[Management strategy for patients with coronary artery disease associated with valve disease].
The indication of combined operation of coronary artery bypass (CAB) and valve surgery is controversial. Between April 1992 and January 2000, 13 patients underwent a combined operation with CAB and valve replacement, and 4 patients (2 were overlapped) who had had a previous CAB underwent a reoperative valve replacement. One patient who underwent AVR and reCAB 11 years after the initial CAB died. Another patient with preoperative MRSA pneumonia and received MVR and CAB died 4 months after surgery with MRSA sepsis. However, others showed an excellent post-operative course. The causes of necessitating the reoperation were: unawareness of aortic stenosis at the initial emergency CAB in 1 patient, progression of aortic stenosis in 1 patient, progression of aortic regurgitation in 1 patient, and progression of mitral regurgitation in 1 patient. The results of the combined CAB and valve replacement operation were acceptable. Patients with mild-moderate valve disease should be considered as candidates for valve surgery at the time of CAB.


Do patients with Down's syndrome recognize Mickey Mouse?
In 47 patients with Down's syndrome who were too retarded to understand a conventional oddball paradigm, we studied event-related potentials (ERPs) by using task-irrelevant visual stimuli. As the patients had expressed interest in Disney cartoons and books, five pictures of Disney characters such as Mickey Mouse or Peter Pan were employed as the rare stimuli, and nine ordinary scenes such as mountains as the frequent stimuli. Five sets were constructed by intermingling each rare picture with nine frequent pictures, and each picture was presented on a TV screen. ERPs to the rare stimuli (N270-P380), which were different from the averaged waveforms to frequent stimuli and electrooculograms (EOGs), were clearly recorded in 35 out of 47 patients. Only 24 of these patients had ERPs using a conventional auditory oddball paradigm. The peak latencies in patients were significantly prolonged relative to age-matched normal controls, probably due to a slowed neural processing. The amplitude in patients was slightly larger than normal controls, probably due to the patients' greater interest or surprise when confronted with the Disney characters.


The effect of wintering sites on the survival and reproduction of Gyraulus acronicus (Gastropoda) in a partly frozen river.
In a boreal river about 95% of the individuals of Gyraulus acronicus overwinter in the littoral zone which freezes solid each year. These snails were compared with those overwintering in the unfrozen sublittoral area: The littoral snails had a higher survival rate, a higher tissue dry mass/CaCO3 ratio, and they deposited a higher number of eggs. Littoral snails had a more pronounced tissue degrowth during winter. High winter survival in the frozen littoral zone, a refuge totaly free from predation, indicates that overwintering here is advantageous. However, during frozen periods of short duration (<1 month) the high initial mortality to which the snails were exposed when freezing into the ice was not compensated for by higher survival after the initial phase. Under such conditions when the frozen period is very short the snails would have higher survival in unfrozen parts and are thus expected to avoid the ice.


Effect of DHCR7 for the co-occurrence of hypercholesterolemia and vitamin D deficiency in type 2 diabetes: Perspective of health prevention.
Type 2 diabetes mellitus (T2DM) is a complex disease caused by multiple factors, which are often accompanied by the disorder of glucose and lipid metabolism and the lack of vitamin D.Over the years, researchers have conducted numerous studies into the pathogenesis and prevention strategies of diabetes. In this study, diabetic SD rats were randomly divided into type 2 diabetes group, vitamin D intervention group, 7-dehydrocholesterole reductase (DHCR7) inhibitor intervention group, simvastatin intervention group, and naive control group. Before and 12 weeks after intervention, liver tissue was extracted to isolate hepatocytes. Compared with naive control group, in the type 2 diabetic group without interference, the expression of DHCR7 increased, the level of 25(OH)D3 decreased, the level of cholesterol increased. In the primary cultured naive and type 2 diabetic hepatocytes, the expression of genes related to lipid metabolism and vitamin D metabolism were differently regulated in each of the 5 treatment groups. Overall, DHCR7 is an indicator for type 2 diabetic glycolipid metabolism disorder and vitamin D deficiency. Targeting DHCR7 will help with T2DM therapy.The management model of comprehensive health intervention can timely discover the disease problems of diabetes patients and high-risk groups and reduce the incidence of diabetes.


Dry-reagent nucleic acid biosensor based on blue dye doped latex beads and lateral flow strip.
In the manuscript, a quantitative lateral flow nucleic acid biosensor (Lateral flow nucleic acid biosensor, LFNB) based on blue dye doped latex beads was proposed and its feasibility for detecting deoxyribonucleic acid (DNA) in plasma was investigated. A 60-mer DNA sequence (T1) was selected as model to demonstrate the protocol. Blue dyes doped latex bead bearing DNA probe would be captured on the corresponding test line in the presence of target DNA, to form an evident blue band. Although qualitative tests are realized by observing the color change of the test zone, quantitative data are obtained by recording the optical responses of the test zone with a portable "Strip Reader" instrument conveniently. The strip has been applied for the detection of synthesized DNA sample in human plasma sample with a detection limit of 3.75 fmol. Interference was not evident even the target DNA was spiked with 50 μL plasma which indicated the well shielding of the latex bead reporters and quantified chromatographic separations of unwanted materials of the strip comparing with traditional gold nanoparticle based LFNB platforms.


Low temperature and limited water activity reveal a pathway to magnesite via amorphous magnesium carbonate.
Forsterite carbonated in thin H2O films to magnesite via amorphous magnesium carbonate during reaction with H2O-bearing liquid CO2 at 25 °C. This novel reaction pathway contrasts with previous studies that were carried out at higher H2O activity and temperature, where more highly hydrated nesquehonite was the metastable intermediate.


Graduating from Laboratory to Operating Rooms-the Way Forward for Future Surgeons!
Changing healthcare and social scenarios are reducing the learning opportunities of surgical postgraduates in our country. Majority of surgical training centers in the developed world use laboratory training as an integral part of their curricula. However, in India, most of surgical residents are still trained by traditional apprenticeship model. To describe the role of laboratory training in improving the competency of surgical postgraduates. Laboratory dissection was used as an educational intervention for postgraduates in tertiary care teaching hospital. Thirty-five (35) trainees from various surgical subspecialties performed cadaveric dissection led by senior faculty members. The perceived knowledge and operative confidence of trainees were assessed before and three weeks after the course using a five-point Likert scale. A structured questionnaire was administered to explore the experience of training. Results were tabulated in percentage and proportion. Wilcoxon signed-rank test was applied to find any difference between pre and post perception of knowledge and operative competence of participants. Thirty four (34/35; 96%) were males; 65.7% (23/35) trainees demonstrated improvement in knowledge level after dissection (p < 0.0001) and 74.3% (26/35) in operative confidence (p < 0.0001). Majority believe that cadaveric dissection helps to improve knowledge of procedural anatomy (33/35; 94.3%) and enhances technical skill (25/35; 71.4%). Thirty participants (86%) rated cadaveric dissection as the best tool for surgical training of postgraduates better than operative manuals, surgical videos, and virtual simulators. Laboratory training including cadaveric dissection is feasible, relevant, effective, and acceptable to postgraduate surgical trainees with few disadvantages, which can be taken care of. Trainees felt it should be made part of curriculum.


Extrapleural infusion of levobupivacaine versus levobupivacaine-sufentanil-adrenaline after video-assisted thoracoscopic surgery (VATS): A randomised controlled trial.
Peripheral blocks are increasingly used for analgesia after video-assisted thoracic surgery (VATS). We hypothesised that addition of sufentanil and adrenaline to levobupivacaine would improve the analgesic effect of a continuous extrapleural block. We randomised 60 patients undergoing VATS to a 5-mL h-1 extrapleural infusion of levobupivacaine at 2.7 mg mL-1 (LB group) or levobupivacaine at 1.25 mg mL-1 , sufentanil at 0.5 μg mL-1 , and adrenaline at 2 μg mL-1 (LBSA group). The primary outcome was the cumulative morphine dose administered as patient-controlled analgesia (PCA-morphine) at 48 and 72 h. The secondary outcomes were pain according to numerical rating scale (NRS) at rest and after two deep breaths twice daily, peak expiratory flow (PEF) daily, quality of recovery (QoR)-15 score at 1 day and 3 weeks postoperatively, serum levobupivacaine concentrations at 1 h after the start and at the end of the intervention, and adverse events. At 48 h, the median cumulative PCA-morphine dose for the LB group was 6 mg (IQR, 2-10 mg) and for the LBSA group 7 mg (IQR, 3-13.5 mg; p = .378). At 72 h, morphine doses were 10 mg (IQR, 3-22 mg) and 12.5 mg (IQR, 4-21 mg; p = .738), respectively. Median NRS score at rest and after two deep breaths was 3 or lower at all time points for both treatment groups. PEF did not differ between groups. Three weeks postoperatively, only the LB group returned to baseline QoR-15 score. The LB group had higher, but well below toxic, levobupivacaine concentrations at 48 and 72 h. The incidence of nausea, dizziness, pruritus and headache was equally low overall. For a continuous extrapleural block, and compared to plain levobupivacaine at 13.5 mg h-1 , levobupivacaine at 6.25 mg h-1 with addition of sufentanil and adrenaline did not decrease postoperative morphine consumption. The levobupivacaine serum concentrations after 48 and 72 h of infusion were well below toxic levels, therefore our findings support the use of the maximally recommended dose of levobupivacaine for a 2- to 3-day continuous extrapleural block.


