Cost-Effectiveness Analysis of Helicobacter pylori Eradication Therapy for Prevention of Gastric Cancer: A Markov Model.
Helicobacter pylori (H. pylori) eradication can reduce the prevalence of gastric cancer. However, whether H. pylori eradication therapy should be performed in infected patients, especially in asymptomatic cases, is still controversial. The aims of this study were to determine whether H. pylori screening and eradication could prevent gastric cancer in a cost-effective way, and further whether eradication therapy should be administered to asymptomatic individuals. Cost-effectiveness analysis was performed using a Markov model. We established two groups, each with 10,000 hypothetical Chinese individuals at the age of 40 years. Clinical outcomes and cost of H. pylori eradication were compared between the eradication and control groups. There was a lower morbidity with gastric cancer in the eradication group than in the control group, which was most significant after running the model for 15 years. The eradication group experienced an average of 34.64 quality-adjusted life years (QALYs) per person, and the average cost was US $1706.52 per person. The control group exhibited an average of 32.63 QALYs per person, and the average cost was US $2045.10 per person. The cost-effectiveness analysis showed that eradication saved $1539 per LY per person and $168.45 per QALY per person. H. pylori screening and eradication therapy effectively reduces the morbidity of gastric cancer and cancer-related costs in asymptomatic infected individuals. Therefore, we believe that H. pylori eradication can prevent gastric cancer in a cost-effective way.


Closing the gap - development of an analytical methodology using volumetric absorptive microsampling of finger prick blood followed by LC-HRMS/MS for adherence monitoring of antihypertensive drugs.
Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is a promising tool for adherence monitoring. This study focused on development of an analytical methodology to improve VAMS-based strategies for adherence assessment by analyzing angiotensin-converting-enzyme (ACE) inhibitors, loop diuretics, a potassium-sparing diuretic, and a thiazide diuretic. Development included sample preparation, chromatographic conditions, mass spectrometry settings, validation, and demonstrating proof of concept. Quantification of analytes, by name furosemide, hydrochlorothiazide, lisinopril, torasemide, and the active metabolites, canrenone, enalaprilat, and ramiprilat in finger prick blood (FPB), was validated based on international guidelines. Selectivity, carryover, and within/between-run accuracy and precision were in accordance with the recommendations. The matrix effect was evaluated at three different hematocrit levels (HT: 20%, 40%, 60%) and the coefficients of variation did not exceed 15%. Dilution integrity (1:10 and 1:20) was given for all analytes except lisinopril, yet for lisinopril, the therapeutic range was already covered by the calibration range. Long-term stability in VAMS tips was tested for 2 weeks at 24 °C in the dark and revealed no degradation of analytes. The proof of concept was performed by analyzing 35 intakes of ACE-inhibitors and diuretics in 18 VAMS and matched plasma samples. Hereby, determined concentration in FPB and plasma cannot be used interchangeably, and thus specific reference ranges for whole blood must be established. Nevertheless, the VAMS-based strategy was shown to be suitable for assessing adherence of all classes of antihypertensive drugs used in the guidelines to manage hypertension.


Maternal ethanol consumption and synaptic membrane glycoproteins in offspring.
The present study was undertaken to assess the influences of chronic maternal ethanol consumption, prior to and during gestation, on the development of synaptic plasma membranes (SPMs) and on the synthesis of SPM glycoproteins in offspring. Comparisons were made between animals whose mothers were pair-fed a control or 6.6% (v/v) ethanol liquid diet in which protein accounted for either 18% (original) (C & E) or 21% (revised) (*C & *E) of the calories. In addition, groups of pups that were either cross-fostered (*C & *E) with chow-fed surrogate mothers or reverse cross-fostered (offspring of chow-fed mothers with *C & *E mothers) were examined. Ethanol and matched (same dietary group) control pups had comparable brain and body weights, brain protein content, and yield of SPM proteins during the 10-24 day age period examined. However, the yield of SPM proteins from ethanol and control offspring of and/or reared by the three groups of rat mothers that received the *E and *C liquid diets was greater than that of the offspring of rats that were fed the original diets. This suggests that the original diets were not nutritionally adequate for pregnant rats. Despite the fact that the content of SPM proteins was comparable in ethanol and matched control pups, the offspring of ethanol-treated rats had an abnormal distribution of [3H]- or [14C]-fucose-derived radioactivity among SPM glycoproteins. The SPM abnormalities were most severe in the non-cross-fostered offspring of E rats. No SPM glycoprotein abnormalities were found in the reverse cross-fostered group. The results of the present study demonstrate that chronic maternal ethanol consumption prior to parturition has a severe effect on the synthesis of SPM glycoproteins in developing offspring without affecting the content of SPMs per se. It also demonstrates the importance of optimizing the composition of liquid diets used to feed pregnant rats.


Sequential morphological studies of the esophageal carcinoma of rats induced by N-methyl-N-amylnitrosamine.
N-Methyl-N-amylnitrosamine was given to male Wistar rats in the drinking water at a concentration of 0.003% for 8 weeks. Three rats were autopsied weekly from the first to the 25th week. The stages of hyperplasia, dysplasia and squamous cell carcinoma in the esophagus were chronologically observed. Hyperplasia and dysplasia were found by the 6th week and continuously observed until the end of the experiment. Early squamous cell carcinomas were found in the 13th week. They showed endophytic or exophytic growths. Histologically, the endophytic growths were well-differentiated squamous cell carcinomas and the exophytic growths were poorly-differentiated. Advanced carcinomas were first found in the 15th week and were almost well-differentiated. Carcinomas were not found in papillomas. The incidence of carcinomas increased with time, being 9 out of 15 rats (60%) in the final 21st through 25th weeks. Lymph node metastasis was found in one rat, killed at the 24th week.


Optimization of activity, selectivity, and liability profiles in 5-oxopyrrolopyridine DPP4 inhibitors leading to clinical candidate (Sa)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778).
Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.


Hybrid nanocomposites of ZIF-8 with graphene oxide exhibiting tunable morphology, significant CO2 uptake and other novel properties.
Hybrid nanocomposites of graphene oxide (GO) with ZIF-8 exhibit tunable nanoscale morphology and porosity, both determined by the GO content, coordination modulation being responsible for such properties. These materials also give rise to high CO2 storage capability and can be used as precursors to prepare GO@ZnS nanocomposites.


Adsorption of ions onto high silica volcanic glass.
Chemical fingerprint techniques are frequently applied to airborne volcanic eruption products, so-called tephra, such as ash and pumice for archeological and geoscientific purposes. However, in some cases, a meaningful interpretation of the results is complicated by superficial contaminations. Therefore, this situation was simulated by the use of powdered rhyolitic pumice to investigate its capability to adsorb several ions from aqueous solutions. Using neutron activation analysis, adsorption could be proven for Cr(3+), Cr(2)O(7)(2-) (dichromate), Fe(3+), Co(2+), HAsO(4)(2-) (hydrogen arsenate), Rb(+), Sr(2+), Cs(+), Ba(2+), La(3+), Ce(3+), Ce(4+), Sm(3+), Th(4+) and UO(2)(2+), which is a clear evidence for the interaction of those ions with the volcanic glass. In our experiments, pumice powder showed the ability to adsorb ions in the range from 1.8 mg kg(-1) (in case of HAsO(4)(2-)) to 5.8 wt% (in case of Fe(3+)). Adsorption is probably due to ion-exchange reactions. It could also be shown that a few ions are not adsorbed in detectable quantities: Na(+), K(+), Fe(2+), Zn(2+) and Nd(3+). The knowledge about adsorption of ions enables us not only to examine the possible influence of contaminations where chemical fingerprinting methods are applied to volcanic material for archaeometry, but it also suggests the technical application of pumiceous materials for technical purposes, like water purification or as an adsorbent in the final storage of nuclear waste. In another series of INAA supported experiments, the influence of chemicals like ascorbic acid, acetic acid, HCl, HF, HNO(3), H(2)O, H(2)O(2), H(3)PO(4), H(2)SO(4), NaOH and NH(3) on the bulk composition of pumice powder was investigated-resulting in no detectable change. We conclude that superficially contaminated tephra can be washed in diluted HF to remove contaminations without influencing the chemical fingerprint.


Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing.
Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.


[Transient apical ballooning syndrome during dobutamine stress echocardiography].
The transient left ventricular apical ballooning syndrome, also known as Tako-Tusbo syndrome, has an acute onset, is more common in postmenopausal women, and is characterized by transient left ventricular apical ballooning, chest pain, electrocardiographic abnormalities, and slight elevation of markers for myocardial injury, mimicking a myocardial infarction in patients with no significant coronary lesions. However, before making the diagnosis, other causes of reversible left ventricular dysfunction must be ruled out, such as subarachnoid hemorrhage, pheochromocytoma crisis, acute myocarditis, or the presence of tachycardiomyopathy. The case is presented of a patient who developed ST elevation electrocardiographic changes with apical transient dyskinesia during dobutamine stress echocardiography.


Evaluation of metallic osseous implants with nuclear medicine.
Nuclear medicine has proven to have a valuable role in the evaluation of osseous metallic implants, particularly with joint prostheses, but can assist with evaluation of other appliances as well. The nuclear arthrogram has become an invaluable adjunct to simultaneously performed radiographic contrast arthrography. This application has been best evaluated in what is one of the most common of orthopedic prosthesis problems, namely, loosening of total hip prostheses. Experience indicates that both sensitivity and specificity of loosening of the femoral component can be increased to over 90% through combined use of nuclear with radiographic contrast arthrography. Furthermore the combination of routine skeletal scintimaging with the nuclear arthrogram adds a significant dimension to precise localizing of the nuclear arthrographics agent In-111 chloride. Nuclear medicine also plays an important role in further evaluating the presence of infection associated with metallic implants with In-111 WBC preparations being superior to Ga-67 as the radiopharmaceutical tracer. Infection has been detected with a sensitivity of 73% and a specificity of 93% in our series using combined In-111 WBC and simultaneous skeletal imaging with conventional Tc-99m MDP. Acute infections are more readily identifiable than chronic in association with prostheses.


