, P = 0.78), whereas cardiac arrest (HR: 2.44, 95% CI: 1.00-5.97, P = 0.05), syncope (HR: 1.70, 95% CI: 1.18-2.46, P = 0.005), and dyspnea (HR: 1.66, 95% CI: 1.31-2.10, P < 0.001) were associated with higher long-term mortality compared with patients with typical isolated chest pain. Similar trends were observed in STEMI and NSTEMI populations. Atypical clinical presentation is observed in about 20% of AMI patients. Cardiac arrest, dyspnea, and syncope represent independent predictors of long-term mortality in STEMI and NSTEMI populations.


[Experience with long-term outpatient use of cordarone in the prevention of paroxysms of atrial fibrillation (flutter)].
In a group of 250 patients suffering from frequent paroxysms of atrial fibrillations (flutters), the application of cordarone for 1 to 5 years prevented the occurrence of arrhythmic paroxysms in 23.6%, contributed to a reduction of their numbers up to 1 a year in 35.6%, up to 2-3 a year in 20.4%. Good and satisfactory results were obtained nearly in 80% of the patients. Cordarone failed to act in 10.4%. In 12.8%, the "escape" phenomenon was observed, i.e. loss of the agents' action following its long-acting effect when the patients were on a maintenance dosage. The results of the preventive usage of cordarone were not clearly related to the degree of atrial dilatation and the pattern of cardiac disease.


A statistical model for early estimation of the prevalence and severity of an epidemic or pandemic from simple tests for infection confirmation.
Epidemics and pandemics require an early estimate of the cumulative infection prevalence, sometimes referred to as the infection "Iceberg," whose tip are the known cases. Accurate early estimates support better disease monitoring, more accurate estimation of infection fatality rate, and an assessment of the risks from asymptomatic individuals. We find the Pivot group, the population sub-group with the highest probability of being detected and confirmed as positively infected. We differentiate infection susceptibility, assumed to be almost uniform across all population sub-groups at this early stage, from the probability of being confirmed positive. The latter is often related to the likelihood of developing symptoms and complications, which differs between sub-groups (e.g., by age, in the case of the COVID-19 pandemic). A key assumption in our method is the almost-random subgroup infection assumption: The risk of initial infection is either almost uniform across all population sub-groups or not higher in the Pivot sub-group. We then present an algorithm that, using the lift value of the pivot sub-group, finds a lower bound for the cumulative infection prevalence in the population, that is, gives a lower bound on the size of the entire infection "Iceberg." We demonstrate our method by applying it to the case of the COVID-19 pandemic. We use UK and Spain serological surveys of COVID-19 in its first year to demonstrate that the data are consistent with our key assumption, at least for the chosen pivot sub-group. Overall, we applied our methods to nine countries or large regions whose data, mainly during the early COVID-19 pandemic phase, were available: Spain, the UK at two different time points, New York State, New York City, Italy, Norway, Sweden, Belgium, and Israel. We established an estimate of the lower bound of the cumulative infection prevalence for each of them. We have also computed the corresponding upper bounds on the infection fatality rates in each country or region. Using our methodology, we have demonstrated that estimating a lower bound for an epidemic's infection prevalence at its early phase is feasible and that the assumptions underlying that estimate are valid. Our methodology is especially helpful when serological data are not yet available to gain an initial assessment on the prevalence scale, and more so for pandemics with an asymptomatic transmission, as is the case with Covid-19.


Full-mouth rehabilitation of a patient with ectodermal dysplasia with dental implants.
Oral findings in patients with ectodermal dysplasia (ED) include complete or partial hypodontia, anodontia, loss of vertical dimension of occlusion, protuberant lips, malformed and widely spaced conical-shaped teeth, and underdeveloped alveolar ridges. These patients present a substantial challenge in dental treatment. This case report presents oral rehabilitation of a 22-year-old male patient diagnosed with ED using an implant tooth-supported telescopic partial denture at the mandible and a tooth-supported telescopic partial denture at the maxilla. Implants in the mandible were placed at the sites of the right and left lateral incisor teeth. Following implant placement, the remaining buccal bone dehiscence was filled with deproteinized bovine bone graft and covered with resorbable membrane. To manage the vestibular insufficiency and to increase the keratinized mucosa in maxilla, bilateral acellular dermal matrix allograft was used on the right and left buccal aspects. The treatment described here improved the patient's functional and esthetic status while significantly restoring his oral health and self-esteem.


Optical coherence tomography for serial in vivo imaging of aortic plaque in the rabbit: a preliminary experience.
In this pilot feasibility study, we aimed to establish a reproducible means of performing serial optical coherence tomography (OCT) procedures in the abdominal aorta of the cholesterol-fed rabbit. Eight cholesterol-fed New Zealand White rabbits were assigned to abdominal aortic balloon injury at baseline (n=6) or as controls (n=2). Three of the balloon injured rabbits received statins from weeks 6 to 12 post balloon injury. OCT of the abdominal aorta in each rabbit was performed at baseline±week 6±week 12 via alternate vascular access points (left or right femoral artery or left carotid artery). OCT sequences were analysed to derive an indexed plaque volume and other OCT measures of plaque complexity, and results were compared between groups. Histopathological correlations with OCT images were made following terminal procedures. Of the 16 OCT procedures in these rabbits (6 at baseline, 4 at 6 weeks, 6 at 12 weeks), excellent and analysable images were obtained on 15 occasions (94%). Inability to obtain adequate arterial access for the OCT catheter was the major experimental limitation encountered in the early part of our experience. Balloon injured rabbits developed larger volume and more complex plaque than non-balloon injured rabbits on all OCT indices measured (eg, both mean plaque volume and lumen stenosis were approximately double in the balloon injured group, p<0.0001). A significant correlation between 12 week measures of plaque area by OCT and histology was demonstrated (Pearson correlation coefficient: 0.992, p<0.0001). Our preliminary experience suggests that serial OCT of the abdominal aorta in the New Zealand White rabbit is feasible and a potentially promising means of performing serial studies of aortic atherosclerosis.


The relation between radon in schools and in dwellings: A case study in a rural region of Southern Serbia.
Recognized as a significant health hazard, radon (Rn) has been given increasing attention for years. Surveys of different kinds have been performed in many countries to assess the intensity and the geographical extent of possible Rn problems. Common surveys cover mainly dwellings, the indoor place with highest occupancy, and schools, where people spend a large fraction of their lifetime and which can also be considered exemplary for Rn exposure at workplaces; it has however been observed that relating them is difficult. It was unclear whether residential Rn at a location, or in a region, can be predicted by Rn at a school of that location, or vice versa. To current knowledge, no general rule seems applicable, as few models to describe the relationship between Rn in dwellings and in schools have been developed. In Southern Serbia, a Rn survey in a predominantly rural region was based on measurements in primary schools. The question arose whether or to which degree the results can be considered as indicative or even representative for residential Rn concentrations. To answer the question an additional survey of indoor Rn concentrations in dwellings was initiated, designed and performed in Sokobanja district in 2010-2012 in a manner to be able to detect a relationship if it exists. In the study region, 108 dwellings in 12 villages and towns were selected, with one primary school each. In this paper, we investigate how a relation between Rn in schools and dwellings could be identified and quantified, by developing a model and using experimental data from both the above main and additional surveys. The key criterion is the hypothesis that the relation dwellings - schools, if it exists, is stronger for dwellings closer to a school than for those dwellings further away. We propose methods to test the hypothesis. As result, the hypothesis is corroborated at 95% significance level. More specifically, on town level (typical size about 1 km), the Rn concentration ratio dwelling/school is about 0.8 (geometrical mean), with geometrical standard deviation (GSD) about 1.9. For dwelling and school hypothetically in the same location, the ratio is estimated about 0.7 with GSD about 1.5. We think that the methodology can be applied to structurally similar problems. The results could be used to create "conditional maps" of Rn concentration in dwellings, i.e., for example a map of probabilities that indoor Rn concentrations in dwellings exceed 100 Bq/m3, as function of Rn concentration in the local school.