Use of electron-beam computed tomography in the evaluation of chest pain patients in the emergency department.
We sought to determine whether electron-beam computed tomography (EBCT) could be used as a triage tool in the emergency department for patients with angina-like chest pain, no known history of coronary disease, normal or indeterminate ECG findings, and normal initial cardiac enzyme concentrations. We conducted a prospective observational study of 105 patients admitted between December 1995 and October 1997 to the ED of a large tertiary care hospital with 70,000 annual ED visits. The study group was comprised of women aged 40 to 65 years and men aged 30 to 55 years who presented with angina-like chest pain requiring admission to the hospital or chest pain observation unit. All patients underwent EBCT of the coronary arteries, along with other cardiac testing as deemed necessary by staff physicians. Of the 105 patients, 100 underwent other cardiac testing during hospitalization. Evaluation included treadmill exercise testing in 58, coronary angiography in 25, radionuclide stress testing in 19, and echocardiography in 11. Results of EBCT and cardiac testing were negative for both in 53 patients (53%), positive for both in 14 (14%), positive for tomography and negative for cardiac testing in 32 (32%), and negative for tomography and positive for cardiac testing in only 1 patient. This positive test result, on a treadmill exercise test, was ruled a false positive by an independent staff cardiologist. Two other female patients with normal exercise sestamibi or coronary angiography and EBCT findings also had false-positive treadmill exercise results. The sensitivity of EBCT was 100% (95% confidence interval, 77% to 100%), with a negative predictive value of 100% (95% confidence interval, 94% to 100%). Specificity was 63% (95% confidence interval, 54% to 75%). EBCT is a rapid and efficient screening tool for patients admitted to the ED with angina-like chest pain, normal cardiac enzyme concentrations, indeterminate ECG findings, and no history of coronary artery disease. Our study suggests that patients with normal initial cardiac enzyme concentrations, normal or indeterminate ECG findings, and negative results on EBCT may be safely discharged from the ED without further testing or observation. Larger studies are required to confirm this conclusion.


The Surgical Management of Ileal Pouch Strictures.
Total proctocolectomy with IPAA reconstruction is the surgical approach of choice in ulcerative colitis, indeterminate colitis, familial adenomatous polyposis, and selected patients with Crohn's disease. Pouch stricture is a common complication after IPAA. This study aims to identify surgical management options for pouch stricture and offer a treatment algorithm. A computer-assisted search of the online bibliographic databases MEDLINE and Embase from 1990 to 2021 was performed. Randomized controlled trials, cohort studies, observational studies, and case reports were considered. Mechanical dilation, strictureplasty, stapler resection, pouch advancement, bypass, and repeat IPAA were included. Twenty-three articles were considered eligible. Overall incidence of strictures varied from 5% to 38%. Strictures were categorized into 3 areas: pouch inlet (with a reported incidence of 9% to 56%), mid-pouch (with a reported incidence of 2%), and pouch-anal anastomosis (with a reported incidence of 43% to 87%). Pouch-anal strictures were initially managed using bougie or Hegar dilation, with various surgical procedures advocated when initial dilation failed. Mid-pouch strictures are relatively unstudied with scant data. Pouch inlet strictures can be surgically managed by various transabdominal techniques' including resection and reconnection, strictureplasty, or bypass. Pouch-anal strictures should be managed in a step-up strategy as conservative procedures are associated with acceptable success rates. Initial mechanical dilation using bougie or Hegar dilation has a success rate of >80%, although it is likely to require repeat dilations. When these measures fail, transanal surgical approaches using strictureplasty, stapler resection' or pouch advancement should be offered. Transabdominal pouch revision should be offered to patients refractory to a transanal approach. In mid-pouch strictures, the treatment of choice is pouch revision and reanastomosis. Pouch inlet strictures can be managed by resection, strictureplasty, or bypass depending on the location and length of the stricture and surgeon experience. Studies were often small and retrospectively analyzed. There were no randomized controlled trials or comparison between different treatment options.


Salvage of an impacted canine associated with an adenomatoid odontogenic tumour: a case report.
The adenomatoid odontogenic tumour (AOT) has been known by a number of descriptive names (adenoameloblastoma, ameloblastic adenomatoid tumour, glandular ameloblastoma, and adenomatoid ameloblastoma) since it was first reported and later recognised as a distinct odontogenic lesion unrelated to ameloblastoma. Although it was considered to be a variant of ameloblastoma at one time leading surgeons to perform unduly aggressive surgery, the treatment outcome experience has borne out the benign, nonaggressive nature of this lesion. The AOT is now considered to be a hamartoma with completely benign behaviour. Recurrence seldom if ever occurs after surgical curettage. Thus, it appears needless to extract involved anterior teeth associated with the tumour, especially in children. We report a case in which surgical and orthodontic treatment helped to salvage an impacted mandibular canine associated with an AOT in an adolescent girl. We have not found such a procedure to have been done for this tumour in the literature.


Worldwide review with meta-analysis of women's awareness about breast cancer.
To summarize the awareness levels of breast cancer (BC) worldwide and investigate factors associated with BC awareness to determine differences in awareness between China and other countries. This systematic review followed the PRISMA guidelines and included 92 articles up to July, 2021. We calculated percentages for BC awareness levels and conducted subgroup analysis and cumulative meta-analysis. A total 84% (95% confidence interval [95%CI]: 78-90%) of women knew about BC; however, only 51% (95%CI: 37-66%) and 40% (95%CI: 24-56%) of women were aware of BC symptoms and BC risk factors, respectively. The most commonly known BC symptom was breast lump (71%, 95%CI: 62-80%), and BC family history was the most well-known BC risk factor (61%, 95%CI: 54-69%). Subgroup analysis showed lower awareness levels among Chinese and Asian women than women from other countries. Cumulative meta-analysis showed no obvious progress in BC awareness levels over time. We investigated 15 awareness-related factors, the most frequent of which were education level (61.8%), occupation (29.4%), and age (26.5%). BC awareness levels remain low. Improving BC awareness is critical, especially in developing countries. Effective education programs are urgently needed to improve women's BC awareness.


Determination of the different oxidation states of As and Sb by a new electrochemical hydride generator coupled with atomic fluorescence spectrometry.
A novel disk electrochemical hydride generator has been developed for the determination of As and Sb. Compared with the traditional thin-layer cell, the disk cell combined the advantages of quick assembly and easy operation. This electrochemical system for hydride generation in neutral buffer solutions has been studied for analytical usefulness in coupling with atomic fluorescence spectrometry. It was found that the use of neutral phosphate buffer solution could markedly increase the fluorescence intensity of As(III) and Sb(III) and reduce the impact of cathode erosion on the stability of signal intensity. At the same time, the fluorescence intensity of As(V) and Sb(V) were almost suppressed totally. The detection limits (3 sigma) of 0.031 microgL(-1) As(III) and 0.026 microgL(-1) Sb(III) in aqueous solutions were obtained, respectively. The precisions (n=11) for 20 microgL(-1) As(III) and Sb(III) were 2.0% and 2.7%, respectively. The method was successfully applied for determination of different oxidation states of As and Sb in environmental samples.


What are the true volumes of SEGA tumors? Reliability of planimetric and popular semi-automated image segmentation methods.
To evaluate the reliability of the standard planimetric methodology of volumetric analysis and three different open-source semi-automated approaches of brain tumor segmentation. The volumes of subependymal giant cell astrocytomas (SEGA) examined by 30 MRI studies of 10 patients from a previous everolimus-related trial (EMINENTS study) were estimated using four methods: planimetric method (modified MacDonald ellipsoid method), ITK-Snap (pixel clustering, geodesic active contours, region competition methods), 3D Slicer (level-set thresholding), and NIRFast (k-means clustering, Markov random fields). The methods were compared, and a trial simulation was performed to determine how the choice of approach could influence the final decision about progression or response. Intraclass correlation coefficient was high (0.95; 95% CI 0.91-0.98). The planimetric method always overestimated the size of the tumor, while virtually no mean difference was found between ITK-Snap and 3D Slicer (P = 0.99). NIRFast underestimated the volume and presented a proportional bias. During the trial simulation, a moderate level of agreement between all the methods (kappa 0.57-0.71, P < 0.002) was noted. Semi-automated segmentation can ease oncological follow-up but the moderate level of agreement between segmentation methods suggests that the reference standard volumetric method for SEGA tumors should be revised and chosen carefully, as the selection of volumetry tool may influence the conclusion about tumor progression or response.


Synthesis, cellular uptake of, and cell photosensitization by a porphyrin bearing a quinoline group.
A tetraphenyl porphine linked to a 7-chloroquinoline (5,10,15,20-tetraphenyl-1-3-[4-(4-aminobutyl)7-chloroquinoline] propioamidoporphine, TPPQ) was synthesized and examined as a potential photosensitizer for photodynamic therapy (PDT) of proliferative diseases. With respect to haematoporphyrin, TPPQ is a good in vitro photodynamic sensitizer producing singlet oxygen in 1% Triton X100 solutions. As with other hydrophobic porphyrins used in PDT, blood lipoproteins strongly bind TPPQ. Thus one low density lipoprotein (LDL) can incorporate 25 TPPQ molecules and 17 TPPQ molecules are taken up by one high density lipoprotein (HDL). Cell delivery of TPPQ using HDL or human serum albumin (HSA) as carrier is rather weak. However, an efficient TPPQ delivery to human skin fibroblasts is observed, partly aided by receptor-mediated endocytosis of LDL. Fluorescence spectroscopy shows that the cellular localization of TPPQ is both carrier and time dependent. During its delivery with LDL, TPPQ does not significantly impair the endocytosis of LDL-receptor complexes. After delivery with LDL, TPPQ is as efficient as other haematoporphyrin derivatives used in the PDT of cancers in photosensitizing human skin fibroblasts.


Changes in the medial-lateral hamstring activation ratio with foot rotation during lower limb exercise.
This paper investigated whether the ratio of medial-lateral hamstring muscular activation could be altered with changes in foot rotation position (both internal and external rotation) during three standard lower limb exercises. It has been suggested that those with medial compartment knee OA activate the lateral hamstrings more than the medial to help unload the diseased compartment; therefore, preferential activation of this muscle during lower limb exercise may help to further decrease the stresses on the articular cartilage and be an effective intervention for knee OA and lateral hamstring injury. Thirteen healthy young adult subjects were tested and average medial and lateral hamstring EMG data during the full exercise, as well as the concentric and eccentric phases, were used to calculate the medial-lateral (M-L) hamstring activation ratio for each exercise and foot position. Results suggest that internal foot rotation increases the M-L hamstring activation ratio while external foot rotation decreases this ratio. Therefore, altering the position of the foot during standard lower limb exercise can help selectively activate the medial or lateral hamstring muscle groups. This selective activation may have implication in treating symptoms of knee osteoarthritis and hamstring injury; but, longitudinal intervention studies would be needed to determine clinical utility.