Quantitative microbial risk assessment of enteroviruses in raw-eatable vegetables irrigated by wastewater: examining different scenarios of washing.
Due to the increasing water crisis, the reuse of wastewater deserves attention as a method to reduce the pressure of the water crisis, especially in developing countries. The application of health risk assessment models is a way to estimate disease burdens associated with crop irrigation by wastewater effluents. In this study, a quantitative microbial risk assessment (QMRA) with probabilistic Monte-Carlo simulation was used to estimate the annual risk of enteroviruses (EVs) infection and disease burden for consumers of effluent-irrigated raw vegetables in Tehran, the capital of Iran. Wastewater effluent samples were collected over two seasons: summer and winter. EVs were analyzed in three stages, concentration and separation, cell culture, and real-time PCR (RT-PCR). A questionnaire was used to determine the dominant patterns of vegetable washing by consumers. There were 4 vegetable washing steps: wiping away mud (A), rinsing (B), using detergents (C), using disinfectants (D). 5 patterns of washing were examined in the laboratory and the concentration of enteroviruses was measured in every pattern. pattern 1: just wiping away mud (A), pattern 2: wiping away mud and rinsing (AB), pattern 3: wiping away mud by using detergents and rinsing (ABCB), pattern 4: wiping away mud by using disinfectants and rinsing (ABDB), and pattern 5: wiping away mud by using detergents and disinfectants and rinsing (ABCBDB). For washing pattern 1, pattern 2, and pattern 3, the estimated annual infection risk of EVs was estimated to be 5.6 × 10-1, 3.6 × 10-1, 1.7 × 10-1 (risk/per.day), and burden of disease was calculated as 3 × 10-2, 2 × 10-2, and 9 × 10-3 (burden/year), respectively. The results showed that if vegetables are washed according to method 5, the microbial risk will be minimized and the excess prevalence of viral infections will be eliminated.


Tamoxifen as a modulator of CXCL12-CXCR4-CXCR7 chemokine axis: A breast cancer and glioblastoma view.
The chemokine stromal cell-derived-factor 1 (SDF)-1/CXCL12 acts by binding to its receptors, the CXC-4 chemokine receptor (CXCR4) and the CXC-7 chemokine receptor (CXCR7). The binding of CXCL12 to its receptors results in downstream signaling that leads to cell survival, proliferation and migration of tumor cells. CXCL12 and CXCR4 are highly expressed in breast cancer (BC) and glioblastoma (GBM) compared to normal cells. High expression of this chemokine axis correlates with increased therapy resistance and grade, tumor spread and poorer prognosis in these tumors. Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) that inhibits the expression of estrogen-regulated genes, including growth and angiogenic factors secreted by tumor cells. Additionally, TMX targets several proteins, such as protein kinase C (PKC), phospholipase C (PLC), P-glycoprotein (PgP), phosphatidylinositol-3-kinase (PI3K) and ion channels. This drug showed promising antitumor activity against both BC and GBM cells. In this review, we discuss the role of the CXCL12-CXCR4-CXCR7 chemokine axis in BC and GBM tumor biology and propose TMX as a potential modulator of this axis in these tumors. TMX modulates the CXCL12-CXCR4-CXCR7 axis in BC, however, there are no studies on this in GBM. We propose that studying this axis in GBM cells/patients treated with TMX might be beneficial for these patients. TMX inhibits important signaling pathways in these tumors and the activation of this chemokine axis is associated with increased therapy resistance.


Parent Perspectives on Exclusive Enteral Nutrition for the Treatment of Pediatric Crohn Disease.
Exclusive enteral nutrition (EEN) is infrequently used in the United States but is an effective treatment for pediatric Crohn disease (CD). Limited data exists regarding patient and parent perspectives on this treatment modality. The aim of this study was to determine parent and provider perspectives regarding EEN and understand parent-cited barriers to its use. We surveyed the parents/guardians of children ages 1 through 17 with CD in our institution regarding EEN. Healthcare provider perspectives regarding reason for stopping EEN and those cited by survey respondents were compared using retrospective chart review. One hundred fifteen (62.5%) out of 184 recipients responded to the survey. Ninety percentage of respondents had heard of EEN but of these, 26% had not discussed it with their gastroenterologist. Thirty-eight patients (33%) were treated in the past and 15 (13%) were currently on EEN. Common barriers cited by current EEN users were cost/finances and difficult social situations. Of the children who stopped EEN, most did so as parents felt it was not working (n = 14, 37%). In these cases, their primary gastroenterologist cited treatment failure for 4 cases and nonadherence for 6. Despite the efficacy of EEN and interest in dietary treatments by patients with CD, there are many barriers surrounding effective communication and successful implementation of dietary therapies. Future research is needed regarding patient-physician communication, cost mitigation, and coping with the social limitations of dietary therapies.


Assessment of regurgitation fractions by radionuclide ventriculography.
The ratio A for left ventricular and right ventricular enddiastolic-endsystolic count differences was used for quantitative evaluation of aortic and mitral valve regurgitation. The mean value of A for patients without valvular insufficiencies was determined (Am = 1.43 +/- 0.27).23 (96%) of 24 patients with aortic or mitral valve regurgitation showed significantly increased A values (A greater than 2). The numerical value was used for classification of the degree of insufficiency and for comparison with angiography. The correlation between A and the average angiographic degree of insufficiency was 0.79.


Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor with documented anaplasia and nephrogenic rests.
The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS.


Surface texture evaluation of glass ionomer restorative materials polished utilizing poly(acrylic acid) gel.
This study evaluated the surface texture of three different glass ionomer restorative materials and a composite resin, polished by a new method using poly(acrylic acid) gel. Conventional polishing methods and finishing agents were compared to the proposed new procedure. Evaluations were carried out employing three techniques: profilometry, scanning electron microscopy and microhardness testing. The use of a poly(acrylic acid) gel with polishing discs gave significantly better results, and is therefore recommended for clinical applications.


Serum 25-hydroxyvitamin D concentrations of New Zealanders aged 15 years and older.
Vitamin D plays an important role in bone health. Our purpose was to measure serum 25-hydroxyvitamin D concentrations and their determinants in a national sample (n=2,946) of New Zealanders aged 15 years and over. Mean (99% CI) serum 25-hydroxyvitamin D concentrations were 47 (45-50) nmol/l in women and 52 (49-55) nmol/l in men. Mean concentrations in New Zealand European and Others (NZEO, n=2,440), Māori (n=370), and Pacific (n=136) were 51 (49-53), 42 (38-46) and 37 (33-42) nmol/l, respectively. Three percent of New Zealanders had serum 25-hydroxyvitamin D concentrations indicative of deficiency (<or=17.5 nmol/l); 48% and 84% were insufficient based on cutoffs of <or=50 and <or=80 nmol/l. Determinants of serum 25-hydroxyvitamin D concentrations in women were age, ethnicity, obesity, latitude and season; determinants in men were ethnicity and season. Serum 25-hydroxyvitamin D in women declined with age; mean concentration was 13 (8-18) nmol/l lower in women 65 years or older and 9 (5-13) nmol/l lower in women 45-64 years compared with women 15-18 years. Spring to summer differences in serum 25-hydroxyvitamin D were 31 (28-34) and 28 (25-31) nmol/l in women and men, respectively. Obese women had lower vitamin status than normal-weight women by 6 (3-10). Women living in the South Island had a mean serum 25-hydroxyvitamin D that was 6 (3-9) nmol/l lower than women living in the North Island. Ethnicity and season are the major determinants of serum 25-hydroxyvitamin D in New Zealanders. The high prevalence of vitamin D insufficiency in New Zealanders, particularly in older women, may warrant strategies to improve vitamin D status.


Emotional response to a high-fidelity trauma simulation: An observational study.
The emotional environment created during a simulation session can influence learning. Positive emotions improve perceptual processing and facilitate learning, while negative emotions can reduce working memory, resulting in poorer learning outcomes. The aim of this study was to investigate the impact of simulation training on emotions during all phases of a high-fidelity simulation using standard prebriefing and «good judgement debriefing » techniques. This was an observational study that included 74 anesthesiologists participating in a simulation-based training. A standardized prebriefing was followed by «good judgement debriefing». In order to assess emotions, we used the circumplex model of emotion, and asked participants to complete the affect grid scale before prebriefing (Stage 1), before starting the simulation (Stage 2), before debriefing (Stage 3) and following debriefing (Stage 4). The affect grid scores obtained from 67 participants were analyzed. Following debriefing, the experience of the polytrauma patient simulation was significantly more pleasant compared to previous stages (P<0.01). In addition, participants perceived the activity as becoming increasingly active as it progressed (P<0.01). High-fidelity trauma simulation creating a safe environment using a standardized prebriefing and «good judgement debriefing» is experienced as a pleasant and active activity at all stages of the simulation. Further investigation is needed to assess the impact of these results on learning.


Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.
These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma. Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma? Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma. Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma? Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery. Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas? Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas? Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques. Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy. Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies IMMUNOTHERAPY: Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies. Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.


