Frequency of Breakfast Eating and Obesity Prevalence in Primary School Teachers.
There is a lack of research using objective measures about teachers' physical characteristics and lifestyle. The purpose of the study was to evaluate the relationship between frequency of breakfast consumption and body size, body composition, blood pressure and lifestyle factors in teachers from Hungary. The study analyzed data collected from 99 female primary school teachers (50.6 ± 6.6 year) before the COVID-19 pandemic. Anthropometric and resting blood pressure measurements were taken for each participant. Questionnaires were used to assess lifestyle factors (i.e., physical activity level, smoking status and eating breakfast). The frequency of eating breakfast was classified as rarely or never (0-2 days), some days (3-5 days) and regularly (6-7 days). Sixty-five percent of female teachers consumed breakfast 6-7 days/week, and this regular eating habit was positively associated with a lower risk of obesity (OR 0.29; CI: 0.10-0.80). In our sample, a higher frequency of breakfast consumption was not significantly associated with smoking (OR 2.65; CI: 0.17-1.37), hypertension (OR 0.61; CI: 0.23-1.65) and inactivity (OR 2.80; CI: 0.26-1.84). A beneficial effect of eating breakfast regularly was found on body composition in female teachers. Further studies should focus on the health behaviors of teachers and their relationship with physical activity or diagnosed diseases in urban and rural areas.


Diagnostic performance of endocytoscopy with normal pit-like structure sign for colorectal low-grade adenoma compared with conventional modalities.
A "resect-and-discard" strategy has been proposed for diminutive adenomas in the colorectum. However, this strategy is sometimes difficult to implement because of the lack of confidence in differentiating low-grade adenoma (LGA) from advanced lesions such as high-grade adenoma or carcinoma. To perform real-time precise diagnosis of LGA with high confidence, we assessed whether endocytoscopy (EC) diagnosis, considering normal pit-like structure (NP-sign), an excellent indicator of LGA, could have additional diagnostic potential compared with conventional modalities. All the neoplastic lesions that were observed by non-magnifying narrow-band imaging (NBI), magnifying NBI (M-NBI), magnifying pit pattern, and EC prior to pathological examination between 2005 and 2018 were retrospectively investigated. The neoplastic lesions were classified into two categories: LGA and other neoplastic lesions. We assessed the differential diagnostic ability of EC with NP-sign between LGA and other neoplastic lesions compared with that of NBI, M-NBI, pit pattern, and conventional EC in terms of sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC). A total of 1376 lesions from 1097 patients were eligible. The specificity (94.9%), accuracy (91.5%), and area under the receiver operating characteristic curve (0.95) of EC with NP-sign were significantly higher than those of NBI, M-NBI, pit pattern, and conventional EC. EC diagnosis with NP-sign has significantly higher diagnostic performance for predicting colorectal LGA compared with the conventional modalities and enables stratification of neoplastic lesions for "resect-and-discard" with higher confidence.


Effect of xylitol-containing chewing gums on interdental plaque-pH in habitual xylitol consumers.
The aim was to investigate the effect of high and low amounts of xylitol on the interdental plaque-pH, directly and after sucrose challenge, in schoolchildren with habitual consumption. The study group consisted of 11 healthy children (10-15 years) with low caries risk and the experiment had a single-blind crossover (Latin square) design. After a 2-week run-in period with a daily 4.0 g xylitol intake, the children were subjected to single-dose exposures of chewing gums with (i) paraffin (CTR; no xylitol), (ii) low-dose xylitol (LX; 2.0 g xylitol), and (iii) high-dose xylitol (HX; 6.0 g xylitol) in a randomized order separated by a washout period of 1 week. Samples of chewing-stimulated whole saliva were collected prior to and after the experimental period for determination of bacterial counts. The outcome measures were in situ plaque-pH (micro-touch method) and area under the pH curve (AUC). The AUC was significantly greater (p < 0.05) in the HX group compared to the LX and control groups during the first 5 min after chewing. After a 10% sucrose rinse, the interdental plaque-pH dropped in all groups but the HX regimen displayed significantly less reduction 0-5 min after chewing (p < 0.05). No significant alterations of the total viable counts or mutans streptococci levels in saliva were disclosed during the 4-week experimental period. The present results suggested that a high single dose of xylitol had a short and limited beneficial effect on interdental plaque-pH in habitual xylitol consumers, while a low single dose, resembling normal chewing gum use, did not differ from the control.


Long-Term Durability of Transcatheter Aortic Valve Implantation With Self-Expandable Valve System (from a Real-World Registry).
As transcatheter aortic valve Implantation (TAVI) moves to younger and lower risk patients with longer life expectancy, the long-term durability of TAVI is becoming an increasingly relevant issue. We sought to evaluate the long-term clinical outcome and prosthesis performance of the CoreValve self-expandable valve. Clinical registry of 182 patients consecutively treated with TAVI in a tertiary center from January 2009 to July 2017. Of these, 111 died during an average follow-up (FU) of 1,026 ± 812 days (median IQR: 745, 477 to 1,400 days; longest survival 11 years; 61% mortality at Kaplan-Meier analysis). At 1 month, functional profile improved in all survivors, with 93.9% of them achieving NYHA class I or II. At Cox analysis, the Society of Thoracic Surgeons score (HR: 1.55; p = 0.001), left ventricular ejection fraction <40% (HR: 1.65; p = 0.017) and incident acute kidney injury (HR: 1.96; p = 0.001) were independently associated with all-cause mortality. During FU, echocardiographically assessed mean transprosthetic aortic gradient remained substantially unchanged (from 9.0 ± 2.7 after TAVI to 9.0 ± 5.0 mm Hg at FU; p >0.05). Most patients had none and/or trivial (34%), or mild (58%), fewer had moderate (8%) and none had severe perivalvular leak, without significant change during FU. At 11 years, cumulative incidence of bioprosthetic valve failure and moderate structural valve deterioration (SVD) were 2.9% (95% CI 0.8% to 10%) and 9.3% (95% CI 3.3% to 26.7%), respectively. In conclusion, our registry confirmed that TAVI with the self-expandable CoreValve system was associated with favorable long-term clinical outcomes, with a reassuring low rate of significant bioprosthetic valve failure and moderate SVD.


Conformational analysis of the ΜΒΡ83-99 (Phe91) and ΜΒΡ83-99 (Tyr91) peptide analogues and study of their interactions with the HLA-DR2 and human TCR receptors by using molecular dynamics.
The two new synthetic analogues of the MBP(83-99) epitope substituted at Lys(91) (primary TCR contact) with Phe [MBP(83-99) (Phe(91))] or Tyr [MBP(83-99) (Tyr(91))], have been structurally elucidated using 1D and 2D high resolution NMR studies. The conformational analysis of the two altered peptide ligands (APLs) has been performed and showed that they adopt a linear and extended conformation which is in agreement with the structural requirements of the peptides that interact with the HLA-DR2 and TCR receptors. In addition, Molecular Dynamics (MD) simulations of the two analogues in complex with HLA-DR2 (DRA, DRB1*1501) and TCR were performed. Similarities and differences of the binding motif of the two analogues were observed which provide a possible explanation of their biological activity. Their differences in the binding mode in comparison with the MBP(83-99) epitope may also explain their antagonistic versus agonistic activity. The obtained results clearly indicate that substitutions in crucial amino acids (TCR contacts) in combination with the specific conformational characteristics of the MBP(83-99) immunodominant epitope lead to an alteration of their biological activity. These results make the rational drug design intriguing since the biological activity is very sensitive to the substitution and conformation of the mutated MBP epitopes.


Survivin -31G/C promoter polymorphism and sporadic colorectal cancer.
Survivin is an apoptotic inhibitor, plays an important role in cell cycle regulation, and may be involved in the development and progression of cancer. A common polymorphism at the survivin gene promoter (-31 G/C) has been shown to influence survivin expression and the risk for cancer. The aim of the present study was to investigate whether this polymorphism could be involved in the sporadic colorectal cancer (CRC) development, prognosis, and survival. The -31G/C polymorphism of survivin promoter was analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism method in biopsies from 312 patients with sporadic CRC and 362 healthy individuals. Survivin messenger RNA (mRNA) expression in CRC tissues was detected by quantitative reverse transcriptase PCR. The genotype frequencies for -31GG, -31GC, and -31CC were 21.79%, 41.99%, and 36.22% in CRC patients and 33.98%, 45.03%, and 20.99% in healthy subjects, respectively. The frequencies of the survivin -31C allele and CC genotype were significantly higher in CRC patients than in healthy subjects (p < 0.0001). Homozygotes for the -31CC survivin genotype, expressed 1.6-fold higher mRNA levels of survivin compared to cases with the -31GG and -31GC genotypes. The -31CC genotype of survivin promoter is associated with CRC and may be a risk factor for CRC.


Ultrasonographic differentiation between metastatic and benign lymph nodes in patients with papillary thyroid carcinoma.
The purpose of this study was to evaluate the ultrasonographic characteristics of metastatic lymph nodes in patients with papillary thyroid carcinoma. The ultrasonographic characteristics of lymph nodes were analyzed in 112 consecutive patients who underwent thyroidectomy and lymph node dissection, with the diagnosis being confirmed by anatomopathologic examination. A total of 198 lymph nodes were metastatic, and 152 were benign (normal or with nonspecific lymphadenitis). Minimum axial diameters of 7 mm for level II (upper internal jugular chain) and 6 mm for the rest of the neck were observed in 93% of metastatic lymph nodes, absence of an echogenic hilum in 88%, hyperechogenicity in relation to the adjacent muscles in 86%, a round shape in 80%, calcifications in 49.5%, and intranodal cystic necrosis in 20%. These ultrasonographic characteristics were observed in 17%, 10%, 4.5%, 29.5%, 0%, and 0% of benign lymph nodes, respectively. Even basic ultrasonographic characteristics (shape, echogenicity and echogenic hilum, calcifications, and intranodal cystic necrosis) help in the differentiation between metastatic and nonmetastatic lymph nodes in patients with papillary thyroid carcinoma.