Artificial Intelligence-Enabled Electrocardiogram Improves the Diagnosis and Prediction of Mortality in Patients With Pulmonary Hypertension.
Pulmonary hypertension is a disabling and life-threatening cardiovascular disease. Early detection of elevated pulmonary artery pressure (ePAP) is needed for prompt diagnosis and treatment to avoid detrimental consequences of pulmonary hypertension. This study sought to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify patients with ePAP and related prognostic implications. From a hospital-based ECG database, the authors extracted the first pairs of ECG and transthoracic echocardiography taken within 2 weeks of each other from 41,097 patients to develop an AI model for detecting ePAP (PAP > 50 mm Hg by transthoracic echocardiography). The model was evaluated on independent data sets, including an external cohort of patients from Japan. Tests of 10-fold cross-validation neural-network deep learning showed that the area under the receiver-operating characteristic curve of the AI model was 0.88 (sensitivity 81.0%; specificity 79.6%) for detecting ePAP. The diagnostic performance was consistent across age, sex, and various comorbidities (diagnostic odds ratio >8 for most factors examined). At 6-year follow-up, the patients predicted by the AI model to have ePAP were independently associated with higher cardiovascular mortality (HR: 3.69). Similar diagnostic performance and prediction for cardiovascular mortality could be replicated in the external cohort. The ECG-based AI model identified patients with ePAP and predicted their future risk for cardiovascular mortality. This model could serve as a useful clinical test to identify patients with pulmonary hypertension so that treatment can be initiated early to improve their survival prognosis.


Race does not predict pancreas graft failure after pancreas transplantation in the modern era.
African-American (AA) has historically been associated with inferior graft survival after pancreas transplantation. However, with the improvement of immunosuppression and surgical technique, we hypothesized that the racial disparity has been neutralized. We analyzed data from the Scientific Registry of Transplant Recipients (1989-2018). Using Kaplan-Meier estimation and Cox proportional hazards regression, we examined the influence of race on pancreatic graft survival. Before 2009, AA recipients had a higher risk of pancreatic graft failure after adjusting for confounding factors (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.08-1.24), but the risks for Hispanic and Asian recipients were both comparable to their Caucasian counterparts. However, the risk of pancreatic graft failure in AA recipients dropped to 1% and was no longer significant since 2009 (HR: 1.01, 95%CI: 0.88-1.16). Interestingly, donor race showed similar results. Furthermore, the concordance statistic of the complete pancreas donor risk index (including donor race) was 0.582, whereas the concordance did not change when donor race was eliminated from the model. AA and other races have shown similar pancreatic graft survival in the modern era. Furthermore, donor racial disparity also seems neutralized; thus, donor race should not be considered as an indicator of pancreatic donor quality.


Rate of detection of unsuspected pregnancies after implementation of mandatory point-of-care urine pregnancy testing prior to hysterosalpingography.
The aim of this study was to determine the rate of detection of unsuspected pregnancies after the implementation of mandatory point-of-care urine pregnancy testing before hysterosalpingography (HSG). At the authors' institution, HSGs are scheduled to occur during days 8 to 12 of the menstrual cycle. Upon arrival in the radiology department, all women undergo point-of-care urine pregnancy testing before HSG (at a cost of $1.25 per test). Urine pregnancy test results were retrospectively reviewed. Four hundred ten women (mean age, 25.9 years; range, 22-50 years) underwent point-of-care urine pregnancy testing before HSG between October 2010 and July 2012. Study indications were infertility evaluation (90.7% [372 of 410]) and tubal patency assessment after placement of tubal occlusive devices (9.3% [38 of 410]). Two positive urine pregnancy test results (0.5%) were recorded. One positive result was deemed a false-positive because the patient had received an intramuscular injection of β-human chorionic gonadotropin before the scheduled HSG, and follow-up laboratory testing showed declining β-human chorionic gonadotropin levels. The second positive result was a true-positive, and the patient was determined to be 4.5 weeks pregnant on the date of the scheduled HSG. One of 410 women presenting for HSG was found to have an unsuspected early pregnancy, which was detected with a point-of-care urine pregnancy test. Consideration should be given to routine pregnancy testing of women before HSG because scheduling on the basis of menstrual cycle dates can be unreliable.


Determination of trace amounts of Ga(III) by adsorptive stripping voltammetry with in situ plated bismuth film electrode.
The determination of trace gallium using adsorptive stripping voltammetry at an in situ plated bismuth film electrode was described. The method was based on simultaneous film formation and the Ga(III)-cupferron complex preconcentration at -0.65 V and its cathodic stripping during the potential scan. The effect of Bi(III) and cupferron concentration, the influence of deposition potential and time, and the scan rate on the determination of Ga(III) were studied. A linear response in the concentration range of 3×10(-10) to 3×10(-7) mol L(-1) (r=0.998) was obtained with detection limit of 1.05×10(-10) mol L(-1) using accumulation time of 180 s. Finally, the bismuth film electrode was successfully applied for the determination of Ga(III) in certified reference material seawater NASS-5 with satisfactory results.


From prospective clinical trial to reducing social inequalities in health: The DESSEIN trial, concept and design of a multidisciplinary study in precarious patients with breast cancer.
In France during the last 15 years, precariousness among women has increased. In breast cancer, precariousness has been associated with an increase in mortality, but the links between precariousness, stage at diagnosis and care pathway are little explored. Our study aims to evaluate the impact of precariousness on care pathways, treatment and recovery phase according to a multidisciplinary analysis. Comparative prospective observational multicenter study of exposed / unexposed category. Patients with breast cancer are recruited in the Ile de France area. Three scores are used to identify precarious patients. Precarious patients are matched to non-precarious patients by age group. Questionnaires are distributed to patients at different times of care. The main objective is to compare the stage of the disease at diagnosis between two groups. The secondary objectives are: comparison of socio-economic and geographical characteristics, direct and indirect costs, personal trajectories of care and health. Analysis include multidisciplinary approaches. A geographical information systems method will evaluate the accessibility to health facilities and the characteristics of the places of residence of the patients. An anthropological analysis will be conducted through observation of consultations and semi-directed interviews with patients. These methods will allow to analyze the diagnostic and therapeutic routes, placing it in a life history and an economic, socio-cultural and health environment. The economic analysis will include a comparison of direct, indirect costs and out-off pocket costs, from the patient's point of view and from the societal perspective. Conducted in a clinical setting and coupled with a qualitative study, this study will provide a better understanding of how contextual factors, combined with individual factors, can influence the course of health and thus the stage of the disease at diagnosis. The multidisciplinary approach, involving clinicians, geographers, an anthropologist, an economist and a health epidemiologist, will allow a multidimensional approach to the impact of precariousness on breast cancer. ClinicalTrials.gov Identifier: NCT02948478 registered October 28, 2016. 2016-A00589-42. protocol version: 2.1. decembre 13, 2018.


Distress, problems and unmet rehabilitation needs after treatment for gynecological cancer.
The prevalence of distress, problems and need for rehabilitation among women treated for gynecological cancer is largely unknown. The aims of this study were to examine the prevalence of distress, problems and unmet rehabilitation needs in the first years after treatment for gynecological cancer. Women treated for gynecological cancer within the last 2 years were invited. Participants responded to the National Comprehensive Cancer Network Distress Thermometer and Problem List measuring distress and problems. They also answered a questionnaire regarding physical endurance, muscle strength, and need for rehabilitation services. Of 114 eligible women, 92 (81%) agreed to participate. Mean time since last treatment was 7.6 months (range 0-24.5 months). A total of 57% of the participants reported distress. The four most common problems reported were fatigue (58%), tingling in hands/feet (54%), worry (53%), and problems with memory/concentration (50%). Problems associated with distress were: dealing with partner, all emotional problems (i.e. depression, fears, nervousness, sadness, worry, and loss of interest in usual activities), appearance, memory/concentration, pain, sex, sleep, and problems with physical endurance and muscle strength. Fifty-two percent reported unmet needs for rehabilitation services. Women with distress reported more unmet rehabilitation needs than those in the non-distressed group. The prevalence of distress in this population of women treated for gynecological cancer was high. Having a high number of problems and having unmet needs for rehabilitation services were both associated with distress. Hence, measurement of distress seems to be helpful when assessing the need for rehabilitation services.


NGF and nitrosative stress in patients with Huntington's disease.
Huntington's disease (HD) is a neurodegenerative genetic disorder caused by expansion of polyglutamine repeats in the huntingtin gene and characterised by the loss of striatal and cortical neurons. Few studies to date have focussed on peripheral neurotrophic-factor levels in patients with HD. To measure plasma NGF levels in Huntington's disease and investigate their correlation with disease intensity. Nineteen patients with HD and nineteen age- and sex-matched healthy subjects took part in this cross-sectional study. Plasma levels of NGF, BDNF, GDNF, nitrotyrosine, and myeloperoxidase (MPO) were measured; lactate dehydrogenase (LDH) levels were determined and white blood cell (WBC) counts were evaluated. NGF levels were significantly lower, nitrotyrosine levels were higher and LDH activity was greater in HD patients than in healthy subjects. There was no significant difference in MPO levels or WBC counts, whereas the MPO/WBC ratio was considerably higher in HD patients. The data obtained suggested that biochemical and haematological changes correlated with disease severity. NGF levels are lower in HD patients than in healthy subjects. However, further research is required to confirm the role of NGF in HD.


Potential causes, mechanisms, and implications of post exercise hypotension.
Post exercise hypotension (PEH) is a phenomenon of a prolonged decrease in resting blood pressure in the minutes and hours following acute exercise. Knowledge of PEH is potentially useful in designing first line strategies against hypertension as well as allowing a further understanding of blood pressure regulation in both health and disease. Following a brief review of blood pressure responses to exercise, this paper will provide a current and comprehensive summary of PEH and integrate the current state of knowledge surrounding it.