Surgical Site Infection After Open Upper Extremity Fracture and the Effect of Urgent Operative Intervention.
To identify which factors are predictive of surgical site infection in upper extremity fractures, and to assess whether the timing of operative debridement influences infection risk. Retrospective database review. Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Patients in the NSQIP database with fractures involving the upper extremity. Surgical management of upper extremity fracture, including operative debridement for open injuries. Surgical site infection, including both superficial and deep infections. A total of 22,578 patients were identified, including 1298 patients with open injuries (5.7% of total). The overall wound infection rate was 0.79%. Patients with open injuries were found to have a higher incidence of infection compared with those with closed injuries (1.7% vs. 0.7%, P < 0.001). Independent risk factors for 30-day infection included open fracture diagnosis, obesity, smoking, and American Society of Anesthesiolgists class >2 (all P < 0.05). Of patients with open fractures, 79.7% were taken expediently to the operating room. The rate of infection did not differ based on whether surgery was performed expediently or not (1.8% vs. 1.1%, P = 0.431). Based on an analysis of the NSQIP database, the overall risk of surgical site infection following intervention for open or closed upper extremity fractures remains low. Risk factors for infection include open injury, obesity, and cigarette smoking. There was no difference in the infection rate based on the urgency of operative debridement. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Inhibition of GOT1 sensitizes colorectal cancer cells to 5-fluorouracil.
Almost all colorectal cancer (CRC) cell lines are known to overexpress aspartate aminotransferase (GOT1), which potentially regulates the intracellular levels of reactive oxygen species (ROS) via the production of NADPH, and supports tumor growth. In our study, the role of GOT1 in the anticancer efficacy of 5-fluorouracil (5-FU) was examined. HCT116, SW480, and HT-29 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against GOT1. Following 5-FU treatment, cellular proliferation was evaluated, the NADP+/NADPH ratio was monitored, ROS was measured, and intracellular levels of glutamine (Gln), Aspartate (Asp), oxaloacetate (OAA), malate, and pyruvate were investigated using liquid chromatography-mass spectrometry (LC-MS). A CRC subcutaneous tumor model was performed to determine the impact of GOT1 inhibition on 5-FU efficacy in vivo. In response to 5-FU administration, CRC cells undergo metabolic adaptation, resulting in increased glutamine flux for the synthesis of aspartate. GOT1 is responsible for the conversion of glutamine-derived aspartate into OAA, which subsequently can be converted into malate and pyruvate. The GOT1-mediated metabolic process is able to maintain the NADP+/NADPH ratio, which counteracts 5-FU-induced oxidative stress. Inhibition of GOT1 impaired the defense against 5-FU-induced ROS, thereby sensitizing cells to 5-FU. The importance of GOT1 in supporting tumor growth during 5-FU treatment was also indicated in an in vivo tumor model of CRC. These findings show that GOT1 could serve as a promising target for increasing the anticancer efficacy of the conventional therapy in patients with CRC.


The pathogenic role of interleukin-27 in autoimmune diabetes.
Interleukin (IL)-27 is an IL-12-related cytokine that can promote both anti- and pro-inflammatory immune responses. This study investigated the potential role of IL-27 in autoimmune diabetes. We detected a high level of IL-27 in diabetic NOD mice. In addition, blockade of IL-27 significantly delayed the onset of diabetic splenocyte-transferred diabetes, while IL-27-treated diabetic splenocytes promoted the onset of the disease, compared with untreated controls. Furthermore, IL-27 up-regulated pro-inflammatory cytokines IFN-gamma and IL-17 and down-regulated anti-inflammatory cytokines IL-4, TGF-beta, and IL-10 secreted by diabetic splenocytes. These results demonstrate a pathogenic role of IL-27 in T cell-mediated autoimmune diabetes.


Cavernomas of the spinal cord: report of two cases.
Two cases of intramedullary cavernomas are presented. Both patients showed progressive neurological deficit. Cavernoma must be considered in the differential diagnosis of spinal cord tumors.


Direct evidence for a release of acetylcholine from the myenteric plexus of guinea pig small intestine by substance P.
Myenteric plexus-longitudinal muscle strips from guinea pig small intestine were labeled with [3H]choline while under continuous field stimulation. Release of newly synthesized [3H]acetylcholine was studied in the presence of substance P afterwards. Substance P evoked release of [3H]acetylcholine in a dose-related fashion. Both tetrodotoxin and [D-Pro2,D-Phe7,D-Trp9]substance P, a synthetic antagonist of substance P, completely blocked this release and provided evidence for a cholinergically mediated mechanism of substance P on enteric neurons.


The Abbott RealTime MTB assay and the Cepheid GeneXpert assay show comparable performance for the detection of Mycobacterium tuberculosis in sputum specimens.
To evaluate the performance of the newly developed technology Abbott RealTime MTB assay (RealTime MTB assay) for the detection of Mycobacterium tuberculosis in sputum specimens and to compare its performance with that of the Cepheid GeneXpert assay. Sputum specimens were collected from 270 subjects suspected to have tuberculosis (TB). Smear microscopy, culture, identification, RealTime MTB, and GeneXpert assays were performed according to standard protocols. Accuracy measures of the method evaluated were determined using solid culture as the reference standard. The RealTime MTB assay showed similar positive detection rates as the GeneXpert assay in smear-positive, culture-positive, and smear/culture-negative groups; no significant differences were found in these groups between the two assays. The RealTime MTB assay demonstrated a sensitivity of 100% and a specificity of 84.4%; the GeneXpert assay had a sensitivity of 96.9% and specificity of 89.6%. After the resolution of discordant results by PCR-based molecular method, the sensitivities and specificities of the RealTime MTB and GeneXpert assays were 100% vs. 97% and 90.0% vs. 95.6%, respectively; no significant difference in sensitivity or specificity was found between the RealTime MTB and GeneXpert assays. This study demonstrated that the Abbott RealTime MTB and Cepheid GeneXpert assays have similar sensitivity and specificity. The Abbott RealTime MTB assay is a highly promising method for the diagnosis of TB.


A circulating non-coding RNA panel as an early detection predictor of non-small cell lung cancer.
Early non-small cell lung cancer (NSCLC) diagnosis is generally poor due to the lack of convenient and noninvasive tools. MicroRNAs (miRNAs) and the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) are non-coding RNAs, that have attracted increased attention for their use as NSCLC tumor diagnostic markers. We constructed a serum miRNA and MALAT1 non-coding RNA panel and tested its diagnostic performance as an NSCLC biomarker. We tested the expression of 11 candidate miRNAs and MALAT1 in a training set (36 NSCLCs vs. 36 controls) by quantitative reverse transcription polymerase chain reactions. The serum non-coding RNA panel's diagnostic efficiency was tested and validated in a second validation sample set (120 NSCLCs and 71 controls) by receiver operating characteristic (ROC) curve analyses. In the training set, the expression of the four non-coding RNAs (miR-1254, miR-485-5p, miR-574-5p, and MALAT1) was obviously different between the NSCLC patients and healthy controls. Risk score analysis revealed that the four non-coding RNA panel can distinguish NSCLC patient samples from controls. The ROC curve results revealed areas under the curves (AUCs) of 0.861 (95% confidence interval (CI) 0.771-0.952) and 0.844 (95% CI0.778-0.910) for the training set and validation set, respectively. The four non-coding RNA risk scores were also associated with NSCLC progression, and its diagnostic efficiency was relatively high for stages I/II/III. In conclusion, these data indicate that the four non-coding RNA panel can serve as a convenient tool for early NSCLC diagnosis.


Evaluation of learning outcomes of humanities curricula in medical students. A meta-review of narrative and systematic reviews.
To assess the expected learning outcomes of medical humanities subjects in medical studies curricula. To connect those expected learning outcomes with the types of knowledge to be acquired in medical education. Meta-review of systematic and narrative reviews. Cochrane Library, MEDLINE (Pubmed), Embase, CINAHL, and ERIC were searched. In addition, references from all the included studies were revised, and the ISI Web of Science and DARE were searched. A total of 364 articles were identified, of which six were finally included in the review. Learning outcomes describe the acquisition of knowledge and skills to improve the relationship with patients, as well as the incorporation of tools to reduce burnout and promote professionalism. Programs that focus on teaching humanities promote diagnostic observation skills, the ability to cope with uncertainty in clinical practice, and the development of empathetic behaviors. The results of this review show heterogeneity in the teaching of medical humanities, both in terms of content and at the formal level. Humanities learning outcomes are part of the necessary knowledge for good clinical practice. Consequently, the epistemological approach provides a valid argument for including the humanities in medical curricula.


Interleukin-34 Limits the Therapeutic Effects of Immune Checkpoint Blockade.
Interleukin-34 (IL-34) is an alternative ligand to colony-stimulating factor-1 (CSF-1) for the CSF-1 receptor that acts as a key regulator of monocyte/macrophage lineage. In this study, we show that tumor-derived IL-34 mediates resistance to immune checkpoint blockade regardless of CSF-1 existence in various murine cancer models. Consistent with its immunosuppressive characteristics, the expression of IL-34 in tumors correlates with decreased frequencies of cellular (such as CD8+ and CD4+ T cells and M1-biased macrophages) and molecular (including various cytokines and chemokines) effectors at the tumor microenvironment. Then, a neutralizing antibody against IL-34 improved the therapeutic effects of the immune checkpoint blockade in combinatorial therapeutic models, including a patient-derived xenograft model. Collectively, we revealed that tumor-derived IL-34 inhibits the efficacy of immune checkpoint blockade and proposed the utility of IL-34 blockade as a new strategy for cancer therapy.