Management of Gynecomastia and Male Benign Diseases.
Gynecomastia is a common benign breast disease involving abnormally increased mammary gland tissue that can affect men of all ages. It is usually due to a hormonal imbalance without a definitive underlying cause (idiopathic), or secondary to medications/drugs, systemic disorders, or malignancy. Gynecomastia is often self-limiting, and its management is watchful waiting. Other male benign breast diseases, such as cysts, lipomas, seromas, infections, and pseudoangiomatous stromal hyperplasia, should be worked up in a similar manner and often require surgical drainage or excision.


Construction of tissue-engineered bone with differentiated osteoblasts from adipose-derived stem cell and coral scaffolds at an ectopic site.
Cell sheets from bone marrow mesenchymal stem cells (BMSC) have been widely used in the field of bone tissue engineering, although their source remains a challenging issue. In this study, adipose-derived stem cells (ADSC) were induced to differentiate into osteoblasts, and the incorporation of coral scaffolds with ADSC sheets for bone formation at an ectopic site was also investigated. First, ADSC isolated from inguinal adipose tissue of New Zealand rabbits were cultured for two weeks without passaging under osteogenic induction, and the microstructures of cell sheets were analysed by histological and scanning electron microscope (EM) observation. In addition, the activity of alkaline phosphatase (ALP) and alizarin red staining was also measured to detect their osteogenic ability. Subsequently, ADSC were proved to be able to proliferate well when seeded on the coral scaffolds. Next, coral scaffolds were wrapped in cell sheets to prepare sheet-coral complexes, which were implanted into subcutaneous pockets in nude mice. At eight weeks after implantation, gross examination, microcomputed tomography (MicroCT), and histological analysis were investigated to assess new bone formation. MicroCT scanning and histological analysis showed that there was more highly dense tissue formed in the complex group than control group (p=0.0004). These results indicated that osteoblastic ADSC sheets could be used to construct engineered bone and the incorporation of coral scaffolds with ADSC sheets significantly improved bone formation, providing a newly approach for bone tissue engineering.


Texture segmentation: do the processing units on the saliency map increase with eccentricity?
The saliency map is a computational model and has been constructed for simulating human saliency processing, e.g. pop-out target detection (e.g. Itti & Koch, 2000). In this study the spatial structure on the saliency map was investigated. It is proposed that the saliency map is structured into processing units whose size is increasing with retinal eccentricity. In two experiments the distance between a target in the stimulus and an irrelevant structure in the mask was varied systematically. Our findings had two main points. Firstly, in texture segmentation tasks the saliency signals from two texture irregularities interfere, when these irregularities appear within a critical spatial distance. Second, the critical distances increase with target eccentricity. The eccentricity-dependent critical distances can be interpreted as crowding effects. It is assumed that additionally to the target eccentricity, also the strength of a saliency signal can determine the spatial area of its impairing influence.


Fungal-derived brevianamide assembly by a stereoselective semipinacolase.
Fungal bicyclo[2.2.2]diazaoctane indole alkaloids represent an important family of natural products with a wide-spectrum of biological activities. Although biomimetic total syntheses of representative compounds have been reported, the details of their biogenesis, especially the mechanisms for assembly of diastereomerically distinct and enantiomerically antipodal metabolites, have remained largely uncharacterized. Brevianamide A represents a basic form of the sub-family bearing a dioxopiperazine core and a rare 3-spiro-ψ-indoxyl skeleton. Here, we identified the Brevianamide A biosynthetic gene cluster from Penicillium brevicompactum NRRL 864 and elucidated the metabolic pathway. BvnE was revealed to be an essential isomerase/semi-pinacolase that specifies selective production of the natural product. Structural elucidation, molecular modeling, and mutational analysis of BvnE, and quantum chemical calculations provided mechanistic insights into the diastereoselective formation of the 3-spiro-ψ-indoxyl moiety in Brevianamide A. This occurs through a BvnE-controlled semi-pinacol rearrangement and a subsequent spontaneous intramolecular [4+2] hetero-Diels-Alder cycloaddition.


Are the high mobility group non-histone chromosomal proteins associated with 'active' chromatin?
When 10--20% of the DNA in thymus and liver nuclei is rendered acid-soluble by DNAase I digestion, under conditions which may be expected to specifically degrade away most of the transcribed sequences, very little of the high-mobility-group non-histone proteins are released from the nuclei. Therefore, high-mobility-group proteins are probably not specifically associated with this portion of the genome.


Effect of sloped walking on lower limb muscle forces.
Lower limb joint loadings are increased during sloped walking compared to level walking and muscle forces are major contributors to lower limb joint forces. Therefore, the aim of this study was to analyze lower limb muscle forces during sloped walking at different inclinations. Eighteen healthy male participants (27.0±4.7y, 1.80±0.05m, 74.5±8.2kg) walked at a pre-set speed of 1.1m/s on a ramp at the inclinations of 0°, ±6°, ±12° and ±18°. Kinematic data were captured with a motion capture system and kinetic data were recorded with two force plates imbedded into the ramp. A musculoskeletal model was used to compute lower limb muscle forces (normalized to body weight and gait cycle duration). During downhill walking gluteus maximus, quadriceps, soleus, peroneus and tibialis anterior muscle forces increased (p≤0.002) compared to level walking, while gluteus minimus, piriformis, adductor, iliopsoas, hamstrings and gastrocnemii muscle forces decreased (p≤0.002). Uphill walking decreased gluteus minimus, iliopsoas and tibialis anterior muscle forces (p≤0.002), while all other muscle forces increased (p≤0.002, except gluteus medius). Joint-muscle-force waveforms provided information on possible muscle contributions to joint compression forces. The most important muscles were: gluteus medius for hip forces, quadriceps and gastrocnemii for tibiofemoral forces, quadriceps for patellofemoral forces and triceps surae for ankle forces. The contribution of each muscle changed with the inclination during sloped walking compared to level walking. The current study provided important information on muscle forces during sloped walking that can be useful for rehabilitation and training procedures.


The Size and Prevalence of Bony Hip Morphology Do Not Differ Between Football Players With and Without Hip and/or Groin Pain: Findings From the FORCe Cohort.
To compare the size and prevalence of bony hip morphology in football players with and without hip and/or groin pain. Case-control. We recruited 184 soccer and Australian football players with self-reported hip and/or groin pain of greater than 6 months in duration and a positive flexion, adduction, and internal rotation (FADIR) test (290 hips, 21% women), and 55 football players with no pain and a negative FADIR test (110 hips, 26% women) as a control group. Bony hip morphology was identified by the alpha angle and lateral center-edge angle (LCEA) on anteroposterior pelvis and Dunn 45° radiographs. The alpha angle and LCEA were analyzed as continuous measures (size) and dichotomized using threshold values to determine the presence of bony hip morphology (cam, large cam, pincer, and acetabular dysplasia). Regression analyses estimated differences in the size and prevalence of bony hip morphology between football players with and without pain. In all football players and in men, the size and prevalence of bony hip morphology did not differ between those with and without hip and/or groin pain. Cam morphology was evident in 63% of hips in players without pain and 71% of symptomatic hips in players with hip and/or groin pain. In female football players with hip and/or groin pain compared to those without pain, larger alpha angle values were observed on the Dunn 45° view (5.9°; 95% confidence interval: 1.2°, 10.6°; P = .014). The size and prevalence of bony hip morphology appear to be similar in football players with and without hip and/or groin pain. J Orthop Sports Phys Ther 2021;51(3):115-125. Epub 25 Dec 2020. doi:10.2519/jospt.2021.9622.


Diabetes and cardiovascular events in women with polycystic ovary syndrome: a 20-year retrospective cohort study.
Women with polycystic ovary syndrome (PCOS) are potentially at increased risk of cardiovascular (CV) diseases due to well-established risk factors, including insulin resistance, obesity and type 2 diabetes mellitus (T2DM). However, data showing excess CV events in this population are still lacking. We investigated the incidence and prevalence of CV events in a cohort of women with PCOS. Retrospective cohort study (total follow-up >12,000 person-years). Leicester, Leicestershire and Rutland (Total Female population of 434,859), UK. Two thousand three hundred and one women with PCOS (mean age = 29.6 years) attending a speciality clinic in Leicestershire, UK. T2DM, myocardial infarction (MI), angina, heart failure (HF), stroke and CV-related death. Incidence of T2DM, MI, angina, HF, stroke and CV death was respectively 3.6, 0.8, 1.0, 0.3, 0.0 and 0.4 per 1000 person-years. At the end of follow-up, the prevalence of MI in the age groups 45-54, 55-64 and >65 years was 1.9%, 6.0% and 27.3% and of angina was 2.6%, 6.0% and 27.3%, respectively. Age-group-specific odds ratios for the prevalence of MI and angina compared to the local female population ranged between 2.6 (95% CI: 1.0-6.3) and 12.9 (CI: 3.4-48.6) with the highest ratio being for MI in the group >65 years old. Age, history of hypertension and smoking had significant correlations with CV outcomes in the PCOS patients. We have shown a high incidence and age-group-specific prevalence of T2DM, MI and angina in the women with PCOS, with over a quarter having had MI or angina in those >65 years. These findings should be considered in the treatment strategies and long-term planning for women with PCOS.


Challenges and Opportunities for Graduate Medical Education: Steps to Keep Physician Training in North Carolina Exceptional.
Changes in health care present many challenges and opportunities to North Carolina's exceptional graduate medical education programs. Steps to keep these programs exceptional include boosting leadership training, championing well-being, expanding rural training, and more described here.


Impact of an Institution-Wide Goals of Care Program on the Timing of Referrals to Outpatient Palliative Care.
Palliative care has received increased interest since the COVID-19 pandemic due to its role in guiding goals of care (GOC) discussions. We assessed the change in the timing of outpatient palliative care referrals before and after implementing an institution-wide multicomponent interdisciplinary GOC (myGOC) program. We reviewed 200 random supportive care center (SCC) consult visits each from June to November 2019 (before myGOC) and June to November 2020 (after myGOC). Data regarding Edmonton Symptom Assessment Scale (ESAS) scores, time from hospital registration to SCC visit, SCC visit until death/last follow-up, and advance care planning (ACP) notes were collected. Kaplan-Meier curves were used to evaluate overall survival (OS). The median OS from the SCC consult visit was 15.2 months (95% CI:11.7-19.7) before and 14.0 months (95% CI:10.8-17.9) after the myGOC program (P = 0.646). There were no significant differences in the median time between the SCC consult visit to death/last follow-up (11.95 vs. 12.0 months after myGOC; P = 0.841) and the first visits to our cancer center and SCC (6.1 vs. 5.29 months after myGOC; P = 0.689). Patients seen after myGOC had significantly lower ESAS symptom scores, better performance status (2 [1-2] vs. 2 [1-3]; P = 0.018], and more ACP notes composed by medical oncology teams (25.5% vs. 4.5%; P < 0.001). There were no significant differences in OS among patients seen in the SCC before and after myGOC, likely related to a ceiling effect. More oncologists had ACP discussions with patients, and patients had lower symptom scores on ESAS after myGOC, likely indicating that more patients were referred for GOC discussions and ACP rather than for symptom distress.