Comparison of non-Gaussian and Gaussian diffusion models of diffusion weighted imaging of rectal cancer at 3.0 T MRI.
Water molecular diffusion in vivo tissue is much more complicated. We aimed to compare non-Gaussian diffusion models of diffusion-weighted imaging (DWI) including intra-voxel incoherent motion (IVIM), stretched-exponential model (SEM) and Gaussian diffusion model at 3.0 T MRI in patients with rectal cancer, and to determine the optimal model for investigating the water diffusion properties and characterization of rectal carcinoma. Fifty-nine consecutive patients with pathologically confirmed rectal adenocarcinoma underwent DWI with 16 b-values at a 3.0 T MRI system. DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models (IVIM-mono, IVIM-bi and SEM) on primary tumor and adjacent normal rectal tissue. Parameters of standard apparent diffusion coefficient (ADC), slow- and fast-ADC, fraction of fast ADC (f), α value and distributed diffusion coefficient (DDC) were generated and compared between the tumor and normal tissues. The SEM exhibited the best fitting results of actual DWI signal in rectal cancer and the normal rectal wall (R2 = 0.998, 0.999 respectively). The DDC achieved relatively high area under the curve (AUC = 0.980) in differentiating tumor from normal rectal wall. Non-Gaussian diffusion models could assess tissue properties more accurately than the ADC derived Gaussian diffusion model. SEM may be used as a potential optimal model for characterization of rectal cancer.


Combined toxicity of polystyrene microplastics and sulfamethoxazole on zebrafish embryos.
Despite extensive investigation on the toxicity of microplastics (MPs), an emerging global concern, little is known about the combined toxicity of MPs and co-occurring pollutants in aquatic environments. In this study, the combined toxicity of polystyrene MPs and sulfamethoxazole (SMZ) antibiotics was explored in zebrafish embryos in terms of the developmental, physiological, and endocrine toxicities. Exposure to PS and SMZ induced mortality (rate: 25.0 ± 7.5%) and malformation (rate: 20~35%) at multiple regions and stages of zebrafish development. Physiological toxicity was also induced as shown by the significant decrease in fetal movement (by 31.1~37.0%) and swimming frequency (by 26.9~36.8%) and the increase in heartbeat rate (by 19.0~20.9%). Finally, PS and SMZ exposure also induced extensive endocrine toxicities in zebrafish as confirmed by increases in various biomarkers including vitellogenin, 17β-estradiol, testosterone, and triiodothyronine. The combination index showed that antagonistic effects were present between PS and SMZ toxicity, which slightly decreased their combined toxicity. This study aims to further understand the combined toxicity of MPs and co-occurring pollutants in aquatic environments.


Outcomes of esophagectomy for patients with esophageal squamous cell carcinoma accompanied by recurrent laryngeal nerve palsy at diagnosis.
Hoarseness is one of the classical symptoms in patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC), and it results from recurrent laryngeal nerve palsy, which is caused by nodal metastasis along the recurrent laryngeal nerve or by main tumors. We reviewed the short-term and long-term results of esophagectomy for patients with locally advanced ESCC and hoarseness at diagnosis. Patients who initially presented with hoarseness from recurrent laryngeal nerve palsy between 2009 and 2018 and underwent esophagectomy for thoracic ESCC were eligible for this study. Pharyngolaryngectomy or cervical ESCC were exclusionary. A total of 15 patients were eligible, and 14 underwent resection of the recurrent laryngeal nerves. The remaining patient had nerve-sparing surgery. Nine patients (60%) had post-operative complications ≥ Clavien-Dindo class II and, pulmonary complications were most common. Two patients (13%) died in the hospital. The 5-year overall survival rate for all patients was 16%. Age (≤ 65 years), cT1/T2 tumor, and remarkably good response to neoadjuvant treatment were likely related to longer survival; however, these relationships were not statistically significant. Esophagectomy for ESCC patients who are diagnosed with recurrent laryngeal nerve paralysis at initial presentation could be a treatment option if the patient is relatively young, has a cT1/T2 tumor, or shows a remarkably good response to neoadjuvant treatment. However, clinicians should be aware of the possibility of postoperative pulmonary complications, which were frequently observed with the procedure.


A Review of Planned, Ongoing Clinical Studies and Recent Development of BNCT in Mainland of China.
Boron neutron capture therapy (BNCT) is a promising cancer treatment modality that combines targeted boron agents and neutron irradiation to selectively destroy tumor cells. In mainland China, the clinical implementation of BNCT has made certain progress, primarily driven by the development of compact neutron source devices. The availability, ease of operation, and cost-effectiveness offered by these compact neutron sources make BNCT more accessible to cancer treatment centers. Two compact neutron sources, one being miniature reactor-based (IHNI-1) and the other one being accelerator-based (NeuPex), have entered the clinical research phase and are planned for medical device registration. Moreover, several accelerator-based neutron source devices employing different technical routes are currently under construction, further expanding the options for BNCT implementation. In addition, the development of compact neutron sources serves as an experimental platform for advancing the development of new boron agents. Several research teams are actively involved in the development of boron agents. Various types of third-generation boron agents have been tested and studied in vitro and in vivo. Compared to other radiotherapy therapies, BNCT in mainland China still faces specific challenges due to its limited clinical trial data and its technical support in a wide range of professional fields. To facilitate the widespread adoption of BNCT, it is crucial to establish relevant technical standards for neutron devices, boron agents, and treatment protocols.


Screening for conditions of public health importance in people arriving in Australia by boat without authority.
To determine the prevalence of tuberculosis, hepatitis B carriage and markers of hepatitis C and HIV infection in people detained in immigration reception and processing centres in Australia. Eighteen-month survey of medical conditions of public health importance in people detained at the immigration reception and processing centres at Curtin and Port Hedland in Western Australia and Woomera in South Australia. 7000 detainees (5742 adults and 1258 children and teenagers aged < 18 years) between 1 January 2000 and 30 June 2001. People treated for active tuberculosis; issuing of health undertakings to report to a chest clinic for follow-up of inactive tuberculosis; and confirmation of hepatitis B carrier status or hepatitis C or HIV infection. Eleven people required treatment for tuberculosis (in nine the diagnosis was confirmed bacteriologically), representing a prevalence of 157 cases per 100,000 population. This rate is much higher than the incidence in Australia in 1998 of 4.93 cases per 100,000 population, but comparable with rates in the source countries. Health undertakings were issued to 973 people (13.9%). Of these, 682 (70.1%) were for inactive tuberculosis (26 in association with hepatitis B carriage or hepatitis C infection); and 156, 58 and two health undertakings were for hepatitis B carriage, and hepatitis C and HIV infection, respectively. The health-screening program at immigration reception and processing centres detects significant numbers of conditions of public health importance, enabling treatment and surveillance to the benefit of the people detained and the Australian community.


Non-apoptotic TRAIL function modulates NK cell activity during viral infection.
The role of death receptor signaling for pathogen control and infection-associated pathogenesis is multifaceted and controversial. Here, we show that during viral infection, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) modulates NK cell activity independently of its pro-apoptotic function. In mice infected with lymphocytic choriomeningitis virus (LCMV), Trail deficiency led to improved specific CD8+ T-cell responses, resulting in faster pathogen clearance and reduced liver pathology. Depletion experiments indicated that this effect was mediated by NK cells. Mechanistically, TRAIL expressed by immune cells positively and dose-dependently modulates IL-15 signaling-induced granzyme B production in NK cells, leading to enhanced NK cell-mediated T cell killing. TRAIL also regulates the signaling downstream of IL-15 receptor in human NK cells. In addition, TRAIL restricts NK1.1-triggered IFNγ production by NK cells. Our study reveals a hitherto unappreciated immunoregulatory role of TRAIL signaling on NK cells for the granzyme B-dependent elimination of antiviral T cells.


Women's experiences of cervical ripening as inpatients on an antenatal ward.
To gain an insight into women's lived experiences of inpatient cervical ripening, in the context of usual care, whilst they were admitted as inpatients on an antenatal ward. A qualitative design was used guided by an interpretative phenomenological approach. Seven women who had experienced inpatient cervical ripening on an antenatal ward in Wales (UK) agreed to participate in the study. Data were gathered from semi-structured interviews and analysed thematically. Four overarching themes were identified relating to participants' support from significant others, their understanding of the procedure, perception of their own physiological sensations, and their sense of freedom within the ward environment. Strict adherence to ward rules and procedures appeared to undermine women's experiences of cervical ripening as inpatients on an antenatal ward. Facilitating the continued presence of family members, improving the provision of information, listening to women and enhancing their perception of freedom within the ward environment are strategies that may have a positive influence on women's experiences of inpatient cervical ripening. This study has provided an insight into women's experiences of usual care, during the cervical ripening procedure, as inpatients on an antenatal ward.


[Lumbar spinal angiolipoma].
Spinal angiolipomas are fairly infrequent benign tumours that are usually located in the epidural space of the thoracic column and represent 0.14% to 1.3% of all spinal tumours. Lumbar angiolipomas are extremely rare, representing only 9.6% of all spinal extradural angiolipomas. We report the case of a woman who complained of a lumbar pain of several months duration with no neurological focality and that had intensified in the last three days without her having had any injury or made a physical effort. The MR revealed an extradural mass L1-L2, on the posterior face of the medulla, decreasing the anteroposterior diameter of the canal. The patient symptoms improved after surgery. Total extirpation of the lesion is possible in most cases, and the prognosis is excellent even if the lesion is infiltrative. For this reason, excessively aggressive surgery is not necessary to obtain complete resection.


Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results.
To evaluate glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging at 3T in the assessment of the GAG content of cervical IVDs in healthy volunteers. Forty-two cervical intervertebral discs of seven healthy volunteers (four females, three males; mean age: 21.4 ± 1.4 years; range: 19-24 years) were examined at a 3T MRI scanner in this prospective study. The MRI protocol comprised standard morphological, sagittal T2 weighted (T2w) images to assess the magnetic resonance imaging (MRI) based grading system for cervical intervertebral disc degeneration (IVD) and biochemical imaging with gagCEST to calculate a region-of-interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). GagCEST of cervical IVDs was technically successful at 3T with significant higher gagCEST values in NP compared to AF (1.17% ± 1.03% vs. 0.79% ± 1.75%; p = 0.005). We found topological differences of gagCEST values of the cervical spine with significant higher gagCEST effects in lower IVDs (r = 1; p = 0). We could demonstrate a significant, negative correlation between gagCEST values and cervical disc degeneration of NP (r = -0.360; p = 0.019). Non-degenerated IVDs had significantly higher gagCEST effects compared to degenerated IVDs in NP (1.76% ± 0.92% vs. 0.52% ± 1.17%; p < 0.001). Biochemical imaging of cervical IVDs is feasible at 3T. GagCEST analysis demonstrated a topological GAG distribution of the cervical spine. The depletion of GAG in the NP with increasing level of morphological degeneration can be assessed using gagCEST imaging.