Real-World Effectiveness of Belimumab in the Treatment of Systemic Lupus Erythematosus: Pooled Analysis of Multi-Country Data from the OBSErve Studies.
The real-world effectiveness of belimumab for systemic lupus erythematosus (SLE) in six countries was evaluated in the OBSErve program. The aim of this post hoc analysis (GSK study 206351) was to pool individual patient OBSErve data to further evaluate the effectiveness of belimumab in a large sample of patients with SLE. OBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults ≥ 18 years of age with SLE, who were prescribed belimumab as part of standard therapy (index: date of belimumab initiation). Endpoints (month 6 vs. index) included physician-assessed overall clinical response to belimumab in the overall population (primary) and high disease activity subgroups (secondary; patients with a SLEDAI-2K/SELENA-SLEDAI score ≥ 10 or patients with high anti-dsDNA or low complement at index); other secondary endpoints included changes in glucocorticosteroid (GCS) use and changes in disease activity. Factors associated with physician-assessed overall clinical response were also evaluated. In total, 830 patients were included in the overall population (mean [standard deviation (SD)] age: 41.9 [12.57] years; female: 89.3%; 60.4% from the USA). Nearly half (48.1%) of belimumab-treated patients experienced a ≥ 50% physician-assessed improvement in their overall manifestations, and 13% achieved a near normalization of their condition (equal to ≥ 80% improvement). Initiating belimumab while on high-dose (> 7.5 mg/day) GCS use was associated with ≥ 50% clinical improvement at month 6 (OR: 1.9, p = 0.003). Most (78.1%; n = 518/663) patients were able to reduce or discontinue their oral GCS dose after 6 months of belimumab, with a mean (SD) change of - 8.5 (10.74) mg/day prednisone-equivalent. The mean (SD) change from belimumab initiation in disease activity score (SLEDAI-2K/SELENA-SLEDAI) was - 5.7 (4.5; n = 344). Belimumab improves clinical manifestations of SLE and is associated with GCS dose reductions in a real-world clinical setting, supporting the real-world effectiveness of belimumab for SLE.


Central venous catheter repair is not associated with an increased risk of central line infection or colonization in intestinal failure pediatric patients.
The intestinal failure (IF) population is dependent upon central venous catheters (CVC) to maintain minimal energy requirements for growth. Central venous catheter infections (CVCI) are frequent and an independent predictor of intestinal failure associated liver disease. A common complication in children with long-term CVC is the risk of line breakage. Given the often-limited usable vascular access sites in this population, it has been the standard of practice to perform repair of the broken line. Although widely practiced, it is unknown if this practice is associated with increased line colonization rates and subsequent line loss. A retrospective review of our institutional IF population over the past 8years (2006-2014) was performed. Utilizing a prospectively constructed database, all pediatric patients (n=13, ages 0-17 years) with CVC dependency enrolled in the Children's Intestinal Rehabilitation Program with IF were included who underwent a repair and/or replacement procedure of their line. The control replacement group was CVCs that were replaced without being repaired (36), the experimental repair group was CVCs that were repaired (8). The primary outcome of interest was the mean number of days in each group from the intervention (replacement or repair) to line infection/colonization. Mann-Whitney tests for significance were performed with p-values <0.05 being the threshold value for significance. There were no catheter repair associated CVCI. The mean number of days from the replacement or repair of a CVC to its removal owing to infection/colonization was 210.0 and 162.8days respectively. There was no statistically significant difference between these groups in time to removal owing to line infection (p=0.55). Repair of central venous catheters in the pediatric population with intestinal failure does not lead to an increased rate of central venous catheter infection and should be performed when possible.


Characterization of the role of calcium and sodium channels in the stimulus secretion coupling of 5-hydroxytryptamine release from porcine enterochromaffin cells.
Strips of the porcine small intestine were incubated in vitro and the outflow of 5-hydroxytryptamine (5-HT) was determined by HPLC with electrochemical detection. Spontaneous outflow of 5-HT from the porcine small intestine was reduced by about 70% after removal of the extracellular calcium or by addition of 1 mM gadolinium. Tetrodotoxin reduced the outflow of 5-HT by 30%, an effect which has previously been shown to be caused by inhibition of an excitatory cholinergic input. The sodium channel opener veratridine (up to 100 microM) did not affect the outflow of 5-HT. omega-Conotoxin GVIA (500 nM) or nifedipine (10 microM) reduced the outflow of 5-HT only by about 50%, and their effects were not additive. The inhibitory effects of omega-conotoxin GVIA occurred also in the presence of tetrodotoxin. Elevation of extracellular potassium to 40 mM caused a marked and sustained increase in 5-HT outflow. High potassium evoked release of 5-HT was blocked by omega-conotoxin GVIA, nifedipine and gadolinium. When omega-conotoxin GVIA and nifedipine were present in combination, their inhibitory effects on the high potassium evoked 5-HT release vanished. BAY K 8644 (1-10 microM) did not facilitate 5-HT release, but markedly reduced the spontaneous and high potassium evoked release of 5-HT. In conclusion, the enterochromaffin cells are endowed with multiple calcium channels, but voltage-sensitive calcium channels of a neuronal L-type which are sensitive to dihydropyridines and omega-conotoxin GVIA appear to play a major role.


Sequence analysis of two tandemly linked Em genes from wheat.
DNA sequences are presented for two members of the wheat Em gene family. The sequences correspond to the two linked genes at the Xem-1AL locus. Comparisons of these sequences with that of another wheat Em gene and two Em cDNA clones reveals substantial homology within the protein-coding regions, and the presence in the 5'-flanking regions of the genomic sequences of motifs characteristic of ABA-responsive cis-acting elements.


[The study on endometrial estrogen receptor and progesterone receptor isoforms in medical abortion women].
To determine the expression and location of estrogen and progesterone receptor isoforms in the endometrium after abortion and discuss the relationship between the changes of isoforms and prolonged uterine bleeding after medical abortion. 45 endometrium biopsy were obtained from 15 women with prolonged bleeding after medical abortion, 15 women with prolonged bleeding after vacuum aspiration and 15 without prolonged bleeding after vacuum aspiration as control group. Immunohistochemical staining intensity of ER alpha, ER beta, PR-A and PR-B in endometrium were compared among these groups, as medical abortion group, surgical abortion group and control group. The endometrial ER alpha, ER beta, PR-A and PR-B H-Scores of medical abortion group were 166.7 (88.5), 161.5 (84), 180.0 (109) and 136.5 (119.0), The endometrial ER alpha, ER beta, PR-A and PR-B H-Scores of control group were 306.7 (45.9), 230.0 (75.0), 224.2 (57) and 389.6 (106.6). The endometrial ER alpha, ER beta, PR-A and PR-B H-Scores of surgical abortion group were 109.4 (114.6), 225.0 (120.0), 175.5 (225) and 50.0 (89.0). The endometrial ER alpha, ER beta, PR-B H-Scores of medical abortion group were significantly lower than those of control group. And in surgical abortion group ER alpha and PR-B H-Scores were significantly lower than those in control group. But there was no significant difference between ER beta H-Scores of surgical abortion group and control group. There were no significant differences of ER and PR isoforms level ratios of endometrial glands to endometrial stroma among three groups. The decreased ER alpha, ER beta and PR-B levels in the human endometrium may be related to prolonged uterine bleeding after medical abortion by mifepristone accompanied with misopristol. The endometrial ER alpha, PR-B decreased in women after vacuum aspiration abortion may be related to abnormal prolonged uterine bleeding. The changes of endometrial ER, PR isoforms in glands and stroma were simultaneous after medical abortion and surgical abortion.


Risk factors for depression and anxiety in healthcare workers deployed during the COVID-19 outbreak in China.
This study was conducted to evaluate the status of depression and anxiety of healthcare workers and to explore the risk factors during the outbreak of COVID-19 in China. A cross-sectional study was designed using convenience sampling to obtain a sample of healthcare workers. A structured questionnaire was designed to collect the information of the basic characteristics, workload, and the health condition. Burnout, coping style, anxiety, and depression were measured by specific scales. Multiple logistic regression model was performed to explore the risk factors of anxiety or depression. There were 902 questionnaires received between February 9, 2020 and February 11, 2020. The proportion of healthcare workers with symptoms of moderate/severe anxiety and moderate/severe depression were 16.63% and 18.29%, respectively. There were 24.50% healthcare workers experiencing moderate/severe anxiety and depression at the same time. The increased workload, respiratory symptoms, digestive symptoms, having done specific test(s) related to COVID-19, having family member needs to be taken care of, negative coping style, and job burnout were the independent risk factors of anxiety. Furthermore, the increased workload, respiratory symptoms, digestive symptoms, having done specific test(s) related to COVID-19, negative coping style, and job burnout were the independent risk factors of depression. More attention should be paid to the mental health of frontline healthcare workers at the outbreak of COVID-19 in China. Taking steps to reduce the intensity of the work and burnout will be effective to stabilize the mental state of them.