Influence of study design on reported mortality and morbidity rates after abdominal aortic aneurysm repair.
The mortality and morbidity rates of elective abdominal aortic aneurysm (AAA) surgery, as reported over the past 12 years, were graded and analysed by levels of evidence. Articles on elective AAA surgery published between 1985 and 1996 were retrieved and classified into five levels of evidence. Level 1 contains prospective studies and is subdivided into population-based (level 1a) and hospital-based (level 1b) studies. Level 2 includes retrospective studies, subdivided into population-based studies (level 2a), hospital-based studies (level 2b) and hospital-based studies concerning a specified group of selected patients (level 2c). Operative mortality and systemic and local/vascular complication rates with 95 per cent confidence intervals were calculated for each level of evidence. Seventy-two articles describing a total of 37 654 patients could be included: two level 1a studies (692 patients), nine level 1b studies (1677 patients), 13 level 2a studies (21 409 patients), 32 level 2b studies (12019 patients) and 16 level 2c studies (1857 patients). The mean 30-day mortality rates of the two population-based levels were similar: 8.2 (95 per cent confidence interval 6.4-10.6) per cent for the prospective (la) and 7.4 (7.0-7.7) per cent for the retrospective (2a) series. These figures were significantly higher than the remarkably similar hospital-based mortality rates: 3.8 (3.0-4.8) per cent for the prospective (1b), 3.8 (3.5-4.2) per cent for the retrospective (2b) and 3.5 (2.8-4.4) per cent for selected patient group (2c) studies. The most frequent complication was of cardiac origin. In the population-based series the cardiac complication rates were 10.6 (8.5-13.2) and 11.1 (9.1-13.6) per cent for levels 1a and 2a respectively. This compared well with 12.0 (10.5-13.9) per cent for the prospective hospital-based series (level 1b). The cardiac complication rates in the retrospective hospital-based studies were significantly lower: 8.9 (8.4-9.5) and 6.1 (4.9-7.6) per cent for levels 2b and 2c respectively. There is a clear and consistent disagreement in reported mortality rates between hospital-based and population-based studies of elective surgery for AAA. Prospective studies give the best documentation of postoperative morbidity.


Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group.
The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.


How I do it: intradural anterior petrosectomy.
The anterior transpetrosal approach (ATPA) is a cranial base approach for addressing upper petroclival or lateral pontine lesions. It is fundamentally an epidural procedure involving the drilling of the petrous apex. However, this approach has significant procedure-related morbidity, and the surgeon must perform a complete petrosectomy, as the intradural structures are not in view during the drilling. For selected cases, a rationale exists for choosing a tailor-made intradural anterior petrosectomy (IAP). This article describes the relevant surgical anatomy and the different surgical steps of the IAP. IAP represents a feasible alternative to the standard ATPA with the advantage of minimizing the extent of petrous bone removal to the individual need.


A rare case of anterior chest closure only with omental flap after devastating mediastinitis: case report.
We describe a case of 73-year-old patient who has been operated in emergency on triple coronary artery bypass graft (CABG), which was complicated with respiratory insufficiency and devastating mediastinitis. The anterior mediastinum was closed with an omental flap that was allowed to epithelize spontaneously. The patient was discharged after 110 days. Despite the large number of cases with mediastinitis described in the literature, the chest closure with only an omental flap without closure of subcutaneous tissue and skin is rare.


The concentration of lactoferrin in tears during post-operative ocular inflammation.
Tear concentration of lactoferrin (LF) was measured by an ELISA technique and followed in 25 patients undergoing cataract surgery. The pre-operative concentration of LF in tears was 773 +/- 60 micrograms/ml (+/- SE) (range: 407-1514 micrograms/ml). On the first day following surgery, there was a significant decrease in tear LF concentration to 377 +/- 45 micrograms/ml followed by a gradual return to the initial value during a post-operative observation period of twelve days. There was an inverse linear relationship between the LF concentration and the tear secretion rate measured by a modified Schirmer I test (1 min) suggesting a constant LF secretion rate by the tear glands. The contribution of LF from neutrophils to the tear fluid seems to be of minor importance. Since LF has known antibacterial and anti-inflammatory effects, our results may contribute to a further understanding of the microbial vulnerability or resistance of the eye following surgical procedures.


Systematic analysis of errors in target localization and treatment delivery in stereotactic radiosurgery (SRS).
To systematically analyze the spatial uncertainties associated with each step of the stereotactic radiosurgery (SRS) procedure and the overall spatial accuracy in the treatment delivery. A special test device has been designed and fabricated to permit accurate simulation, localization and treatment portal verification of a SRS target. This device with simulated targets dispersed in 3-D space can be rigidly attached to the BRW CT or angio frame for localization, to the BRW phantom base for target coordinate determination, and to the floor stand for portal verification. The setup allows evaluation of the accuracy of each procedure separately as well as the overall accuracy in the delivery of SRS treatment. Biplanar film localizations reveal a systematic error in the phantom base pointer of the order of 0.1 mm that is applied as a correction to the measured target coordinates. Targets localized by planar film angiography had a mean positional error of 0.38 +/- 0.1 mm compared to 1.0 +/- 0.7 mm for digital angiographic localization. The positional accuracy associated with CT localization was superior when a 2 mm vs. 4 mm slice thickness was used (0.9 +/- 0.3 mm vs. 1.6 +/- 0.5 mm error). Cumulative mean errors, including inaccuracies associated with treatment setup, were 1.0 +/- 0.4 mm for radiographic localization, 1.2 +/- 0.5 mm for CT with a 512 x 512 matrix and 2 mm slice thickness, and 2.0 +/- 0.6 mm for CT at a 4 mm slice thickness (256 x 256 matrix). Larger errors would be expected in the clinical setting. Spatial errors in stereotactic radiosurgery are best estimated using a systematic approach to isolate independent contributing factors. The accuracy in target localization determines the overall accuracy of SRS procedure, provided the mechanical accuracy of the treatment apparatus is assured. Biplanar treatment portal verification with a fiducial localization frame is an accurate method of verifying the target coordinates before delivering treatment.


A murine model of pseudorabies virus latency.
The mouse is a useful laboratory animal for studying various aspects of pseudorabies virus (PRV) virulence. Mice are highly susceptible hosts for PRV infection and are unable to survive acute viral infection. Because of this, mouse models have not been useful for studying PRV latent infections. Here, we report an efficient strategy for establishing latent PRV infections in laboratory mice. Passive transfer of high titered neutralizing antibodies to mice prior to inoculation with highly lethal doses of PRV (Bartha) resulted in survival rates of at least 60% with establishment of latent infections in survivors. Latent PRV infection in mice was demonstrated by: (1) recovery of infectious PRV-Bartha from explants of trigeminal ganglion (TG), and (2) detection of PRV nucleic acids in latently infected TGs by in situ hybridization and polymerase chain reaction (PCR), between 2-8 months post-infection. This PRV latency model indicates that attenuated PRV strains, those currently used extensively in vaccination programs worldwide, can establish a reactivatable latent infection in an experimental host. The mouse model may be particularly useful for examining the molecular bases of PRV latency and reactivation.


Dysregulation of Neuregulin-1/ErbB signaling in the prefrontal cortex and hippocampus of rats exposed to chronic unpredictable mild stress.
Exposure to chronic stress increases the likelihood of developing depression, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in neural development and function, and NRG1 has emerged as a novel modulator involved in the response of brain to stress, there is limited evidence concerning the effects of chronic stress exposure on NRG1/ErbB signaling. To fill this critical gap, we examined the protein expression of NRG1 and ErbB receptors in the brain of rats following chronic unpredictable mild stress (CUMS) exposure. After 6weeks of CUMS procedures, the rats were induced to a depression-like state. The stressed rats displayed elevated expression of NRG1 and phosphorylated ErbB4 (pErbB4) in the prefrontal cortex, whereas ErbB2 and pErbB2 were inhibited. In the hippocampus, CUMS also attenuated activation of the both ErbB receptors and suppressed the downstream Akt and ERK phosphorylation. Meanwhile, administration of sertraline enhanced NRG1/ErbB signaling and partly normalized the stress-induced behavioral changes and the disturbances of NRG1/ErbB system in CUMS rats. Combined, our data firstly showed the aberrant changes of NRG1/ErbB system in the brain of the animal model of depression, providing new evidence for the involvement of NRG1/ErbB pathway in the development and treatment of depression.


Safety of selamectin in cats.
The safety of the avermectin, selamectin, was evaluated for topical use on the skin of cats of age six weeks and above, including reproducing cats and cats infected with adult heartworms. All studies used healthy cats. Acute safety was evaluated in domestic cross-bred cats. Margin of safety was evaluated in domestic-shorthaired cats, starting at six weeks of age. Reproductive, heartworm-infected, and oral safety studies were conducted in adult, domestic-shorthaired cats. Studies were designed to measure the safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body weight. Assessments included clinical, biochemical, pathologic, and reproductive indices. Selected variables in the margin of safety study and the reproductive studies were subjected to statistical analyses by using a mixed linear model. Cats received large doses of selamectin at the beginning of the margin of safety study when they were six weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin had no adverse effect on reproduction in adult male and female cats. There were no adverse effects in heartworm-infected cats. Oral administration of the topical formulation, which might occur accidentally, caused mild, intermittent, self-limiting salivation and vomiting. Selamectin is a broad-spectrum avermectin endectocide that is safe for use in cats starting at six weeks of age, including heartworm-infected cats and cats of reproducing age, when administered topically to the skin monthly at the recommended dosage to deliver at least 6mgkg(-1).