Refocusing formative feedback to enhance learning in pre-registration nurse education.
The essential feature of a teaching system designed to enhance learning and emulate professional practice is that the crucial assessments should be performance-based, allowing plenty of opportunity for students to offer their own ideas and solutions. This involves the use of formative assessment and feedback. High quality formative assessment has been linked to enhancement of learning and ultimately to higher student achievement. Although formative assessment is acknowledged as important in its effect on students' approaches to learning, it appears that the assessment practice is under utilized in pre-registration nurse education. This paper refocuses on the purpose of formative assessment of theory. It examines, from educational literature, some of the benefits of formative assessment and its pedagogical implications on deep learning, motivation and self-esteem, self-regulated learning and employability. It discusses what constitutes quality feedback to highlight that it is not just an essential component but also a central feature of formative assessment. The extent to which formative assessment and feedback can be applied to pre-registration nurse education is also explored. If formative assessment and feedback is well planned and conducted in assessment practice, it is suggested that effective learning can be facilitated in everyday learning activity.


Enzyme-guided DNA Sewing Architecture.
With the advent of nanotechnology, a variety of nanoarchitectures with varied physicochemical properties have been designed. Owing to the unique characteristics, DNAs have been used as a functional building block for novel nanoarchitecture. In particular, a self-assembly of long DNA molecules via a piece DNA staple has been utilized to attain such constructs. However, it needs many talented prerequisites (e.g., complicated computer program) with fewer yields of products. In addition, it has many limitations to overcome: for instance, (i) thermal instability under moderate environments and (ii) restraint in size caused by the restricted length of scaffold strands. Alternatively, the enzymatic sewing linkage of short DNA blocks is simply designed into long DNA assemblies but it is more error-prone due to the undeveloped sequence data. Here, we present, for the first time, a comprehensive study for directly combining DNA structures into higher DNA sewing constructs through the 5'-end cohesive ligation of T4 enzyme. Inspired by these achievements, the synthesized DNA nanomaterials were also utilized for effective detection and real-time diagnosis of cancer-specific and cytosolic RNA markers. This generalized protocol for generic DNA sewing is expected to be useful in several DNA nanotechnology as well as any nucleic acid-related fields.


Tetraploidy with hydrops fetalis, cystic nuchal hygroma and 90, XX karyotype.
In the present report we describe a mid-trimester Turner fetus with cystic nuchal hygroma, hydrops fetalis and 90, XX karyotype. This observation suggests that the development of a typical Turner syndrome in humans is apparently caused by a specific autosome/X chromosome ratio (44:1 in 45, X patients or 88:2 in the present fetus) rather than by an X-chromosome monosomy.


Children and youth with diabetes are not at increased risk for hospitalization due to COVID-19.
The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), responsible for the coronavirus disease COVID-19, was first identified in Wuhan, China in December 2019. Diabetes, as well as other cardiovascular comorbidities, has been recognized as a major risk factor for outcomes and mortality in adults with COVID-19, particularly in the elderly with type 2 diabetes. Based on these conclusions, COVID-19 data on adults have been generalized to youth with diabetes. Nevertheless, experience from pediatric diabetes practices in China (Wuhan), Italy, Spain (Catalonia), and the United States (San Francisco Bay Area) consistently report only a single severe case of COVID-19 in a 20-year-old female youth with type 1 diabetes (T1D) that was hospitalized for bilateral pneumonia and was subsequently discharged without complications. In Italy, information on COVID-19 in all children with diabetes is collected on a weekly basis and those with positive swab test or infection-related symptoms reported to a dedicated national registry. Of a total of 15 500 children tested, 11 subjects with T1D (age 8-17y) tested positive for COVID-19; 6/11 were asymptomatic and the rest presented with mild symptoms. In the rest of locations, youths with T1D diagnosed with COVID-19 were based on clinical suspicion and a confirmatory PCR test (Wuhan:0; Catalonia-HSJD:3; California-Stanford:2). All of them were asymptomatic or had a mild course. We suggest that COVID-19 data from adults should not be generalized to children, adolescents, and youth with diabetes as their outcomes and prognosis seem to be similar to their non-diabetic-peers and consistently milder than adults with diabetes.


The dexamethasone suppression test and antidepressant response in major depression.
We conducted a prospective open pilot study of 34 consecutively admitted patients with the DSM-III diagnosis of MD who were admitted to a general psychiatric unit. Patients underwent a 1 mg DST and were randomly assigned to treatment with either maprotiline or trazodone. Antidepressant dosages were increased as tolerated clinically and according to treatment response. mean final oral doses were 193 mg for maprotiline and 328 mg for trazodone. The mean treatment duration was 4.5 weeks for maprotiline and 5.9 weeks for the trazodone group. Of these 34 patients 44% showed DST nonsuppression (41% maprotiline, 45% trazodone). Seventy-six per cent of the patients responded to treatment (76% for both drugs) as defined by GAS. Eighty-seven per cent of the nonsuppressors responded to treatment (86% maprotiline, 88% trazodone) and 68% of the suppressors responded (70% maprotiline, 67% trazodone). Of the eight treatment nonresponders six showed DST suppression. The implications of these findings are discussed.


Efficient immobilization and utilization of chromite ore processing residue via hydrothermally constructing spinel phase Fe2+(Cr3+X, Fe3+2-x)O4 and its magnetic separation.
Chromite ore processing residue (COPR) has been a severe environmental contaminant which is worthy of attention. In this study, we developed an eco-friendly and practical technology for effectively stabilizing and recovering Cr(VI) in COPR via combining FeSO4 reducing agent and the hydrothermal treatment. A stable spinel phase product was formed during detoxification. In addition, the ferrochrome resources in the treated COPR can be obtained by magnetic separation. As we studied, the hydrothermal environment promoted the release of unstable Na2CrO4 from COPR into the solution, and the released CrO42- was reduced to Cr(III) by FeSO4. Subsequently, Cr(III), Fe(II) and Fe(III) were hydrothermally mineralized to form the magnetic spinel phase Fe2+(Cr3+X, Fe3+2-x)O4 (FeCr spinel substance), which was conducive to the magnetic separation of ferrochrome resources. Under the optimal hydrothermal conditions (0.15 g FeSO4/2 g COPR, treatment at 180 °C for 8 h), the total Cr leaching concentration of treated COPR (COPR-HT) was decreased from 120.51 mg L-1 to 0.23 mg L-1, well below the regulatory limit of 1.5 mg L-1 (HJ/T 301-2007, China EPA). After 300 days aging under atmospheric conditions, the total Cr leaching concentration of COPR-HT was still below 1.5 mg L-1. Besides, the COPR-HT after magnetic separation contained 11.52 wt% Cr2O3 and 53.44 wt% Fe2O3, which can be used as the raw material for steel industry. The underlying mechanism of COPR stabilization was explained by XRD, XPS and SEM-EDS analysis. This work converted the toxic and unstable Cr(VI) in COPR into the long-term stable FeCr spinel substance that is easy to magnetically separate. It has important reference for the harmless disposal and resource utilization of other chromium-containing hazardous wastes including chromium slag and electroplating sludge.


Direct application of bFGF without edge trimming on human subacute tympanic membrane perforation.
To investigate the feasibility of direct application of basic fibroblast growth factor (bFGF) without edge trimming on human subacute traumatic tympanic membrane perforation (TMP). A total of 29 patients with traumatic TMPs beyond 1 month after trauma were enrolled. Patients were placed into two groups: an observation group (n=17) and a bFGF-treated group (n=12). The bFGF-treated group was treated by direct application of bFGF, in which the margin of the perforation was not trimmed. All patients were followed at least once per week until the perforation was completely closed or for up to 6 months. The closure rate and closure time were estimated. At 6 months, 11/12 (91.7%) perforations achieved complete closure after bFGF treatment. The mean closure time was 18.1 ± 11.4 days (range=3-65 days). Purulent otorrhea was found after treatment in five patients, but resolved after oral amoxicillin and ofloxacin ear drops. Of these five patients, four achieved complete closure. However, only 9/17 (52.9%) perforations achieved complete spontaneous closure in the observation group. FGF-treated groups had significantly improved closure rates compared to the observation group (91.7% vs. 52.9%, respectively, P=0.03). Although the margin of the perforation was not trimmed, direct application of bFGF on human subacute TMP was feasible, and it could significantly improve the closure rate of the subacute TMPs. The technique was simple and convenient. Thus, direct application of bFGF should be recommended pre-myringoplasty.


Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and environmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal individuals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL-1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42-0.95; P < 0.05 relative to reference genotype and OR = 0.62, CI = 0.42-0.93; P < 0.05 relative to homozygous genotypes). For all other studied alleles and genotypes, there were no significant differences concerning genotype frequencies between patients and controls. A significant increase in IL-1RN rs315952 T allele frequency was noted in patients with a hematologic manifestation (OR = 1.75; 95 % CI = 1.07-2.84; P = 0.033). Polymorphism in IL-1RN rs315952 was significantly associated with SLE in Iranian patients, rs315952CT genotype being a protective factor. We found that IL-1RN rs315952 T allele frequency was significantly higher in patients with hematologic manifestations. Variation at this locus may affect IL-1 receptor antagonist activity, supporting the hypothesis that altered or imbalanced IL1 production may affect the risk of developing SLE.


Will neurology residents with large student loan debts become academicians?
Medical education in the United States is expensive, with 4-year tuition at some institutions totaling more than 150,000 US dollars. Most US graduates have student debt burdens. Using an internet survey, we tested the hypothesis that high student debt adversely affects neurology residents' desire to pursue careers in academic neurology. The results indicate median year 2000 US graduate neurology resident student debt is in the 50,000 to 75,000 US dollars range and that this debt burden may deter US graduates from pursuing careers in academic neurology.