How hand and wrist trauma has changed during covid-19 emergency in Italy: Incidence and distribution of acute injuries. What to learn?
the purpose is to gather and analyze the statistical datas of wrist and hand injuries admitted to the Hand and Reconstructive Microsurgery and Replantation Hub center of Careggi Hospital, Florence during the first two months of COVID-19 epidemic in Italy. The Authors investigated how the drastic changes in daily activities modified the epidemiology of hand trauma lesions. The Authors analyzed the characteristics of hand and wrist traumatic disorders during the months of February and March comparing 2019 to 2020. Collected data included age distribution, traumatic etiology, diagnosis and type of surgical procedures. The total number of orthopedic and trauma patients significantly decrease in 2020 compared to 2019 (3360 vs 1470). The number of hand and wrist injuries didn't show a significant difference between 2019 and 2020 instead (192 vs 131). The overall number of patients hospitalized and surgically treated at our Operative Unit (OU) was 168 in 2019 and 120 in 2020. Male patients resulted prevalent (60,7 M vs 39,3F/2019; 63,2 M vs 36,8F/2020). In terms of patient age, in 2020 we registered a significant reduction of cases in the 20-35-year-old age group and a significant increase in the 51-65 and 66-80-year-old age groups. Traffic-related, sport-related and fortuitous injuries significantly decreased in 2020, while the number of domestic accidents significantly increased. Analyzing the Hospital Discharge Records (HDR), we found a significant increase in the number of proximal and middle phalanx fractures; no significant differences were found for other kinds of discharge diagnosis. As for the choice of surgical treatment options, no differences were found between 2019 and 2020. Even during drastic movement restrictions and the prolonged suspension of work and leisure activities secondary to COVID-19 epidemic in 2020, hand and wrist traumas rate remained almost the same compared to the same period of the previous year. Nevertheless, a significant change in the etiology and patient age was registered. In fact, sport and traffic-related traumas decreased respect to domestic traumas, while the previous prevalent involvement of young adults was surpassed by accidental hand traumas in the elderly and active adults.


Drug therapy and medication adherence in type 2 diabetes in a care facility: A cross sectional survey.
Adherence to medications improves glycaemic control and reduces diabetes-related morbidity and mortality. The study assessed drug therapy for type 2 diabetes, glycaemic control and association of medication adherence with socio-demographic and clinical data, among adult diabetic patients attending a healthcare facility. Cross-sectional survey and hospital records were used to obtain data. The study included 200 adults with type 2 diabetes mellitus in a Nigerian healthcare facility. Data on patients clinical characteristics, diabetes drug therapy and medication adherence were collected, entered and anlaysed using SPSS version 24 (P < 0.05). Primary outcome measure was medication adherence among the patients, while secondary outcome measures was glycaemic control. A total of 200 (100%) respondents participated in the study and the majority 141(70.5%) were over 60 years old. Oral medications were mostly used 187(93.5%), particularly, metformin 199(99.5%) and pioglitazone 100(50.0%), while dipeptidyl peptidase-4 inhibitors were not used at all. Patients mostly had poor glycaemic control 159 (79.5%) and majority 152(76.0%) did not practice self-blood glucose monitoring. Moderate medication adherence was predominant in the population. Class of medicine and socio-demographics were not significantly associated with medication adherence (P > 0.05), unlike results of blood glucose self-tests (p = 0.001). Oral antidiabetics, particularly metformin and pioglitazone were mostly used. Poor glycaemic control and moderate adherence were found in the patients, and medication adherence was associated with self-glucose monitoring. This emphasises the need for regular diabetes education on medication adherence.


Psychological correlates of the dexamethasone suppression test response and of the shortened REM sleep latency in depressed outpatients.
The overlap between REM sleep latency and DST response was investigated in a group of 117 mildly depressed outpatients. No significant correlation between these two biological markers could be evidenced. The MMPI profile of the DST suppressors was clearly different from the non-suppressors' profile indicating a more severe clinical condition at that moment. REM sleep latency did not contribute to the psychological and clinical subtyping of this depressive sample.


Understanding type I and type II errors, statistical power and sample size.
The results of a clinical trial may be subject to random error because of the variability in the measured data, which arises purely by chance. There are two types of random error - type I error and type II error. In this study, type I and type II errors are explained, and the important concepts of statistical power and sample size estimation are discussed. The most important way of minimising random errors is to ensure adequate sample size; that is, a sufficient large number of patients should be recruited for the study.


Using and understanding RepeatMasker.
RepeatMasker is a program that screens DNA sequences for interspersed repeats and low-complexity DNA sequences. In this chapter, we present the procedure to routinely use this program on a personal computer.


Determination of residual tetrachloroethylene in olive oil by headspace-gas chromatography.
This study describes a method for the quantitative determination of residual tetrachloroethylene or perchloroethylene (PCE) in olive oil by headspace-gas chromatography. The analysis of the chlorinated product is performed by electron-capture gas chromatography, using a fused silica capillary column, CP Sil 8 CB. The absolute detection limit for PCE was 1 pg. Forty samples of olive oil and 5 other commodities have been analysed. Only one sample exceeded the proposed maximum level of 1 mg/kg.


Demystifying Histologic Conundrum of Adenoid Ameloblastoma: Case Report with Literature Review.
Introduction: Odontogenic tumors encompass a heterogeneous group of lesions that range from hamartomatous lesions to malignancy. Considerable variation in histologic presentation can mislead their accurate diagnosis and categorization. Ameloblastoma is generally well understood and is easy to diagnose but there has been a constant change in the classification systems ever since Broca classified odontogenic tumors in the year 1867. Over the years, it has been modified by the World Health Organization with many additions and omissions. This dynamic change is based on the result and conclusions of molecular and genetic studies with the last modification in 2017. Case Report: We present two cases of females aged 32 and 60 years who reported with facial swellings, revealed the presence of distinct histopathological findings and were diagnosed as ameloblastoma with dentinoid or adenoid ameloblastoma. Literature search revealed dearth of distinct forms of ameloblastoma that show the formation of duct like structures and dentinoid. Conclusion: It is interesting to highlight such cases as the biological behavior is still unexplored due to paucity of relevant studies and follow up of patients. Understanding the pathogenesis and the histopathological characteristics of the newer entities will enable the prompt diagnosis, treatment plan and expanding the spectrum of the lesions. The online version contains supplementary material available at 10.1007/s12070-023-03534-6.


[Treatment of mastitis in dry cows: treatment of all cows vs treatment of infected cows only (author's transl)].
Within a herd, three groups have been randomly constituted. -- No dry cow therapy. -- Total Treatment group: all cows were submitted to dry cow therapy, in their four quarters. -- Limited Treatment group: cows were submitted to dry cow therapy in their four quarters, only if at least one quarter had given a CMT larger than or equal to +++, in the month before drying-off. --The cows were treated either with cloxacillin or with penicillin-streptomycin in 3% monostearate. The number of cows and quarters examinated and treated are given in table 1; the results of treatments are indicated in table 2. No significant differences can be found between Total and Limited Treatment groups; a slight improvement was observed when compared to CONTROL GROUP. Cloxacillin and penicillin-steptomycin gave similar results. The pathogenic and practical signification of these results is discussed.


Solvent effects on the photooxidation of indolepyrazines.
Photodestruction of 2-(pyrazin-2'-yl)-1H-indole and 2,5-di(1H-indol-2'-yl)pyrazine involves singlet oxygen generation and its rapid insertion into the indole ring with the formation of benzoxazinone derivatives: 2-(pyrazin-2-yl)-4H-3,1-benzoxazin-4-one and 2-[5-(1H-indol-2-yl)pyrazin-2-yl]-4H-3,1-benzoxazin-4-one. The quantum yield of this reaction strongly depends on the environment. It is definitely smaller in protic methanol than in aprotic acetonitrile or n-hexane. The observed effect of photostabilization is explained by formation of hydrogen bonded complexes between the chromophore and alcohol, which results in lower triplet formation efficiency and, in consequence, decrease of singlet oxygen formation quantum yield.


Diagnosis and Management of Infantile Hemangiomas in the Neonate.
Infantile hemangiomas (IH) are a common benign tumor of infancy, most being uncomplicated and not requiring therapy. Some IH may require treatment; the pediatric provider must be familiar with morphology, distribution, natural history, and associations of IH. Several treatment options are available for IH: current standard of care, oral propranolol. Other therapies include wound care; topical beta-blocker therapy for small, superficial, and uncomplicated IH; treatment of IH residua. In addition to functional compromise and other complications, potential for permanent deformity and eventual psychosocial stigmatization are important when considering the need for treatment of IH in a neonate or infant.


Structure and photobleaching process of chicken iodopsin.
Iodopsin, a dominant cone pigment in a chicken retina, has an absorption spectrum in longer wavelength region than rhodopsin. To account for this red-shift of iodopsin, we had proposed a structural model from retinal analogue experiments, in which iodopsin would have a relatively long distance between the protonated Schiff base nitrogen and the counterion. This was confirmed by a resonance Raman spectroscopy. The photochemical properties of iodopsin were studied and compared with those of rhodopsin, which revealed the following differences. The regeneration rate of iodopsin with 11-cis-retinal was 240 times faster than rhodopsin. Meta-iodopsin II, the signalling state of iodopsin, decayed about 100 times faster than meta-rhodopsin II. The Km value of meta-iodopsin II and rhodopsin kinase was lower than meta-rhodopsin II. These results are in consistent with rapid adaptation and low photosensitivity of cones relative to those of rods.


The distribution of attention within objects in multiple-object scenes: prioritization by spatial probabilities and a center bias.
This study investigates how the attentional distribution within objects is affected by spatial probabilities, bias toward objects' centers (Alvarez & Scholl, 2005), and object motion. In a multiple-object tracking task, observers tracked line objects while simultaneously detecting probes appearing on the objects. Experiments 1 and 2 manipulated the probabilities of probes appearing at the centers and ends of objects. Overall, probe detection was better at centers than at ends, but it was also affected by probe location probabilities; when probe locations were 100% certain, the center advantage was eliminated. Experiment 3 manipulated rotational, translational, and size-change components of object motion. The center advantage still occurred with stationary objects, and its magnitude was not affected by different motion types. These results indicate that attention is biased toward the centers of objects in multiple-object scenes, both for stationary and moving objects. They also imply that attentional prioritizations based on spatial probabilities can accompany moving objects.