TWINKLE is an essential mitochondrial helicase required for synthesis of nascent D-loop strands and complete mtDNA replication.
Replication of the mammalian mitochondrial DNA (mtDNA) is dependent on the minimal replisome, consisting of the heterotrimeric mtDNA polymerase (POLG), the hexameric DNA helicase TWINKLE and the tetrameric single-stranded DNA-binding protein (mtSSB). TWINKLE has been shown to unwind DNA during the replication process and many disease-causing mutations have been mapped to its gene. Patients carrying Twinkle mutations develop multiple deletions of mtDNA, deficient respiratory chain function and neuromuscular symptoms. Despite its importance in human disease, it has been unclear whether TWINKLE is the only replicative DNA helicase in mammalian mitochondria. Furthermore, a substantial portion of mtDNA replication events is prematurely terminated at the end of mitochondrial control region (D-loop) and it is unknown whether TWINKLE also has a role in this abortive replication. Here, we present a conditional mouse knockout for Twinkle and demonstrate that TWINKLE is essential for mouse embryonic development and thus is the only replicative DNA helicase in mammalian mitochondria. Conditional knockout of Twinkle results in severe and rapid mtDNA depletion in heart and skeletal muscle. No replication intermediates or deleted mtDNA molecules are observed after Twinkle knockout, suggesting that TWINKLE once loaded is very processive. We also demonstrate that TWINKLE is essential for nascent H-strand synthesis in the D-loop, thus showing that there is no separate DNA helicase responsible for replication of this region. Our data thus suggest that the relative levels of abortive D-loop synthesis versus complete mtDNA replication are regulated and may provide a mechanism to control progression to complete mtDNA replication.


[Bidimensional-ultrasound guided-craniotomy in the excision of supratentorial brain tumours].
With this 1-year retrospective study we aimed to analyze our experience on the utilization of real-time bidimensional (2-D) ultrasonography as an aid for the localization of deep-seated supratentorial brain tumours. During the year 2006 we performed 2-D ultrasonographic localization studies in patients undergoing excision of subcortical supratentorial brain tumours whose nature was pathologically proven. The ultrasound machines utilized were 2410 A ultrasounds HP and Phillips HDI 3500 ATL. To check gross anatomical structures we used a 3 MHz probe and then a 5 MHz sound to define the brain tumour characteristics. Coronal and sagittal cuts were obtained during parietal or temporal craniotomies, and axial and sagittal slices in the case of frontal masses. After brain tumour removal and after a thorough irrigation with saline, new image acquisitions were performed to confirm the completeness of tumour excision. The amount of removed tumour was also verified by a post-contrast computerized tomography (CT) scan performed after the surgery. The study group was composed by 30 patients with ages comprised between 28 and 82 years. The time required for tumour localization was 17.5 (+/- 1.9) min. The lesions were approached though 8 temporal, 7 parieto-occipital, 8 parietal, 2 fronto-parietal and 5 temporo-parietal craniotomies. Mean depth of the lesions was 5.3 (+/- 1.6) cm. The histopathologic diagnosis was 17 high-grade gliomas, 3 low-grade astrocytomas, 8 metastatic lesions and 2 oligo-astrocytomas. High-grade gliomas were more echogenic than low-grade tumours and than oedema. No residual tumour was detected at the end of the surgery except in two cases in which a tumoral rest was left due to the proximity of the lesion to eloquent cerebral areas. Postoperative CT scans confirmed the completeness of tumour removal in the patients of the study as assessed by intraoperative ultrasounds. Real-time 2-D ultrasonography affords an adequate image quality for performing guided-craniotomy in supratentorial brain tumours, as it allows for a safe and accurate localization of the lesions. Its use is mainly indicated in the removal of tumours located in, or close to, important anatomical and functional brain areas and to depict the presence of tumour rests after surgical removal of cerebral neoplasms.


A novel 8-mm Schlemm's canal scaffold reduces outflow resistance in a human anterior segment perfusion model.
To study the effect on outflow facility and outflow resistance of a nitinol microstent implanted into Schlemm's canal. Using a constant pressure perfusion method, outflow facility and outflow resistance were measured in 26 pairs of dissected anterior segments from donated human eyes. Measurements were made at perfusion pressures of 10, 20, 30 and 40 mm Hg. The Hydrus Microstent was placed in Schlemm's canal of one eye and the contralateral eye underwent a sham procedure. Outflow facility and outflow resistance were measured again after the microstent implantation or sham procedure. The Hydrus Microstent significantly increased outflow facility from 0.33 ± 0.17 μL/min/mm Hg to 0.52 ± 0.19 μL/min/mm Hg (P < 0.001). Outflow resistance was significantly reduced from 4.38 ± 3.03 mm Hg/μL/min at baseline to 2.34 ± 1.04 mm Hg/μL/min (P < 0.001) with the microstent. There was a linear correlation between outflow resistance at baseline and decrease in outflow resistance with the microstent (R(2) = 0.89, P < 0.0001). The increase in outflow facility and decrease in resistance supports the potential use of the Hydrus Microstent as a surgical option to reduce intraocular pressure (IOP). The IOP-lowering effect may be higher in eyes with higher outflow resistance (and IOP) as compared with eyes with lower outflow resistance (and IOP).


Testing antiepileptic drugs in children.
Few drugs have been approved by the Food and Drug Administration specifically for the treatment of pediatric patients with epilepsy in the United States. There are many factors that make tests of drugs in this group different from studies among adults. This report reviews issues that must be considered in designing studies that will help bring to market antiepileptic drugs for children. Information on the wide variety of antiepileptic drugs rapidly being developed can only be obtained through well-controlled, well-designed clinical trials. Despite the obstacles and pitfalls, trials among the pediatric population are necessary to establish the unique efficacy and safety profile of each drug and to determine the target, population most likely to benefit from each drug.


The association of mammographic density with risk of contralateral breast cancer and change in density with treatment in the WECARE study.
Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these. We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association between %MD and CBC, adjusted for age, treatment, and other factors related to CBC, were estimated using logistic regression. Linear regression was used to estimate the association between treatment modality and change in %MD in 467 women with mammograms at both time points. For %MD assessed following diagnosis, there was a statistically significant trend of increasing CBC with increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but weaker, associations were noted for %MD measurements prior to/at diagnosis. The relationship appeared strongest in women aged < 45 years and non-existent in women aged 50 to 54 years. A decrease of ≥ 10% in %MD between first and second mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI 0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were associated with statistically significant 3% decreases in %MD (p < 0.01). Post-diagnosis measures of %MD may be useful to include in CBC risk prediction models with consideration of age at diagnosis. Chemotherapy is associated with reductions in %MD, similar to tamoxifen.


Association between body size and colorectal adenoma recurrence.
Obesity has been associated with increased risk for colorectal adenoma, although its role as a risk factor after polypectomy for recurrence is unclear. Therefore, we sought to evaluate the effect of anthropometric measures of obesity on adenoma after polypectomy. Subjects with baseline adenomas (n = 2465) and follow-up colonoscopy data were drawn from 2 randomized trials designed to prevent adenoma recurrence. Over a mean follow-up period of 3.1 years presence of a body mass index (BMI) > or = 30 kg/m2 was associated with a nonsignificant 17% increase in the odds for any adenoma recurrence among all subjects (odds ratio [OR], 1.17; 95% confidence interval [CI], 0.92-1.48). This result was confined to men (OR, 1.36; 95% CI, 1.01-1.83) and not observed for women (OR, 0.90; 95% CI, 0.60-1.33). Results for waist circumference did not reach statistical significance, although trends were similar to those for BMI. Analyses of the effects of obesity on more clinically significant lesions demonstrated that high BMI was a slightly stronger risk factor for advanced adenoma recurrences in men (OR, 1.62; 95% CI, 1.04-2.53) when compared with non-advanced lesions (OR, 1.26; 95% CI, 0.91-1.75). In addition, we observed an association for obesity and odds of adenoma recurrence among participants reporting a family history of colorectal cancer (OR, 2.25; 95% CI, 1.32-3.84) but not for those without (OR, 1.00; 95% CI, 0.77 to 1.31; P(int) = P = .008). Our results support obesity as a risk factor for subsequent short-interval (mean follow-up time 3.1 years) development of colorectal adenomas, particularly among men and persons with a family history of colorectal cancer. Furthermore, obesity in men appears to be strongly associated with the development of clinically advanced lesions.


Animus: human-embodied animals.
We review recent research to introduce human brain organoids into the brains of infant rats. This research shows these organoids integrate and function to affect behaviour in rats. We argue that this raises issues of moral status that will imminently arise and must be addressed through functional studies of these new life forms. We situate this research in the broader context of the biological revolution, arguing we already have the technological power to create fully human embodied animals. This raises profound, so far unaddressed ethical issues which call for urgent attention.