Pediatric radiation oncology in Germany: a study of availability and application.
Radiotherapy plays a pivotal role in many multimodal therapy concepts in pediatric oncology. However, the absolute number of irradiated children is estimated to be quite low. The aim of this study was to evaluate the availability and application of pediatric radiation oncology in Germany. In summer 2007, a standardized questionnaire was sent to all radiotherapy facilities in Germany. The questions regarded the structure of the departments, the number of irradiated children each year including the distribution of the different diagnoses, the number of curative treatments, inclusion in study trials, and existence of special contact persons for pediatric radiotherapy as well as technical aspects of irradiation of children. Answers to the questionnaires were obtained from 171 departments (77.4%). Of these, 67 (39%) stated to regularly treat children. These departments treated one to nine children in median each year (<5 children/year: 23 departments; >or=20 children: 15 departments). Most of these children suffered from brain tumors, Hodgkin's disease and acute lymphatic leukemia (ALL). Three-dimensional conformal radiotherapy was the most frequent treatment technique; special techniques like intensity-modulated radiotherapy (IMRT) or brachytherapy were rare. Due to quite low patient numbers treated in most radiotherapy facilities, individual experiences in pediatric radiation oncology can be assumed to be quite limited. As radiotherapy is part of multimodal therapy approaches in pediatric oncology and children treated with radiotherapy are at special risk for potential side effects, pediatric radiation oncology remains a sophisticated area. Therefore radiotherapy reference-institutions implemented by the therapy optimizing protocols are of fundamental importance.


Cancer and wood-related occupational exposure in the Amazon region of Brazil.
The occurrence of neoplasms, particularly nasal cavities and paranasal sinus tumors, has been associated with exposure to wood dust. The wood industry occupies an important place in the State of Pará, Brazil, where are located 90% of all the wood-related companies in the Brazilian Amazon market as a whole. The aim of this study was an exploratory analysis of cancer occurrence in woodworkers in the State of Pará. The proportional cancer incidence ratio (PCIR) was calculated for a group of 138 male woodworkers 20 years or older with a histological diagnosis of neoplasm treated at the Ofir Loyola Cancer Hospital in the state capital of Belém from 1991 to 1999. The cancer mortality odds ratio (CMOR) was also calculated in order to compare the cancer mortality among men 20 years or older residing in the State of Pará whose occupations involved wood exposure with that of men of the same age and place of residence but with different occupations. High and statistically significant PCIRs were observed for tumors of the oral cavity/pharynx, 2.44 (1.44--3.85), and stomach, 3.57 (2.41--5.10), in comparison to the population of Goiânia as well as in comparison to the population of Porto Alegre (oral cavity/pharynx, 1.97 (1.17--3.12), stomach, 3.12 (2.11--4.47)). We also observed a high and statistically significant PCIR for Hodgkin's disease, 5.30 (1.09--15.47), in comparison to the population of Goiânia. A CMOR of 8.86 (5.26--14.83) was observed for liver cancer. CMORs greater than 1 but not statistically significant were observed for neoplasms of the larynx. In agreement with the literature, woodworkers in Pará presented a high cancer incidence in specific anatomical sites. The results highlight the need for further epidemiological investigation to better evaluate this occupational exposure in the Amazon region.


In-Hospital Deaths From Ambulatory Care-Sensitive Conditions Before and During the COVID-19 Pandemic in Japan.
The COVID-19 pandemic may have played a role in the deterioration of access to medical care for ambulatory care-sensitive conditions (ACSCs). To ascertain whether the number of in-hospital deaths and in-hospital mortality rate associated with ACSC changed after the declaration of the COVID-19 national state of emergency in Japan. This cohort study used a difference-in-differences design to compare outcomes for ACSC in the period before (January 1, 2015, to December 31, 2019) vs the period after (January 1, 2020, to December 31, 2020) Japan declared a national state of emergency for the COVID-19 pandemic. Analyses used discharge summary data from 242 acute care hospitals across Japan. The sample comprised unscheduled hospitalizations of patients with ACSC during the study period (January 1, 2015, to December 31, 2020). Data analyses were performed between August 16 and December 7, 2022. The declaration of the COVID-19 national state of emergency announced by the Japanese government in April 2020 was considered to be an exogenous shock. Primary outcomes were the ACSC-associated number of in-hospital deaths, number of hospitalizations, and in-hospital mortality rate. A total of 28 321 ACSC-related hospitalizations were observed involving 15 318 males (54.1%), with a median (IQR) age of 76 (58-85) years. The number of in-hospital deaths was 2117 (7.5%). The number of hospitalizations decreased overall (incidence rate ratio [IRR], 0.84; 95% CI, 0.75-0.94), for chronic conditions (IRR, 0.84; 95% CI, 0.77-0.92), and for vaccine-preventable conditions (IRR, 0.58; 95% CI, 0.44-0.76). However, in-hospital deaths (IRR, 1.66; 95% CI, 1.15-2.39) and in-hospital deaths within 24 hours of hospital arrival (IRR, 7.27 × 106; 95% CI, 1.83 × 106 to 2.89 × 107) increased for acute conditions. The in-hospital mortality rate increased for acute conditions (IRR, 1.71; 95% CI, 1.16-2.54), and the 24-hour in-hospital mortality rates also increased overall (IRR, 1.87; 95% CI, 1.19-2.96), for acute conditions (IRR, 2.15 × 106; 95% CI, 5.25 × 105 to 8.79 × 106), and for vaccine-preventable conditions (IRR, 4.64; 95% CI, 1.28-16.77). This cohort study found that in Japan, the number of in-hospital deaths increased after the declaration of the COVID-19 national state of emergency in 2020, particularly for acute ACSC and deaths within 24 hours of hospital admission. This finding suggests that access to good-quality primary care and inpatient care for patients with acute ACSC may have been compromised during the pandemic.


Evaluation of paramalleolar and inframalleolar bypasses in dialysis- and nondialysis-dependent patients with critical limb ischemia.
The aim of this study was to elucidate the efficacy of paramalleolar or inframalleolar bypass (PIMB) in hemodialysis-dependent (HD) patients with critical limb ischemia (CLI) and nonhemodialysis-dependent (NHD) patients in terms of clinical outcomes. Between January 2000 and December 2013, there were 333 consecutive arteriosclerosis obliterans patients with CLI who underwent 401 PIMB procedures for limb salvage (LS). Of the 333 patients, 188 (56.5%) were HD patients. Vein grafts were exclusively used, and 172 paramalleolar and 229 inframalleolar bypasses were performed. Five-year primary and secondary cumulative graft patency, LS, and amputation-free survival (AFS) rates were compared between the two groups, and the independent determinants of these outcomes were identified in each group. The 5-year primary and secondary cumulative graft patency rates were 53% and 82% in HD patients and 69% and 92% in NHD patients (primary cumulative graft patency, P < .05; secondary cumulative graft patency, nonsignificant), respectively. The LS rates were 87% and 99% (P < .01) in HD patients and NHD patients, respectively. Overall, 48% and 70% of HD and NHD patients were ambulatory before PIMB (P < .01), and 73% and 85% of HD and NHD patients were ambulatory 12 months after PIMB (including 1-year survivors; nonsignificant), respectively, demonstrating drastic post-PIMB improvement in HD patients. The 5-year AFS rates in the HD and NHD groups were 27% and 69% (P < .01), respectively, demonstrating very poor AFS rates in HD patients. In HD patients, factors negatively associated with AFS were female gender (hazard ratio [HR], 2.102; 95% confidence interval [CI], 1.254-3.524), history of congestive heart failure (HR, 2.075; 95% CI, 1.395-3.085), and preoperative nonambulatory status (HR, 1.974; 95% CI, 1.305-2.986), whereas older age (HR, 2.601; 95% CI, 1.372-4.931) and history of congestive heart failure (HR, 2.928; 95% CI, 1.496-5.731) were identified as independent factors negatively associated with AFS in NHD patients. The use of PIMB for CLI was associated with excellent LS rates in both HD and NHD patients with low operative mortality and complications. However, the AFS rate observed in HD patients was significantly lower than that observed in NHD patients, indicating the necessity of a specific management program to improve AFS after LS in HD patients.


Optic neuropathy secondary to granulomatosis with polyangiitis in a patient with Graves' disease: a case report.
Dysthyroid optic neuropathy is the most commonly suspected diagnosis of optic neuropathy in Graves' patients; however, other causes need to be ruled out. We present a unique case of optic neuropathy secondary to hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be antithyroid drug related. A 79-year-old Japanese male presented with acute visual loss in the left eye. He had a 24-year history of Graves' disease and was taking methimazole. Best-corrected visual acuity was 0.8 in the right eye and light perception in the left eye, and relative afferent pupillary defect in the left eye was seen. Ocular movement was normal, and there were no findings explaining visual loss in intermediate optic media and fundus in the left eye. Contrast-enhanced magnetic resonance imaging demonstrated thickened dura mater. Tests for myeloperoxidase-antineutrophil cytoplasmic antibody, proteinuria, and hematuria were positive; pulmonary nodule lesions and a blood clot in the left lower leg were also found. After excluding the presence of diseases that could lead to hypertrophic pachymeningitis, we diagnosed optic neuropathy due to hypertrophic pachymeningitis with granulomatosis with polyangiitis-a subtype of antineutrophil cytoplasmic antibody-associated vasculitis. Since he had history of using methimazole, antineutrophil cytoplasmic antibody-associated vasculitis was considered as drug related. We started high-dosage steroid pulse therapy followed by 1 mg/kg body weight daily of oral prednisolone, and subsequently tapered. Methimazole was stopped. Best-corrected visual acuity recovered to 0.9, 2 weeks after starting treatment. Though myeloperoxidase-antineutrophil cytoplasmic antibody remained negative, the symptom relapsed 6 months after treatment initiation. We gave a second high-dose steroid pulse therapy followed by prednisolone tapered together with methotrexate. Remission remained, and using 4 mg/week methotrexate without prednisolone, myeloperoxidase-antineutrophil cytoplasmic antibody was kept within the normal limit until now, 4 years after onset. We present a case of optic neuropathy with hypertrophic pachymeningitis related to antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be drug related. The patient had good visual recovery after quitting the drug and receiving immunosuppressive therapy with systemic steroids. Hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis related to antithyroid drugs should be considered as a differential diagnosis for optic neuropathy in Graves' patients in whom optic nerve compression is not obvious.


Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease.
Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article "Identification of proteins that are differentially expressed in brains with Alzheimer's disease using iTRAQ labeling and tandem mass spectrometry" (Minjarez et al., 2016) [1].