[Persistence of the Japanese encephalitis virus in L929 cells. Correlation of viral and cellular factors].
The paper presents the results of the study of the first stage of Japanese encephalitis (JE) virus persistence in cultures of L929 cells. The main parameters of the establishment and development of JE virus persistence in these cells characterizing the system as a chronically infected one. A possible role in the mechanism of persistence of various cellular and viral factors: interferon, ts-mutants, defective particles, was studied. Interferon was shown to be the main factor of virus carrier state perpetuation in the L-JE system. The role of defective particles, ts-mutants, and possible association of JE virus genome with nuclear DNA of L929 cells in the mechanism of persistence is discussed.


Furosemide pharmacokinetics in very low birth weight infants.
The pharmacokinetics of furosemide were studied longitudinally during long-term administration in 10 very low birth weight infants with bronchopulmonary dysplasia. Mean birth weight of the infants was 829 +/- 217 g, mean gestational age at birth was 26.6 +/- 2.9 weeks, and mean postnatal age at the start of therapy was 2.4 +/- 1.0 weeks. Serial determinations of furosemide pharmacokinetic parameters were performed during 2 weeks to 3 months of long-term therapy. Plasma half-life was prolonged in infants less than 31 weeks postconceptional age (gestational + postnatal age), frequently exceeding 24 hours. All infants less than 29 weeks postconceptional age whose dosing schedule was once every 12 hours accumulated furosemide to potentially ototoxic levels. Furosemide renal clearance increased and plasma half-life decreased in association with increasing postconceptional age. Furosemide secretory clearance was very low in patients less than 31 weeks postconceptional age, resulting in a reliance on glomerular filtration to deliver drug to its main site of action within the lumen of the loop of Henle. Thus elevated plasma levels may be required to ensure adequate luminal delivery and adequate diuresis in these infants with low secretory clearance. Nevertheless, the current dosing schedule (once every 12 hours) of furosemide should be modified to once every 24 hours in infants of low postconceptional age to avoid possible toxic effects.


Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield.
Artemisia annua is the major natural source of artemisinin, an anti-malarial medicine commonly used worldwide. Here, we present chromosome-level haploid maps for two A. annua strains with different artemisinin contents to explore the relationships between genomic organization and artemisinin production. High-fidelity sequencing, optical mapping, and chromatin conformation capture sequencing were used to assemble the heterogeneous and repetitive genome and resolve the haplotypes of A. annua. Approximately 50,000 genes were annotated for each haplotype genome, and a triplication event that occurred approximately 58.12 million years ago was examined for the first time in this species. A total of 3,903,467-5,193,414 variants (SNPs, indels, and structural variants) were identified in the 1.5-Gb genome during pairwise comparison between haplotypes, consistent with the high heterozygosity of this species. Genomic analyses revealed a correlation between artemisinin concents and the copy number of amorpha-4,11-diene synthase genes. This correlation was further confirmed by resequencing of 36 A. annua samples with varied artemisinin contents. Circular consensus sequencing of transcripts facilitated the detection of paralog expression. Collectively, our study provides chromosome-level allele-aware genome assemblies for two A. annua strains and new insights into the biosynthesis of artemisinin and its regulation, which will contribute to conquering malaria worldwide.


Inhaled nitric oxide (NO) for the treatment of early allograft failure after lung transplantation. Munich Lung Transplant Group.
Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantation. Prospective clinical dose-response study. Anesthesiological intensive care unit of a university hospital. 8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2) of less than 13.3 kPa (100 mmHg). Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator. Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p < 0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5(5.2/6.0) kPa at control to 5.1(4.7/5.6) kPa at 1 ppm, 4.9(4.3/5.3) kPa at 4 ppm, and to 4.7(4.1/5.1) kPa at 8 ppm. PaO2 increased from 12.7(10.4/17.1) to 19.2(12.4/26.0) kPa at 1 ppm NO, to 23.9(4.67/26.7) kPa at 4 ppm NO and to 24.5(11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO2), all were subject to long-term inhalation (1-19 days). All were successfully weaned from NO and were discharged from the intensive care unit. The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation.


The calcium sensor CBL7 is required for Serendipita indica-induced growth stimulation in Arabidopsis thaliana, controlling defense against the endophyte and K+ homoeostasis in the symbiosis.
Calcium is an important second messenger in plants. The activation of Ca2+ signalling cascades is critical in the activation of adaptive processes in response to environmental stimuli. Root colonization by the growth promoting endophyte Serendipita indica involves the increase of cytosolic Ca2+ levels in Arabidopsis thaliana. Here, we investigated transcriptional changes in Arabidopsis roots during symbiosis with S. indica. RNA-seq profiling disclosed the induction of Calcineurin B-like 7 (CBL7) during early and later phases of the interaction. Consistently, reverse genetic evidence highlighted the functional relevance of CBL7 and tested the involvement of a CBL7-CBL-interacting protein kinase 13 signalling pathway. The loss-of-function of CBL7 abolished the growth promoting effect and affected root colonization. The transcriptomics analysis of cbl7 revealed the involvement of this Ca2+ sensor in activating plant defense responses. Furthermore, we report on the contribution of CBL7 to potassium transport in Arabidopsis. We analysed K+ contents in wild-type and cbl7 plants and observed a significant increase of K+ in roots of cbl7 plants, while shoot tissues demonstrated K+ depletion. Taken together, our work associates CBL7 with an important role in the mutual interaction between Arabidopsis and S. indica and links CBL7 to K+ transport.


Relationship between sleep disorders and the prognosis of neurological function after stroke.
This study aims to investigate the effects of sleep disorders on the prognosis of neurological function after stroke and other factors affecting the prognosis after stroke. We designed a cohort study. A total of 1,542 patients with their first stroke were hospitalized in the department of neurology of Tianjin Huanhu Hospital from 2015.6.1 to 2016.12.31. We recorded the personal histories of patients. The MMSE (mini-mental state examination), MoCA (Montreal Cognitive Assessment), HAMD (Hamilton Depression Scale), National Institutes of Health Stroke Scale (NIHSS) score, mRS (Modified Rankin Scale), BI (Barthel Index), PSQI (Pittsburgh Sleep Quality Index), ESS (Epworth Sleepiness Scale), Berlin questionnaire, and nocturnal TST (Total sleep time) were assessed before discharge, 3 months, 6 months, and 4 years (2019-2020) after stroke. Low sleep quality (OR 2.019, 95%CI 1.199-3.398, p = 0.008), nocturnal TST (<7 h) (OR 4.060, 95%CI 1.494-11.034, p = 0.006), nocturnal TST (>8 h) (OR 5.928, 95% CI 2.134-16.464, p = 0.001) were risk factors for poor neurological function recovery at 3 months after stroke. Nocturnal TST (<7 h) (OR 13.042, 95%-CI 2.576-66.027, p = 0.002) and nocturnal TST (>8 h) (OR 11.559, 95%-CI 2.108-63.390, p = 0.005) were risk factors for poor neurological function at 6 months after stroke. Nocturnal TST (<7 h) (OR 2.668, 95% CI 1.250-5.698, p = 0.011) and nocturnal TST (>8 h) (OR 2.516, 95% CI 1.080-5.861, p = 0.033) were risk factors for poor neurological function at 4 years after stroke. High risk of OSA (HR 1.582, 95%CI 1.244-2.012, p < 0.001) was a risk factor for all-cause death in patients followed up for 4 years after stroke. Low sleep quality is associated with short-term poor neurological function after stroke. Unusual nocturnal TST (long or short) is associated with short-term or long-term poor neurological function after stroke. A high risk of OSA is associated with a higher risk of all-cause death after stroke.


Prenatal maternal stress prospectively relates to shorter child buccal cell telomere length.
Prenatal exposure to stress increases risk for suboptimal child and adult mental and physical health outcomes, hypothesized to occur via fetal exposure to maternal stress hormones that alter growth and development. One proposed pathway through which stress exposure in utero could affect the offspring is by accelerating cellular aging in the form of telomere attrition. We tested this hypothesis in a cohort of 111 mother-child dyads, where mothers were assessed over 6 or more years, beginning prior to conception, and later during pregnancy, postpartum, and when the children were 3-5 years old. Adjusting for child age and concurrent maternal stress, we found that higher maternal perceived stress in the 3rd trimesters of pregnancy was predictive of shorter child buccal telomere length (bTL) (β = -0.24, p < .05), while maternal preconception and postpartum maternal stress were not associated with bTL (all p's > 0.42). These findings suggest a vulnerable time period in pregnancy when maternal stress influences offspring telomere length, suggesting the early embedding of adult disease might occur through biological aging pathways.


Hemichorea hemiballism syndrome: the first presentation of type 2 diabetes mellitus as a rare cause of chorea.
Hemichorea-hemiballism (HCHB) syndrome, which is most commonly related to non-ketotic hyperglycemia, is a rare type of chorea. Here, we present an unusual case of HCHB syndrome who was not a known case of diabetes. This case highlights the importance of recognising underlying non-ketotic hyperglycemia, as control of hyperglycemia is helpful in the quick relief of symptoms.


Studies of interactions between uracil-based hybrid molecules and P-glycoprotein--search for multidrug resistance modulators.
The hybrid molecules having structural features of anticancer drug, 5-fluorouracil, and MDR modulator, propafenone, have been studied for their interactions with P-glycoprotein (P-gp). Some of the molecules (5, 8, and 9) show considerable interactions with P-gp and could be the potential candidates for their in vivo evaluation as MDR modulators. Further investigations show the dependence of P-gp interacting properties of these compounds on their physico-chemical parameters like logP and total polar surface area.