Incomplete cell disruption of resistant microbes.
Biomolecules for OMIC analysis of microbial communities are commonly extracted by bead-beating or ultra-sonication, but both showed varying yields. In addition to that, different disruption pressures are necessary to lyse bacteria and fungi. However, the disruption efficiency and yields comparing bead-beating and ultra-sonication of different biological material have not yet been demonstrated. Here, we show that ultra-sonication in a bath transfers three times more energy than bead-beating over 10 min. TEM imaging revealed intact gram-positive bacterial and fungal cells whereas the gram-negative bacterial cells were destroyed beyond recognition after 10 min of ultra-sonication. DNA extraction using 10 min of bead-beating revealed higher yields for fungi but the extraction efficiency was at least three-fold lower considering its larger genome. By our critical viewpoint, we encourage the review of the commonly used extraction techniques as we provide evidence for a potential underrepresentation of resistant microbes, particularly fungi, in ecological studies.


Evaluation the effect of preserving intercostobrachial nerve in axillary dissection for breast cancer patient.
The Intercostobrachial nerve (ICBN) is responsible for sensory function in the axillar and upper arm. The majority of surgeons routinely sacrifice the ICBN during axillary lymph node dissection (ALND) because of technical difficulties. Therefore, the aim of this study was to assess the effects of the preservation or division of the ICBN on the incidence of post-operative sensory disturbance, health-related quality of life (HRQOL), and the physical functions of the upper limbs. We performed a randomized double-blind trial comparing the incidence of sensory disturbance, HRQOL and physical functions of upper limbs in the preservation and the removal of the ICBN. Clinicians performed sensory evaluation at 2 weeks and 3 months after surgery. The sensory evaluation included questionnaires (subjective evaluation) and physical examination (objective evaluation) to evaluate sensory disturbance of the upper arm. HRQOL and physical function of upper limbs was accessed before surgery and at three months after surgery, using Short Form-36 and QuickDASH questionnaires, both in Thai language versions. At the end of the surgical procedures there were 15 patients in the preserved group (group P) and 28 patients in the non-preserved group (group N). In as-treated analysis, there was no significant difference between the groups in pain, sensory loss, physical examination of touch and pinprick sensation, and areas of sensory dullness. HRQOL found that the reported pain in P group was higher than N group in both intention-to-treat and as-treated analysis. In the QuickDASH scores of physical functions of the upper limbs there was a significant difference, 9.1 in group P and 20.5 in group N (P=0.013). ICBN preservation provides no benefit to improving sensation, but there are benefits in HRQOL and physical functions of upper limbs at three months after surgery.


Atomic force microscopy and its related techniques in biomedicine.
The atomic force microscope (AFM), invented in 1986, is a new instrument which provides three-dimensional surface images of samples by scanning a sharp probing tip over the sample surface. Unlike electron microscopes (EM), the AFM has the advantage to obtain high-resolution pictures not only in a vacuous but also in a non-vacuous (i.e., air or liquid) environment. This paper reviews our recent studies on the AFM application to the biomedical fields. AFM is useful for observing biological structures such as DNA, collagen molecules, collagen fibrils and chromosomes. AFM images of living cultured cells in liquid can be used for investigating the movement of cellular processes in relation to subcellular cytoskeletal elements. Recently, numerous AFM-related microscopes, or scanning probe microscopes (SPM), have been invented in parallel with the development of the AFM itself. These microscopes allow the simultaneous collection of topographical and other (e.g., viscoelastic, near-field optical) images of samples in the same portions. Thus, the combination of AFM and the other SPM has great potential for providing valuable new findings on structure and function of cells and tissues.


Evaluation of matrix-assisted laser desorption ionization mass spectrometry for polymer characterization.
A protocol for the preparation of polymeric samples for time-of-flight matrix-assisted laser desorption ionization mass spectrometry (TOF-MALDI-MS) analysis was developed. Dithranol was identified as a good matrix for polystyrene (PS), and the addition of silver for cationization of molecules was determined to be necessary. Based on this preparative method, low molecular weight samples of other polymers [polyisoprene, polybutadiene, poly(ethylene oxide), poly(methyl methacrylate), and polydimethylsiloxane] were analyzed with molecular weights up to 49 ku. The effects of laser intensity were determined to influence the molecular weight distribution of intact oligomers, most significantly for low molecular weight polymers. Linear and reflectron modes of analysis were evaluated; better signal intensity and resolution were obtained in the reflectron mode. The TOF-MALDI-MS measurements are compared with time-of-flight secondary ion mass spectrometry (TOF-SIMS) and gel permeation chromatography (GPC) for the same polymers. The M n values calculated by TOF-MALDI-MS consistently are higher than values calculated by TOF-SIMS for all classes of polymers with molecular weights up to 8 ku. The molecular weights of the PS calculated from TOF-MALDI-MS are in good agreement with GPC (±10%). The composition of the terminal group on a polymer chain may affect the ion yields. The ion yields of intact oligomers were evaluated as a function of end group composition for both TOF-MALDI-MS and TOF-SIMS. The slight disparity of results between TOF-SIMS and TOF-MALDI-MS for the perfluoroalkyl-terminated PS suggests that the oligomers are desorbed preferentially from the surface in the TOF-SIMS analysis, rather than having an increased ionization probability.


The role of toll-like receptor 9 in chronic stress-induced apoptosis in macrophage.
Emerging evidence implied that chronic stress has been exerting detrimental impact on immune system functions in both humans and animals. Toll-like receptors (TLRs) have been shown to play an essential role in modulating immune responses and cell survival. We have recently shown that TLR9 deficiency protects against lymphocyte apoptosis induced by chronic stress. However, the exact role of TLR9 in stress-mediated change of macrophage function remains unclear. The results of the current study showed that when BALB/c mice were treated with restraint stress (12 h daily for 2 days), the number of macrophages recruited to the peritoneal cavity was obviously increased. Results also demonstrated that the sustained effects of stress elevated cytokine IL-1β, TNF-α and IL-10 production yet diminished IFN-γ production from macrophage, which led to apoptotic cell death. However, TLR9 deficiency prevented the chronic stress-mediated accumulation of macrophages. In addition, knocking out TLR9 significantly abolished the chronic stress-induced imbalance of cytokine levels and apoptosis in macrophage. TLR9 deficiency was also found to reverse elevation of plasma IL-1β, IL-10 and IL-17 levels and decrease of plasma IFN-γ level under the condition of chronic stress. These results indicated that TLR9-mediated macrophage responses were required for chronic stress-induced immunosuppression. Further exploration showed that TLR9 deficiency prevented the increment of p38 MAPK phosphorylation and reduction of Akt/Gsk-3β phosphorylation; TLR9 deficiency also attenuated the release of mitochondrial cytochrome c into cytoplasm, caused upregulation of Bcl-2/Bax protein ratio, downregulation of cleavage of caspase-3 and PARP, as well as decreased TUNEL-positive cells in macrophage of stressed mice. Collectively, our studies demonstrated that deficiency of TLR9 maintained macrophage function by modulating macrophage accumulation and attenuating macrophage apoptosis, thus preventing immunosuppression in restraint-stressed mice.


Adaptive changes in the genomes of wild rabbits after 16 years of viral epidemics.
Since its introduction to control overabundant invasive European rabbits (Oryctolagus cuniculus), the highly virulent rabbit haemorrhagic disease virus (RHDV) has caused regular annual disease outbreaks in Australian rabbit populations. Although initially reducing rabbit abundance by 60%, continent-wide, experimental evidence has since indicated increased genetic resistance in wild rabbits that have experienced RHDV-driven selection. To identify genetic adaptations, which explain the increased resistance to this biocontrol virus, we investigated genome-wide SNP (single nucleotide polymorphism) allele frequency changes in a South Australian rabbit population that was sampled in 1996 (pre-RHD genomes) and after 16 years of RHDV outbreaks. We identified several SNPs with changed allele frequencies within or close to genes potentially important for increased RHD resistance. The identified genes are known to be involved in virus infections and immune reactions or had previously been identified as being differentially expressed in healthy versus acutely RHDV-infected rabbits. Furthermore, we show in a simulation study that the allele/genotype frequency changes cannot be explained by drift alone and that several candidate genes had also been identified as being associated with surviving RHD in a different Australian rabbit population. Our unique data set allowed us to identify candidate genes for RHDV resistance that have evolved under natural conditions, and over a time span that would not have been feasible in an experimental setting. Moreover, it provides a rare example of host genetic adaptations to virus-driven selection in response to a suddenly emerging infectious disease.


Genetics of resistance to phosphonoacetic acid in strain KOS of herpes simplex virus type 1.
A DNA- temperature-sensitive mutant of herpes simplex virus type 1 exhibiting thermolabile DNA polymerase activity, tsD9, was shown to be resistant to phosphonoacetic acid (PAA) when plated at the permissive temperature. ts+ revertants of tsD9 were PAA sensitive and exhibited DNA polymerase activity intermediate between that of the wild-type virus and tsD9, indicating that both temperature sensitivity and sensitivity to PAA are controlled by the same gene. Since the position of tsD9 on the existing herpes simplex virus type 1 linkage map is known, the locus for PAA resistance--and therefore for the structural gene for viral DNA polymerase--has been identified.