Erratum to: Loss of glucocorticoid receptor activation is a hallmark of BRCA1-mutated breast tissue.
Erratum to: Breast Cancer Res Treat (2013),142:283–296,DOI 10.1007/s10549-013-2722-8. In the original publication of the article, the blot corresponding to the total P38 protein content for the conditions siCtl and siBRCA1 in Fig. 7a was incorrectly laid out. The corrected Fig. 7a is given in this erratum.The


Production and characterization of nisin-like peptide produced by a strain of Lactococcus lactis isolated from fermented milk.
An isolate of Lactococcus lactis from fermented milk was found to produce a bacteriocin peptide. The isolate could grow in a medium with an initial pH of 11.0, in which it produced the bacteriocin extracellularly at the highest level. The level of the bacteriocin in the medium increased in parallel to the bacterial growth and reached its peak during the late exponential phase; thereafter it plateaued. The bacteriocin had a broad antibacterial spectrum similar to that of nisin and inhibited several related species of lactic acid bacteria and other gram-positive bacteria. The inhibitory activity of the bacteriocin was found to be stable over a wide range of pH and temperature. The molecular weight of the peptide was judged to be 2.5 kDa by SDS-polyacrylamide gel electrophoresis.


In silico models in drug development: where we are.
The use and utility of computational models in drug development has significantly grown in the last decades, fostered by the availability of high throughput datasets and new data analysis strategies. These in silico approaches are demonstrating their ability to generate reliable predictions as well as new knowledge on the mode of action of drugs and the mechanisms underlying their side effects, altogether helping to reduce the costs of drug development. The aim of this review is to provide a panorama of developments in the field in the last two years.


Iron-binding ligands in the catalytic site of protocatechuate 3,4-dioxygenase.
The tryptophan fluorescence maximum for holoprotocatechuate 3,4-dioxygenase(holo PCD) is blue-shifted slightly (3 nm) from that of the apoenzyme. In the preparation of apoenzyme, increases in tryptophan fluorescence intensity coincided with decreases in enzyme activity and decreases in iron content. The tryptophan emission intensity of reconstituted enzyme having full enzyme activity was about 90% of that of the holoenzyme. Although apo PCD has similar molecular weight, amino acid content and essentially the same gross quaternary conformation as holo PCD, the absence of iron in apo PCD causes the changes in emission intensity of tryptophan. Findings indicate that some tryptophan residues may be (or may be near) the iron-binding ligands in the catalytic site of protocatechuate 3,4-dioxygenase.


A taste of pineapple evolution through genome sequencing.
The genome sequence assembly of the highly heterozygous Ananas comosus and its varieties is an impressive technical achievement. The sequence opens the door to a greater understanding of pineapple morphology and evolution.


Vaccination of calves against bovine herpesvirus-1: assessment of the protective value of eight vaccines.
Eight separate, but related experiments, were carried out in which groups of six calves were vaccinated with one of eight commercial vaccines. In each experiment the vaccinated calves were subsequently exposed to three calves infected with virulent bovine herpesvirus-1 (BHV-1). In each experiment, all infected donor calves developed a typical severe infectious bovine rhinotracheitis (IBR) infection and excreted virus in their nasal secretions of up to 10(8.00) TCID50/0.1 ml. One live BHV-1 gE-negative vaccine (A) and three modified live vaccines (B, C, D), administered intranasally, all protected against clinical disease. The calves vaccinated with one vaccine (C) also did not excrete virus in the nasal secretions, whereas the calves protected by vaccines A, B and D excreted virus in their nasal secretions but at low titres (10(0.66)-10(1.24) TCID50/0.1 ml). A fourth modified live vaccine (E), given intramuscularly, failed to prevent mild clinical disease in the calves which also excreted virus in the nasal secretions at titre of 10(1.00) TCID50/0.1 ml. An analogous result was given by the calves vaccinated with either of the two inactivated vaccines (F and G) or with a BHV-1 subunit vaccine (H). All calves developed mild clinical signs and excreted virus at titres of 10(2.20)-10(3.12) TCID50/0.1 ml. Calves vaccinated with C vaccine were subsequently given dexamethasone, following which virus was recovered from their nasal secretions. The virus isolates did not cause disease when calves were infected and appeared to be closely related to the vaccine strain.


Optimized high-yield synthesis of chitin nanocrystals from shrimp shell chitin by steam explosion.
This study attempted for the first time to prepare chitin nanocrystals (ChNCs) from shrimp shell chitin using steam explosion (SE) method. Response surface methodology (RSM) approach was used to optimize the SE conditions. Optimum SE conditions to acquire a maximum yield of 76.78 % were acid concentration (2.63 N), time (23.70 min), and chitin to acid ratio (1:22). Transmission electron microscopy (TEM) revealed the ChNCs produced by SE had an irregular spherical shape with an average diameter of 55.70 ± 13.12 nm. FTIR spectra showed ChNCs were slightly different than chitin due to a shift in peak positions to higher wavenumber and higher peak intensities. XRD patterns indicated ChNCs were a typical α-chitin structure. Thermal analysis revealed ChNCs were less thermally stable than chitin. Compared to conventional acid hydrolysis, the SE approach described in this study is simple, fast, easy, and requires less acid concentration and acid quantity, making it more scalable and efficient for synthesizing ChNCs. Furthermore, the characteristics of the ChNCs will shed light on the potential industrial uses for the polymer.


Engineering a versatile and retrievable cell macroencapsulation device for the delivery of therapeutic proteins.
Encapsulated cell therapy holds a great potential to deliver sustained levels of highly potent therapeutic proteins to patients and improve chronic disease management. A versatile encapsulation device that is biocompatible, scalable, and easy to administer, retrieve, or replace has yet to be validated for clinical applications. Here, we report on a cargo-agnostic, macroencapsulation device with optimized features for protein delivery. It is compatible with adherent and suspension cells, and can be administered and retrieved without burdensome surgical procedures. We characterized its biocompatibility and showed that different cell lines producing different therapeutic proteins can be combined in the device. We demonstrated the ability of cytokine-secreting cells encapsulated in our device and implanted in human skin to mobilize and activate antigen-presenting cells, which could potentially serve as an effective adjuvant strategy in cancer immunization therapies. We believe that our device may contribute to cell therapies for cancer, metabolic disorders, and protein-deficient diseases.


Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase.
Streptococcus pneumoniae causes bacterial pneumonia with high mortality and morbidity. The emergency of multidrug-resistant bacteria threatens the treatment of the disease. Leucyl-tRNA synthetase (LeuRS) plays an essential role in cellular translation and is an attractive drug target for antimicrobial development. Here we report the compound ZCL039, a benzoxaborole-based derivative of AN2690, as a potent anti-pneumococcal agent that inhibits S. pneumoniae LeuRS (SpLeuRS) activity. We show using kinetic, biochemical analyses combined with the crystal structure of ZCL039-AMP in complex with the separated SpLeuRS editing domain, that ZCL039 binds to the LeuRS editing active site which requires the presence of tRNA(Leu), and employs an uncompetitive inhibition mechanism. Further docking models establish that ZCL039 clashes with the eukaryal/archaeal specific insertion I4ae helix within editing domains. These findings demonstrate the potential of benzoxaboroles as effective LeuRS inhibitors for pneumococcus infection therapy, and provide future structure-guided drug design and optimization.


Response of urethral smooth muscles to pharmacological agents. II. Noncholinergic, nonadrenergic agonists and antagonists.
We studied the effects of a variety of noncholinergic, nonadrenergic agents on the smooth muscles of the cat urethra. Prostaglandin F2 alpha contracted both urethral muscle layers to a similar extent. Prostaglandin E2 contracted the longitudinal and relaxed the circular muscle layers. The effects of the prostaglandins seem to be directly myogenic since cholinergic and adrenergic blockers and tetrodotoxin did not affect them. Bradykinin and substance P contracted both urethral muscle layers. Other tested agonists (neurotensin, vasoactive intestinal peptide, cyclic 3,5 adenosine monophosphate, adenosine diphosphate sodium, cyclic 3,5 guanosine monophosphate sodium, bombesin) had no effect on the cat urethral smooth muscles.


Maternal TSH-receptor antibodies and TSH antibodies in screening for congenital hypothyroidism.
Serum samples from 30 mothers who had given birth to at least one child with a positive neonatal thyrotropin (TSH) screening test were analysed for TSH-receptor antibodies. One mother with hypothyroidism after thyroiditis who had two sons who had had transient congenital hypothyroidism, showed significantly elevated concentrations of TSH receptor blocking IgG antibodies in her serum. The three daughters of another mother had neonatal hyperthyrotropinaemia but normal thyroid hormone levels. This woman had elevated serum levels of TSH but was clinically and biochemically euthyroid. The apparent hyperthyrotropinaemia in this family was due to an artifact in the TSH radioimmunoassay caused by maternal anti-TSH IgG antibodies. It is obvious that placental transfer of maternal IgG antibodies to the thyroid TSH receptor is one cause of transient congenital hypothyroidism. Likewise, maternal IgG directed against TSH interferes with radioimmunoassays of TSH and the results may be falsely interpreted as hyperthyrotropinaemia. It is concluded that in neonatal hyperthyrotropinaemia analysis of the mother's serum is indicated, and that maternal TSH receptor blocking antibodies must be considered as a cause of congenital hypothyroidism, especially if the mother has a history of thyroid dysfunction.


The correlation of cardiac biomarkers and myocardial iron overload based on T2* MRI in major beta-thalassemia.
Cardiac hemosiderosis is the primary factor to derive the pathogenesis of cardiac dysfunction in patients with transfusion dependent thalassemia. Biomarkers assessment along with T2 * MRI study could be employed to evaluate the severity of iron deposition-related damage and determination of the diagnostic and prognostic value of these inflammatory factors. The study was conducted on 62 patients (12-44 years old) with major thalassemia. The patients were under regular blood transfusion and they had no signs of cardiac defects, and chronic diseases. The serum levels of inflammatory factors (NT-proBNP, CRP, Copeptin HS) were determined before routine transfusion. Cardiac iron overload was assessed by T2* MRI (within the last three months), and T2* lower than 20 ms was considered as cardiac siderosis. The obtained results were analyzed using statistical methods. 92% of patients showed an increased level of hs-CRP (> 2 µg/dL). All cases showed increased levels of NT-proBNP (> 150 pg/mL). Only 29% of subjects showed high level of Copeptin, 25.8% of patients demonstrated cardiac siderosis based on the T2* MRI (< 20 ms) results. The serum levels of inflammatory factors were not significantly correlated with cardiac siderosis. Given the obtained results, it could be deduced that the serum levels of inflammatory factors could not be exploited for early detection of cardiac siderosis in major beta-thalassemia patients.