Effects of the salivary gland massage program in older type 2 diabetes patients on the salivary flow rate, xerostomia, swallowing and oral hygiene: A randomized controlled trial.
To evaluate the effect of a salivary gland massage program to improve salivary flow, swallowing, and oral hygiene in older type 2 diabetes patients. This randomized control trial consisted of 73 older diabetes patients with a low salivary flow; 39 and 34 in intervention and control groups, respectively. The intervention group received a salivary gland massage from a trained dental nurse, whereas the control group received a dental education. The salivary flow rates were collected using spit methods at baseline, 1-month and 3-month follow up. All participants were examined for the objective and subjective symptoms of xerostomia, the Simplified Debris Index and the Repetitive Saliva Swallowing Test. After 3 months, the resting (0.32 vs 0.14 mL/min, P < 0.001) and stimulating salivary flow (3.66 vs 2.83 mL/min, P = 0.025) in the intervention group was significantly higher than the control group. The objective symptoms in the intervention group were significantly lower than the control group after 3 months (1.41 vs 2.26, P = 0.001). The participants who were able to swallow least three times in the Repetitive Saliva Swallowing Test in the intervention group increased by 35.89% after 3 months, whereas the control group increased by 8.82%. Oral hygiene was improved in both groups, but the changes in the intervention were significantly greater than in the control group. The 3-month salivary glands massage program increases the salivary flow rate, and affects swallowing, objective dry mouth symptoms and oral hygiene in older patients with type 2 diabetes. Geriatr Gerontol Int 2023; 23: 549-557.


Lactate administration attenuates cognitive deficits following traumatic brain injury.
Moderately head injured patients often suffer long term neurological sequelae. There is no therapy for brain trauma and current treatments aim only to minimize secondary damage. These secondary effects are often triggered by the inability to re-establish ionic homeostasis after injury, due to large energy demands. Recent reports have demonstrated that neurons are capable of utilizing lactate as an energy source, thus this report examines the usefulness of lactate administration in the attenuation of behavioural deficits following a moderate brain injury. Lactate infusion (i.v.) was started 30 min after lateral fluid percussion injury and continued for 3 h. Cognitive deficits were determined using the Morris water maze. Lactate infused injured animals demonstrated significantly less cognitive deficits than saline infused injured animals. Thus, lactate infusion attenuated the cognitive deficits normally observed in this model, and therefore may provide moderately head injured patients with a treatment to help ameliorate the sequelae.


Triple arthrodesis stabilization: a quantitative analysis of screw versus staple fixation in fresh cadaveric matched-pair specimens.
Qualitative analyses of midfoot stabilization in triple arthrodeses utilizing bone staple versus 4.5-mm cannulated cancellous screw fixation, with and without washers, were performed in fresh cadaveric specimens. Twenty-two trials (11 matched-pair feet) were used for direct comparison. Stiffness, defined as force/displacement, was determined at each talonavicular and calcaneocuboid joint. Ultimate load failure points of each specimen were also calculated. Trial results showed no statistically significant difference in stiffness or ultimate failure between these two forms of midfoot fixation for triple arthrodeses.


The importance of dose: lymphomas as a model of chemosensitive malignancies.
Chemotherapy dose intensity is probably important to the success of treatment for some human malignancies. Recombinant human haemopoietic growth factors have recently become available to clinicians to ameliorate the myelosuppression that follows cytotoxic chemotherapy. Their use to increase the dose intensity of treatment, either by simply allowing the administration of the planned dose on schedule or by increasing the dose or dose rate above the conventional ones, is being actively investigated by several European and American groups. In several reported studies, neutropenia is no longer dose limiting when granulocyte colony-stimulating factor is used to help to intensify cytotoxic chemotherapy, but thrombocytopenia or mucositis are. The use of circulating haemopoietic progenitor cells, released into the blood stream by growth factors and infused with or without autologous bone marrow, has been reported to consistently reduce the overall period and severity of thrombocytopenia following intensive chemotherapy in patients without pre-existing severe bone marrow damage. However, no clear improvements in survival have yet been documented with the use of these techniques. Difficulties in study design include a number of variables potentially involved (tumour model, patient population, adjuvant or advanced disease, dose of cytotoxics, intervals, end-points, etc.), and there is clearly a need for more studies and longer follow-up. Lymphomas, both non-Hodgkin and Hodgkin's disease, are the prototypes of chemosensitive malignancies curable by chemotherapy alone even in disseminated disease. Therefore, they would seem to be adequate models to test the dose intensity hypothesis in the clinic. However, there are important differences between these two types of disorder. The success of conventional therapies in these conditions suggests that further improvements in outcome and long-term survival by further increases in dose intensity with current drugs will require careful study designs, due attention to prognostic factors, and reasonable expectations.


[Ultramicroscopic structure of the cyst wall of Entamoeba invadens, E. histolytica and E. coli].
The ultrastructure of the wall of E. invadens cysts induced in axenic cultures was compared by transmission electron microscopy of thin sections, with that of E. histolytica and E. coli cysts obtained from feces of human asymptomatic carriers. The cyst wall of the three species studied had similar ultrastructural features; in all, the wall was composed mainly by the aggregation of filaments adjacent to the plasma membrane. The cytoplasmic components which might be involved in the synthesis and deposit of the cyst wall of E. invadens appear to be different to those of E. coli and E. histolytica cysts.


Immunofluorescent analysis of murine leukemia virus-infected cells by flow microfluorometry.
Flow microfluorometric assay with a Cytofluorograf model 4801 in combination with immunofluorescence was applied to the quantitative assay of cells exogenously infected with mouse leukemia viruses and to the chemical induction of virus in AKR cells. The Cytofluorograf provides sensitivity equal to the visual method and is capable of assaying up to 5000 cells/sec with specificity equivalent to that of the direct visual immunofluorescence assay, thereby providing a large, statistically valid sampling in a fraction of the time required by visual counting. Flow microfluorometry also provides a method of quantitatively resolving fluorescent cell populations on the basis of relative size and degree of fluorescence.


Improving Matching Between Recipient and Donor in Liver Transplantation: Are Scores Able to Predict Long-term Survival?
The primary goal was to calculate the value of delta Model for End-Stage Liver Disease (D-MELD) and Balance of Risk (BAR) scores in patients who underwent liver transplant. The secondary objective was to evaluate D-MELD and BAR scores' ability to predict patient and graft survival. We retrospectively evaluated 336 patients who underwent liver transplant in a tertiary medical center between January 2010 and December 2020. The D-MELD and the BAR scores were evaluated through a receiver operating characteristic curve with the calculation of area under the curve (AUC) to evaluate the predictive score power for 3-month, 6-month, 1-year, and 5-year patient and graft survivals. The AUCs of D-MELD score in predicting 5-year patient and graft survival were 0.506 (95% CI, 0.43-0.57) and 0.49 (95% CI, 0.42-0.56), respectively. The AUCs of BAR score in predicting 5-year patient and graft survival were 0.50 (95% CI, 0.33-0.66) and 0.49 (95% CI, 0.30-0.67), respectively. We could not confirm the ability to predict long-term survival by using D-MELD and BAR scores in our sample; however, there is a statistically significant trend in receiver operating characteristic curves of 5-year patient and graft survivals. We encourage the use of new scoring systems with a greater external validation to improve allograft allocation.


Identification and characterization of caspases genes in rainbow trout (Oncorhynchus mykiss) and their expression profiles after Aeromonas salmonicida and Vibrio anguillarum infection.
Caspases are highly conserved cysteine-dependent aspartyl-specific proteases that play an important role in regulating cell death and inflammation. However, the caspase genes have not been systematically studied in rainbow trout (Oncorhynchus mykiss). Rainbow trout experienced 4 rounds (4R) of genome duplication in the evolutionary history. Thereby an increased numbers of paralogs are observed in trout, probably with more complicated gene functions. We identified 18 caspase genes in rainbow trout, including two inflammatory caspases (casp1a, casp1b), six apoptosis executioner caspases (casp3, casp3a1, casp3a2, casp3b, casp6, and casp7), nine apoptosis initiator caspases (casp2a, casp2b, casp8, casp9a, casp9b, casp10a, casp10b, casp20a, and casp20b) and one uncategorized caspase gene (casp17). To investigate the potentially physiological functions of caspase genes, we challenged the rainbow trout with Aeromonas salmonicida (A. salmonicida) and Vibrio anguillarum (V. anguillarum). Results showed that the CASP3-regulated intrinsic apoptosis was activated after A. salmonicida infection, while the CASP8 and CASP6-regulated extrinsic apoptosis exerted the greatest effect on trout challenged with V. anguillarum. In response to V. anguillarum infection, the data of RNA-Seq further showed the casp8 was tightly integrated with the significantly enriched Gene Ontology terms and functional pathways, including apoptosis regulation, pathogen detection and immunomodulation. Our study provides a foundation for the physiological functions and regulatory network of the caspase genes in teleosts.


Correction: Effects of Mirror Therapy Using a Tablet PC on Central Facial Paresis in Stroke Patients.
[This corrects the article on p. 347 in vol. 41, PMID: 28758071.].


Immunophenotypic analysis of mast cells in mastocytosis: When and how to do it. Proposals of the Spanish Network on Mastocytosis (REMA).
Mastocytosis is a term used for a heterogeneous group of disorders characterized by an abnormal proliferation and accumulation of mast cells (MCs) in one or multiple tissues including skin, bone marrow, liver, spleen, and lymph nodes, among others. In recent years, multiparameter flow cytometric studies have shown that pathologic MCs from patients with mastocytosis display unique aberrant immunophenotypic characteristics as compared with normal MCs. Among other features, pathologic MCs show aberrant expression of CD25 and CD2 antigens and abnormally high levels of the CD11c and CD35 complement receptors, the CD59 complement regulatory molecule, the CD63 lysosomal membrane antigen, and the CD69 early-activation antigen. In addition, MCs from mastocytosis express abnormally low levels of CD117 and unexpectedly high light scatter and autofluorescence characteristics. These aberrant immunophenotypic features are of great relevance for the assessment of tissue involvement in mastocytosis with consequences in the diagnosis, classification, and follow-up of the disease and in its differential diagnosis with other entities. In this paper we provide the reader with information for the objective and reproducible identification of pathologic MCs by using quantitative multiparametric flow cytometry, information for their phenotypic characterization, and the criteria currently used for a correct interpretation of the immunophenotypic results obtained.


Rapid oral desensitisation procedure in clopidogrel hypersensitivity.
We describe a patient who developed generalised pruritus with oedema and rash two weeks after she had started taking clopidogrel following coronary stent implantation. In the absence of other likely causative agents, clopidogrel hypersensitivity was probable. She was treated with a rapid oral desensitisation procedure, after which a daily dose of 75 mg clopidogrel was well tolerated. No major adverse events occurred during a follow-up period of eight months. Oral desensitisation in clopidogrel hypersensitivity seems to be a safe method to reduce the risk of coronary stent thrombosis. (Neth Heart J 2008;16:21-3.).