Effect of gender on trunk and pelvis control during lateral movements with perturbed landing.
In lateral reactive movements, core stability may influence knee and hip joint kinematics and kinetics. Insufficient core stabilisation is discussed as a major risk factor for anterior cruciate ligament (ACL) injuries. Due to the higher probability of ACL injuries in women, this study concentrates on how gender influences trunk, pelvis and leg kinematics during lateral reactive jumps (LRJs). Perturbations were investigated in 12 men and 12 women performing LRJs under three different landing conditions: a movable landing platform was programmed to slide, resist or counteract upon landing. Potential group effects on three-dimensional trunk, pelvic, hip and knee kinematics were analysed for initial contact (IC) and the time of peak pelvic medial tilt (PPT). Regardless of landing conditions, the joint excursions in the entire lower limb joints were gender-specific. Women exhibited higher trunk left axial rotation at PPT (women: 4.0 ± 7.5°, men: -3.1 ± 8.2°; p = 0.011) and higher hip external rotation at both IC and PPT (p < 0.01). But women demonstrated higher knee abduction compared to men. Men demonstrated more medial pelvic tilt at IC and especially PPT (men: -5.8 ± 4.9°, women: 0.3 ± 6.3°; p = 0.015). Strategies for maintaining trunk, pelvis and lower limb alignment during lateral reactive movements were gender-specific; the trunk and hip rotations displayed by the women were associated with the higher knee abduction amplitudes and therefore might reflect a movement strategy which is associated with higher injury risk. However, training interventions are needed to fully understand how gender-specific core stability strategies are related to performance and knee injury.


[Sonographic volumetry of the thyroid gland in the control o thyroxin and iodide treatment of non-toxic goiter].
In a prospective study 39 patients with diffuse euthyroid goitre were treated for one year with 100 micrograms levothyroxine (n = 19) or 500 micrograms iodide (n = 20). Efficacy of treatment was assessed by sonographic thyroid volumetry . In both forms of treatment maximum volume decrease was already seen within the first six months. After treatment for one year the mean decrease of thyroid volumes was 27.5% in the thyroxine group and 22% in the iodide group. This difference was statistically not significant. There was no difference in the extent of goitre size reduction within the thyroxine group among patients with complete TSH suppression and with still positive TRH test. Significant increases of T4 and of fT4 values within the normal range were observed already after one month with thyroxine treatment and only after 3 months with iodide treatment. There were no changes of the T3 values. In one female patient iodine-induced hyperthyroidism occurred. However, there were no further side effects in both treatment groups. This randomised study documents for the first time that both 500 micrograms of iodide and 100 micrograms of levothyroxine have a comparable efficacy for reduction of goitres.


Knowledge and attitudes toward transgender community among speech-language pathologists in India: A questionnaire-based exploration.
Background: During the transition process, transgender individuals may require voice and communication services. Speech-language pathologists are increasingly involved in rendering clinical services and assisting transgender clients in voice and communication therapy. Previous studies in different countries have highlighted the lack of competence expressed by the speech-language pathologists toward serving the members of the lesbian, gay, bisexual, transgender, and queer communities. Presently, no such findings are available in the Indian context. Thus, a need was felt for identifying the concerns toward treatment for transgender individuals in speech-language pathology settings in India. Aim: The aim of the present study was to assess the knowledge, comfort levels and attitudes of speech-language pathologists practicing in India regarding the transgender community. Method: An online survey method was used to assess the knowledge and attitudes among speech-language pathologists working in India toward the transgender community. Results: The findings of the study revealed higher comfort levels as compared to self-rated knowledge levels in addressing issues related to transgender healthcare. Evidence-based practices toward transgender healthcare emerged as the topic needing more information. The study also helped to identify several moral beliefs and practices for voice therapy for the transgender population. Conclusion: There is a strong need to educate the speech language pathologists toward transgender healthcare in order to promote better cultural competence. The findings of the present study help to identify the lacunae in knowledge as well as to highlight the need to have continuing education programs in this area.


Perceptual limits for a robotic rehabilitation environment using visual feedback distortion.
Imperceptible visual distortion, in the form of a disguised progression of performance goals, may be a helpful addition to rehabilitation after stroke and other brain injuries. This paper describes work that has been done to lay the groundwork for testing this hypothesis. We have constructed and validated an experimental environment that provides controllable visual distortion and allows precise force and position measurements. To estimate the amount of visual distortion that should be imperceptible, we measured the limits for force and distance/position perception in our rehabilitation environment for young and elderly unimpaired subjects and for a single traumatic brain injury (TBI) patient. We found the Just Noticeable Difference (JND) for produced force to be 19.7% (0.296 N) and the JND for movement distance/finger position to be 13.0% (3.99 mm) for young subjects (ages 18-35). For elderly subjects (ages 61-80), the JND for force was measured to be 31.0% (0.619 N) and the JND for distance/po'sition was 16.1% (5.01 mm). JNDs of 46.0% (0.920 N) and 45.0% (14.8 mm) were found for the motor-impaired individual. In addition, a subject's rating of effort was found to be profoundly influenced by visual feedback concerning the force magnitude. Even when this feedback was distorted, it accounted for 99% of the variance of the effort rating. These results indicate that substantial visual distortions should be imperceptible to the subject, and that visual feedback can be used to influence the subject's perceived experience in our robotic environment. This means that we should be able to use imperceptible visual distortion to alter a patient's perception of therapeutic exercise in a robotic environment.


Recent food shortage is associated with leprosy disease in Bangladesh: a case-control study.
Leprosy is remaining prevalent in the poorest areas of the world. Intensive control programmes with multidrug therapy (MDT) reduced the number of registered cases in these areas, but transmission of Mycobacterium leprae continues in most endemic countries. Socio-economic circumstances are considered to be a major determinant, but uncertainty exists regarding the association between leprosy and poverty. We assessed the association between different socio-economic factors and the risk of acquiring clinical signs of leprosy. We performed a case-control study in two leprosy endemic districts in northwest Bangladesh. Using interviews with structured questionnaires we compared the socio-economic circumstances of recently diagnosed leprosy patients with a control population from a random cluster sample in the same area. Logistic regression was used to compare cases and controls for their wealth score as calculated with an asset index and other socio-economic factors. The study included 90 patients and 199 controls. A recent period of food shortage and not poverty per se was identified as the only socio-economic factor significantly associated with clinical manifestation of leprosy disease (OR 1.79 (1.06-3.02); p = 0.030). A decreasing trend in leprosy prevalence with an increasing socio-economic status as measured with an asset index is apparent, but not statistically significant (test for a trend: OR 0.85 (0.71-1.02); p = 0.083). Recent food shortage is an important poverty related predictor for the clinical manifestation of leprosy disease. Food shortage is seasonal and poverty related in northwest Bangladesh. Targeted nutritional support for high risk groups should be included in leprosy control programmes in endemic areas to reduce risk of disease.


Combining many-objective radiomics and 3D convolutional neural network through evidential reasoning to predict lymph node metastasis in head and neck cancer.
Lymph node metastasis (LNM) is a significant prognostic factor in patients with head and neck cancer, and the ability to predict it accurately is essential to optimizing treatment. Positron emission tomography (PET) and computed tomography (CT) imaging are routinely used to identify LNM. Although large or highly active lymph nodes (LNs) have a high probability of being positive, identifying small or less reactive LNs is challenging. The accuracy of LNM identification strongly depends on the physician's experience, so an automatic prediction model for LNM based on CT and PET images is warranted to assist LMN identification across care providers and facilities. Radiomics and deep learning are the two promising imaging-based strategies for node malignancy prediction. Radiomics models are built based on handcrafted features, while deep learning learns the features automatically. To build a more reliable model, we proposed a hybrid predictive model that takes advantages of both radiomics and deep learning based strategies. We designed a new many-objective radiomics (MaO-radiomics) model and a 3D convolutional neural network (3D-CNN) that fully utilizes spatial contextual information, and we fused their outputs through an evidential reasoning (ER) approach. We evaluated the performance of the hybrid method for classifying normal, suspicious and involved LNs. The hybrid method achieves an accuracy (ACC) of 0.88 while XmasNet and Radiomics methods achieve 0.81 and 0.75, respectively. The hybrid method provides a more accurate way for predicting LNM using PET and CT.