Inhibitory effect of processed Aconiti tuber on the development of antinociceptive tolerance to morphine: evaluation with a thermal assay.
In the previous studies, we demonstrated that an oriental herbal medicine processed Aconiti tuber (PAT) at subanalgesic doses could inhibit the development of mechanical antinociceptive tolerance to morphine using the tail pressure test. In the present study, we evaluated whether PAT could inhibit thermal antinociceptive tolerance to morphine using the high temperature (55 degrees C) hot plate test. Mice received subcutaneous morphine (10mg/kg), and oral PAT at doses that did not inhibit the hot plate response (0.3, 0.5, 1.0, and 2.0 g/kg), once daily for 14 days. The thermal nociceptive latency was measured at 30 min after daily morphine injections. Compared with placebo, oral PAT partially and dose-dependently inhibited the development of morphine tolerance in morphine-naïve mice, and reversed already-developed morphine tolerance in morphine-tolerant mice. These data suggested that PAT at subanalgesic doses could dose-dependently inhibit and reverse thermal antinociceptive tolerance to morphine.


Serum-dependent regulation of proliferation of cultured rat fibroblasts in G1 and G2 phases.
We reported that: (i) 3Y1tsF121 cells, a temperature-sensitive (ts) mutant of rat 3Y1 fibroblasts, are reversibly arrested either in the G1 or in the G2 phase, at the nonpermissive temperature. (ii) Cells retain the ability to resume proliferation at the permissive temperature after prolonged arrest in the G1 phase (for 5 days), whereas they lose it after prolonged arrest in the G2 phase (over 24 h). (iii) The G1 arrest is overcome at the nonpermissive temperature by the addition of fresh serum (H. Zaitsu and G. Kimura (1984) J. Cell. Physiol. 119, 82; (1985) J. Cell. Physiol. 124, 177). In the present study, the G2 arrest was overcome by exposing the cells to fresh serum, at the nonpermissive temperature. The G2 arrest occurred only at a higher cell density than that of the G1 arrest. The efficiency of the overcome was higher in the case of the G2 arrest than in case of the G1 arrest. When cells synchronized at the G1/S border by aphidicolin at the permissive temperature were released from the block, they divided in the absence of serum, at the permissive temperature. Even if they had passed through the previous G2 phase in a very high concentration of fresh serum at the permissive temperature, mitotic cells did not enter the S phase in the absence of serum, even at the permissive temperature. When the cells arrested in the G1 phase (not in G0) due to the ts defect were incubated in the absence of serum at the permissive temperature, only 34% entered the S phase and only 15% divided. These results suggest that (i) the ts defect in 3Y1tsF121 limiting cellular proliferation in both the G1 and the G2 phases is probably due to a single mutational event, and is a serum-requiring event. (ii) Preparation of the serum-requiring event which is required for the G2 traverse is completed in the G1 phase, under ordinary conditions. (iii) However, cells are able to fulfill the serum-requiring event in the G2 phase as well as in the G1 phase when the preparation is below the required level. (iv) The commitment to DNA synthesis is not necessarily a commitment to cell division. (v) Cells are arrested in the G1 phase more safely and more effectively than in the G2 phase, by the serum-related mechanism.


The decline of plant mineral nutrition under rising CO2: physiological and molecular aspects of a bad deal.
The elevation of atmospheric CO2 concentration has a strong impact on the physiology of C3 plants, far beyond photosynthesis and C metabolism. In particular, it reduces the concentrations of most mineral nutrients in plant tissues, posing major threats on crop quality, nutrient cycles, and carbon sinks in terrestrial agro-ecosystems. The causes of the detrimental effect of high CO2 levels on plant mineral status are not understood. We provide an update on the main hypotheses and review the increasing evidence that, for nitrogen, this detrimental effect is associated with direct inhibition of key mechanisms of nitrogen uptake and assimilation. We also mention promising strategies for identifying genotypes that will maintain robust nutrient status in a future high-CO2 world.


Reprogramming progeny cells of embryonic RPE to produce photoreceptors: development of advanced photoreceptor traits under the induction of neuroD.
In examining the prospect of producing functional photoreceptors by reprogramming the differentiation of RPE progeny cells, this study was conducted to investigate whether reprogrammed cells can develop highly specialized ultrastructural and physiological traits that characterize retinal photoreceptors. Cultured chick RPE cells were reprogrammed to differentiate along the photoreceptor pathway by ectopic expression of neuroD. Cellular ultrastructure was examined with electron microscopy. Cellular physiology was studied by monitoring cellular free calcium (Ca(2+)) levels in dark-adapted cells in response to light and in light-bleached cells in response to 9-cis-retinal. Reprogrammed cells were found to localize red opsin protein appropriately to the apex. These cells developed inner segments rich in mitochondria, and while in culture, some formed rudimentary outer segments, analogous to those of developing photoreceptors in the retina. In response to light, reprogrammed cells reduced their Ca(2+) levels, as observed with developing retinal photoreceptors in culture. Further, on exposure to 9-cis-retinal, the light-bleached, reprogrammed cells increased their Ca(2+) levels, reminiscent of visual cycle recovery. These results indicate the potential of reprogrammed cells to develop advanced ultrastructural and physiological traits of photoreceptors and point to reprogramming progeny cells of embryonic RPE as a possible alternative in producing developing photoreceptors.


5'-OH-5-nitro-Indirubin oxime (AGM130), an Indirubin derivative, induces apoptosis of Imatinib-resistant chronic myeloid leukemia cells.
Imatinib is a highly effective drug for the treatment of chronic myeloid leukemia (CML) that targets the BCR-ABL kinase. However, a number of patients have CML that is resistant to Imatinib treatment. In this report, we developed AGM130 as a potential therapeutic drug for Imatinib-resistant CML treatment. The AGM130 compound is derived from Indirubin, which is an ingredient of Danggui Longhui Wan and known as a cyclin-dependent kinase (CDK) inhibitor. The water solubility of AGM130 is more enhanced than that of the original form of Indirubin, which has very poor water solubility. Our data showed that the AGM130 compound efficiently decreased the viability of CML-derived K562 cells. Moreover, this compound also efficiently decreased the viability of Imatinib-resistant K562 cells in in vitro and in vivo systems. In addition, like Indirubin, AGM130 also inhibited phosphorylation of retinoblastoma protein (Rb), which is a major substrate of CDK. Conclusively, our data suggest that AGM130 is a strong candidate for treating Imatinib-resistant CML.


Syndromes of compression of the median nerve in the proximal forearm (pronator teres syndrome; anterior interosseous nerve syndrome).
Entrapment of the median nerve in the proximal forearm is seen in two forms: the pronator teres syndrome, and the anterior interosseous nerve (or Kiloh-Nevin) syndrome. Both syndromes are rare, and they comprised approximately 1% of the compression syndromes of the upper limb which were treated operatively by the authors. The symptoms, signs, etiologies, and intraoperative findings are discussed. It is pointed out that certain of the clinical features may resemble those of irritation of the median nerve by a supracondylar process or Struthers' ligament. Although both proximal median entrapment syndromes have a favorable prognosis when treated non-operatively, the authors recommend operative treatment in cases in which there is no perceptible improvement following 8 weeks of non-operative treatment, since this is likely to speed and enhance recovery. Nine cases of the pronator teres syndrome (8 treated successfully by operation, 1 failure) and 2 cases of the anterior interosseous nerve syndrome (both fully recovered) are added to the cases reported previously in the literature.


Detection of superior mesenteric and coeliac artery stenosis with colour flow Duplex imaging.
Measurements of blood velocity in the coeliac axis (CA) and the superior mesenteric artery (SMA) before and after a standard meal in normal people have been studied by several authors. However, information about the ability to detect stenotic lesions is lacking. The aim of our study was to determine the accuracy of Duplex scanning in detecting angiographically proven lesions. Twenty normal volunteers (13 males and seven females) and 24 patients (19 males and five females) with visceral artery stenosis on angiography were examined in the supine position (angle of insonation 60.5) with colour flow Duplex imaging (CFDI) (3.5 MHz probe), in the fasting state and after a standard meal at 15, 40, 60 and 90 min. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were determined in both CA and SMA. The PSV was the best indicator of stenosis. After the meal, there was an increase in both PSV and EDV but neither of the postprandial measurements improved the accuracy of the test. The results indicate that CFDI can detect the presence of significant stenosis (> 50% in the CA and SMA with a sensitivity and specificity of > 80%.


UAS Safety Operation - Legal Issues on Reporting UAS Incidents.
This paper examines regulations which govern procedures for reporting incidents other than accidents or serious incidents related to unmanned aircraft system (UAS) operations. The regulations are discussed in the context of available data and the paper included an analysis of them from both a European and national perspective. The goal of the paper is to provide a series of recommendations with regard to the procedures for reporting and analyzing UAS incidents in order to improve the safe integration of unmanned and manned aviation. This article also explores the legal consequences that arise from the midair collision between a UAS and a manned aircraft. The method of study comprises a content analysis of existing legislations. The current doctrine was confronted with existing regulations, documents and materials. The results of the study show that there is a practical problem of objectively identifying operators of a UAS as well as in defining what exactly constitutes an "incident". It can be reasonably concluded that reporting and analyzing UAS-related incidents allows for the assessment and development of strategies for integrating manned and unmanned aviation. It is worth mentioning that drones and UAS technology requires refinement, especially in technological terms. It is reasonable to take action aimed at raising awareness amongst UAS users of the need to report incidents, as well as engaging UAS users in the investigative process which follows such occurrences.