Cognitive flexibility during breath alcohol plateau is associated with previous drinking measures.
Although the biphasic effects of acute alcohol during ascending and descending Breath Alcohol Concentrations (BrACs) are well described, the plateau period between peak and steadily descending BrACs is generally unrecognized and under-studied by researchers. Naturalistic examinations indicate such periods persist for substantial intervals, with a time frame of onset suggesting BrAC plateaus may co-occur with potentially risky behaviors (e.g., driving). The current pilot study examined neurocognitive performance during this period. Participants were healthy, community-residing moderate drinkers (n = 18). In the first phase of the study, the Digit Symbol Substitution and Trail Making Tasks were administered during BrAC plateau (M = 62 mg/dL). BrACs were negatively correlated with Digit Symbol performance but unrelated to other tasks. In contrast, performance on a derived Trail Making measure of set-shifting was positively associated with the maximum alcohol doses consumed in the preceding 6 months. Phase 2 analyses demonstrated that relationships between previous alcohol experience and cognitive performance were absent among individuals receiving placebo beverages. Taken together, these data suggest a relationship worthy of investigation between previous drinking experiences and cognitive flexibility during the plateau phase.


Contrast-Induced Acute Kidney Injury: Pathophysiology, Manifestations, Prevention, and Management.
Contrast-induced acute kidney injury is a phenomenon that has been extensively studied throughout the years. There is a large volume of literature documenting this risk, and most radiology departments and radiologists use this information when making decisions regarding contrast administration. A review of the current information on the topic of contrast-induced acute kidney injury is necessary to ensure that the risks of intravenous contrast are properly weighed against the benefits of a contrast-enhanced computed tomography scan.


Symmetric 1,1'-Dimethylferrocene-Derived Amino Acids: Their Synthesis, Characterization, Ligational and Biological Properties With Cu(II), Co(II) and Ni(II) Ions.
Some novel symmetric 1,1'-dimethylferrocene derived amino acids have been prepared by the reaction of 1,1'-ferrocenedimethyldichloride with amino acids (glycine, alanine, phenylalanine and tyrosine). Their Cu(II), Co(II) and Ni(II) complexes, of the type [M(L)] where [M = Cu(II) and L = L(1)-L(5)] and [M(L)Cl(2)] where [M-Co(II)and Ni(II), L = L(1)-L(5)] have been prepared. The dicarboxylic acids and their metal complexes were characterized by their physical, analytical and spectral data. The [M(L)] complexes showed a square planar geometry whereas an octahedral geometry was observed for [M(L)Cl(2)] complexes. The title dicarboxylic acids and their metal complexes have also been screened for their antibacterial activity.


Early stress responses in Atlantic salmon (Salmo salar) exposed to environmentally relevant concentrations of uranium.
Uranium (U) is a naturally occurring heavy metal widely used in many military and civil applications. Uranium contamination and the associated potential adverse effects of U on the aquatic environment have been debated during recent years. In order to understand the effect and mode of action (MoA) of U in vivo, juvenile Atlantic salmon (Salmo salar) were exposed to 0.25 mg/L, 0.5 mg/L and 1.0mg/L waterborne depleted uranyl acetate, respectively, in a static system for 48 h. The U concentrations in the gill and liver were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and the resulting biological effects were determined by a combination of analysis of gene expression and micronuclei formation. The hepatic transcriptional level of 12 biomarker genes from four stress-response categories, including oxidative stress (γ-glutamyl cysteine synthetase (GCS), glutathione reductase (GR), glutathione peroxidase (GPx)), DNA damage and repair (P53, cyclin-dependent kinase inhibitor 1 (P21), growth arrest and DNA damage-inducible gene gamma (Gadd45G), proliferating cell nuclear antigen (PCNA), Rad51), apoptosis (Bcl2-associated X protein (BAX), Bcl-x, Caspase 6A,) and protein degradation (Ubiquitin) were evaluated by quantitative real-time polymerase chain reaction (q-rtPCR). The results clearly showed accumulation of U in the gill and liver with increasing concentrations of U in the exposure water. The effects of U on differential hepatic gene expression also occurred in a concentration-dependent manner, although deviations from ideal concentration-response relationships were observed at the highest U concentration (1.0 mg/L). All the genes tested were found to be up-regulated by U while no significant micronuclei formation was identified. The results suggest that U may cause oxidative stress in fish liver at concentrations greater than 0.25 mg/L, giving rise to clear induction of several toxicologically relevant biomarker genes, although no significant adverse effects were observed after the relatively short exposure period.


Aluminium loading in children receiving long-term parenteral nutrition.
Eight children on long-term, total parenteral nutrition (TPN) were found to have elevated aluminium (Al) levels in plasma (51 +/- 11 microg 1/1), urine (223 +/- 78 microg 24 h) and bone. The load of Al in TPN solution was 232 +/- 89 microg/day, and, among the different parenteral solution components high Al concentrations were found in amino-acids, calcium gluconate, potassium lactate, and trace elements, representing respectively 40%, 30%, 15%, and 10% of the total Al intakes. The authors conclude that children receiving long-term TPN have excessive Al intakes and are exposed to Al toxicity. The prevention of Al contamination requires careful control of the TPN components.


DNA damage checkpoints and cancer.
DNA damage checkpoint is one of the surveillance systems to maintain genomic integrity. Checkpoint systems sense the DNA damage and execute cell cycle arrest through inhibiting the activity of cell cycle regulators. This pathway is essential for the maintenance of genome stability and prevention of tumor development. Recent studies have showed that the cellular responses towards DNA damage, such as cell cycle arrest, DNA repair, chromatin remodeling, and apoptosis are well coordinated. Here we describe the molecular mechanisms of checkpoint activation in response to DNA damage and the correlation between checkpoint gene mutation and genomic instability.


Mechanisms of Ventricular Arrhythmias and Implications for Catheter Ablation.
Ventricular arrhythmias present with a wide spectrum of clinical manifestations, from mildly symptomatic frequent premature ventricular contractions to life-threatening events. Pathophysiologically, idiopathic ventricular arrhythmias occur in the absence of structural heart disease or ion channelopathies. Ventricular arrhythmias in the context of structural heart disease are usually determined by scar-related reentry and are associated with increased mortality. Catheter ablation is safe and highly effective in treating ventricular arrhythmias. The proper characterization of the arrhythmogenic substrate is essential for accurate procedural planning. We provide an overview on the main mechanisms of ventricular arrhythmias and their implications for catheter ablation.


In vitro response of relaxin-treated rat uterus to prostaglandins and oxytocin.
Paired segments of rat uterus were treated in vitro with relaxin (W1164-3, 150 GPU/mg) until the amplitude of contraction was reduced to at least 50% of the pre-treatment amplitude. Test segments then received 100 ng of either PGE1, PGE2, PGF2alpha or 250 uU of oxytocin. Control segments remained untreated. There was a significant increase in contraction amplitude in response to the spasmogens (P less than 0.05) but no increase was seen in controls.


Oncogenic viruses and hepatocellular carcinoma.
About 80% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections especially in the setting of established cirrhosis or advanced fibrosis, making HCC prevention a major goal of antiviral therapy. HCC tumors are highly complex and heterogeneous resulting from the aberrant function of multiple molecular pathways. The roles of HCV or HBV in promoting HCC development are still either directly or indirectly are still speculative, but the evidence for both effects is compelling. In patients with chronic hepatitis viral infection, cirrhosis is not a prerequisite for tumorigenesis.


Similar oxygen cost of myocardial contractility between DPI 201-106 and epinephrine despite different subcellular mechanisms of action in dog hearts.
The effects of DPI 201-106 (a novel, cyclic AMP-independent positive inotropic agent with Ca(2+)-sensitizing and Na(+)-channel agonistic mechanisms) on myocardial mechanics and energetics were assessed in the excised cross-circulated dog left ventricle. In the first protocol, the relation between left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA) was analyzed before and during administration of DPI 201-106. The reciprocal of the slope of the VO2-PVA relation has been shown to reflect the contractile efficiency, and the VO2-intercept consists of the oxygen cost of contractility-dependent excitation-contraction coupling and basal metabolism. DPI 201-106 increased Emax (contractility index) and elevated the VO2-PVA relation in a parallel manner, i.e., the VO2-intercept increased without a change in the slope. In the second protocol, the increase in the VO2-intercept of the VO2-PVA relation for a unit increase in Emax (i.e., oxygen cost of enhanced contractility) was compared between DPI 201-106 and epinephrine in a paired manner in each heart. Epinephrine significantly abbreviated the time to end systole, whereas DPI 201-106 did not, suggesting that the mechanism of inotropic action differed between the two drugs. However, the oxygen cost of enhanced contractility was the same between the two drugs in each heart. Therefore, DPI 201-106 did not alter the contractile efficiency nor spare the oxygen cost of enhanced contractility as compared to epinephrine under the present experimental conditions. This suggests that the Ca(2+)-sensitizing effect of DPI 201-106, if any, is too small to spare the oxygen cost of contractility in the blood-perfused, non-failing dog heart.


Comparison of outcomes and safety of laparoscopic and robotic-assisted cyst excision and hepaticojejunostomy for choledochal cysts: A systematic review and meta-analysis.
Minimally invasive cyst excision and Roux-en-Y hepaticojejunostomies include laparoscopic and robotic-assisted operations. The current systematic review and meta-analysis compared the efficacy between the 2 groups. A systematic search of PubMed, Web of Science, Embase, Wiley, Cochrane Library and Clinical Trials was performed from May 1995 to December 2021. The primary outcome was postoperative complications, and the secondary outcomes were operative details and postoperative outcomes. The meta-analysis enrolled 6 reports including 484 patients (307 in the laparoscopic group and 177 in the robotic-assisted group). The laparoscopic group was associated with lower expenses (MD = -3851.60$, 95% CI = -4031.84 to -3671.36$, P < 0.00001). No significant difference was found in short-term complications (RR = 1.55, 95% CI = 0.74 to 3.23, P = 0.24), long-term complications (RR = 1.40, 95% CI = 0.63 to 3.10, P = 0.41), total complications (RR = 1.53, 95% CI = 0.59 to 3.94, P = 0.38), operative time (MD = -28.75 min, 95% CI = -77.13 to 19.64 min, P = 0.24), blood loss (MD = 2.28 ml, 95% CI = -13.51 to 18.06 ml, P = 0.78) or hospital stays (MD = 0.89 days, 95% CI = -0.13 to 1.91 days, P = 0.09). In subgroup analysis, the laparoscopic operation had shorter operative time (MD = -4.45 min, P = 0.009), and less blood loss (MD = -63.18 ml, P = 0.01) in adult patients. Laparoscopic and robotic-assisted cyst excision and Roux-en-Y hepaticojejunostomy have comparable postoperative outcomes.