Aesthetic Surgery Training during Residency in the United States: A Comparison of the Integrated, Combined, and Independent Training Models.
Background. Three educational models for plastic surgery training exist in the United States, the integrated, combined, and independent model. The present study is a comparative analysis of aesthetic surgery training, to assess whether one model is particularly suitable to provide for high-quality training in aesthetic surgery. Methods. An 18-item online survey was developed to assess residents' perceptions regarding the quality of training in aesthetic surgery in the US. The survey had three distinct sections: demographic information, current state of aesthetic surgery training, and residents' perception regarding the quality of aesthetic surgery training. Results. A total of 86 senior plastic surgery residents completed the survey. Twenty-three, 24, and 39 residents were in integrated, combined, and independent residency programs, respectively. No statistically significant differences were seen with respect to number of aesthetic surgery procedures performed, additional training received in minimal-invasive cosmetic procedures, median level of confidence with index cosmetic surgery procedures, or perceived quality of aesthetic surgery training. Facial aesthetic procedures were felt to be the most challenging procedures. Exposure to minimally invasive aesthetic procedures was limited. Conclusion. While the educational experience in aesthetic surgery appears to be similar, weaknesses still exist with respect to training in minimally invasive/nonsurgical aesthetic procedures.


A case of localised ureteric amyloidosis.
We describe a case of localised amyloidosis of the distal ureter in a 66-year-old lady who presented with intermittent haematuria. Ureteric transitional cell carcinoma was strongly suspected from the clinical and radiological features, and subsequent nephroureterectomy was performed. Histology revealed nodular eosinophilic deposits in the ureteric wall, with the staining characteristics of amyloid. The literature is reviewed, and conservative surgery is advocated, based on a greater awareness together with improved intraoperative diagnosis of this rare lesion.


COVID-19 associated Kawasaki-like multisystem inflammatory syndrome in an adult.
Recently, few reports have described a serious condition linked to SARS-CoV-2 that mimics Kawasaki disease called Multisystem inflammatory syndrome, especially in children (MIS-C) and young adults. In this work, we report on a severe form of MIS in a young female adult previously infected by SARS-CoV-2. She was treated by plasmapheresis with albumin and steroids, however outcome was fatal. We discuss the pathogenesis of this rare and life threatening entity and suggest some therapeutic regimen. This syndrome should not be misdiagnosed with an infectious or a drug induced cutaneous rash in the current context of COVID-19 pandemic.


[Study on the mechanisms of the intestinal tight-junction destruction caused by Blastocystis hominis infection in rats].
To explore the mechanism of the intestinal barrier damage caused by Blastocystis hominis infections in rats. Thirty SD rats were randomly divided into the control group, and the 1-, 3-, 6- and 9-week-infection groups, of 6 rats in each group. Rats in each infection group were orally infected with B. hominis trophozoites at a density of 2 × 108 parasites per rat, and the control group was given an equal volume of phosphate buffered saline solution. The 7-hour urine samples were collected 1, 3, 6 and 9 weeks post-infection for the measurement of the intestinal permeability. Then, rats were sacrificed using the cervical dislocation method, and the cecum specimens were collected for the detection of the intestinal epithelial cell permeability. The expression of tight junction-related Occludin and Claudin - 1 genes and apoptosis-related Bcl - 2 and Bax genes was quantified in cecum epithelial cells using the real-time fluorescent quantitative PCR (qPCR) assay, and cell apoptosis was detected in the rat cecum using the TdT-mediated dUTP nick-end labeling (TUNEL) assay. The median urinary lactolose to mannitol ratios were 0.29, 0.72, 0.44, 0.46 and 0.38 in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 12.09, P < 0.05). B. hominis invasion and epithelial injury were observed in intestinal epithelial cells of rats infected with B. hominis, and transmission electron microscopy displayed the destruction of tight junctions between intestinal epithelial cells. The relative expression of Occludin, Claudin-1, Bcl-2 and Bax genes was 1.04, 0.62, 0.71, 0.68 and 0.96; 1.03, 0.61, 0.63, 0.76 and 0.86; 1.08, 0.70, 0.75, 0.74 and 1.03; and 1.00, 1.57, 1.33, 1.35 and 1.10 in the control group and the 1-, 3-, 6- and 9-week-infection groups, respectively, and all differences were statistically significant (F = 2.86, 2.85, 3.37 and 4.45, all P values < 0.05). The median number of positive staining cells were 1.00, 13.00, 9.00, 3.50 and 1.00 in rat cecum specimens in the control group, and the 1-, 3-, 6- and 9-week-infection groups, respectively, and the difference was statistically significant (H = 22.95, P < 0.01). B. hominis infection may cause an increase in the rat intestinal permeability through triggering the apoptosis of intestinal epithelial cells to destroy the tight junction between intestinal epithelial cells, thereby destroying the intestinal barrier function.


An integrated strategy for prediction uncertainty analysis.
To further our understanding of the mechanisms underlying biochemical pathways mathematical modelling is used. Since many parameter values are unknown they need to be estimated using experimental observations. The complexity of models necessary to describe biological pathways in combination with the limited amount of quantitative data results in large parameter uncertainty which propagates into model predictions. Therefore prediction uncertainty analysis is an important topic that needs to be addressed in Systems Biology modelling. We propose a strategy for model prediction uncertainty analysis by integrating profile likelihood analysis with Bayesian estimation. Our method is illustrated with an application to a model of the JAK-STAT signalling pathway. The analysis identified predictions on unobserved variables that could be made with a high level of confidence, despite that some parameters were non-identifiable. Source code is available at: http://bmi.bmt.tue.nl/sysbio/software/pua.html.


Transdiagnostic perspective on psychological inflexibility and emotional dysregulation.
Psychological inflexibility and emotional dysregulation are a hallmark of psychopathology, being intrinsically embedded in emotional and personality disorders. However, the transdiagnostic mechanisms of psychological inflexibility and emotional dysregulation domains are still a matter of discussion. The present study aims to explore the relationships between cognitive fusion (as a measure of psychological inflexibility), emotion regulation strategies, such as cognitive reappraisal and emotional suppression and emotional dysregulation domains in two different samples. In a cross-sectional design, 297 individuals were assessed with self-report measures and divided into non-clinical (n = 231) and clinical samples (n = 66), according to diagnosis. Results showed that the degree of cognitive fusion was higher in the clinical sample. However, significant correlations between cognitive fusion, emotional regulation strategies and emotional dysregulation domains were found in the two samples. Cognitive reappraisal and emotional dysregulation domains predicted cognitive fusion and mediated the relationship between cognitive fusion and symptomatology in the two samples. Relationships between cognitive fusion and emotional dysregulation domains were found independent of diagnosis. The implementation of emotion regulation strategies may be related to individual differences. However, cognitive fusion, reappraisal and lack of strategies may be core transdiagnostic features in psychological inflexibility and emotion dysregulation.


The role of temperature and light on inhibition of development of Cooperia oncophora.
Infective Cooperia oncophora larvae were temperature and light conditioned by holding them at various temperatures and daily light intensities for up to 56 days prior to administration to parasite-free calves via stomach tube. The calves were killed either on day 20 or day 21 postinfection. A marked (up to 80.5%) inhibition of development occurred in larvae held at 4 degrees C while little or no inhibition occurred in larvae held at room temperature or in fresh larvae. Marked inhibition also occurred in larvae held at 15 degrees C for 56 days while a low rate of inhibition occurred in larvae held at 17 degrees C for 42 days. Low incidence of inhibition was recorded in two of four calves given larvae held at ambient temperatures of mid-summer while appreciable inhibition of development of larvae occurred in two calves permitted to graze during the second and third week of September in 1975. Temperature conditioning of C. oncophora eggs for 27 days did not result in inhibition of development of infective larvae subsequently cultured from the eggs. Photoperiod or the presence of light did not have any appreciable effect on the development of inhibition of C. oncophora under the conditions of these investigations.