Reductions in sleep quality and circadian activity rhythmicity predict longitudinal changes in objective and subjective cognitive functioning in women treated for breast cancer.
To examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC). Sixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year). WBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood. Objective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.


Downregulation of the growth hormone-induced Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway requires an intact actin cytoskeleton.
Transient activation of the signal transducers and activators of transcription (STAT) proteins in response to growth hormone (GH) and other type II cytokines plays a pivotal role on specific gene transcription. The negative regulation of STATs seems to be exerted at the GH receptor (GHR)/Janus Kinase (JAK) complex and involves two main mechanisms: (1) the GH-induced ubiquitination/internalization of GHR and (2) the action of SOCS proteins. Since GH regulates cellular cytoskeleton with potential implications in GH signaling, we investigated the effects of actin cytoskeleton disruption on the kinetics of GH-activated GHR/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signaling pathway. Disruption of the actin-based cytoskeleton with cytochalasin D (CytoD) did not affect the rapid GH induction of JAK2 and STAT5 activities. However, pretreatment of BRL-4 cells with CytoD prolonged both, JAK2/STAT5 tyrosine phosphorylation and STAT5 DNA binding activity, for at least 2 h. Our results demonstrated that the synthesis of the several SOCS proteins (SOCS-1, -2, and -3) was not affected by treatment of the cells with CytoD. On the other hand, the inhibitory actions of SOCS1, 2, and -3 on GH-induced STAT5 reporter activity were partially blocked by disruption of the cytoskeleton. Disassembly of the actin filaments by CytoD is accompanied by accumulation of ubiquitinated forms of GHR but it does not affect GHR internalization. We conclude that the integrity of the actin cytoskeleton network plays an essential role in the negative regulation of GHR/JAK2/STAT5 signaling pathway by facilitating the GHR ubiquitination/degradation through mechanisms acting downstream SOCS.


Impact of the COVID-19 pandemic on children with and without affective dysregulation and their families.
Analyzing COVID-19-related stress in children with affective dysregulation (AD) seems especially interesting, as these children typically show heightened reactivity to potential stressors and an increased use of maladaptive emotion regulation strategies. Children in out-of-home care often show similar characteristics to those with AD. Since COVID-19 has led to interruptions in psychotherapy for children with mental health problems and to potentially reduced resources to implement treatment strategies in daily life in families or in out-of-home care, these children might show a particularly strong increase in stress levels. In this study, 512 families of children without AD and 269 families of children with AD reported on COVID-19-related stress. The sample comprised screened community, clinical, and out-of-home care samples. Sociodemographic factors, characteristics of child and caregiver before the pandemic, and perceived change in external conditions due to the pandemic were examined as potential risk or protective factors. Interestingly, only small differences emerged between families of children with and without AD or between subsamples: families of children with AD and families in out-of-home care were affected slightly more, but in few domains. Improvements and deteriorations in treatment-related effects balanced each other out. Overall, the most stable and strongest risk factor for COVID-19-related stress was perceived negative change in external conditions-particularly family conditions and leisure options. Additionally, caregiver characteristics emerged as risk factors across most models. Actions to support families during the pandemic should, therefore, facilitate external conditions and focus on caregiver characteristic to reduce familial COVID-19-related stress. Trial registration: German Clinical Trials Register (DRKS), ADOPT Online: DRKS00014963 registered 27 June 2018, ADOPT Treatment: DRKS00013317 registered 27 September 2018, ADOPT Institution: DRKS00014581 registered 04 July 2018.


Intravenous leiomyomatosis: a rare cause of right sided cardiac obstruction.
Intravenous leiomyomatosis involving the right side of the heart is an unusual cause of outflow obstruction. Evaluation of the patient should be directed not only at intracardiac chambers but also at the inferior vena cava. This should include angiography and MRI or CAT scanning. Echocardiography is an important contributory investigation. Surgical therapy should be directed at complete removal of the tumor as recurrence has been reported if a less than complete resection has been performed. Hormonal manipulation has been attempted with variable results.


Eco-friendly bacteria-killing by nanorods through mechano-puncture with top selectivity.
Nanorods can induce mechano-puncture of Staphylococcus aureus (S. aureus) that often impairs osseointegration of orthopedic implants, while the critical nanorod top sharpness able to puncture S. aureus and the predominant contributor between top sharpness and length to mechano-puncture activity remains elusive. Herein, we fabricated three kinds of Al2O3-wrapped nanorods patterned arrays with different lengths and top sharpness. The top-sharp nanorods have lengths of 469 and 884 nm and the shorter show a length identical to the top-flat nanorods. Driven by the equivalent adhesive force of S. aureus, the top-flat nanorods deform cell envelops, showing a bacteriostatic rate of 29% owing to proliferation-inhibited manner. The top-sharp nanorods puncture S. aureus, showing a bactericidal rate of 96% for the longer, and 98% for the shorter that simultaneously exhibits fair osseointegration in bacteria-infected rat tibias, identifying top sharpness as a predominate contributor to mechano-puncture activity. Based on finite-element simulation, such top-flat nanorod derives the maximum stress (Smax) of 5.65 MPa on cell wall, lower than its ultimate-tensile-strength (13 MPa); while such top-sharp and shorter nanorod derives Smax of 20.15 MPa to puncture cell envelop. Moreover, a critical top conical angle of 138° is identified for nanorods able to puncture S. aureus.


Radiolabeled monoclonal antibody B72.3 localization in metastatic lesions of colorectal cancer patients.
We have previously demonstrated a high degree of selective binding of monoclonal antibody (MAb) B72.3 to carcinomas of the colon, ovary, and breast in contrast to normal adult tissues using in vitro assays. In this report we demonstrate selective tumor localization in colorectal cancer patients after intravenously administering 131I-labeled MAb B72.3 IgG. Radiolocalization Indices (RI) (i.e. cpm 131I-labeled MAb per gram of tumor vs cpm per gram of normal tissues), were obtained by direct analyses of biopsy materials. Using an RI of greater than or equal to 3 as a positive localization, tumor lesions in various sites from 17/20 patients scored positive. In eight of these patients, all tumor lesions demonstrated RIs of greater than 3, while in five patients RIs of some lesions were greater than 10 and as high as 30-46. Seventy percent (99/142) of the tumor lesions showed RIs of greater than 3, while only 12 of 210 histologically confirmed normal tissues examined showed RIs of greater than 3. These tissues were either adjacent to the tumor or the draining tumor masses or, as in the case of two patients, was caused by high levels of circulating immune complexes that deposited in the spleen. Positive scintigraphic images (confirmed at surgery) were observed in 14/27 patients. No toxicity or adverse reactions were observed with either MAb. These studies provide absolute quantitative analyses of the actual delivery of radiolabeled MAb to carcinoma lesions vs a wide range of adjacent and distal normal tissues and establishes the means for other diagnostic and potential therapeutic applications of this antibody alone, or in combinations with other monoclonal antibodies.


Diagnostic laparoscopy is needed after abnormal hysterosalpingography to prevent over-treatment with IVF.
The additional value of laparoscopy was investigated with respect to diagnosis and further treatment decisions after abnormal hysterosalpingography (HSG) and prior to intrauterine insemination (IUI). In a retrospective chart review, the number of patients with abnormal HSG who finally need IVF treatment based on the laparoscopic findings was evaluated. Independent of whether HSG showed unilateral or bilateral tubal pathology, IVF was the final treatment decision in only 74 (29%) cases where laparoscopy showed bilateral abnormalities. IUI treatment was advised in 121 (48%) patients with laparoscopically normal findings or unilateral abnormalities. Fifty-seven (23%) patients were treated by IUI after receiving laparoscopic surgery of unilateral adhesions or endometriosis stage 1-2 or after ablation of moderate-severe endometriosis in a second operation. In cases of bilateral tubal abnormalities revealed by HSG, bilateral pathology was confirmed by laparoscopy in at least 58 (46%) patients and they were advised to be treated by IVF after laparoscopy. The agreement between abnormalities found by HSG and abnormalities found by laparoscopy requiring IVF treatment was poor even when HSG showed bilateral pathology. Based on these findings, it is concluded that laparoscopy is mandatory after abnormal HSG findings in the work-up prior to IUI to prevent over-treatment with IVF.


Role of radiotherapy in cavernous hemangioma liver.
To study the effectiveness of local radiotherapy for controlling cavernous hemangioma of liver. This is a retrospective analysis of four diagnosed cases of cavernous hemangiomas of the liver treated with radiotherapy. Hepatic irradiation was given in a tumor dose of 30 Gy in 15 fractions over 3 weeks period. Three of the four cases showed a complete clinical regression of the liver lesions over a period of 8-14 months, but in one case there was only 75% regression of the mass at 12 months of follow up. Localized radiotherapy is effective in the treatment of giant cavernous hemangiomas of the liver and a tumor dose of 30 Gy is optimum with minimal morbidity.


Genetic polymorphisms of 54 mitochondrial DNA SNP loci in Chinese Xibe ethnic minority group.
We analyzed the genetic polymorphisms of 54 mitochondrial DNA (mtDNA) variants in Chinese Xibe ethnic minority group. A total of 137 unrelated healthy volunteers from Chinese Xibe group were the objects of our study. Among the selected loci, there were 51 variable positions including transitions and transversions, and single nucleotide transitions were common (83.93%) versus transversions. These variations defined 64 different mtDNA haplotypes exclusive of (CA)n and 9 bp deletion variation. The haplotype diversity and discrimination power in Xibe population were 0.9800 ± 0.004 and 0.9699, respectively. Besides, we compared Xibe group with 18 other populations and reconstructed a phylogenetic tree using Neighbor-Joining method. The result revealed that Xibe group was a close to Xinjiang Han and Yanbian Korean groups. Our data also indicated that Xibe group has a close relationship with Daur and Ewenki groups, which is reflected by the history that Xibe was influenced by Daur and Ewenki groups during the development of these groups. In conclusion, the variants we studied are polymorphic and could be used as informative genetic markers for forensic and population genetic application.