White centered retinal hemorrhages in diabetic retinopathy.
Two hundred fifteen diabetic patients (430 eyes) with early proliferative retinopathy, moderate-to-severe nonproliferative retinopathy, and/or diabetic macular edema in each eye were examined for the presence of white centered retinal hemorrhages (WCRHs). Of the eyes examined, 15.6% demonstrated at least one WCRH and 4.9% showed five or more WCRHs. The prevalence of WCRHs was not significantly related to hypertension, anemia, leukocytosis, thrombocytopenia, thrombocytosis, abnormalities of coagulation, increased serum creatinine, or ingestion of oral contraceptives. Local factors associated with microvascular damage and repair are likely responsible for WCRHs in diabetics. Microaneurysms are at the center of many diabetic WCRHs, and the pale centers of many WCRHs in diabetic retinopathy may be platelet-fibrin aggregates.


A graphical user interface for calculating the arterial input function during dynamic positron emission tomography.
Purpose.Dynamic positron emission tomography (dPET) requires the acquisition of the arterial input function (AIF), conventionally obtained via invasive arterial blood sampling. To obtain the AIF non-invasively, our group developed and combined two novel solutions consisting of (1) a detector, placed on a patient's wrist during the PET scans to measure the radiation leaving the wrist and (2) a Geant4-based Monte Carlo simulation software. The simulations require patient-specific wrist geometry. The aim of this study was to develop a graphical user interface (GUI) allowing the user to import 2D ultrasound scans of a patient's wrist, and measure the wrist features needed to calculate the AIF.Methods.The GUI elements were implemented using Qt5 and VTK-8.2.0. The user imports a patient's wrist ultrasound scans, measures the radial artery and veins' surface and depth to model a wrist phantom, then specifies the radioactive source used during the dPET scan. The phantom, the source, and the number of decay events are imported into the Geant4-based Monte Carlo software to run a simulation. In this study, 100 million decays of18F and68Ga were simulated in a wrist phantom designed based on an ultrasound scan. The detector's efficiency was calculated and the results were analyzed using a clinical data processing algorithm developed in a previous study.Results.The detector's total efficiency decreased by 3.5% for18F and by 51.7% for68Ga when using a phantom based on ultrasound scans compared to a generic wrist phantom. Similarly, the data processing algorithm's accuracy decreased when using the patient-specific phantom, giving errors greater than 1.0% for both radioisotopes.Conclusions.This toolkit enables the user to run Geant4-based Monte Carlo simulations for dPET detector development applications using a patient-specific wrist phantom. Leading to a more precise simulation of the developed detector during dPET and the calculation of a personalized AIF.


Leukodiapedesis and leukocyte migration in the leptomeninges and in the subarachnoid space.
Pleocytosis in cerebrospinal fluid and infiltration of the leptomeningeal tissue have been studied after injection of ferritin into the subarachnoid space (SAS) of cats. The most important source of granulocytes in the leptomeninges are the relatively large veins of the pia mater, which have very thin walls. Passing between the lining cells of the pia mater the granulocytes leave the connective tissue space of the pia mater and reach the SAS. Leukodiapedesis has also been observed in veins crossing the SAS. During this process, gaps between the lining cells of the perivascular leptomeningeal sheath may develop. There are two possible ways for the granulocytes to pass from the vascular pia mater to the avascular arachnoidea: either they migrate actively on the surface of the leptomeningeal trabeculae or they reach the arachnoidea passively by the circulation of the cerebrospinal fluid. Leukodiapedesis in the vessels of the dura mater occurs relatively seldom and would not be able to cause the occasionally massive infiltration of the arachnoidea.


Human megakaryocyte colony-stimulating factor in sera from aplastic dogs: partial purification, characterization, and determination of hematopoietic cell lineage specificity.
We have previously shown that human megakaryocyte colony-stimulating activity (Meg-CSA) is present in sera from patients with bone marrow megakaryocyte aplasia. In this report, we demonstrate that Meg-CSA is also present in sera from dogs rendered aplastic by 1000 rad total body irradiation. Canine serum Meg-CSA has activity comparable to human when assayed in plasma clot cultures containing human bone marrow mononuclear cells. Because of the uniform high potency and ready availability of aplastic canine sera, it was utilized initially for Meg-CSA purification. Sequential ammonium sulfate precipitation to approximately 80% saturation resulted in recovery of 59%-69% of the serum protein and of 75%-103% of the original serum Meg-CSA. The fraction precipitable between ammonium sulfate saturations of 0% and 44%-50% (fraction I) contained 53%-76% of the initial serum Meg-CSA and 25%-32% of the initial serum protein. This represents an enrichment of Meg-CSA specific activity by over 100%. The Meg-CSA eluted from Sephacryl S-300 in a single peak corresponding to a molecular weight of 175,000. This Meg-CSA peak also contained IgG, but the Meg-CSA did not bind to protein A-agarose. Meg-CSA was 90% inactivated by trypsin digestion for 4 h at 37 degrees C and by exposure to 5mM dithiothreitol for 2 h at room temperature. Exposure to either 6 M guanidine for 1 h at room temperature or 8 M urea for 1 h at 4 degrees C resulted in a 70% loss of Meg-CSA. At culture concentrations capable of stimulating maximal megakaryocyte colony formation, fraction I supported no colony growth by myeloid (CFU-GM) or late erythroid (CFU-E) human hematopoietic progenitor cells. Erythroid burst-promoting activity (BPA) was not detected in fraction I from two of three different aplastic canine sera tested. Therefore, Meg-CSA is functionally distinct from granulocyte-monocyte colony-stimulating factor (GM-CSF), erythropoietin, and BPA. The data indicate that serum Meg-CSA is a 175,000-dalton protein (megakaryocyte colony-stimulating factor, Meg-CSF) in which higher order structure and disulfide bonding are necessary for biologic activity. Partially purified Meg-CSF manifests functional specificity for the CFU-Meg hematopoietic progenitor cell.


Lack of effect of increased pineal serotonin content on H3-tryptophan uptake.
Major increases in the serotonin concentrations of rat pineal organs were produced by administering Catron, a monoamine oxidase inhibitor, prior to autopsy, or by preincubating the glands with serotonin (3X10-4M). These increases had no effect on pineal uptake of H3-tryptophan, the amino acid precursor for serotonin. These observations provide further evidence that the control of serotonin synthesis involves an important "open-loop" component.


Benchmarking heart rate variability toolboxes.
Heart rate variability (HRV) metrics hold promise as potential indicators for autonomic function, prediction of adverse cardiovascular outcomes, psychophysiological status, and general wellness. Although the investigation of HRV has been prevalent for several decades, the methods used for preprocessing, windowing, and choosing appropriate parameters lack consensus among academic and clinical investigators. A comprehensive and open-source modular program is presented for calculating HRV implemented in Matlab with evidence-based algorithms and output formats. We compare our software with another widely used HRV toolbox written in C and available through PhysioNet.org. Our findings show substantially similar results when using high quality electrocardiograms (ECG) free from arrhythmias. Our software shows equivalent performance alongside an established predecessor and includes validated tools for performing preprocessing, signal quality, and arrhythmia detection to help provide standardization and repeatability in the field, leading to fewer errors in the presence of noise or arrhythmias.


Adjunctive therapy with lipid-lowering agents in COVID-19: a systematic review and meta-analysis of randomized controlled trials.
Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs). We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted. Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation. Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.


Mechanisms of the clasp-knife reflex studied in an animal model.
The mechanisms of the clasp-knife reflex were studied in the soleus muscle of an animal model, the decerebrate cat with a dorsal hemisection of the lower thoracic cord. The reflex is shown to be autogenetic, and to depend on muscle length in keeping with previous suggestions. However, the magnitude of the inhibition increases with increasing initial force, and the inhibition is mimicked by gentle manipulation of the muscle and tendon surface. Concurrent muscle afferent recordings showed that the electromyogram (emg) reduction was not a result of a decline in Ia afferent input and was not well related to secondary or tendon organ afferent discharge. It is now known that many group III and some group IV muscle afferents are also activated by muscle stretch and contraction, and we here report limited stretch sensitivity in four non-spindle group II afferents. Since these fiber groups each include afferents that produce inhibition of extensor motoneurons, it is proposed that the clasp-knife reflex may result from the activation of these slowly conducting afferent fibers.


Resveratrol Reverses the Synaptic Plasticity Deficits in a Chronic Cerebral Hypoperfusion Rat Model.
Dementia is the most prevalent neurological disease in aged people. Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia (VaD) and is also an etiological factor for Alzheimer's disease (AD). However, effective therapy for those two diseases is still missing. Resveratrol is a polyphenol produced by plants that have multiple biological functions, such as increased life span and delay in the onset of diseases associated with aging. It is known supplement with resveratrol could exert neuroprotection against multiple injury factors induced neuronal death and degeneration, as well as the cognitive decline of CCH rat model. The morris water maze was used to evaluate the learning and memory, electrophysiological recording was used to detect the synaptic plasticity, the Golgi staining was used to examine the change of dendritic spines, the western blot was used to detect the proteins levels. We reported that resveratrol pretreatment effectively restore the synaptic plasticity in CCH rats both functional and structural. We also found that the PKA-CREB activation may be a major player in resveratrol-mediated neuroprotection in CCH model. Our data provide the mechanistic evidence for the neuroprotective effects of resveratrol in vascular dementia.