Cultural and social network predictors of drinking among Korean American women.
This study estimated the association of cultural and social mechanisms with Korean American women's drinking behaviors. Data were drawn from telephone interviews with 591 Korean women selected from a random sample of households in California with Korean surnames during 2007. About 62% of eligible respondents completed the interview. Respondents reported any lifetime drinking (yes/no), drinking volume (typical number of drinks consumed on drinking days), level of acculturation, and described their social network by assessing who encouraged or discouraged drinking (drinking support) or drank (drinking models). Multivariable regressions were used for analyses. About 70% (95% confidence interval [95%CI]:, 67, 74) of Korean American women reported any lifetime drinking and current drinkers drank 1.18 (95%CI: 1.07, 1.28) drinks on drinking days. Acculturation was not significantly associated with any lifetime drinking or drinking volume, whereas models and support for drinking were statistically significantly associated with a higher probability of any lifetime drinking and drinking more on drinking days. Each additional encourager, or one or fewer discourager, for drinking in women's social networks was associated with a 2% (95%CI: 1, 3) higher probability of any lifetime drinking and drinking 0.25 (95%CI: -0.53, 1.18) more drinks on drinking days. Each additional drinker in women's networks was associated with a 4% (95%CI: 1, 8) higher probability of any lifetime drinking and drinking 0.26 (95%CI: -0.05, 0.60) more drinks on drinking days. Korean American women's drinking appears to be strongly related to their social networks, although how women take on traits of their new environment was not.


A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts.
Mitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist. We undertook a GWAS of qPCR-assayed mtDNA CN in the Avon Longitudinal Study of Parents and Children (ALSPAC) and the UK Blood Service (UKBS) cohort. After validating and harmonising data, 5461 ALSPAC mothers (16-43 years at mtDNA CN assay) and 1338 UKBS females (17-69 years) were included in a meta-analysis. Sensitivity analyses restricted to females with white cell-extracted DNA and adjusted for estimated or assayed cell proportions. Associations were also explored in ALSPAC children and UKBS males. A neutrophil-associated locus approached genome-wide significance (rs709591 [MED24], β (change in SD units of mtDNA CN per allele) [SE] - 0.084 [0.016], p = 1.54e-07) in the main meta-analysis of adult females. This association was concordant in magnitude and direction in UKBS males and ALSPAC neonates. SNPs in and around ABHD8 were associated with mtDNA CN in ALSPAC neonates (rs10424198, β [SE] 0.262 [0.034], p = 1.40e-14), but not other study groups. In a meta-analysis of unrelated individuals (N = 11,253), we replicated a published association in TFAM (β [SE] 0.046 [0.017], p = 0.006), with an effect size much smaller than that observed in the replication analysis of a previous in silico GWAS. In a hypothesis-generating GWAS, we confirm an association between TFAM and mtDNA CN and present putative loci requiring replication in much larger samples. We discuss the limitations of our work, in terms of measurement error and cellular heterogeneity, and highlight the need for larger studies to better understand nuclear genomic control of mtDNA copy number.


Pomegranate seed oil nanoemulsion enriched by α-tocopherol; the effect of environmental stresses and long-term storage on its physicochemical properties and oxidation stability.
In this study, pomegranate seed oil (PSO) nanoemulsions loading different amounts of α-tocopherol (0-40%) were produced. The nanoemulsions were fabricated by ultra-sonication method and the influence of thermal treatment (20-90 °C), pH (2-8) and ionic strength (0-500 mM NaCl) were investigated on physicochemical properties of all treatments. Moreover, the oxidative stability and α-tocopherol degradation were also assessed on optimal enriched nanoemulsion formulation during 50-day storage. The droplet diameter, viscosity, antioxidant activity, encapsulation efficiency and loading capacity of optimal formulation were 37.5 nm, 514 cp, 92%, 3.45% and 92.5%, respectively. The peroxide value changed in the range of 4.5-5.3 and 6.7-10.5 meq O2/kg in loaded and unloaded nanoemulsions, respectively. Transmission electron microscopy demonstrated spherical morphology of nanoemulsion droplets with diameter average of 40 nm. This study suggested that PSO nanoemulsion loading α-tocopherol could be introduced as delivery system with favorable features under severe environmental conditions.


Cytofluorometric isolation of I937, an Ia antigen-bearing variant of the Ia-negative human monocytic cell line U937.
Cells of the human monocyte cell line U937 are generally considered devoid of any Ia antigens on their surface. In analyzing U937 cells with a large panel of monoclonal anti-human Ia antibodies by flow cytometry, we detected a small number of cells that appeared to react with antibodies to HLA-DR and HLA-DS/DC molecules. These Ia-positive cells were isolated and were cloned, resulting in a human monocyte cell line that expresses high levels of Ia antigens. We analyzed these antigens by one- and two-dimensional polyacrylamide gel electrophoresis, after radiolabeling and immunoprecipitation. Three distinct Ia molecules, alpha 1 beta 1, alpha 1 beta 3 (HLA-DR-like), and alpha 2 beta 2 (HLA-DC/DS-like) are synthesized by I937 cells, alpha 1 beta 3 molecule being the predominant species. The Ia antigen-bearing human monocyte cell line is expected to be useful for studying events involved in antigen presentation.


On dental caries and caries-related factors in children and teenagers.
Dental caries is still a common disease among children and adolescents. The aims of the present thesis were therefore: 1) to investigate the approximal caries prevalence in posterior teeth in 15-year-olds, 2) to study past caries experience in the primary dentition in relation to future caries development and need for treatment, 3) to investigate factors during early childhood which are associated with caries development later in life, and 4) to study the association between age-specific body mass index (isoBMI) and approximal caries status in 15-year-olds. Paper I has a retrospective design and the analyses were based on record data from a randomly selected sample. Papers II, III and IV are based on radiographic analyses of posterior teeth in 15-year-olds followed longitudinally from 1 to 15 years of age. The data for these studies were selected from examinations, interviews and questionnaires from early childhood and school health care records at 15 years (isoBMI values). The result showed that the approximal caries prevalence in 15-year-olds is underestimated in official caries data, since initial caries lesions are not included in these statistics. Two thirds of all 15-year-olds had approximal caries and initial caries constituted 86% of the total number of caries lesions. There was a strong relationship between caries in early childhood and approximal caries prevalence in the posterior teeth at 15 years of age. Children with caries experience at 6 years received significantly more treatment in the primary dentition during the period from 7 to 12 years compared with children who were caries free at the same age. Further, it was pointed out that parents' attitudes to dental health and psychosocial factors during early childhood have an effect on approximal caries in 15-year-olds. Additionally, plaque on primary incisors at 1 year of age and infrequent toothbrushing at 3 years of age were associated with a high caries experience at 15 years. It was also demonstrated that adolescents with overweight and obesity had a significantly higher approximal caries prevalence than those of normal weight. Furthermore, it was shown that children's unfavourable snacking habits at 1 and 3 years of age were associated with approximal caries at 15 years. The main conclusions from this thesis are that: 1) epidemiologicalcaries data should include initial caries lesions on approximal tooth surfaces, in order to show the actual caries prevalence, 2) there is a strong relationship between caries in early childhood and approximal caries prevalence in the posterior teeth at 15 years of age, 3) the psychosocial environment in which children live during their childhood has an impact on dental health later in life, 4) good oral hygiene habits including the use of fluoride toothpaste, established in early childhood, provide a foundation for good dental health in adolescence, and 5) future preventive programmes should include, at a multidisciplinary level, strategies to prevent and reduce both dental caries and obesity at an early age.


The prevalence of quadriceps weakness in COPD and the relationship with disease severity.
Quadriceps strength relates to exercise capacity and prognosis in chronic obstructive pulmonary disease (COPD). We wanted to quantify the prevalence of quadriceps weakness in COPD and hypothesised that it would not be restricted to patients with severe airflow obstruction or dyspnoea. Predicted quadriceps strength was calculated using a regression equation (incorporating age, sex, height and fat-free mass), based on measurements from 212 healthy subjects. The prevalence of weakness (defined as observed values 1.645 standardised residuals below predicted) was related to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and Medical Research Council (MRC) dyspnoea score in two cohorts of stable COPD outpatients recruited from the UK (n = 240) and the Netherlands (n = 351). 32% and 33% of UK and Dutch COPD patients had quadriceps weakness. A significant proportion of patients in GOLD stages 1 and 2, or with an MRC dyspnoea score of 1 or 2, had quadriceps weakness (28 and 26%, respectively). These values rose to 38% in GOLD stage 4, and 43% in patients with an MRC Score of 4 or 5. Quadriceps weakness was demonstrable in one-third of COPD patients attending hospital respiratory outpatient services. Quadriceps weakness exists in the absence of severe airflow obstruction or breathlessness.