[Prophylaxis of cytomegalovirus infection in pancreatic transplantation].
Pancreatic transplantation carries a higher risk of cytomegalovirus (CMV) infection than renal transplantation alone. The management of CMV disease in pancreatic transplantation depends on the risk indicated by the donor's and recipient's serological profiles (CMV IgG) and the use of antibodies as immunosuppressive therapy (especially thymoglobulin). Most clinical guidelines recommend the use of prophylaxis in preference to preemptive therapy in both donor (D)+/recipient (R)- and D+/R+ pancreatic transplantations. In combinations with highest risk (D+/R-), prophylaxis with valganciclovir 900mg per day for 3 to 6 months is recommended, adjusted to renal funtion. In D+/R+ combinations, if antibody therapy was used in the transplant or in rejection, valgancioclovir prophylaxis is also recommended for 1 to 3 months. When prophylaxis is finished, in both cases, viral load determination (quantitative polymerase chain reaction of CMV) or antigenemia should be carried out for the first year. In D-/R-combinations, preemptive therapy can be considered with determinations of viral load or antigenemia at each follow-up visit during the first year. Once prophylaxis has been suspended, special attention should be paid to the development of delayed CMV disease.


Chemometrics analysis of petroleum hydrocarbons sources in the street dust, runoff and sediment of urban rivers in Anzali port - South of Caspian Sea.
Major sources of petroleum hydrocarbons in the south of Caspian Sea (Anzali city) have been investigated through an approach which combines Gas Chromatography-Mass Spectrometry with Principal Component Analysis (PCA) and Multivariate Curve Resolution-Alternating Least Squares chemometric methods. Terpane, catagenetic hopane and sterane hydrocarbons were analyzed in the street dust, filtered sediments of runoff, soluble runoff water and river sediment samples as well as in automobiles exhaust, tires, asphalt, engine oil, gasoline and diesel samples, as possible sources of these hydrocarbons. PCA and MCR-ALS results showed that a large part of the analyzed hydrocarbons in street dust, runoffs and in some of the river sediment samples can be explained by the proposed known sources, while the observed variation of hydrocarbon concentrations in many of the river sediment samples was not much affected by the proposed known sources, and they were most probably receiving other pollution sources not included in our study. This study also has shown that results obtained from hydrocarbon marker molecular ratios, to identify petroleum pollution sources in the environments, are in agreement with those obtained from pollution sources resolved by MCR-ALS simultaneous analysis of all samples and variables.


Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat heart.
We examined the effects on infarct size and mitochondrial function of ischemic (Isch), cyclosporine A (CsA) and isoflurane (Iso) preconditioning and postconditioning in the in vivo rat model. Anesthetized open-chest rats underwent 30 min of ischemia followed by either 120 min (protocol 1: infarct size assessment) or 15 min of reperfusion (protocol 2: assessment of mitochondrial function). All treatments administered before the 30-min ischemia (Pre-Isch, Pre-CsA, Pre-Iso) significantly reduced infarct as compared to control. In contrast, only Post-Iso significantly reduced infarct size, while Post-Isch and Post-CsA had no significant protective effect. As for the postconditioning-like interventions, the mitochondrial calcium retention capacity significantly increased only in the Post-Iso group (+58 % vs control) after succinate activation. Only Post-Iso increased state 3 (+177 and +62 %, for G/M and succinate, respectively) when compared to control. Also, Post-Iso reduced the hydrogen peroxide (H2O2) production (-46 % vs control) after complex I activation. This study suggests that isoflurane, but not cyclosporine A, can prevent lethal reperfusion injury in this in vivo rat model. This might be related to the need for a combined effect on cyclophilin D and complex I during the first minutes of reperfusion.


Why anticipatory postural adjustments in gait initiation need to be modified when stepping up onto a new level?
The study examined why anticipatory postural adjustments (APA) associated to gait initiation in a stepping up to a new level situation (SU) are reduced as compared to a level walking situation (LW), as previously reported. Five young adults performed gait initiation in both situations at normal and fast speed. Data from a force platform provided gait parameters related to the motion of the body's centre of mass (CM) on the anteroposterior (progression) and vertical axes. The electromyographic activity of the soleus of the stance limb (SOst) and the vastus lateralis of the swing limb (VLsw) were analyzed prior to and after the onset of the double stance phase. The results showed that APA and progression CM velocity at the time of foot contact were smaller in SU, whereas the peak of this velocity was similar in both situations. Thus, the change in progression velocity during the double stance phase had to be greater in SU than in LW. In both velocity conditions, the activity of SOst stopped after the time of foot contact in both situations, but clearly later in SU. So, this ankle plantar flexor muscle would be involved not only in the change of body lift but also in forward CM progression. The latter role of this muscle brought supporting evidence for the reduction of APA in SU, enabling the peak of progression velocity to be similar in both situations. Only in SU, the timing of activation of VLsw and deactivation of SOst strongly co-varied, showing the implementation of a motor synergy to fulfil the new requirements of the task, i.e. body lift.


Electroencephalogram alertness responses to blue light stimulus in elderly people with cataract.
Daytime blue light exposure can reduce fatigue and increase alertness in young healthy adults. Little is known of the daytime blue light influence on alertness in elders. A prospective with-in subject study was carried out in Peking University Third Hospital to evaluate the impact of cataract surgery on visual functions and the electroencephalogram alertness response to blue light stimulus before and after surgery. 14 participants diagnosed with age-related cataract were scheduled for monocular cataract surgery with ultraviolet-filtering intraocular lens (IOL) implantation. Best corrected visual acuity (BCVA), color discrimination and electroencephalogram results were measured before and after surgery. Exposure to blue light resulted in decreased delta (0.25-3.00 Hz) activity and increased beta (13.25-30.00 Hz) activity both before and after cataract surgery. Significant improvements in the BCVA and Farnsworth-Munsell-100-hue total error scores were found after cataract surgery. The partial error scores in the red-yellow, green blue-blue, and blue purple-purple red bands also showed significant differences, with the green blue-blue band showing the most obvious improvement. Day-time blue light stimulus can increase alertness in elderly people with significant cataracts. Cataract surgery with ultraviolet-filtering IOL implantation can increase light, particularly blue light transmittance. Opaque lens removal does not increase the alertness responses to blue light 1 day after surgery. Nevertheless, the increase in light especially blue light perception can be beneficial for the health of elder people in the long run.


Associations Between Dynamic Contrast Enhanced Magnetic Resonance Imaging and Clinically Relevant Histopathological Features in Breast Cancer: A Multicenter Analysis.
To provide data regarding relationships between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE MRI) and prognostic factors in breast cancer (BC). Data from 4 Centers (200 female patients, mean age, 51.2±11.5 years) were acquired. The following data were collected: histopathological diagnosis, tumor grade, stage, hormone receptor status, KI 67, and DCE MRI values including Ktrans (volume transfer constant), Ve (volume of the extravascular extracellular leakage space (EES) and Kep (diffusion of contrast medium from the EES back to the plasma). DCE MRI values between different groups were compared using the Mann-Whitney U-test and by the Kruskal-Wallis H test. The association between DCE MRI and Ki 67 values was calculated by the Spearman's rank correlation coefficient. DCE MRI values of different tumor subtypes overlapped significantly. There were no statistically significant differences of DCE MRI values between different tumor grades. All DCE MRI parameters correlated with KI-67: Ktrans, r=0.44, p=0.0001; Ve, r=0.34, p=0.0001; Kep, r=0.28, p=0.002. ROC analysis identified a Ktrans threshold of 0.3 min-1 for discrimination of tumors with low KI-67 expression (<25%) and high KI-67 expression (≥25%): sensitivity, 75.5%, specificity, 73.0%, accuracy, 74.0%, AUC, 0.78. DCE MRI values overlapped between tumors with different T and N stages. Ktrans, Kep, and Ve cannot be used as reliable a surrogate marker for hormone receptor status, tumor stage and grade in BC. Ktrans may discriminate lesions with high and lower proliferation activity.


Erratum: Relationship Between MicroRNA Signature and Arterial Stiffness in Patients With Ischemic Stroke.
This corrects the article on p. 28 in vol. 19, PMID: 36606643.


Diagnostic Usefulness of Low-Dose Nonenhanced Computed Tomography With Coronal Reformations in Patients With Suspected Acute Appendicitis: A Comparison With Standard-Dose Computed Tomography.
The aims of the study were to evaluate the usefulness of low-dose (LD) nonenhanced CT (NECT) with coronal reformation in diagnosing acute appendicitis and to compare LD NECT with standard-dose (SD) NECT and SD contrast-enhanced CT (CECT). A total of 452 patients suspected of having acute appendicitis underwent CT using a scan 1 (SD NECT and SD CECT1, n = 182) or a scan 2 protocol (LD NECT and SD CECT2, n = 270). The diagnostic performance and interobserver agreement for diagnosing acute appendicitis were compared. Although the area under the curves of both reviewers of LD NECT were lower than those of SD CECT2, area under the curves of both reviewers for SD NECT were not significantly different for SD CECT1 and LD NECT (all P > 0.05). The interobserver agreements within each scan were excellent (all κ > 0.8). Low-dose NECT with coronal reformation showed high diagnostic performance and can be used as the first-line imaging tool in the work-up of patients with suspected acute appendicitis.