Summary and overview of the first ISMRM workshop on magnetic resonance elastography, August 25-26, 2022, Berlin, Germany.
An ISMRM workshop on MR elastography was held at Charité-Universitätsmedizin Berlin on August 25-26, 2022. As an exclusively in-person event, 65 participants from 9 countries attended the workshop despite COVID-19-related restrictions. The topics of the workshop covered cellular and microtissue mechanical interactions, the development of MR elastography driver technology, approaches to inverse problems, clinical applications, and integration of MR elastography into multiparametric MRI protocols. The workshop was a great success by promoting direct knowledge exchange as well as for strategizing future directions for MR elastography. In this symposium review, we briefly summarized all oral presentations as well as the concluding panel discussion.


Identification of technical errors and hazard zones in sleeve gastrectomy using OCHRA : "OCHRA for sleeve gastrectomy".
The sleeve gastrectomy is an example of minimally invasive surgery. It is important to determine the critical steps of the procedure in order to reduce complications and increase safety and efficiency. The aim of this study was to detect the key elements of the sleeve gastrectomy and find the potential hazard zones of the procedure. Bariatric department of a large teaching hospital in the Netherlands. A prospective clinical observation study was performed including 60 sleeve gastrectomy procedures. An expert panel determined the key steps, and two experts assessed the procedures systematically for technical errors according to the principles of Observational Clinical Human Reliability Assessment (OCHRA). A total of 213 technical errors have been made, and the majority were made during mobilization of the greater curvature and during stapling of the stomach. In 44.6 %, errors had consequences and 96 additional actions were performed. There was a significant correlation between errors during opening of the lesser sac and postoperative complications, and between repositioning of the stapler and postoperative complications. In this study, the 13 key steps of the SG were defined, and OCHRA was considered a valuable assessment tool for surgical performance and potential hazard zones. Most consequential errors are made during dissection of the greater curvature and during stapling of the stomach. Errors during the start of mobilization of the greater curvature and repositioning of the stapler lead to longer duration of the procedure and are associated with a higher risk of postoperative complications.


Asthma Management for the Otolaryngologist.
Asthma is a chronic inflammatory disease that will frequently be encountered by otolaryngologists as they manage their patients with upper respiratory diseases. Symptoms such as cough should alert otolaryngologists to consider more broadly the potential role of asthma in the differential diagnosis. It is critical for otolaryngologists to appreciate that patients with allergic rhinitis and chronic rhinosinusitis will often have asthma, and that many of them may not be diagnosed at the time of presentation. Appropriate diagnosis of the patient with asthma, as well as effective treatment for its symptoms, will improve patient function and enhance quality of life.


Analysis of Discrepancies Between Pulse Oximetry and Arterial Oxygen Saturation Measurements by Race and Ethnicity and Association With Organ Dysfunction and Mortality.
Discrepancies in oxygen saturation measured by pulse oximetry (Spo2), when compared with arterial oxygen saturation (Sao2) measured by arterial blood gas (ABG), may differentially affect patients according to race and ethnicity. However, the association of these disparities with health outcomes is unknown. To examine racial and ethnic discrepancies between Sao2 and Spo2 measures and their associations with clinical outcomes. This multicenter, retrospective, cross-sectional study included 3 publicly available electronic health record (EHR) databases (ie, the Electronic Intensive Care Unit-Clinical Research Database and Medical Information Mart for Intensive Care III and IV) as well as Emory Healthcare (2014-2021) and Grady Memorial (2014-2020) databases, spanning 215 hospitals and 382 ICUs. From 141 600 hospital encounters with recorded ABG measurements, 87 971 participants with first ABG measurements and an Spo2 of at least 88% within 5 minutes before the ABG test were included. Patients with hidden hypoxemia (ie, Spo2 ≥88% but Sao2 <88%). Outcomes, stratified by race and ethnicity, were Sao2 for each Spo2, hidden hypoxemia prevalence, initial demographic characteristics (age, sex), clinical outcomes (in-hospital mortality, length of stay), organ dysfunction by scores (Sequential Organ Failure Assessment [SOFA]), and laboratory values (lactate and creatinine levels) before and 24 hours after the ABG measurement. The first Spo2-Sao2 pairs from 87 971 patient encounters (27 713 [42.9%] women; mean [SE] age, 62.2 [17.0] years; 1919 [2.3%] Asian patients; 26 032 [29.6%] Black patients; 2397 [2.7%] Hispanic patients, and 57 632 [65.5%] White patients) were analyzed, with 4859 (5.5%) having hidden hypoxemia. Hidden hypoxemia was observed in all subgroups with varying incidence (Black: 1785 [6.8%]; Hispanic: 160 [6.0%]; Asian: 92 [4.8%]; White: 2822 [4.9%]) and was associated with greater organ dysfunction 24 hours after the ABG measurement, as evidenced by higher mean (SE) SOFA scores (7.2 [0.1] vs 6.29 [0.02]) and higher in-hospital mortality (eg, among Black patients: 369 [21.1%] vs 3557 [15.0%]; P < .001). Furthermore, patients with hidden hypoxemia had higher mean (SE) lactate levels before (3.15 [0.09] mg/dL vs 2.66 [0.02] mg/dL) and 24 hours after (2.83 [0.14] mg/dL vs 2.27 [0.02] mg/dL) the ABG test, with less lactate clearance (-0.54 [0.12] mg/dL vs -0.79 [0.03] mg/dL). In this study, there was greater variability in oxygen saturation levels for a given Spo2 level in patients who self-identified as Black, followed by Hispanic, Asian, and White. Patients with and without hidden hypoxemia were demographically and clinically similar at baseline ABG measurement by SOFA scores, but those with hidden hypoxemia subsequently experienced higher organ dysfunction scores and higher in-hospital mortality.


Prenatal Supplementation with Docosahexaenoic Acid Has No Effect on Growth through 60 Months of Age.
Prenatal supplementation with docosahexaenoic acid (DHA) has been shown to increase birth size, but it is unclear whether these differences translate into improved postnatal growth. We assessed the effect of prenatal supplementation with DHA on offspring weight, length, and body mass index (BMI) through 60 mo of age. We examined growth patterns (height, weight, and BMI) in a cohort of 802 Mexican children whose mothers participated in a randomized, controlled trial of daily supplementation with 400 mg/d of DHA or a placebo from week 18-22 of gestation through delivery, with the use of a longitudinal multilevel model of growth. Overall, means ± SDs of height-, weight-, and BMI-for-age z scores relative to WHO growth standards at 60 mo were -0.49 ± 0.91, -1.15 ± 1.07 and 0.13 ± 1.11, respectively. There were no significant differences by treatment group (all P > 0.05) for height, weight, or BMI at any age through 60 mo. Similarly, DHA did not affect the average growth or the trajectories for these measures through 60 mo. Prenatal DHA supplementation did not affect height, weight, or BMI through 60 mo of age. This trial was registered at clinicaltrials.gov as NCT00646360.


Transcytosis of protein through the mammalian cerebral epithelium and endothelium. II. Adsorptive transcytosis of WGA-HRP and the blood-brain and brain-blood barriers.
Morphological evidence of the potential for adsorptive transcytosis of protein through the mammalian blood-brain fluid barriers, first reported from this laboratory in the mouse, has been confirmed and expanded upon in rats injected intravenously or into the lateral cerebral ventricle/subarachnoid space with with exogenous lectin wheatgerm agglutinin (WGA) conjugated to horseradish peroxidase (HRP). Blood-borne WGA-HRP rapidly enters cerebral endothelia by the process of adsorptive endocytosis and labels the vascular tree throughout the CNS. At 3 h post-injection and longer, WGA-HRP occupies the perivascular clefts and labels perivascular cells and basal lamina; this suspected transendothelial transfer of the lectin conjugate from blood to brain involves specific constituents of the endothelial endomembrane system of organelles (e.g., plasmalemma, vesicles, endosomes, Golgi complex). Within 6 h, reaction product is evident in extracellular clefts beyond the perivascular basal lamina and labels endocytic vesicles, endosomes, and dense bodies within cells and processes of the neuropil. Exposure of the abluminal surface of blood-brain barrier endothelia for 1-18 h to WGA-HRP delivered into the cerebral ventricles or subarachnoid space indicates blood-brain barrier endothelia do not engage in demonstrable adsorptive endocytosis at the abluminal surface. In this preparation, no endothelial organelles comparable to those sequestering blood-borne WGA-HRP are labelled with the lectin conjugate; hence, significant adsorptive transcytosis of WGA-HRP through cerebral endothelia from brain to blood is unlikely. The demonstrable difference in membrane internalization of the luminal versus abluminal plasmalemma of blood-brain barrier endothelia suggests the blood-brain barrier is polarized regarding adsorptive endocytosis of WGA-HRP. If adsorptive transcytosis of macromolecules through the blood-brain barrier does occur, the process appears unidirectional, from blood to brain but not from brain to blood. Absence of demonstrable endocytosis at the abluminal front is an enigma in the scheme of transcytosis through the blood-brain barrier from blood to brain insofar as exocytosis and endocytosis are complementary events in the cellular secretory process. This unconventional membrane behavior associated with the abluminal plasmalemma argues against a significant transcytosis of blood-borne protein through blood-brain barrier endothelia. The potential for transcytosis of macromolecules through the blood-cerebrospinal fluid barrier of choroid plexus epithelia is not as problemmatic as that through blood-brain barrier endothelia; additional evidence is provided to suggest choroid plexus epithelia participate in adsorptive endocytosis circumferentially and adsorptive transcytosis of WGA-HRP bidirectionally between the blood and cerebrospinal fluid.


New adhesive resins. A status report for the American Journal of Dentistry.
Adhesive resins called 4-META and Panavia have been developed recently. These resins bond to various metals, porcelain, and tooth structure. They have become popular for cementation of unetched resin-bonded prostheses and various other clinical applications. This paper is a brief literature review of the composition, adhesive properties, and clinical uses of the new adhesive resins.


Negative ion electrospray ionization tandem mass spectrometry in the structural characterization of penicillins.
The mass spectrometry (MS) behaviour of ten commercially available penicillins has been studied by means of electrospray and multiple-stage MS/MS experiments performed using an ion trap instrument. For all the examined compounds negative ions are produced under ESI conditions, with a yield two or three orders of magnitude higher than that observed for positive ions. MSn experiments indicate the occurrence of a fragmentation pathway related to the beta-lactam ring, different from that usually described for positive ions of these compounds, and provide structural information on both the beta-lactam ring and the side chains.