Catalytic Dyad Residues His41 and Cys145 Impact the Catalytic Activity and Overall Conformational Fold of the Main SARS-CoV-2 Protease 3-Chymotrypsin-Like Protease.
Coronaviruses are responsible for multiple pandemics and millions of deaths globally, including the current pandemic of coronavirus disease 2019 (COVID-19). Development of antivirals against coronaviruses, including the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) responsible for COVID-19, is essential for containing the current and future coronavirus outbreaks. SARS-CoV-2 proteases represent important targets for the development of antivirals because of their role in the processing of viral polyproteins. 3-Chymotrypsin-like protease (3CLpro) is one such protease. The cleavage of SARS-CoV-2 polyproteins by 3CLpro is facilitated by a Cys145-His41 catalytic dyad. We here characterized the catalytic roles of the cysteine-histidine pair for improved understanding of the 3CLpro reaction mechanism, to inform the development of more effective antivirals against Sars-CoV-2. The catalytic dyad residues were substituted by site-directed mutagenesis. All substitutions tested (H41A, H41D, H41E, C145A, and C145S) resulted in a complete inactivation of 3CLpro, even when amino acids with a similar catalytic function to that of the original residues were used. The integrity of the structural fold of enzyme variants was investigated by circular dichroism spectroscopy to test if the catalytic inactivation of 3CLpro was caused by gross changes in the enzyme secondary structure. C145A, but not the other substitutions, shifted the oligomeric state of the enzyme from dimeric to a higher oligomeric state. Finally, the thermodynamic stability of 3CLpro H41A, H41D, and C145S variants was reduced relative the wild-type enzyme, with a similar stability of the H41E and C145A variants. Collectively, the above observations confirm the roles of His41 and Cys145 in the catalytic activity and the overall conformational fold of 3CLpro SARS-CoV-2. We conclude that the cysteine-histidine pair should be targeted for inhibition of 3CLpro and development of antiviral against COVID-19 and coronaviruses.


Cross-referencing eukaryotic genomes: TIGR Orthologous Gene Alignments (TOGA).
Comparative genomics promises to rapidly accelerate the identification and functional classification of biologically important human genes. We developed the TIGR Orthologous Gene Alignment (TOGA; <http://www.tigr.org/tdb/toga/toga.shtml>) database to provide a cross-reference between fully and partially sequenced eukaryotic transcribed sequences. Starting with the assembled expressed sequence tag (EST) and gene sequences that comprise the 28 TIGR Gene Indices, we used high-stringency pair-wise sequence searches and a reflexive, transitive closure process to associate sequence-specific best hits, generating 32,652 tentative ortholog groups (TOGs). This has allowed us to identify putative orthologs and paralogs for known genes, as well as those that exist only as uncharacterized ESTs and to provide links to additional information including genome sequence and mapping data. TOGA provides an important new resource for the analysis of gene function in eukaryotes. In addition, an analysis of the most widely represented sequences can begin to provide insight into eukaryotic biological processes.


Fluoroquinolone use and the change in incidence of tendon ruptures in the Netherlands.
Shortly after their introduction, fluoroquinolones were associated with reports of tendinitis and tendon rupture. During the past years, the number of reports has risen, possibly because of an increased use of fluoroquinolones. In this study, we describe the use of fluoroquinolones in the Dutch community and the possible public health effects of an association between fluoroquinolone use and tendon ruptures. In the PHARMO drug database we identified all prescriptions for fluoroquinolones in the period 1991-1996. The incidence of fluoroquinolone use was expressed as the number of fluoroquinolone episodes per 1000 inhabitants in one year, and extrapolated to the Dutch population after standardisation on age and gender. The annual incidence of non-traumatic tendon ruptures in the period 1991-1996 was calculated with data from the nation-wide hospital registry. The expected number of fluoroquinolone attributable tendon ruptures was calculated on the basis of the use of fluoroquinolones, the number of non-traumatic tendon ruptures and an assumed relative risk of 1.5-10. In 1996, approximately 251,000 patients experienced 318,000 episodes of fluoroquinolone use in the Netherlands. Females used more often fluoroquinolones than males, and the number of episodes increased exponentially with age. In the period 1991 through 1996, the absolute number of fluoroquinolone episodes increased by 160%, from 122,000 to 318,000. The absolute number of hospitalised tendon ruptures increased with 28%, from 768 in 1991 to 984 in 1996. Assuming a relative risk of 1.5 to 10.0, 1 to 15 tendon ruptures could be attributed to fluoroquinolone use in 1996. Only 7% of the observed increase could be attributed to the increased use of fluoroquinolones. If the total increase of hospitalised non-traumatic tendon ruptures would be attributable to the increase in fluoroquinolone use, this would mean that the risk of non traumatic tendon ruptures to fluoroquinolones would be more than 250 times the risk during non-use. In the Netherlands, a large simultaneous increase in non-traumatic tendon ruptures and fluoroquinolone use was observed in the period between 1991 to 1996. Assuming a relative risk of 1.5 to 10.0 for tendon ruptures during fluoroquinolone use, only 0.5 to 7% of the increase in non-traumatic tendon ruptures could be attributed to the increased fluoroquinolone use. The increase in the incidence of non-traumatic hospitalised tendon ruptures in the Netherlands is not likely to be explained solely by the increased use of fluoroquinolones.


New observations on antigenic diversification of RNA viruses. Antigenic variation is not dependent on immune selection.
Recent results have revealed novel features in the process of antigenic diversification of FMDV. (i) Antigenic variation is not necessarily the result of immune selection. (ii) Single, critical amino acid replacements may either have a minor effect on antigenic specificity or cause a drastic antigenic change affecting many epitopes on an antigenic site. (iii) The effect of such a critical replacement may be suppressed by additional substitutions at neighbouring sites. (iv) Antigenic diversification does not necessarily involve net accumulation of amino acid substitutions over time. We review evidence that some of these features apply also to other riboviruses and retroviruses. A model is proposed to relate antigenic variation without immune selection to the quasispecies structure of RNA virus populations.


The effect of patient transfer on outcomes after rupture of an abdominal aortic aneurysm.
Centralization of vascular surgery services has resulted in patients being transferred longer distances for treatment of life-threatening conditions. The purpose of this study was to determine whether patient transfer adversely affects the survival of people with a ruptured abdominal aortic aneurysm (RAAA). We performed a retrospective review of all patients undergoing attempted repair of an RAAA at our centre, over a recent 3.5-year period (August 2000-December 2003). Patients were divided into those presenting directly to our centre and those transferred from another hospital. The main outcome variable was in-hospital or 30-day mortality, with secondary variables including time to surgical treatment, mortality in the first 24 hours and length of hospitalization. Eighty-one patients (73% men) underwent attempted open repair of an RAAA at our centre during this period. Twenty-four patients (29.6%) presented directly to our hospital, while 57 (70.4%) were transferred from another institution. The overall mortality rate was 53%. Although transferred patients took twice as long as direct patients to get to the operating room (6.3 v. 3.2 h, p=0.03), there was no difference in mortality between the 2 groups (50% v. 54%, p=ns). However, deaths of transferred patients were more likely to occur in the first 24 postoperative hours, compared with direct patients (40% v. 33%, p<0.05). Neither mean intensive care unit stay (5.8 and 8.1 d) nor total hospitalization (20.9 and 18.8 d) differed between the 2 groups. Although the transfer of patients with RAAA results in a treatment delay, it does not adversely affect the already high mortality rates associated with this condition. These results may be attributed to a preselection of patients who are able to tolerate such a delay.


Simultaneous determination of five tobacco-specific nitrosamines in mainstream cigarette smoke by isotope dilution liquid chromatography/electrospray ionization tandem mass spectrometry.
Tobacco-specific nitrosamines (TSNAs) have been previously implicated as a source of carcinogenicity in tobacco and cigarette smoke. Accurate quantification of these chemicals is needed to help assess public health risk. We have developed and validated a specific and sensitive method to simultaneously measure five TSNAs in the particulate phase of mainstream tobacco smoke. Cigarette smoke particulate, produced using standardized machine smoking protocols, was collected on a Cambridge filter pad. The particulate matter was extracted using methylene chloride, back extracted into aqueous solution, further purified by solid-phase extraction, and analyzed by liquid chromatography/electrospray ionization tandem mass spectrometry using isotopically labeled analogues as internal standards. Limits of detection for this method ranged from 0.05 to 1.23 ng/mL using an injection volume of 20 microL. A linear calibration range spanning 2.5-2500 ng/mL was adequate to measure TSNA levels in cigarette smoke. The method achieved excellent reproducibility and accuracy. The identity of each TSNA was established by chromatographic retention time, analyte-specific fragmentation patterns, and relative peak area ratios of two product/precursor ion pairs. This new method provides higher sensitivity, specificity, and throughput than earlier methods for TSNA determination.