Tests for allergy to housedust.
In an attempt to find a satisfactory combination of method and antigen extract for tests of hypersensitivity to housedust, variations of skin test, RAST, histamine release and basophil degranulation tests have been used to test efficacy of five commonly used extracts of housedust or its components. The Lincoln Multitest for skin prick tests in its present form induced too much trauma for type-I hypersensitivity tests, though it has advantages for comparison of several extracts. Histamine release and two versions of basophil degranulation tests all gave good results but not consistently. RAST gave the best correlation between all extracts, but neither the in vivo nor in vitro tests gave perfect concordance with sensitivity in all patients and all extracts.


CXCR4-targeted nitric oxide nanoparticles deliver PD-L1 siRNA for immunotherapy against glioblastoma.
While immunotherapy has emerged as a promising strategy to treat glioblastoma multiforme (GBM), the limited availability of immunotherapeutic agents in tumors due to the presence of the blood-brain barrier (BBB) and immunosuppressive tumor microenvironment dampens efficacy. Nitric oxide (NO) plays a role in modulating both the BBB and tumor vessels and could thus be delivered to disrupt the BBB and improve the delivery of immunotherapeutics into GBM tumors. Herein, we report an immunotherapeutic approach that utilizes CXCR4-targeted lipid‑calcium-phosphate nanoparticles with NO donors (LCP-NO NPs). The delivery of NO resulted in enhanced BBB permeability and thus improved gene delivery across the BBB. CXCR4-targeted LCP-NO NPs delivered siRNA against the immune checkpoint ligand PD-L1 to GBM tumors, silenced PD-L1 expression, increased cytotoxic T cell infiltration and activation in GBM tumors, and suppressed GBM progression. Thus, the codelivery of NO and PD-L1 siRNA by these CXCR4-targeted NPs may serve as a potential immunotherapy for GBM.


Statistical analysis of structural and kinetic characteristics of fungal colony growth with Trichoderma viride PERS.: S.F. Gray.
The mycelial colonies of Trichoderma viride were grown between two thin cellophane films for exact measurements. The results obtained testify to the fact that in a mature colony the average length of intercalary cells, the average number of intercalary cells in an internode and the average internode length are stable. At this stage of morphogenesis the mean internode length is shown to be equal to the product of the average intercalary cell length and the average number of intercalary cells in an internode. The coefficients of variation of the internode length and the number of intercalary cells in an internode are found to be equal. The length of an intercalary cell and duration of the doubling cycle of an apical cell of T. viride obey the law of Gamma distribution. According to our observations, the Gamma distribution is typical for the length and duration of the doubling cycle of any bacterial cells and cells of any multicellular organisms.


Non-Tuberculosis Mycobacterium Periprosthetic Joint Infections Following Total Hip and Knee Arthroplasty: Case Series and Review of the Literature.
Periprosthetic joint infection (PJI) caused by non-tubercular mycobacteria (NTM) is uncommon but catastrophic. However, conclusive clinical data on PJI caused by NTM are lacking. In this case series and systematic review, the clinical manifestations, diagnosis, and management of NTM PJI are summarized and analyzed. From 2012 to 2020, we retrospectively analyzed consecutive PJI cases caused by NTM in our institution. A literature review was also conducted from January 2000 to December 2021, utilizing the PubMed, MEDLINE, Cochrane Library, and EMBASE databases to identify all reported NTM-induced PJI cases. The clinical characteristics, demographics, pathogen identification, treatment protocols, and prognosis of NTM PJI were summarized and analyzed. In this retrospective analysis, seven patients infected with NTM following total joint arthroplasty at our institution were included, including six cases of PJI caused by NTM and one case of septic arthritis (SA) caused by NTM. There were six men and one woman, and their average age was 62.3 years. The average interval between TJA and PJI onset was 4 months. The preoperative serological markers, including the mean ESR (51 mm/h), CRP (4.0 mg/dL), fibrinogen (5.7 g/L), and D-dimer (1.1 g/L), were increased. Six patients underwent staged revision surgery, and one patient with SA received antibiotic-loaded bone cement beads to treat the infection. After an average of 33 months of observation following surgical intervention, none of the patients showed any symptoms of infection recurrence. From 2000 to 2021, 68 patients with NTM PJI were found in 39 studies in the published literature. Reinfections occurred within 1 year after arthroplasty in more than half (53.2%) of the patients. M. fortuitum and M. abscesses were the most prevalent rapidly growing mycobacteria (RGM) in all PJI patients, whereas Mycobacterium avium intracellulare (MAC) was the most prevalent slowly growing mycobacterium (SGM). The corresponding antibiotics were amikacin and ethambutol. The rate of culture-negative without specific clinical symptoms was as high as 36.4% (12/33), while 45% (18/40) utilized additional diagnostic techniques such as NGS. A final clinical follow-up record was available for 59 patients (86.7%; mean follow-up period, 29 months), and 10.1% of patients failed to respond to treatment. Orthopaedic surgeons should consider NTM in patients with negative routine cultures who are at risk for Mycobacterium infection. Treatment options rely on the accurate result of microbiologic identification and drug sensitivity testing, and to achieve this, it may be necessary to send multiple culture specimens, extend the culture time, and change the culture medium. Every effort should be made to identify NTM and its various subtypes through modern diagnostic tools if necessary.


Early and midterm results of minimally invasive aortic and mitral valve surgery via right mini-thoracotomy.
There are few reports regarding minimally invasive aortic valve replacement concomitant with mitral valve surgery (MIAMVS). The aim of this study was to evaluate early and midterm MIAMVS results. We reviewed the medical records of 21 consecutive patients (nine females, 43%) who underwent MIAMVS through a right mini-thoracotomy from December 2014 to April 2017. Mean patient age was 73 ± 7.4 years and four (19%) were New York Heart Association Class III or IV. Aortic stenosis and mitral valve insufficiency were the most common pathologies. All patients were followed for a mean period of 30 ± 8.5 months. The types of surgery consisted of aortic valve replacement with mitral valve repair in 11 (52%) patients, and replacement of both aortic and mitral valves in 10 (48%), while a tricuspid valve repair, was performed in four. No conversion to a full sternotomy was necessary in any of the cases. Postoperatively, the median intensive care unit and hospital stays were 4.7 and 11.8 days, respectively, with no in-hospital mortality. Following the initial treatment, all 21 patients were followed for a mean period of 30 ± 8.5 months (14-45 months). All patients returned to NYHA Class I or II following the procedure. During the follow-up period, there was no need for a heart valve reoperation for any of the patients and none showed recurrent mitral regurgitation (>mild), though one died from respiratory failure caused by pneumonia. MIAMVS can be performed via a right mini-thoracotomy, with acceptable early and midterm results expected. This may be a feasible alternative to the standard median sternotomy approach.


Spatial structure governs the mode of tumour evolution.
Characterizing the mode-the way, manner or pattern-of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. Sequencing studies have inferred various modes, including branching, punctuated and neutral evolution, but it is unclear why a particular pattern predominates in any given tumour. Here we propose that tumour architecture is key to explaining the variety of observed genetic patterns. We examine this hypothesis using spatially explicit population genetics models and demonstrate that, within biologically relevant parameter ranges, different spatial structures can generate four tumour evolutionary modes: rapid clonal expansion, progressive diversification, branching evolution and effectively almost neutral evolution. Quantitative indices for describing and classifying these evolutionary modes are presented. Using these indices, we show that our model predictions are consistent with empirical observations for cancer types with corresponding spatial structures. The manner of cell dispersal and the range of cell-cell interactions are found to be essential factors in accurately characterizing, forecasting and controlling tumour evolution.


Birth defects after assisted reproductive technologies in China: analysis of 15,405 offspring in seven centers (2004 to 2008).
This first large-scale report of birth defects in 15,405 offspring conceived by assisted reproductive technologies in China found infants born after IVF alone to have a birth defect frequency comparable to that in the general Chinese population; rates were nonsignificantly higher in infants conceived with use of intracytoplasmic sperm injection compared with those conceived after IVF alone.


Joint symbolic analyses of heart rate, blood pressure, and respiratory dynamics.
The dynamics of cardiovascular variables are modulated by respiration. The aim of this study was to assess baroreflex function in normal subjects based on the joint symbolic dynamics of heart rate, blood pressure and respiration. ECG, continuous blood pressure and respiration were recorded in ten healthy subjects during rest in the supine position and upon standing. Beat-to-beat time series of heart rate, systolic blood pressure and respiratory phase were extracted and transformed into binary symbol sequences. Words of length two that were reflective of baroreflex activity were statistically analysed with respect to the respiratory phase. Symbolic analysis showed a significant influence of the respiratory phase on the occurrence of baroreflex patterns. Upon standing, the frequency of baroreflex words increased and the effect of respiration appeared to be reduced. Symbolic dynamics provide a simple representation of cardiovascular dynamics and may be useful for assessing baroreflex function.


Severity and Changes in OCD Dimensions during COVID-19: A Two-Year Longitudinal Study.
The COVID-19 pandemic appears to be associated with a worsening of obsessive-compulsive symptoms in both young people and adults with OCD and it is necessary to analyze the variables involved in this worsening over time. The main aim of this study was to examine long-term changes in total severity and obsessive-compulsive dimensions in obsessive-compulsive patients during the COVID-19 pandemic. A total 250 OCD patients were selected from various associations, clinical centers and hospitals. We discarded 75 as they did not meet the inclusion criteria. A total of 175 obsessive-compulsive participants aged between 16 and 58 years old (M = 33.33, SD = 9.42) were evaluated in obsessive-compulsive symptom severity and dimensions OCD assessed using the Y-BOCS and D-YBOCS scales in T1 (April-June 2020) and in T2 (March-April 2022). The evaluation was carried out through an online survey and face-to-face with a professional clinician at both time points. Intragroup differences in severity were observed, reaching higher scores for patients with contamination, somatic, aggressive and religious. Some patients changed their main dimension, increasing the percentage of patients with contamination and somatic obsessions. COVID-19 was associated with both changes in severity and also affected some dimensions more than others, particularly those related to the virus itself (contamination and somatic).