Odontoid screw placement for Anderson type II odontoid fractures: how do duration from injury to surgery and clinical and radiological factors influence the union rate? A multicenter retrospective study.
Anderson type II odontoid fractures are severe conditions, mostly affecting elderly people (≥ 70 years old). Surgery can be performed as a primary treatment or in cases of failed conservative management. This study aimed to investigate how duration from injury to surgery, as well as clinical, radiological, and surgical risk factors, may influence the union rate after anterior odontoid screw placement for Anderson type II odontoid fractures. The authors conducted a retrospective multicenter study. Demographic, clinical, surgical, and radiological data of patients who underwent anterior odontoid screw placement for Anderson type II fractures were retrieved from institutional databases. Study exclusion criteria were prolonged corticosteroid drug therapy (> 4 weeks), polytraumatic injuries, oncological diagnosis, and prior cervical spine trauma. Eighty-five patients were included in the present investigation. The union rate was 76.5%, and 73 patients (85.9%) did not report residual instability. Age ≥ 70 years (p < 0.001, OR 6), female gender (p = 0.016, OR 3.61), osteoporosis (p = 0.009, OR 4.02), diabetes (p = 0.056, OR 3.35), fracture diastasis > 1 mm (p < 0.001, OR 8.5), and duration from injury to surgery > 7 days (p = 0.002, OR 48) independently influenced union rate, whereas smoking status (p = 0.677, OR 1.24) and odontoid process angulation > 10° (p = 0.885, OR 0.92) did not. Although many factors have been reported as influencing the union rate after anterior odontoid screw placement for Anderson type II fractures, duration from injury to surgery > 7 days appears to be the most relevant, resulting in a 48 times higher risk for nonunion. Early surgery appears to be associated with better radiological outcomes, as reported by orthopedic surgeons in other districts. Prospective comparative clinical trials are needed to confirm these results.


A Systematic Review Comparing the Surgical Outcomes of Open Versus Minimally Invasive Surgery for Congenital Diaphragmatic Hernia Repair.
Introduction: Surgical intervention is the definitive management for congenital diaphragmatic hernia (CDH) repair from 1902. Since this time, two mainstay approaches have been used, open and minimally invasive surgical (MIS) repair. An invasive laparotomy is used in around 91% of cases. So, this systematic review of the published literature will compare the surgical outcomes of open (CDH) repair vs MIS for CDH repair and will determine which approach is superior. Material and Methods: Our literature search across MEDLINE and EMBASE included articles from 2004 to 2022, incorporating pediatric CDH repairs, human subjects only, and English language articles. Primary outcomes analyzed were rate of recurrence, length of surgery, length of hospital stay, use of diaphragmatic patch, mortality, postoperative chylothorax, and extracorporeal membrane oxygenation (ECMO) use postoperatively. Results: After application of exclusion criteria, 32 articles were reviewed. Comparison of MIS repair versus open repair had a rate of recurrence at 8.6% versus 1.6% (P < .00001). Length of hospital stay was 19.6 days versus 33.6 days (P = .0012), mortality rate at 4.6% versus 16.6% (P < .0001), patch repair required in 19.6% versus 55.4% (P = < .00001), and postoperative ECMO use of 3.7% versus 12.3% (P < .00001), respectively. Conclusion: MIS repair is associated with decreased length of hospital stay, reduced mortality rate, and postoperative ECMO usage. Hernia recurrence is still high among MIS repair groups compared to the open repair groups. Large, multicentered randomized control trials are recommended for further analysis to decipher the true superior surgical intervention.


Fluorescence spectra of atmospheric aerosol particles measured using one or two excitation wavelengths: comparison of classification schemes employing different emission and scattering results.
An improved Dual-wavelength-excitation Particle Fluorescence Spectrometer (DPFS) has been reported. It measures two fluorescence spectra excited sequentially by lasers at 263 nm and 351 nm, from single atmospheric aerosol particles in the 1-10 mum diameter size range. Here we investigate the different levels of discrimination capability obtained when different numbers of excitation and fluorescence-emission wavelengths are used for analysis. We a) use the DPFS to measure fluorescence spectra of Bacillus subtilis and other aerosol particles, and a 25-hour sample of atmospheric aerosol at an urban site in Maryland, USA; b) analyze the data using six different algorithms that employ different levels of detail of the measured data; and c) show that when more of the data measured by the DPFS is used, the ability to discriminate among particle types is significantly increased.


Inaccuracy of accumulated degree day models for estimating terrestrial post-mortem intervals in Cape Town, South Africa.
In forensic death investigations, estimating the postmortem interval (PMI) is critical. An accurate PMI estimate increases the speed and accuracy of identifying the remains by narrowing the time frame in which the death occurred, thus reducing the pool of possible decedents. Cape Town, South Africa has a high level of unnatural death, and due to a burdened death investigation system, many remain unidentified. There has been a tendency to broadly apply quantitative models of decomposition across biogeographically unique circumstances. A prime example is the widespread application of the total body score (TBS)/accumulated degree day (ADD) model developed by Megyesi et al. (2005), later refined by Moffatt et al. (2016). However, the appropriateness of applying a single model to a wide range of locations with unique geography and climates remains in question. The aim of the study was to evaluate and compare the accuracy of Megyesi and Moffatt models for estimating PMI in Cape Town, South Africa. Using pig carcasses, Finaughty established baseline data on the rates and patterns of terrestrial decomposition in summer and winter in two different locations in a forensically significant area of Cape Town. Among the baseline data, Finaughty derived TBS values using the Megyesi criteria. The present study used these values to estimate the ADD per the Megyesi and Moffatt models, which would correspond to an estimated PMI. These estimated values were compared to actual ADD values. Estimates of ADD were inaccurate for both models in winter, and only partially in summer. The Moffatt model was more accurate in earlier decomposition stages, with the Megyesi model more accurate in later decomposition stages. These results indicate the Cape Town environments may contain factors that the two models do not consider, producing inaccurate PMI estimations at various TBS' values. ADD does not depict the entire taphonomic story; the decomposition process appears to be too complex for universal modelling based on a single or narrow suite of variables. Seasonality was an important factor in determining the accuracy of the models, primarily resulting in underestimations of the true PMI values. These findings show the impracticality of applying models developed for- or in one region to any other and support the need to establish regionally-specific equations for estimating PMI in a forensic context. Alternatively, more complex models employing "big data" from a more comprehensive suite of variables which influence the rate and pattern of decay could be developed.


[A preliminary study on the relation of peripheral blood lymphocyte beta-adrenoceptors and airway reactivity in asthmatics].
The beta-adrenoceptors on intact peripheral blood lymphocytes were studied in 21 allergic asthmatics. 11 TDI asthmatics and 17 normal subjects with radioligand binding assay technique. The airway responsiveness to methacholine provocation test was determined. The results indicated that beta-adrenoceptor Bmax values in allergic and TDI asthmatics were reduced but the affinity between receptor and ligand was increased there was a positive correlation between the values of Bmax and FEV1%, V25/Pr in both asthmatic groups, a positive correlation between the values of Bmax and PC20 in allergic asthmatics. The beta-adrenoceptor responsiveness was remarkably reduced in allergic asthmatics.


Evaluation and optimization of common lipid extraction methods in cerebrospinal fluid samples.
A typical lipidomics approach aims at the simultaneous analysis of a multitude of lipid species from different lipid classes with highest possible sensitivity for all target lipids. Efficient extraction of lipids from the biological matrix is a crucial step in the analytical workflow. Whereas numerous applications of classical and more recently published extraction methods have been reported for blood serum or plasma samples, very little is known about the applicability of these methods for cerebrospinal fluid (CSF). CSF though represents a highly interesting biofluid for the investigation of neurological disorders, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, or brain cancer. Since CSF comprises substantially lower endogenous lipid concentrations compared to serum or plasma, the use of highly efficient extraction methods is of utmost importance. In addition, literature on lipid extraction methods is often inconsistent in terms of methodological parameters like temperature, mixing times, or the number of repeated extraction cycles. In this study, four liquid-liquid extraction methods (Folch, Bligh & Dyer, MTBE and BUME) and one protein precipitation method (MMC method) were evaluated using a pooled CSF sample, followed by the investigation of key process parameters (temperature and mixing times) and modifications of the most promising methods, in order to achieve a broad coverage of lipid classes as well as high recoveries and repeatabilities. A modified Folch method turned out as most suitable for the efficient extraction of a broad range of lipid classes from CSF including glycerophospholipids, glycerolipids and sphingolipids. In addition, using cooled solvents and equipment was shown to significantly improve lipid extraction efficiencies. Mixing times should be thoroughly optimized for the lipid classes of interest in order to achieve high recoveries without lipid degradation due to unnecessarily long mixing. Finally, acidification led to improved extraction efficiency for acidic glycerophospholipids.